Pharmacology

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Adverse Effects of Phenobarbital

Phenytoin (Dilantin)

The most common adverse effects relate to CNS depression and its effects on body function: depression, confusion, drowsiness, lethargy, fatigue, constipation, dry mouth, anorexia, cardiac arrhythmias and changes in blood pressure, urinary retention, and loss of libido. Specifically, the hydantoins may cause severe liver toxicity, bone marrow suppression, gingival hyperplasia, potentially serious dermatological reactions (e.g., hirsutism, Stevens-Johnson syndrome), and frank malignant lymphoma, all of which are directly related to cellular toxicity phenytoin (diphenylhydantoin)FEN-i-toe-inDilantin-125, Dilantin Infatabsphenytoin sodiumDilantin, PhenytekTherapeutic class: AnticonvulsantsPharmacologic class: Hydantoin derivatives Available Forms phenytoin Oral suspension: 125 mg/5 mL* Tablets (chewable): 50 mg phenytoin sodium Injection: 50 mg/mL (46 mg base) phenytoin sodium (extended) Capsules (extended-release): 30 mg (27.6 mg base); 100 mg (92 mg base); 200 mg (184 mg base); 300 mg (276 mg base) Indications & Dosages To control tonic-clonic (grand mal) and complex partial (temporal lobe) seizures Adults: Highly individualized. Initially, 100 mg (immediate-release, extended-release) PO t.i.d. Adjust dosage at no less than 7- to 10-day intervals until desired response is obtained. Usual range is 300 to 600 mg daily. If patient is stabilized on 100-mg extended-release capsules t.i.d., once-daily dosing with 300-mg extended-release capsules is possible as an alternative. Or, 125 mg oral solution t.i.d. in patients without previous treatment. May increase to 625 mg daily.Children: 5 mg/kg/day in two to three equally divided doses. Adjust dosage at no less than 7- to 10-day intervals. Usual maintenance dose range is 4 to 8 mg/kg daily. Maximum dose is 300 mg/day.To control tonic-clonic (grand mal) and complex partial (temporal lobe) seizures in patients requiring a loading doseAdults: Initially, 1 g (extended-release) PO divided into three doses, which are given at 2-hour intervals with careful monitoring. Begin maintenance dosage of 100 mg (extended-release) PO t.i.d. to q.i.d. 24 hours after loading dose.To prevent and treat seizures occurring during neurosurgeryAdults: 100 to 200 mg IM every 4 hours during and after surgery.Status epilepticusAdults: Loading dose of 10 to 15 mg/kg IV (1 to 1.5 g may be needed) at a rate not exceeding 50 mg/minute; then maintenance dosage of 100 mg PO or IV every 6 to 8 hours.Children: Loading dose of 15 to 20 mg/kg IV, at a rate not exceeding 1 to 3 mg/kg/minute or 50 mg/minute, whichever is slower; then highly individualized maintenance dosages.Elderly patients: May need lower dosages. Administration POGive divided doses with or after meals to decrease adverse GI reactions.For chewable tablets, patient may chew thoroughly before swallowing or may swallow whole.Shake suspension well before use. Administer dose using a calibrated oral dosing syringe.Different oral forms aren't interchangeable.Don't crush or allow patient to chew extended-release capsules.For oral suspension, withhold enteral feedings for 1 hour before and 1 hour after giving drug.IVClear tubing with NSS. Use only clear solution for injection. A slight yellow color is acceptable.To give as an infusion, dilute in NSS to a final concentration of phenytoin sodium in the solution of no less than 5 mg/mL. Begin infusion immediately after mixture has been prepared. Infusion must be completed within 1 to 4 hours.Infusion must begin within 1 hour after preparation and should run through an in-line filter.Check patency of catheter before giving. Monitor site for extravasation because it can cause severe tissue damage.Black Box Warning: Drug must be administered slowly. In adults, don't exceed 50 mg/minute IV. In children, administer drug at a rate not exceeding 1 to 3 mg/kg/minute or 50 mg/minute, whichever is slower because of the risk of severe hypotension and cardiac arrhythmias.Follow each injection with injection of sterile NSS through the same needle or catheter.If possible, don't give by IV push into veins on back of hand to avoid purple glove syndrome. Inject into larger veins or central venous catheter, if available.Continuous monitoring of BP and ECG during IV administration is essential.Discard 4 hours after preparation. Don't refrigerate.Incompatibilities: Amikacin, aminophylline, amphotericin B, bretylium, cephapirin, ciprofloxacin, D5W, diltiazem, dobutamine, enalaprilat, fat emulsions, hydromorphone, insulin (regular), levorphanol, lidocaine, lincomycin, meperidine, morphine sulfate, nitroglycerin, norepinephrine, other IV drugs or infusion solutions, pentobarbital sodium, potassium chloride, procaine, propofol, streptomycin, sufentanil citrate, theophylline, vitamin B complex with C. If giving as an infusion, don't mix drug with D5W because it will precipitate.IMGive IM only if dosage adjustments are made; IM dose is 50% greater than oral dose.Be aware that drug may precipitate at injection site, cause pain, and be absorbed erratically.Don't give by IM route for treatment of status epilepticus as peak plasma levels may not be attained for up to 24 hours. Action May stabilize neuronal membranes and limit seizure activity either by increasing efflux or decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses.RouteOnsetPeakDurationPOUnknown11/2- 3 hrUnknownPO (extended-release)Unknown4-12 hrUnknownIVImmediate1-2 hrUnknownIMUnknownUnknownUnknownHalf-life: Varies with dose and concentration changes. Adverse Reactions CNS: ataxia, decreased coordination, mental confusion, slurred speech, dizziness, headache, insomnia, nervousness, twitching, peripheral neuropathy, vertigo. CV: bradycardia, periarteritis nodosa, hypotension, CV shock. EENT: diplopia, nystagmus, blurred vision, thickening of facial features. GI: gingival hyperplasia, nausea, vomiting, constipation. Hematologic: agranulocytosis, leukopenia, pancytopenia, thrombocytopenia, macrocythemia, megaloblastic anemia. Hepatic: toxic hepatitis. Metabolic: hyperglycemia. Musculoskeletal: osteomalacia. Skin: SJS, toxic epidermal necrolysis, bullous or purpuric dermatitis, discoloration of skin if given by IV push in back of hand, exfoliative dermatitis, hypertrichosis, inflammation at injection site, necrosis, pain, photosensitivity reactions, scarlatiniform or morbilliform rash. Other: lymphadenopathy, SLE. Interactions Drug-drugAcetaminophen: May decrease the therapeutic effects of acetaminophen and increase the incidence of hepatotoxicity. Monitor for toxicity.Amiodarone, antihistamines, chloramphenicol, cimetidine, cycloserine, diazepam, fluconazole, isoniazid, metronidazole, omeprazole, phenylbutazone, salicylates, sulfonamides, ticlopidine, valproate: May increase phenytoin activity and toxicity. Monitor patient for toxicity and adjust dosage as needed.Atracurium, cisatracurium, pancuronium, rocuronium, vecuronium: May decrease the effects of nondepolarizing muscle relaxant. May need to increase the nondepolarizing muscle relaxant dose.Barbiturates, carbamazepine, dexamethasone, diazoxide, folic acid, rifampin: May decrease phenytoin activity. Monitor phenytoin level.Carbamazepine, cardiac glycosides, doxycycline, quinidine, theophylline, valproic acid: May decrease effects of these drugs. Monitor patient.Colesevelam: May impair phenytoin absorption. Administer phenytoin 4 hours prior to colesevelam.Corticosteroids: May decrease phenytoin level and corticosteroid effects. Measure phenytoin level and adjust phenytoin and corticosteroid dosages as needed.Cyclosporine: May decrease cyclosporine levels, risking organ rejection. Monitor cyclosporine levels closely and adjust dosage as needed.Delavirdine: May cause loss of virologic response. Use together is contraindicated.Disulfiram: May increase toxic effects of phenytoin. Monitor phenytoin level closely and adjust dosage as needed.Efavirenz: May increase phenytoin level and decrease efavirenz level. Monitor patient and adjust dosages of either or both drugs if needed.Erlotinib: May increase phenytoin level and decrease erlotinib level. Monitor patient response.Hormonal contraceptives: May increase phenytoin level and decrease contraceptive effectiveness. Monitor phenytoin level and adjust dosage if needed. Alternative form of contraception is recommended during therapy.Isoniazid: May increase phenytoin level. Monitor phenytoin level and patient for toxicity.Lithium: May increase toxicity of lithium, despite normal lithium levels. Monitor patient for adverse effects.Methylphenidate: May increase phenytoin level. Monitor phenytoin level and adjust phenytoin dosage as needed.Protease inhibitors (fosamprenavir, lopinavir-ritonavir): May decrease levels of both drugs. Measure phenytoin level and adjust dosage of phenytoin or protease inhibitor as needed.Warfarin: May increase effects of warfarin. Monitor patient for bleeding.Drug-herbSt. John's wort: May decrease phenytoin level. Monitor phenytoin level.Drug-foodEnteral tube feedings: May interfere with absorption of oral drug. Stop enteral feedings for 2 hours before and 2 hours after drug use. Monitor serum drug level more frequently.Drug-lifestyleAlcohol use (long-term): May decrease drug's activity. Strongly discourage use together. Effects on Lab Test Results May increase alkaline phosphatase, GGT, and glucose levels. May decrease urinary 17-hydroxysteroid, 17-ketosteroid, and Hb levels and hematocrit. May decrease platelet, WBC, RBC, and granulocyte counts. May increase urine 6-hydroxycortisol excretion. May decrease dexamethasone suppression and metyrapone test results. May decrease T3 and T4 levels. May falsely reduce protein-bound iodine or free T4 level test results. Contraindications & Cautions Contraindicated in patients hypersensitive to hydantoin, in those taking delavirdine, and in those with a history of prior acute hepatotoxicity attributable to phenytoin. Parenteral phenytoin is also contraindicated in patients with sinus bradycardia, SA block, second- or third-degree AV block, or Adams-Stokes syndrome. Use cautiously in patients with hepatic dysfunction, hypotension, myocardial insufficiency, diabetes, or respiratory depression; in elderly or debilitated patients; and in those receiving other hydantoin derivatives. Elderly patients tend to metabolize drug slowly and may need reduced dosages. Dialyzable drug: Yes. Overdose Signs & Symptoms: Ataxia, dysarthria, nystagmus, hyperreflexia, lethargy, nausea, slurred speech, tremor, vomiting, coma, hypotension, circulatory and respiratory depression. Pregnancy-Lactation-Reproduction Drug may cause fetal harm. Prenatal exposure may increase the risk of congenital malformations and other adverse outcomes. Avoid use during pregnancy when possible and monotherapy is recommended. If drug is necessary, pregnant women may need dosage adjustments to maintain clinical response. Therapeutic dose needs usually increase during pregnancy. A potentially life-threatening bleeding disorder related to decreased levels of vitamin K-dependent clotting factors that may occur in neonates exposed to phenytoin in utero can be prevented with vitamin K administration to the mother before delivery and to the neonate after birth. Drug may interact with hormone-containing contraceptives; use of nonhormonal contraceptives is recommended. Women exposed to drug during pregnancy should enroll in the North American AED Pregnancy Registry (1-888-233-2334). Drug appears in human milk. Breastfeeding isn't recommended. Nursing Considerations Black Box Warning: Carefully monitor cardiac status during and after IV administration. CV toxicity may increase with infusion rates above those recommended. Toxicity has also been reported at or below the recommended infusion rate. Reduction in administration rate or discontinuation of dosing may be needed.Asian patients who have tested positive for the allele HLA-B∗1502 have a potentially increased risk of serious skin reactions, including SJS and toxic epidermal necrolysis. Monitor these patients carefully.If rash appears, stop drug. If rash is scarlatiniform or morbilliform, resume drug after rash clears. If rash reappears, stop therapy. If rash is exfoliative, purpuric, or bullous, don't resume drug.Don't stop drug suddenly because this may worsen seizures. Call prescriber immediately if adverse reactions develop.Monitor drug level. Therapeutic level of total phenytoin is 10 to 20 mcg/mL in adults and children and 8 to 15 mcg/mL in neonates. Therapeutic range of free phenytoin is 1 to 2 mcg/mL.Long-term use may decrease bone mineral density. Vitamin D and calcium supplements may be needed.Because of the risks of cardiac and local toxicity with parenteral phenytoin, use oral form when possible.Monitor CBC and calcium level every 6 months, and periodically monitor hepatic function. If megaloblastic anemia is evident, prescriber may order folic acid and vitamin B12.Maintain seizure precautions, as needed.Alert: Closely monitor all patients for changes in behavior that may indicate worsening of suicidal thoughts or behavior or depression.Watch for gingival hyperplasia, especially in children.Alert: Doubling the dose doesn't double the level but may cause toxicity. Consult pharmacist for specific dosing recommendations.If seizure control is established with divided doses, once-daily dosing may be considered.Look alike-sound alike: Don't confuse phenytoin with mephenytoin, fosphenytoin, phenelzine, phentermine, or phenobarbital. Don't confuse Dilantin with Dilaudid, diltiazem, or Dipentum. Patient Teaching Tell patient to report all adverse reactions and to notify prescriber if rash develops. Advise patient and caregivers to immediately report changes in behavior that may indicate worsening of suicidal thoughts or behavior or depression. Advise patient to avoid driving and other potentially hazardous activities that require mental alertness until drug's CNS effects are known. Advise patient not to change brands or dosage forms once stabilized on therapy. Dilantin capsules are the only oral form that can be given once daily. Toxic levels may result if any other brand or form is given once daily. Dilantin tablets and oral suspension should never be taken once daily. Tell patient not to use capsules that are discolored. Advise patient to avoid alcohol. Warn patient and parents not to stop drug abruptly. Stress importance of good oral hygiene and regular dental exams. Surgical removal of excess gum tissue may be needed periodically if dental hygiene is poor. Advise female patient of childbearing potential who isn't planning a pregnancy to use effective contraception; warn her that there's a potential for decreased hormonal contraceptive efficacy. Instruct female patient to notify prescriber if she becomes pregnant or intends to become pregnant during therapy, and if she's breastfeeding or intends to breastfeed during therapy. Advise patient that drug may cause an increase in blood glucose levels.

Propofol (Diprivan)

*class*: general anesthetic *Indication*: anesthesia, induction, sedation *Action*: hypnotic, produces amnesia *Nursing Considerations*: - use cautiously with CVD, lipid disorder, increased ICP - can cause apnea, bradycardia, hypotension - burning and pain at insertion site - can turn urine green - assess respiratory status and hemodynamics - maintain patent airway - assess level of sedation SAFETY ALERT! propofol PROE-po-foleDiprivanTherapeutic class: HypnoticsPharmacologic class: Phenol derivatives Available Forms Injection∗: 10 mg/mL Indications & Dosages To induce general anesthesia Adults younger than age 55 classified as American Society of Anesthesiologists (ASA) Physical Status (PS) category I or II: 2 to 2.5 mg/kg IV. Give in 40-mg boluses every 10 seconds until desired response is achieved.Children ages 3 to 16 classified as ASA PS I or II: 2.5 to 3.5 mg/kg IV over 20 to 30 seconds.Adjust-a-dose: In geriatric, debilitated, hypovolemic, or ASA PS III or IV patients, give half the usual induction dose, in 20-mg boluses, every 10 seconds. For cardiac anesthesia, give 20 mg (0.5 to 1.5 mg/kg) every 10 seconds until desired response is achieved. For neurosurgical patients, give 20 mg (1 to 2 mg/kg) every 10 seconds until desired response is achieved.To maintain anesthesiaHealthy adults younger than age 55: 0.1 to 0.2 mg/kg/minute (6 to 12 mg/kg/hour) IV. Or, 25- to 50-mg intermittent boluses, p.r.n.Healthy children ages 2 months to 16 years: Initially, 200 to 300 mcg/kg/minute for 30 minutes, then 125 to 150 mcg/kg/minute (7.5 to 9 mg/kg/hour) IV titrated to achieve desired clinical effect. Younger children may require higher maintenance infusion rates than older children.Adjust-a-dose: In elderly, debilitated, hypovolemic, or ASA PS III or IV patients, give half the usual maintenance dose (0.05 to 0.1 mg/kg/minute or 3 to 6 mg/kg/hour). For cardiac anesthesia with secondary opioid, 100 to 150 mcg/kg/minute; low dose with primary opioid, 50 to 100 mcg/kg/minute. For neurosurgical patients, 100 to 200 mcg/kg/minute (6 to 12 mg/kg/hour).Monitored anesthesia careHealthy adults younger than age 55: Initially, 100 to 150 mcg/kg/minute (6 to 9 mg/kg/hour) IV for 3 to 5 minutes or a slow injection of 0.5 mg/kg over 3 to 5 minutes. For maintenance dose, give infusion of 25 to 75 mcg/kg/minute (1.5 to 4.5 mg/kg/hour) for first 10 to 15 minutes, then reduce dosage to 25 to 50 mcg/kg/minute or incremental 10- or 20-mg boluses.Adjust-a-dose: In elderly, debilitated, or ASA PS III or IV patients, give 80% of usual adult maintenance dose. Don't use rapid bolus.To sedate intubated ICU patientsAdults: Initially, 5 mcg/kg/minute (0.3 mg/kg/hour) IV for 5 minutes. Increments of 5 to 10 mcg/kg/minute (0.3 to 0.6 mg/kg/hour) over 5 to 10 minutes may be used until desired sedation is achieved. Maintenance rate, 5 to 50 mcg/kg/minute (0.3 to 3 mg/kg/hour). Administration IVAlert: Maintain strict aseptic technique when handling solution. Drug can support growth of microorganisms; don't use if solution might be contaminated. Don't access vial more than once or use on multiple patients.Shake well.Dilute only with D5W. Don't dilute to less than 2 mg/mL.Don't use if emulsion shows evidence of separation.Don't infuse through a filter with a pore size smaller than 5 microns. Give via larger veins in arms to decrease injection-site pain.Titrate drug daily to maintain minimum effective level. Allow 3 to 5 minutes between dosage adjustments to assess effects.Discard tubing and unused portions of drug after 12 hours.Store between 40° and 77° F (4° and 25° C); don't freeze. Protect from light.Incompatibilities: Other IV drugs, blood and plasma. Action Unknown. Rapid-acting IV sedative-hypnotic.RouteOnsetPeakDurationIV<40 secUnknown10-15 minHalf-life: Initial (distribution) phase, about 2 to 10 minutes; second (redistribution) phase, 21 to 70 minutes; terminal (elimination) phase, 11/2 to 31 hours. Adverse Reactions CNS: dystonic or choreiform movement. CV: bradycardia, hypotension, HTN, decreased cardiac output. Metabolic: hyperlipidemia. Respiratory: apnea, respiratory acidosis. Skin: rash, pruritus. Other: burning or stinging at injection site. Interactions Drug-drugInhaled anesthetics (enflurane, halothane, isoflurane), opioids (alfentanil, fentanyl, meperidine, morphine), sedatives (barbiturates, benzodiazepines, chloral hydrate, droperidol): May increase anesthetic and sedative effects and further decrease BP and cardiac output. Monitor patient closely.Drug-lifestyleAlcohol use: May enhance CNS depressant effect of alcohol. Monitor therapy. Effects on Lab Test Results May increase serum triglyceride levels. Contraindications & Cautions Contraindicated in patients hypersensitive to drug or its components (soybean oil, glycerol, egg lecithin, disodium edetate, sodium hydroxide); in patients with allergies to eggs, egg products, soybeans, or soy products; and in those unable to undergo general anesthesia or sedation. Alert: Repeated or lengthy use of general anesthetic and sedation drugs during surgeries or procedures in children younger than age 3 or in pregnant women during the third trimester may affect the development of children's brains. Weigh benefits of appropriate anesthesia in young children and pregnant women against risks. Drug isn't recommended for obstetric surgery, including cesarean deliveries, because of potential neonatal depression. Use cautiously in patients who are hemodynamically unstable or who have seizures, disorders of lipid metabolism, or increased ICP. Dialyzable drug: Unknown. Overdose Signs & Symptoms: Cardiorespiratory depression. Pregnancy-Lactation-Reproduction There are no adequate studies in pregnant women. Use only if clearly needed. Drug isn't recommended for obstetric uses as it may cause neonatal CNS and respiratory depression. Drug appears in human milk. Avoid use in breastfeeding women. Nursing Considerations If drug is used for prolonged sedation in ICU, urine may turn green. For general anesthesia or monitored anesthesia care sedation, trained staff not involved in the surgical or diagnostic procedure should give drug. For ICU sedation, persons skilled in managing critically ill patients and trained in cardiopulmonary resuscitation and airway management should give drug. Continuously monitor vital signs. Alert: The FDA issued an alert after receiving reports of chills, fever, and body aches in several clusters of patients shortly after patients received propofol for sedation or general anesthesia. Various lots of the drug were tested, but no toxins, bacteria, or other signs of contamination were found. The FDA advises all health care providers to carefully follow the handling and use sections of the prescribing information for this drug. They recommend that all patients be evaluated for possible reactions following use of the drug, and that anyone experiencing signs of acute febrile reactions be evaluated for possible bacterial sepsis. They ask that any adverse events following the use of propofol be reported to MedWatch. Monitor patient at risk for hyperlipidemia for elevated triglyceride levels. Drug contains 0.1 g of fat (1.1 kcal)/mL. Reduce other lipid products if given together. Some formulations contain ethylenediaminetetraacetic acid, a strong metal chelator. Consider supplemental zinc during prolonged therapy and in patients predisposed to zinc deficiency (those with burns, sepsis, or diarrhea). Some formulations contain sodium metabisulfite, a sulfite, which may cause allergic-type reactions, including anaphylactic signs and symptoms and life-threatening or less severe asthmatic episodes, in certain susceptible people. When giving drug in the ICU, assess patient's CNS function daily to determine minimum dose needed. Stop drug gradually to prevent abrupt awakening and increased agitation. Drug may be misused. Manage drug to prevent risk of diversion. Look alike-sound alike: Don't confuse Diprivan with Ditropan or Diflucan. Patient Teaching Advise patient that performance of activities requiring mental alertness may be impaired for some time after drug use. Tell patient that abnormal dreams or anesthesia awareness may occur. Alert: Discuss with parents or caregivers of child younger than age 3 and with pregnant patients the benefits, risks, and appropriate timing of surgery or procedures requiring anesthetic and sedation drugs.

Indomethacin (Indocin)

Adult 75-150 mg/d PO in three to four divided doses. Pediatric (<2y) In special circumstances, 2mg/kg/d PO in divided doses Action May inhibit prostaglandin synthesis, to produce anti-inflammatory, analgesic, and antipyretic effects.RouteOnsetPeakDurationPO30 min2 hr4-6 hrIVImmediateImmediate4-6 hrPRUnknownUnknown4-6 hrHalf-life: Adults (mean), 41/2 hours; Tivorbex 71/2 hours. Adverse Reactions PO and rectal CNS: headache, dizziness, depression, fatigue, somnolence, syncope, vertigo.CV: edema, HTN.EENT: hearing loss, tinnitus.GI: pancreatitis, abdominal pain, constipation, diarrhea, dyspepsia, GI bleeding, nausea, peptic ulceration, vomiting.Other: hypersensitivity reactions.IVGU: hematuria, interstitial nephritis, proteinuria. Interactions Drug-drug ACE inhibitors (benazepril, enalaprilat), angiotensin II receptor blockers (candesartan, valsartan): May reduce antihypertensive effects; may worsen renal function in those with impaired renal function. Monitor patient closely.Aminoglycosides, cyclosporine, methotrexate: May enhance toxicity of these drugs. Avoid using together.Anticoagulants: May cause bleeding. Monitor patient closely.Antihypertensives: May decrease antihypertensive effect. Monitor patient closely.Antihypertensives, furosemide, thiazide diuretics: May impair response to both drugs. Avoid using together, if possible.Aspirin: May increase adverse reactions, including risk of GI toxicity. Avoid using together.Bisphosphonates: May increase risk of gastric ulceration. Monitor patient for symptoms of gastric irritation or GI bleeding.Corticosteroids: May increase risk of GI toxicity. Avoid using together.Cyclosporine: May increase cyclosporine toxicity. Use cautiously and monitor renal function.Diflunisal, probenecid: May decrease indomethacin excretion. Watch for increased indomethacin adverse effects.Digoxin: May prolong half-life of digoxin. Use together cautiously.Dipyridamole: May enhance fluid retention. Avoid using together.Lithium: May increase lithium level. Monitor patient for toxicity.Methotrexate: May increase methotrexate toxicity. Use together cautiously.Penicillamine: May increase bioavailability of penicillamine. Monitor patient closely.Phenytoin: May increase phenytoin level. Monitor patient closely.SSRIs: May increase risk of GI bleeding. Adjust dosage as needed.Triamterene: May cause nephrotoxicity. Avoid using together.Drug-herbAlfalfa, anise, bilberry, dong quai, garlic: May cause bleeding. Discourage use together.Senna: May inhibit diarrheal effects. Discourage use together.White willow: Herb and drug contain similar components. Don't use together.Drug-lifestyleAlcohol use: May cause GI toxicity. Discourage use together. Effects on Lab Test Results May increase potassium level. May decrease Hb level and hematocrit. May increase LFT values. Contraindications & Cautions Contraindicated in patients hypersensitive to drug and in those with a history of aspirin- or NSAID-induced asthma, rhinitis, or urticaria. Contraindicated in neonates with untreated infection, active bleeding, coagulation defects or thrombocytopenia, congenital heart disease needing patency of the ductus arteriosus, necrotizing enterocolitis, or significant renal impairment. Black Box Warning: NSAIDs can increase risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease.Black Box Warning: Risk of heart attack or stroke can occur as early as the first weeks of NSAID use. Risk appears greater at higher doses. Use lowest effective dose for shortest duration possible.Black Box Warning: NSAIDs may increase risk of serious GI adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients and patients with a prior history of peptic ulcer disease or GI bleeding are at greater risk for serious GI events.Alert: Avoid use in patients with severe HF unless benefits are expected to outweigh risk of worsening HF.Suppositories are contraindicated in patients with history of proctitis or recent rectal bleeding.Black Box Warning: Contraindicated for the treatment of perioperative pain after CABG surgery.Use cautiously in elderly patients, those with history of GI disease, and those with epilepsy, parkinsonism, hepatic or renal disease, CV disease, infection, and mental illness or depression.Safety and effectiveness in children age 14 and younger (age 17 and younger for Tivorbex) haven't been established.Dialyzable drug: Unknown.Overdose Signs & Symptoms: Drowsiness, lethargy, confusion, nausea, vomiting, paresthesia, numbness, aggressive behavior, disorientation, seizures, headache, dizziness, GI bleeding. Pregnancy-Lactation-Reproduction Alert: Drug can cause fetal harm starting at 30 weeks' gestation and cause premature closure of the ductus arteriosus; avoid use. Before 30 weeks' gestation, use during pregnancy only if potential benefit justifies potential risk to the fetus. Drug appears in human milk. Use in breastfeeding women isn't recommended by most manufacturers. Long-term use of NSAIDs in women of reproductive age may be associated with infertility that's reversible upon discontinuation of drug. Nursing Considerations Because of the high risk of adverse effects from long-term use, drug shouldn't be used routinely as an analgesic or antipyretic. Alert: Watch for and immediately evaluate signs and symptoms of heart attack (chest pain, shortness of breath or trouble breathing) or stroke (weakness in one part or side of the body, slurred speech). If ductus arteriosus reopens, a second course of one to three doses may be given. If ineffective, surgery may be needed. Watch for bleeding in patients receiving anticoagulants, patients with coagulation defects, and neonates. Because NSAIDs impair synthesis of renal prostaglandins, they can decrease renal blood flow and lead to reversible renal impairment, especially in patients with renal failure, HF, or hepatic dysfunction; in elderly patients; and in those taking diuretics. Monitor these patients closely. Drug causes sodium retention; watch for weight gain (especially in elderly patients) and increased BP in patients with HTN. Monitor patient for rash and respiratory distress, which may indicate a hypersensitivity reaction. Because of their antipyretic and anti-inflammatory actions, NSAIDs may mask signs and symptoms of infection. Black Box Warning: NSAIDs cause an increased risk of serious GI adverse events, including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. Elderly patients are at greater risk.Black Box Warning: NSAIDs may increase the risk of serious thrombotic events, MI, or stroke, which can be fatal. The risk may be greater with longer use or in patients with CV disease or risk factors for CV disease.Monitor patient on long-term oral therapy for toxicity by conducting regular eye exams, hearing tests, CBCs, and kidney function tests. Patient Teaching Tell patient to take oral dose with food, milk, or antacid to prevent GI upset. Alert: Advise patient to seek medical attention immediately if chest pain, shortness of breath or trouble breathing, weakness in one part or side of the body, or slurred speech occurs. Alert patient that using oral form with aspirin, alcohol, other NSAIDs, or corticosteroids may increase risk of adverse GI reactions. Teach patient signs and symptoms of GI bleeding (blood in vomit, urine, or stool; coffee-ground vomit; and black, tarry stools) and to notify prescriber immediately if any of these occurs. Tell patient to immediately report signs or symptoms of cardiac events, such as chest pain, shortness of breath, weakness, and slurred speech. Warn patient to avoid hazardous activities that require mental alertness until CNS effects are known. Tell patient to notify prescriber immediately if visual or hearing changes occur. Tell patient to notify prescriber if unexplained weight gain or edema occurs.

Baclofen (Lioresal)

Baclofen is available in oral and intrathecal forms and can be administered via a delivery pump for the treatment of central spasticity. Cyclobenzaprine is available in a controlled release oral form for continual control of the discomfort without repeated dosings. Methocarbamol is available in both oral and parenteral forms. Most of these agents are rapidly absorbed and metabolized in the liver. Baclofen is not metabolized, but like the other skeletal muscle relaxants, it is excreted in the urine. baclofen BAK-loe-fenGablofen, Lioresal IntrathecalTherapeutic class: Skeletal muscle relaxantsPharmacologic class: Gamma-aminobutyric acid derivatives Available Forms Intrathecal injection: 50 mcg/mL; 500 mcg/mL; 1,000 mcg/mL, 2,000 mcg/mL Tablets: 5 mg; 10 mg; 20 mg Indications & Dosages Adjust-a-dose (for all indications): For patients with impaired renal function, decrease oral and intrathecal doses.Spasticity in MS; spinal cord injuryAdults and children age 12 and older: Initially, 5 mg PO t.i.d. for 3 days; then 10 mg t.i.d. for 3 days, 15 mg t.i.d. for 3 days, 20 mg t.i.d. for 3 days. Increase daily dosage, based on response, to maximum of 80 mg (given as 20 mg q.i.d.).Adjust-a-dose: For patients with psychiatric or brain disorders and for elderly patients, increase dose gradually.To manage severe spasticity in patients who don't respond to or can't tolerate oral baclofen therapyAdults: For screening phase, after test dose to check responsiveness, give drug via implantable infusion pump. Give test dose of 1 mL of 50 mcg/mL dilution into intrathecal space by barbotage over 1 minute or longer. Significantly decreased severity or frequency of muscle spasm or reduced muscle tone should appear within 4 to 8 hours. If response is inadequate, give second test dose of 75 mcg/1.5 mL 24 hours after the first. If response is still inadequate, give final test dose of 100 mcg/2 mL after 24 hours. Patients unresponsive to the 100-mcg dose shouldn't be considered candidates for implantable pump.Children age 4 and older: Initial test dose is the same as that for adults (50 mcg); for very small children, initial dose is 25 mcg.For maintenance therapy: Adjust first dose based on screening dose that elicited an adequate response. Double this effective dose and give over 24 hours. However, if screening dose effectiveness was maintained for 8 hours or longer, don't double dose. After first 24 hours, increase dose slowly as needed and tolerated by 10% to 30% increments at 24-hour intervals in spasticity of spinal cord origin. In children with spasticity of spinal cord origin and adults and children with spasticity of cerebral origin, increase by 5% to 15% increments at 24-hour intervals. During prolonged maintenance therapy, increase daily dose by 10% to 40% in spasticity of spinal cord origin, or increase daily dose by 5% to 20% in spasticity of cerebral origin, if needed; if patient experiences adverse effects, decrease dose by 10% to 20%. Maintenance dosages range from 12 to 2,003 mcg daily based on diagnosis, but experience with dosages of more than 1,000 mcg daily is limited. Most patients need 300 to 800 mcg daily for spasticity of spinal cord origin and 90 to 703 mcg daily for spasticity of cerebral origin. Administration POGive drug with meals or milk to prevent GI distress.IntrathecalBlack Box Warning: Don't discontinue abruptly. This can result in high fever, altered mental status, exaggerated rebound spasticity, and muscle rigidity, which in rare cases, has led to rhabdomyolysis, multiple organ-system failure, and death.Don't give intrathecal injection by IV, IM, subcut, or epidural route.Maintenance infusions that require dilution must be diluted with sterile preservative-free sodium chloride for injection.If patient suddenly requires a large intrathecal dose increase, check for a catheter complication, such as kinking or dislodgment.With long-term intrathecal use, about 5% of patients may develop tolerance to drug. In some cases, this may be treated by hospitalizing patient and slowly withdrawing drug over a 2- to 4-week period. After the "drug holiday," drug may be restarted at the initial continuous infusion dose. Action Hyperpolarizes fibers to reduce impulse transmission. Appears to reduce transmission of impulses from the spinal cord to skeletal muscle, thus decreasing the frequency and amplitude of muscle spasms in patients with spinal cord lesions.RouteOnsetPeakDurationPOUnknown30 min-4 hrUnknownIntrathecal30 min-1 hr4 hr4-8 hrHalf-life: Oral, children with cerebral palsy, 41/2 hours; adults, 23/4 to 43/4 hours. Intrathecal, 11/2 hours over first 4 hours. Adverse Reactions CNS: agitation, drowsiness, dizziness, headache, weakness, fatigue, hypotonia, confusion, insomnia, seizures with intrathecal use, paresthesia, asthenia, pain, speech disorder, depression. CV: hypotension, peripheral edema. EENT: nasal congestion. GI: nausea, constipation, dry mouth, vomiting. GU: urinary frequency, urine retention, erectile dysfunction, incontinence. Metabolic: hyperglycemia, weight gain. Musculoskeletal: muscle rigidity or spasticity, muscle weakness. Respiratory: dyspnea, pneumonia. Skin: rash, pruritus, urticaria, excessive sweating. Other: chills, accidental injury. Interactions Drug-drugCNS depressants: May increase CNS depression. Avoid using together.Black Box Warning: Opioid class warning: May cause slow or difficult breathing, sedation, and death. Avoid use together. If use together is necessary, limit dosage and duration of each drug to minimum necessary for desired effect. Drug-lifestyleAlcohol use: May increase CNS depression. Discourage use together. Effects on Lab Test Results May increase alkaline phosphatase, AST, CK, and glucose levels. May increase leukocyte count. Contraindications & Cautions Contraindicated in patients hypersensitive to drug. Use cautiously in patients with impaired renal function, respiratory disease, or seizure disorder or when spasticity is used to maintain motor function. Use cautiously in patients with psychotic disorders, schizophrenia, or confusional states. Exacerbations of these conditions have occurred. Black Box Warning: Opioids should only be prescribed with benzodiazepines or other CNS depressants to patients for whom alternative treatment options are inadequate.Safety and effectiveness in children younger than age 4 (intrathecal use) and age 12 (oral use) haven't been established.Dialyzable drug: Yes.Overdose Signs & Symptoms: Coma, dizziness, light-headedness, diminished reflexes, vomiting, hypotonia, increased salivation, drowsiness, vision changes, respiratory depression, seizures. Pregnancy-Lactation-Reproduction Use in pregnant women only when potential benefits justify possible risks to the fetus. Oral drug appears in human milk. It isn't known if drug appears in human milk after intrathecal administration. Patient should avoid breastfeeding during therapy unless the potential benefit justifies the potential risks to the infant. Nursing Considerations Alert: Don't use oral drug to treat muscle spasm caused by rheumatic disorders, cerebral palsy, Parkinson disease, or stroke because drug's effectiveness for these indications hasn't been established. Alert: Life-threatening CNS depression, CV collapse, and respiratory failure may occur with intrathecal use. Have trained staff and resuscitation equipment available during screening, dosage titration, and pump refill. Avoid contamination of sterile surfaces through contact with the nonsterile exterior of the Gablofen prefilled syringe while refilling implantable intrathecal pumps. Use of the prefilled syringe in an aseptic setting (e.g., operating room) to fill sterile intrathecal pumps before implantation in patients isn't recommended unless external surface of syringe is treated to ensure sterility. Reservoir refilling must be performed by fully trained and qualified personnel following directions provided by the pump manufacturer. Alert: Use extreme caution when filling an FDA-approved implantable pump equipped with an injection port that allows direct access to the intrathecal catheter. Direct injection into the catheter through the catheter access port may cause a life-threatening overdose. Watch for sensitivity reactions, such as fever, skin eruptions, and respiratory distress. Expect an increased risk of seizures in patients with seizure disorder. The amount of relief determines whether dosage (and drowsiness) can be reduced. Some degree of muscle tone and spasticity may be necessary to sustain upright posture and balance with movement or to obtain optimal function, help support circulatory function, and prevent formation of DVT. When switching to intrathecal baclofen, attempt to discontinue concomitant oral antispasmodics to avoid overdose or increased adverse effects. Reduce oral antispasmodic dosage slowly while monitoring patient closely. Black Box Warning: Don't withdraw intrathecal drug abruptly after long-term use unless severe adverse reactions demand it; doing so may precipitate seizures, high fever, hallucinations, or rebound spasticity.Look alike-sound alike: Don't confuse baclofen with Bactroban. Patient Teaching Black Box Warning: Advise patient and caregivers, especially patients with spinal cord injuries at T6 or above, communication difficulties, or history of withdrawal symptoms from oral or intrathecal baclofen, of risks associated with abrupt discontinuation of intrathecal form. Tell them to keep scheduled refill visits and teach them the signs and symptoms of baclofen withdrawal.Instruct patient to take oral form with meals or milk to reduce GI upset.Black Box Warning: Opioid class warning: Caution patient or caregiver of patient taking an opioid with a benzodiazepine, CNS depressant, or alcohol to seek immediate medical attention for dizziness, light-headedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.Tell patient to avoid activities that require alertness until CNS effects of drug are known. Drowsiness usually is transient.Tell patient to avoid alcohol and OTC antihistamines while taking drug.Advise patient to follow prescriber's orders regarding rest and physical therapy.Teach patient and caregivers about the signs and symptoms of overdose and what to do if an overdose occurs.Teach patient and caregivers proper home care of pump and insertion site.

Tolcapone (Tasmar)

COMT inhibitor used in conjunction with l-DOPA to treat Parkinson's disease. tolcapone TOLE-ka-pone Tasmar Therapeutic class: Antiparkinsonians Pharmacologic class: Catechol-O-methyltransferase inhibitors Available Forms Tablets: 100 mg Indications & Dosages Adjunct to levodopa-carbidopa for signs and symptoms of idiopathic Parkinson disease in patients who have symptom fluctuation or haven't responded to other adjunctive treatment Adults: Initially, 100 mg PO t.i.d. with levodopa-carbidopa. May increase dosage to 200 mg PO t.i.d. if clinical benefit is justified, as this dosage is associated with increased frequency of ALT elevation. Recommended daily dosage is 100 mg PO t.i.d. Levodopa dosage may need to be reduced by about 30% to minimize risk of dyskinesias, especially when levodopa dose is over 600 mg daily. Stop drug if patient shows no benefit within 3 weeks. Administration POGive drug without regard for food.Give first dose of the day with first daily dose of levodopa-carbidopa. Give subsequent doses 6 and 12 hours later. Action May reversibly inhibit catechol-O-methyltransferase when given with levodopa-carbidopa, increasing levodopa bioavailability. This causes a more constant dopaminergic stimulation in the brain.Route Onset Peak Duration PO Unknown 2 hr Unknown Half-life: 2 to 3 hours. Adverse Reactions CNS: dyskinesia, sleep disorder, dystonia, excessive dreaming, somnolence, confusion, headache, hallucinations, dizziness, fever, hyperkinesia, hypertonia, fatigue, falling, syncope, balance loss, depression, tremor, speech disorder, paresthesia, agitation, irritability, mental deficiency, hyperactivity, hypokinesia, euphoria. CV: orthostatic complaints, chest pain, chest discomfort, palpitations, hypotension. EENT: cataract, tinnitus, pharyngitis, sinus congestion. GI: nausea, anorexia, diarrhea, vomiting, flatulence, constipation, abdominal pain, dyspepsia, dry mouth. GU: UTI, urine discoloration, hematuria, micturition disorder, urinary incontinence, impotence. Hepatic: hepatotoxicity. Musculoskeletal: muscle cramps, stiffness, arthritis, neck pain, myalgia. Respiratory: bronchitis, dyspnea, URI. Skin: increased sweating, rash, alopecia. Other: flulike syndrome, infection, accidental injury. Interactions Drug-drug Antihypertensives, PDE5 inhibitors: May enhance hypotensive effect of tolcapone. Use together cautiously. CNS depressants: May cause additive effects. Monitor patient closely. Nonselective MAO inhibitors (phenelzine, tranylcypromine): May cause hypertensive crisis. Avoid using together. Phenytoin, tolbutamide: May increase serum concentrations of these drugs. Monitor patient closely. SSRIs, TCAs: May increase risk of adverse effects. Use together cautiously. Warfarin: May cause increased warfarin level. Monitor INR and adjust warfarin dosage as needed. Drug-herb Herbs with hypotensive properties (black cohosh, garlic, hawthorn): May enhance hypotensive effect of tolcapone. Use together cautiously. Kava kava: May enhance CNS depressant effect of tolcapone. Monitor therapy.Drug-lifestyle Alcohol use: May increase CNS depressant effect of alcohol. Avoid use together. Effects on Lab Test Results May increase LFT values. Contraindications & Cautions Contraindicated in patients with liver disease, in those who were withdrawn from tolcapone because of evidence of drug-induced hepatocellular injury, in those who have demonstrated hypersensitivity to drug or its components, and in those with history of drug-related confusion and hyperpyrexia or nontraumatic rhabdomyolysis. Black Box Warning: Don't initiate tolcapone therapy if patient exhibits clinical evidence of liver disease or two ALT or AST values greater than ULN. Black Box Warning: Use cautiously in patients with severe dyskinesia or dystonia. Black Box Warning: Cases of severe hepatocellular injury, including fulminant liver failure resulting in death, have been reported. Use cautiously in patients with severe renal impairment. May cause new or worsening mental status and behavioral changes, which may be severe and include psychotic-like behavior, hallucinations, paranoid ideation, delusions, confusion, disorientation, aggressive behavior, agitation, and delirium. Reports suggest that patients may experience an intense urge to gamble, increased sexual urges, intense urge to spend money, binge eating, or other intense urges, and the inability to control these urges. Dialyzable drug: Unlikely. Overdose Signs & Symptoms: Nausea, vomiting, dizziness. Pregnancy-Lactation-Reproduction There are no adequate studies in pregnant women. Use only if potential benefit justifies potential risk to the fetus. It isn't known if drug appears in human milk. Use cautiously in breastfeeding women. Nursing Considerations Black Box Warning: Because of risk of hepatotoxicity, stop treatment if patient shows no benefit within 3 weeks.Black Box Warning: Because of risk of fatal hepatic failure, use drug only in patients taking levodopa-carbidopa who don't respond to or who aren't appropriate candidates for other adjunctive therapies. If drug is discontinued because of hepatocellular injury, don't reintroduce. Drug shouldn't be used by patient until there has been a complete discussion of the risks; make sure patient provides written informed consent before taking drug. Black Box Warning: Prescribers who elect to use drug in the face of the increased risk of liver injury are strongly advised to monitor patients for evidence of emergent liver injury. Black Box Warning: Monitor LFT results before starting drug, every 2 to 4 weeks for first 6 months of therapy, then periodically at intervals deemed clinically relevant. If dosage is increased to 200 mg t.i.d., obtain liver enzyme levels before increasing dosage, then every 2 to 4 weeks for 6 months, then periodically. Also, discontinue treatment if ALT or AST level exceeds 2 × ULN or if clinical signs and symptoms suggest onset of hepatic failure. Frequent lab monitoring may not prevent fulminant liver failure. Early detection of hepatic injury along with immediate withdrawal of the suspect drug may enhance likelihood for recovery.Monitor patient for orthostatic hypotension and syncope. Monitor patient closely and adjust other dopaminergic treatments as needed if drug is discontinued. Syndrome resembling NMS may occur.Look alike-sound alike: Don't confuse tolcapone with tolazamide, tolbutamide, or tolterodine. Patient Teaching Advise patient to take drug exactly as prescribed and not to stop drug abruptly. Black Box Warning: Teach patient to immediately report signs and symptoms of liver injury (clay-colored stools, yellow eyes or skin, fatigue, loss of appetite, persistent nausea, itching, dark urine, right upper abdominal tenderness, lethargy). Inform patient that routine lab monitoring is required during therapy. Warn patient that dizziness may occur upon standing up quickly; advise patient to stand up cautiously. Advise patient to avoid hazardous activities until CNS effects of drug are known. Tell patient that nausea may occur early in therapy. Inform patient that diarrhea is common, sometimes occurring 2 to 12 weeks after therapy begins, and usually resolves when therapy stops. Advise patient about risk of increased problems making voluntary movements or impaired muscle tone. Inform patient and caregivers that drug may cause new or worsening mental status and behavioral changes, which may be severe and include psychotic-like behavior, hallucinations, paranoid ideation, delusions, confusion, disorientation, aggressive behavior, agitation, and delirium.Instruct patient and caregivers to report intense urges to gamble, increased sexual urges, increased urge to spend money, binge eating, and other intense urges as well as the inability to control these urges. Tell female patient to notify prescriber about planned, suspected, or known pregnancy. Inform patient that drug may be taken without regard to meals.

Lithium

Works on concentration and toxicity can be fatal, patient needs periodic labs to check level, patient needs to be taught how to recognize toxicity symptoms, drink plenty of fluids. Mental disorders are thought process disorders that may be caused by some inherent dysfunction within the brain. A psychosis is a thought disorder, and schizophrenia is the most common psychosis in which delusions and hallucinations are hallmarks. Antipsychotic drugs are generally dopamine receptor blockers that are effective in helping people organize thought patterns and respond appropriately to stimuli. Antipsychotics can cause hypotension, anticholinergic effects, sedation, and extrapyramidal effects, including parkinsonism, ataxia, and tremors Available Forms lithium carbonate Capsules: 150 mg; 300 mg; 600 mg Tablets: 300 mg Tablets (extended-release) : 300 mg; 450 mg lithium citrate Syrup (sugarless): 8 mEq lithium/5 mL; 5 mL lithium citrate liquid contains 8 mEq lithium; equal to 300 mg lithium carbonate Indications & Dosages Adjust-a-dose (for all indications): In elderly patients and patients with CrCl of 30 to 89 mL/minute, start at lower doses. Immediate-release lithium isn't recommended in patients with CrCl of less than 30 mL/minute.Acute mania in bipolar disorderAdults and children age 7 and older weighing more than 30 kg: Initially, 300 mg (immediate-release tablets or capsules) or 5 mL (8 mEq lithium) PO t.i.d. Increase by 300 mg or 5 mL every 3 days to a goal of 600 mg or 10 mL (16 mEq) PO b.i.d. or t.i.d.Children age 7 and older weighing 20 to 30 kg: 300 mg (immediate-release tablets or capsules) or 5 mL (8 mEq lithium) PO b.i.d. Increase by 300 mg or 5 mL weekly to a goal of 600 to 1,500 mg or 16 to 40 mEq (10 to 25 mL) PO in divided doses daily.Adults and children age 12 and older (extended-release tablets): 900 mg PO b.i.d. or 600 mg PO t.i.d.Adjust-a-dose: Individualize dosage according to serum concentrations and clinical response. Titrate to serum lithium concentrations of 0.8 to 1.2 mEq/L (immediate-release forms) or 1 to 1.5 mEq/L (extended-release form).Long-term control in bipolar disorderAdults and children age 7 and older weighing more than 30 kg: Usual dose, 300 to 600 mg (immediate-release tablets or capsules) or 5 to 10 mL (8 to 16 mEq lithium) PO b.i.d. or t.i.d.Children age 7 and older weighing 20 to 30 kg: Usual dose, 600 to 1,200 mg (immediate-release tablets or capsules) or 10 to 20 mL (16 to 32 mEq lithium) PO in divided doses daily.Adults and children age 12 and older (extended-release tablets): 900 to 1,200 mg/day in divided doses. Usual dose, 600 mg PO b.i.d.Adjust-a-dose: Individualize dosage according to serum concentrations and clinical response. Titrate immediate-release formulations to serum lithium concentrations of 0.8 to 1 mEq/L. Desirable serum lithium concentrations for extended-release formulation is 0.6 to 1.2 mEq/L. Administration POGive drug after meals with plenty of water to minimize GI upset.Don't crush extended-release tablets. Action Probably alters chemical transmitters in the CNS, possibly by interfering with ionic pump mechanisms in brain cells, and may compete with or replace sodium ions.RouteOnsetPeakDurationPO (immediate-release)Unknown30 min-3 hrUnknownPO (extended-release)Unknown2-6 hrUnknownPO (syrup)Unknown1/4-1 hrUnknownHalf-life: 18 to 36 hours. Adverse Reactions CNS: fatigue, lethargy, coma, seizures, tremors, drowsiness, headache, confusion, restlessness, dizziness, psychomotor retardation, blackouts, EEG changes, worsened organic mental syndrome, impaired speech, ataxia, incoordination. CV: arrhythmias, bradycardia, reversible ECG changes, severe bradycardia, hypotension, Brugada syndrome. EENT: blurred vision, exophthalmos, nystagmus, tinnitus. GI: vomiting, anorexia, diarrhea, thirst, nausea, metallic taste, dry mouth, abdominal pain, flatulence, indigestion. GU: polyuria, renal toxicity with long-term use, glycosuria, decreased CrCl, albuminuria, urinary incontinence, erectile dysfunction. Hematologic: leukocytosis. Metabolic: transient hyperglycemia, goiter, hypothyroidism, hyponatremia. Musculoskeletal: muscle weakness. Skin: pruritus, rash, diminished or absent sensation, drying and thinning of hair, psoriasis, acne, alopecia. Other: ankle and wrist edema. Interactions Drug-drugACE inhibitors: May increase lithium level. Monitor lithium level; adjust lithium dosage, as needed.Aminophylline, sodium bicarbonate, urine alkalinizers: May increase lithium excretion. Avoid excessive salt, and monitor lithium levels.Antiarrhythmics and other drugs that prolong QT interval: May increase risk of life-threatening arrhythmias. Avoid use together.Calcium channel blockers (verapamil): May decrease lithium levels and may increase risk of neurotoxicity. Use together cautiously.Carbamazepine, fluoxetine, methyldopa, NSAIDs, probenecid: May increase effect of lithium. Monitor patient for lithium toxicity.Neuromuscular blockers: May cause prolonged paralysis or weakness. Monitor patient closely.Thiazide diuretics: May increase reabsorption of lithium by kidneys, with possible toxic effect. Use with caution, and monitor lithium and electrolyte levels (especially sodium).Drug-foodCaffeine: May decrease lithium level and drug effect. Advise patient who ingests large amounts of caffeine to tell prescriber before stopping caffeine. Adjust lithium dosage, as needed.Sodium (salt): May change renal elimination of drug if sodium intake changes. Avoid major changes in sodium intake. Effects on Lab Test Results May increase glucose and creatinine and TSH levels. May decrease sodium, T3, T4, and protein-bound iodine levels. May increase 131I uptake and WBC and neutrophil counts. Contraindications & Cautions Contraindicated if therapy can't be closely monitored. Use extreme caution in patients receiving neuromuscular blockers and diuretics; in elderly or debilitated patients; and in patients with thyroid disease, seizure disorder, infection, renal or CV disease, severe debilitation or dehydration, or sodium depletion. Patients with Brugada syndrome (abnormal ECG with increased risk of sudden death) or with risk factors for this condition shouldn't take lithium. Dialyzable drug: Yes. Overdose Signs & Symptoms: Diarrhea, vomiting, drowsiness, muscular weakness, lack of coordination, giddiness, ataxia, blurred vision, confusion, tinnitus, large output of dilute urine, slurred speech, loss of consciousness, myoclonic limb movements, agitation, urinary or fecal incontinence, seizures, arrhythmias, hypotension, peripheral vascular collapse, coma. Pregnancy-Lactation-Reproduction Drug may cause fetal harm if used during pregnancy; data from lithium birth registries suggest an increase in cardiac and other anomalies. If drug is used in women of childbearing potential or during pregnancy, or if patient becomes pregnant while taking drug, apprise patient of potential hazard to the fetus. If patient decides to continue lithium during pregnancy, monitor serum lithium concentration and adjust dosage if indicated. Two to three days before delivery, decrease lithium dosage or discontinue drug to reduce risk of maternal or neonatal toxicity. Monitor neonate and provide supportive care until lithium is excreted and toxic signs and symptoms disappear, which may take up to 14 days. Consider fetal echocardiography between 16 and 20 weeks' gestation in a woman with first-trimester lithium exposure, because of the potential increased risk of cardiac malformations. Drug appears in human milk. Use in breastfeeding women isn't recommended. Nursing Considerations Black Box Warning: Lithium toxicity is closely related to serum lithium levels and can occur at doses close to therapeutic levels. Facilities for prompt and accurate serum lithium determinations should be available before initiation of therapy.Monitor patient and discontinue drug for signs and symptoms of lithium toxicity (ataxia, drowsiness, weakness, tremor, vomiting).When drug level is less than 1.5 mEq/L, adverse reactions are usually mild.Monitor baseline ECG, thyroid studies, renal studies, and electrolyte levels.Check fluid intake and output, especially when surgery is scheduled.Weigh patient daily; check for edema or sudden weight gain.Adjust fluid and salt ingestion to compensate if excessive loss occurs from protracted diaphoresis or diarrhea. Under normal conditions, fluid intake should be 21/2 to 3 L daily, and patient should follow a balanced diet with adequate salt intake.Check urine specific gravity and report level below 1.005, which may indicate diabetes insipidus.Drug alters glucose tolerance in diabetic patients. Monitor glucose level closely.Perform outpatient follow-up of thyroid and renal function every 2 to 3 months during 6 months of treatment, then as clinically indicated. Monitor CBC and ECG (patients older than age 40) before therapy and as needed. Monitor lithium level twice weekly, 12 hours after the last oral dose, until patient and levels are stable, then every 1 to 2 months or as needed.Palpate thyroid to check for enlargement. Monitor weight before and during therapy.Look alike-sound alike: Don't confuse lithium carbonate with lanthanum carbonate. Patient Teaching Tell patient to take drug with plenty of water and after meals to minimize GI upset. Explain the importance of having regular blood tests to determine drug levels and to monitor therapy; even slightly high values can be dangerous. Warn patient and caregivers to expect transient nausea, large amounts of urine, thirst, and discomfort during first few days and to watch for evidence of toxicity. Instruct patient to withhold one dose and call prescriber immediately if signs and symptoms of toxicity appear, but not to stop drug abruptly. Warn patient to avoid hazardous activities that require alertness and good psychomotor coordination until CNS effects are known. Tell patient not to switch brands or take other prescription or OTC drugs without prescriber's guidance. Advise patient to immediately seek emergency assistance if fainting, light-headedness, abnormal heartbeat, or shortness of breath occurs because these signs and symptoms are associated with a potentially life-threatening heart disorder known as Brugada syndrome. Tell patient to wear or carry medical identification at all times.

Dantrolene (Dantrium)

dantrolene sodium DAN-troe-leenDantrium, Dantrium IV, Revonto, RyanodexTherapeutic class: Skeletal muscle relaxantsPharmacologic class: Hydantoin derivatives Available Forms Capsules: 25 mg; 50 mg; 100 mg Injection: 20 mg/vial; 250 mg/vial Indications & Dosages Spasticity and sequalae from severe chronic disorders, such as MS, cerebral palsy, spinal cord injury, and stroke Adults: Initially, 25 mg PO daily; then 25 mg t.i.d, 50 mg t.i.d., and finally 100 mg t.i.d. Maintain each dosage level for 7 days to determine response. May increase t.i.d. to q.i.d. if necessary. Maximum, 400 mg daily.Children age 5 and older: Initially, 0.5 mg/kg PO daily; then 0.5 mg/kg t.i.d., 1 mg/kg t.i.d., and finally 2 mg/kg t.i.d. Maintain each dosage level for 7 days to determine response. May increase t.i.d. to q.i.d. if necessary. Maximum, 100 mg q.i.d.Adjust-a-dose: If no further benefit is observed at next higher dose, decrease dosage to previous lower dosage. Stop drug if benefits aren't evident within 45 days.To manage malignant hyperthermic crisisAdults and children: Initially, 1 mg/kg by continuous rapid IV push and continuing until symptoms subside or maximum cumulative dose of 10 mg/kg has been reached.To prevent or attenuate malignant hyperthermic crisis in susceptible patients who need surgeryAdults and children age 5 and older: 4 to 8 mg/kg PO daily in three or four divided doses for 1 or 2 days before procedure. Give final dose 3 or 4 hours before procedure. Or, 2.5 mg/kg IV about 1.25 hours before anesthesia; infuse Dantrium or Revonto over 1 hour or for Ryanodex over at least 1 minute.To prevent recurrence of malignant hyperthermic crisisAdults and children age 5 and older: 4 to 8 mg/kg PO daily in four divided doses for up to 3 days after hyperthermic crisis. Administration POGive drug without regard to food.Prepare oral suspension for single dose by dissolving capsule contents in juice or other liquid. For multiple doses, use acid vehicle and refrigerate. Use within several days.IVReconstitute Dantrium or Revonto by adding 60 mL of sterile water for injection and shaking vial until clear. Don't use NSS, D5W, or a diluent that contains a bacteriostatic drug.Reconstitute Ryanodex with 5 mL of sterile water and shake until suspension becomes orange. Don't use NSS, D5W, or a diluent that contains a bacteriostatic drug.Don't dilute or transfer reconstituted suspension to another glass container for infusion.Administer Ryanodex reconstituted suspension into the IV catheter while an infusion of NSS or D5W is freely running or into the indwelling catheter, without a freely running infusion, after ensuring its patency. Flush the line to ensure no residual drug remains in the catheter.Protect solution from light, and use reconstituted solution within 6 hours.Incompatibilities: Any IV drugs or solutions mixed in a syringe. Action Acts directly on skeletal muscle to decrease excitation and contraction coupling and reduce muscle strength by interfering with intracellular calcium movement.RouteOnsetPeakDurationPOUnknown5 hrUnknownIVUnknownUnknown3 hr after infusionHalf-life: PO, 9 hours; IV, 4 to 8 hours. Adverse Reactions CNS: drowsiness, dizziness, malaise, fatigue, seizures, headache, light-headedness, confusion, nervousness, insomnia, fever, depression. CV: tachycardia, BP changes, phlebitis, thrombophlebitis, HF. EENT: excessive lacrimation, speech disturbance, diplopia, visual disturbances. GI: anorexia, constipation, cramping, dysphagia, metallic taste, severe diarrhea, GI bleeding, vomiting. GU: urinary frequency, hematuria, incontinence, nocturia, dysuria, crystalluria, difficult erection, urine retention. Hematologic: leukopenia, thrombocytopenia, lymphocytic lymphoma, aplastic anemia, anemia. Hepatic: hepatitis. Musculoskeletal: muscle weakness, myalgia, back pain. Respiratory: pleural effusion with pericarditis, pulmonary edema. Skin: eczematous eruption, pruritus, urticaria, abnormal hair growth, diaphoresis, photosensitivity, acnelike rash. Other: chills. Interactions Drug-drugClofibrate, warfarin: May decrease protein binding of dantrolene. Use together cautiously.CNS depressants: May increase CNS depression. Avoid using together.Estrogens: May increase risk of hepatotoxicity. Use together cautiously.IV verapamil and other calcium channel blockers: May cause hyperkalemia, ventricular fibrillation, and myocardial depression. Stop verapamil before giving IV dantrolene.Black Box Warning: Opioids: May cause slow or difficult breathing, sedation, and death. Avoid use together. If use together is necessary, limit dosage and duration of each drug to the minimum necessary for desired effect. Vecuronium: May increase neuromuscular blockade effect. Use together cautiously.Drug-lifestyleAlcohol use: May increase CNS depression. Discourage use together.Sun exposure: May cause photosensitivity reactions. Advise patient to avoid excessive sunlight exposure. Effects on Lab Test Results May increase ALT, AST, alkaline phosphatase, LDH, bilirubin, and BUN levels. Contraindications & Cautions Capsules are contraindicated for spasms in rheumatic disorders and when spasticity is used to maintain motor function. Contraindicated in patients with upper motor neuron disorders or active hepatic disease. Black Box Warning: Risk of hepatic injury is increased in those taking high doses, women, patients older than age 35, and patients with hepatic disease (such as cirrhosis or hepatitis) or severely impaired cardiac or pulmonary function.Black Box Warning: Opioids should only be prescribed with benzodiazepines or other CNS depressants to patients for whom alternative treatment options are inadequate.Dialyzable drug: Unknown.Overdose Signs & Symptoms: Muscle weakness, altered level of consciousness, vomiting, diarrhea, crystalluria. Pregnancy-Lactation-Reproduction There are no adequate well-controlled studies in pregnant women. Use during pregnancy only if clearly needed and potential benefit justifies potential risk to the fetus. Drug appears in human milk. A decision should be made to discontinue breastfeeding or discontinue drug, taking into account importance of drug to the mother. Nursing Considerations Start therapy as soon as malignant hyperthermia reaction is recognized. Black Box Warning: Liver damage may occur with short- or long-term use. Use the lowest possible effective dose for each patient. If benefits don't occur within 45 days, stop therapy.Black Box Warning: Obtain LFT results at start of therapy. Monitor hepatic function, including AST and ALT, frequently.Alert: Watch for fever, jaundice, severe diarrhea, weakness, and sensitivity reactions, including skin eruptions. Withhold dose and notify prescriber. Look alike-sound alike: Don't confuse Dantrium with Daraprim. Patient Teaching Tell patient to eat carefully to avoid choking. Some patients may have trouble swallowing during therapy. Black Box Warning: Caution patient or caregiver of patient taking an opioid with a benzodiazepine, CNS depressant, or alcohol to seek immediate medical attention if patient experiences dizziness, light-headedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness. Warn patient to avoid driving and other hazardous activities until CNS effects of drug are known. Advise patient to avoid combining drug with alcohol or other CNS depressants. Advise patient to notify prescriber if skin or eyes turn yellow, skin itches, or fever develops. Tell patient to avoid photosensitivity reactions by using sunblock and wearing protective clothing, to report abdominal discomfort or GI problems immediately, and to follow prescriber's orders regarding rest and physical therapy. Advise female patient to consult prescriber before becoming pregnant or breastfeeding.

Tramadol

traMADol hydrochloride TRAM-uh-dohlConZip, Durela, Ralivia, Tridural, Ultram, Zytram XLTherapeutic class: AnalgesicsPharmacologic class: Synthetic centrally active analgesicsControlled substance schedule: IV Available Forms Capsules (extended-release) : 100 mg; 150 mg; 200 mg; 300 mg Tablets: 50 mg Tablets (extended-release) : 75 mg; 100 mg; 150 mg; 200 mg; 300 mg; 400 mg Indications & Dosages Alert: Initiate dosing regimen for each patient individually, taking into account patient's severity of pain, response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse. Use lowest effective dosage for shortest duration consistent with individual patient treatment goals.Moderate to moderately severe chronic painAdults age 17 and older: Initially, 25 mg (immediate-release) PO in the morning. Adjust by 25 mg every 3 days to 100 mg/day (25 mg q.i.d.). Thereafter, adjust by 50 mg every 3 days to reach 200 mg/day (50 mg q.i.d.). Thereafter, give 50 to 100 mg PO every 4 to 6 hours p.r.n. Maximum, 400 mg daily.Adults age 18 and older not taking immediate-release tablets: 100 mg extended-release form PO once daily. Titrate by 100 mg every 5 days to relieve pain. Do not exceed 300 mg/day.Adults age 18 and older currently taking immediate-release tablets: Calculate the 24-hour tramadol immediate-release dose and initiate a total daily dose of extended-release product rounded down to the next lowest 100-mg increment. Subsequently, individualize according to patient need. Maximum dose is 300 mg daily.Adjust-a-dose: For immediate-release form, if CrCl is less than 30 mL/minute, increase dose interval to every 12 hours; maximum is 200 mg daily. For patients with cirrhosis, give 50 mg (immediate-release) every 12 hours. For patients older than age 75, maximum is 300 mg (immediate-release) daily in divided doses. Don't use extended-release form in patients with severe hepatic or renal impairment. Administration POBlack Box Warning: To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the FDA has required a REMS for these products. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to health care providers. Further information on the Opioid Analgesic REMS is available by calling 1-800-503-0784 or at www.opioidanalgesicrems.com.Give drug without regard for meals in a consistent manner.Extended-release capsules and tablets must be swallowed whole; don't break or crush tablets. Action Unknown. Thought to bind to opioid receptors and inhibit reuptake of norepinephrine and serotonin.RouteOnsetPeakDurationPO1 hr2-3 hrUnknownPO (extended-release)Unknown10-12 hrUnknownHalf-life: 6 to 7 hours; extended-release, 8 to 10 hours. Adverse Reactions CNS: dizziness, headache, somnolence, vertigo, seizures, anxiety, asthenia, CNS stimulation, confusion, coordination disturbance, euphoria, malaise, nervousness, sleep disorder, fever, paresthesia, tremor, depression, agitation, apathy. CV: vasodilation, HTN, peripheral edema. EENT: visual disturbances, nasopharyngitis, pharyngitis, rhinitis, sinusitis. GI: constipation, nausea, vomiting, abdominal pain, anorexia, diarrhea, dry mouth, dyspepsia, flatulence. GU: menopausal symptoms, proteinuria, urinary frequency, urine retention, pelvic pain, UTI, prostate disorder. Metabolic: weight loss. Musculoskeletal: hypertonia, arthralgia, neck pain, myalgia. Respiratory: bronchitis, respiratory depression. Skin: diaphoresis, pruritus, rash. Other: chills, withdrawal syndrome, accidental injury. Interactions Drug-drugBlack Box Warning: Benzodiazepines, CNS depressants: May cause slow or difficult breathing, sedation, and death. Avoid use together. If use together is necessary, limit dosage and duration of each drug to minimum necessary for desired effect. Carbamazepine: May increase tramadol metabolism. Patients receiving long-term carbamazepine therapy up to 800 mg daily may need up to twice the recommended tramadol dose.CNS depressants, opioids: May cause additive effects. Use together cautiously; tramadol dosage may need to be reduced.Cyclobenzaprine, MAO inhibitors, neuroleptics, other opioids, SSNRIs, SSRIs, TCAs: May increase risk of seizures. Monitor patient closely.Black Box Warning: CYP2D6 inhibitors: May decrease therapeutic effect of tramadol. Monitor therapy closely. Black Box Warning: CYP3A4 inducers: May decrease tramadol serum concentration. Monitor therapy closely. Black Box Warning: CYP3A4 inhibitors: May increase tramadol serum concentration. Monitor therapy closely. Quinidine: May increase level of tramadol. Monitor patient closely.Alert: Serotonergic drugs (amoxapine, antiemetics [dolasetron, granisetron, ondansetron, palonosetron], antimigraine drugs, buspirone, cyclobenzaprine, dextromethorphan, linezolid, lithium, MAO inhibitors, maprotiline, methylene blue, mirtazapine, nefazodone, SSNRIs, SSRIs, TCAs, trazodone, tryptophan, vilazodone): May increase risk of serotonin syndrome. Use together cautiously and monitor patient for serotonin syndrome.Vitamin K antagonists (warfarin): May increase anticoagulant effects. Monitor therapy closely.Drug-herbKava kava: May increase CNS depression. Monitor therapy closely.Alert: St. John's wort: May increase risk of serotonin syndrome. Use together cautiously and monitor patient for serotonin syndrome.Drug-lifestyleBlack Box Warning: Alcohol use: May have additive effects. Don't use together. Effects on Lab Test Results May increase creatinine, GGT, and liver enzyme levels. May decrease Hb level. Contraindications & Cautions Contraindicated in patients hypersensitive to drug or opioids, in patients with severe renal or hepatic impairment, suicidal patients, and in those with acute intoxication from alcohol, hypnotics, centrally acting analgesics, opioids, or psychotropic drugs. Contraindicated in patients with GI obstruction, including paralytic ileus. Contraindicated with concomitant use or within 14 days of MAO inhibitor therapy. Contraindicated in patients with significant respiratory depression or acute or severe bronchial asthma or hypercapnia in unmonitored settings or where resuscitative equipment isn't available. Black Box Warning: Contraindicated for use to treat pain in children younger than age 12 and to treat pain in children younger than age 18 after surgery to remove tonsils or adenoids.Black Box Warning: May cause fatal respiratory depression, especially during initiation or dosage increase.Black Box Warning: The effects of concomitant use or discontinuation of CYP3A4 inducers or inhibitors, or CYP2D6 inhibitors with tramadol are complex and require careful consideration of the effects on parent drug, tramadol, and the active metabolite, M1.Black Box Warning: Opioids should only be prescribed with benzodiazepines or other CNS depressants to patients for whom alternative treatment options are inadequate.Alert: Serious hypersensitivity reactions can occur, usually after the first dose. Patients with history of anaphylactic reaction to codeine and opioids may be at increased risk.Alert: Patients are at increased risk for oversedation and respiratory depression if they snore or have a history of sleep apnea, haven't used opioids recently or are first-time opioid users, have increased opioid dosage requirements or opioid habituation, have received general anesthesia for longer lengths of time or received other sedating drugs, have preexisting pulmonary or cardiac disease, or have thoracic or other surgical incisions that may impair breathing. Monitor patients carefully.Use cautiously in patients at risk for seizures or respiratory depression; in patients with increased ICP or head injury, acute abdominal conditions, or renal or hepatic impairment; and in patients with physical dependence on opioids. Withdrawal symptoms may occur if drug is abruptly discontinued.Alert: Drug can cause life-threatening serotonin syndrome.Alert: Use cautiously in patients who are experiencing depression or an emotional disturbance because of the increased risk of suicide.Alert: Drug may lead to rare but serious decrease in adrenal gland cortisol production.Alert: Drug may cause decreased sex hormone levels with long-term use.Black Box Warning: Avoid use in adolescents ages 12 to 18 who are obese or have such conditions as obstructive sleep apnea or severe lung disease or other risk factors that may increase their sensitivity to tramadol's respiratory depressant effects.Black Box Warning: Patients who are CYP2D6 ultrarapid metabolizers shouldn't use tramadol because of the risk of life-threatening or fatal respiratory depression.Use with extreme caution in elderly patients, especially those older than age 75.Dialyzable drug: 7%.Overdose Signs & Symptoms: Lethargy, somnolence, stupor, coma, seizures, skeletal muscle flaccidity, respiratory depression, cool clammy skin, miosis, bradycardia, hypotension, cardiac arrest, death. Pregnancy-Lactation-Reproduction Safe use in pregnant women hasn't been established. Use only if potential benefit justifies potential risk to the fetus. Black Box Warning: Prolonged use during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated according to neonatology expert protocols. If opioid use is required for a prolonged period during pregnancy, advise patient of the risk of neonatal opioid withdrawal syndrome; ensure her that appropriate treatment will be available.Use in breastfeeding women isn't recommended due to the risk of serious adverse reactions in breastfed infants, such as excess sleepiness, difficulty breastfeeding, or serious breathing problems that could result in death. Nursing Considerations Black Box Warning: Caution patient or caregiver of patient taking an opioid with a benzodiazepine, CNS depressant, or alcohol to seek immediate medical attention for dizziness, light-headedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.Black Box Warning: Tramadol exposes patients to the risk of addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient's risk before prescribing; monitor patient regularly for development of abnormal behaviors.Reassess patient's level of pain at least 30 minutes after administration.Monitor CV and respiratory status, especially within first 24 to 72 hours of therapy initiation and after dosage increases; adjust dosage accordingly. Withhold dose and notify prescriber if respirations are shallow or rate is below 12 breaths/minute.Alert: Carefully monitor vital signs, pain level, respiratory status, and sedation level in all patients receiving opioids, especially those receiving IV drugs, even those given postoperatively.Monitor bowel and bladder function. Anticipate need for stimulant laxative.For better analgesic effect, give drug before onset of intense pain.Monitor patients at risk for seizures. Drug may reduce seizure threshold.In the case of an overdose, naloxone may also increase risk of seizures.Monitor patient for drug dependence. Drug can produce dependence similar to that of codeine and thus has potential for abuse.Alert: Don't stop drug abruptly; withdraw slowly and individualize the gradual tapering plan to prevent signs and symptoms of withdrawal, worsening pain, and psychological distress in physically dependent patients. Refer to manufacturer's label for specific tapering instructions.Alert: When tapering opioids, monitor patient closely for signs and symptoms of opioid withdrawal (restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, mydriasis, irritability, anxiety, insomnia, backache, joint pain, weakness, abdominal cramps, anorexia, nausea, vomiting, diarrhea, increased BP or HR, increased respiratory rate). Such signs and symptoms may indicate a need to taper more slowly. Also monitor patient for suicidal thoughts, use of other substances, and mood changes.Alert: If patient is taking opioids with serotonergic drugs, watch for signs and symptoms of serotonin syndrome (agitation, hallucinations, rapid HR, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, diarrhea), especially when starting treatment or increasing dosages. Signs and symptoms may occur within several hours of coadministration but may also occur later, especially after dosage increase. Discontinue the opioid, serotonergic drug, or both if serotonin syndrome is suspected.Alert: Monitor patient for signs and symptoms of adrenal insufficiency (nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, low BP). Perform diagnostic testing if adrenal insufficiency is suspected. If adrenal insufficiency is confirmed, treat with corticosteroids and wean patient off opioids if appropriate. Discontinue corticosteroids when clinically appropriate.Alert: Monitor patient for signs and symptoms of decreased sex hormone levels (low libido, erectile dysfunction, amenorrhea, infertility). If signs and symptoms occur, evaluate patient and obtain lab testing.Look alike-sound alike: Don't confuse tramadol with trazodone or trandolapril. Patient Teaching Black Box Warning: Caution patient or caregiver of patient taking an opioid with a benzodiazepine, CNS depressant, or alcohol to seek immediate medical attention if patient experiences dizziness, light-headedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.Black Box Warning: Advise patient that crushing, chewing, or dissolving extended-release form can cause rapid release of the drug and a potentially fatal dose.Black Box Warning: Tell patient to keep drug away from children. Accidental ingestion of even one dose of tramadol, especially in children, can result in fatal overdose.Alert: Warn patient and caregivers of patient taking tramadol to watch for slow or shallow breathing, difficulty or noisy breathing, confusion, excessive sleepiness, trouble breastfeeding, or limpness. If any of these signs or symptoms occur, tell them to stop drug and seek immediate emergency medical attention.Explain assessment and monitoring process to patient and family. Instruct them to immediately report difficulty breathing or other signs or symptoms of a potential adverse opioid-related reaction.Tell patient to take drug as prescribed and not to increase dose or dosage interval unless ordered by prescriber.Caution ambulatory patient to be careful when rising and walking. Warn outpatient to avoid driving and other potentially hazardous activities that require mental alertness until drug's CNS effects are known.Advise patient to check with prescriber before taking OTC drugs because drug interactions can occur.Alert: Counsel patient not to discontinue opioids without first discussing the need for a gradual tapering regimen with prescriber.Alert: Encourage patient to report all medications being taken, including prescription and OTC medications and supplements.Advise patient that drug may cause constipation.Alert: Caution patient to immediately report signs and symptoms of serotonin syndrome, adrenal insufficiency, and decreased sex hormone levels.

Partial seizures

Partial seizures, or focal seizures, are so called because they involve one area of the brain, usually originate from one site or focus, and do not spread throughout the entire organ. The presenting symptoms depend on exactly where in the brain, the excessive electrical discharge is occurring. Partial seizures can be further classified as follows: Simple partial seizures, which occur in a single area of the brain and may involve a single muscle movement or sensory alteration Complex partial seizures, which involve a series of reactions or emotional changes and complex sensory changes such as hallucinations, mental distortion, changes in personality, loss of consciousness, and loss of social inhibitions. Motor changes may include involuntary urination, chewing motions, diarrhea, and so on. The onset of complex partial seizures usually occurs by the late teens.

Monoamine Oxidase Inhibitors Clinically Important Drug-Drug Interactions

Drug interactions of MAOIs with other antidepressants include increased risk of hypertensive crisis, coma, and severe convulsions with TCAs, and an increased risk of potentially life-threatening serotonin syndrome with SSRIs. The exact timing will vary, but a period of 6 weeks after stopping an SSRI may be needed before beginning therapy with an MAOI. If MAOIs are given with other sympathomimetic drugs (e.g., methyldopa), sympathomimetic effects increase. Combinations with insulin or oral antidiabetic agents result in additive hypoglycemic effects. Patients who receive these combinations must be monitored closely, and appropriate dose adjustments should be made. isocarboxazid(Marplan) phenelzine(Nadril) tranylcypromine(Parnate) Treatment if depression not responsive to other agents

Functions of the Brain Anatomy

The hindbrain, which runs from the top of the spinal cord into the midbrain, is the most primitive area of the brain and contains the brainstem, where the pons and medulla oblongata are located. These areas of the brain control basic, vital functions, such as the respiratory centers, which control breathing; the cardiovascular centers, which regulate blood pressure; the chemoreceptor trigger zone and emetic zone, which control vomiting; the swallowing center, which coordinates the complex swallowing reflex. The cerebellum—a part of the brain that looks like a skein of yarn and lies behind the other parts of the hindbrain—coordinates the motor function that regulates posture, balance, and voluntary muscle activity. The midbrain sits above the hindbrain and is a small area. It contains cranial nerves related to the specific senses (sight, smell, hearing, balance, taste) and some muscle activity of the head and neck (e.g., chewing, eye movement), and the reticular activating system (RAS), which controls arousal and awareness of stimuli and contains the sleep center. The RAS filters the billions of incoming messages, selecting only the most significant for response. When levels of serotonin become high in the RAS, the system shuts down and sleep occurs. The medulla absorbs serotonin from the RAS; when the levels are low enough, consciousness or arousal results. The forebrain contains the two cerebral hemispheres and the thalamus, hypothalamus, and the limbic system (see Fig. 19.7). The thalamus sends direct information into the cerebrum to transfer sensations, such as cold, heat, pain, touch, and muscle sense. The hypothalamus, which is poorly protected by the blood-brain barrier, acts as a major sensor for activities in the body. Areas of the hypothalamus are responsible for temperature control, water balance, appetite, and fluid balance. In addition, the hypothalamus plays a central role in the endocrine system and in the autonomic nervous system. The limbic system is an area of the brain that sits just above the thalamus contains high levels of three neurotransmitters: epinephrine, norepinephrine, and serotonin. Stimulation of this area, which appears to be responsible for the expression of emotions, may lead to anger, pleasure, motivation, stress, and so on. This part of the brain seems to be largely responsible for the "human" aspect of brain function. Drug therapy aimed at alleviating emotional disorders such as depression and anxiety often involves attempting to alter the levels of epinephrine, norepinephrine, and serotonin. The two cerebral hemispheres are joined together by an area called the corpus callosum. These two hemispheres contain the sensory neurons, which receive nerve impulses, and the motor neurons, which send them. They also contain areas that coordinate speech and communication and seem to be the area where learning takes place (see Fig. 19.7). Different areas of the brain appear to be responsible for receiving and sending information to specific areas of the body. When the brain is viewed at autopsy, it looks homogeneous, but scientists have mapped the general areas that are responsible for sensory response, motor function, and other functions (Fig. 19.8). In conjunction with the cerebellum, groups of ganglia or nerve cell bodies called the basal ganglia, located at the bottom of the brain, make up the extrapyramidal motor system. This system coordinates motor activity for unconscious activities such as posture and gait.

Alefacept (Amevive)

- *immunosuppressive fusion protein* that interferes with lymphocyte activation - useful in treating plaque psoriasis -T-Cell inhibitors *Therapeutic Actions and Indications The exact mechanism of action of the T- and B-cell suppressors is not clearly understood. It has been shown that they block antibody production by B cells, inhibit suppressor and helper T cells, and modify the release of interleukins and of T-cell growth factor. The T- and B-cell suppressors are indicated for the prevention and treatment of specific transplant rejections. See Table 17.2 for usual indications of each agent. *Pharmacokinetics Alefacept is rapidly absorbed and can be given IM or IV. It reaches peak levels in 4 to 6 hours and has a half-life of 270 hours. *Contraindications and Cautions The use of T- and B-cell suppressors is contraindicated in the presence of any known allergy to the drug or its components to prevent hypersensitivity reactions and during pregnancy and lactation because of the potential serious adverse effects on the fetus or neonate. Caution should be used with renal or hepatic impairment, which could interfere with the metabolism or excretion of the drug, and in the presence of known neoplasms, which potentially could spread with immune system suppression. Adverse Effects Patients receiving these drugs are at increased risk for infection and for the development of neoplasms due to their blocking effect on the immune system. Other potentially dangerous adverse effects include hepatotoxicity, renal toxicity, renal dysfunction, and pulmonary edema. Patients may experience headache, tremors, secondary infections such as acne, GI upset, diarrhea, and hypertension. *Clinically Important Drug-Drug Interactions There is an increased risk of toxicity if these drugs are combined with other drugs that are hepatotoxic or nephrotoxic. Extreme care should be used if such combinations are necessary. Other reported drug-drug interactions are drug specific; consult a drug guide or drug handbook.

Succinycholine (Anectine)

- rapid onset (30-60 seconds) - short duration (5-10 mins) - metabolized by butyrylcholine esterase in the plasma - genetic variants of butyrylcholine esterase can affect duration of action Preferred Use surgical procedures; intubation; mechanical ventilation Special Considerations May cause myalgia secondary to muscle contraction; associated with increased intraocular pressure; increased intragastric pressure, which may cause vomiting; more likely to cause malignant hyperthermia The adverse effects of succinylcholine are the same as those for nondepolarizing NMJ blockers. In addition, succinylcholine is associated with muscle pain related to the initial muscle contraction reaction. A nondepolarizing NMJ blocker may be given first to prevent some of these contractions and the associated discomfort. Aspirin also alleviates much of this pain after the procedure. Malignant hyperthermia, which may occur in susceptible patients, is a serious condition characterized by massive muscle contraction, sharply elevated body temperature, severe acidosis, and if uncontrolled death (Fig. 28.4). This reaction is most likely with succinylcholine, and treatment involves dantrolene (see Chapter 25) to inhibit the muscle effects of the NMJ blocker.

Aldesleukin (Proleukin)

-Human interleukin produced by recombinant DNA technology using Escherichia coli bacteria -Antineoplastic agent, biological response modulator, interleukin-2 recombinant *Prototype Summary: Aldesleukin Indications: Metastatic renal cell carcinoma in adults, treatment of metastatic melanomas. Actions: Activates human cellular immunity and inhibits tumor growth through increases in lymphocytes, platelets, and cytokines. Pharmacokinetics: Route: IV Onset: 5 min Peak: 13 min Duration: 3-4 hr T1/2: 85 minutes, metabolized in the kidney and excreted in the urine. Adverse Effects: Mental status changes, dizziness, hypotension, sinus tachycardia, arrhythmias, pruritus, nausea, vomiting, diarrhea, anorexia, gastrointestinal bleed, bone marrow suppression, respiratory difficulties, fever, chills, pain.

Administration of General Anesthesia

-administered by inhalation or IV injection,or both -balanced anesthesia is using different types of agents to provide hypnosis, amnesia, analgesia, muscle relaxation, and reduced reflexes etc -can use opiods and hypnotics with anesthesia as an adjunct or for sedation before surgery General anesthesia is delivered by a physician or nurse anesthetist trained in the delivery of these potent drugs along with intubation, mechanical ventilation, and full life support. During the delivery of anesthesia, the patient can go through predictable stages (Fig. 27.1), referred to as the depth of anesthesia: Stage 1, the analgesia stage, refers to the loss of pain sensation with the patient still conscious and able to communicate. Stage 2, the excitement stage, is a period of excitement and often combative behavior with many signs of sympathetic stimulation (e.g., tachycardia, increased respirations, blood pressure changes). Stage 3, surgical anesthesia, involves relaxation of skeletal muscles, return of regular respirations, and progressive loss of eye reflexes and pupil dilation. Surgery can be safely performed in stage 3. Stage 4, medullary paralysis, is very deep CNS depression with loss of respiratory and vasomotor center stimuli in which death can occur rapidly. If a patient reaches this level, the anesthesia has become too intense, and the situation is critical. General anesthesia administration is also divided into three phases: induction, maintenance, and recovery.

Entanercept (Enbrel)

-neutralizes TNF (rheumatoid arthritis drug) -biologic DMARD Adverse effects: -Serious infections (invasive fungal infections, TB, HBV) -Severe allergic reactions (SJS, TEN, erythema multiforme), -Heart failure (new develops or existing gets worse) -Cancer (risk of lymphoma in children, adolescence and young adults) -Hematologic disorders (neutropenia, thrombocytopenia, and aplastic anemia-fatal) -Liver injury (liver failure, rare) -Central nervous system (CNS) demyelinating disorders (MS, myelitis, and optic neuritis all rare)

Evaluation of patient on Levodopa

.Monitor patient response to the drug (improvement in signs and symptoms of Parkinson disease). Monitor for adverse effects (CNS changes, urinary retention, GI depression, tachycardia, increased sweating, flushing). Evaluate the effectiveness of the teaching plan (patient can give the drug name and dosage, name possible adverse effects to watch for and specific measures to prevent them, and discuss the importance of continued follow-up). Monitor the effectiveness of support measures and compliance with the regimen.

GABA (gamma-aminobutyric acid)

A major inhibitory neurotransmitter. Undersupply linked to seizures, tremors, and insomnia. Gamma-aminobutyric acid or GABA, which is found in the brain, inhibits nerve activity and is important in preventing overexcitability or stimulation such as seizure activity.

Adverse Effects of Vaccines

Adverse effects of vaccines are associated with the immune or inflammatory reaction that is being stimulated: Moderate fever, rash, malaise, chills, fretfulness, drowsiness, anorexia, vomiting, and irritability. Pain, redness, swelling, and even nodule formation at the injection site are also common. In rare instances, severe hypersensitivity reactions have been reported.

Haloperidol (Haldol)

An antipsychotic drug thought to block receptor sites for dopamine, making it effective in treating the delusional thinking, hallucinations and agitation commonly associated with schizophrenia. haloperidol ha-loe-PER-i-dolehaloperidol decanoateHaldol Decanoate, Haloperidol LAhaloperidol lactateHaldolTherapeutic class: AntipsychoticsPharmacologic class: Butyrophenone derivatives Available Forms haloperidol Tablets: 0.5 mg; 1 mg; 2 mg; 5 mg; 10 mg; 20 mg haloperidol decanoate Injection: 50 mg/mL*; 100 mg/mL* haloperidol lactate Injection: 5 mg/mL Oral solution (concentrate): 2 mg/mL Indications & Dosages Adjust-a-dose (for all indications): For indications with oral dosing and for oral dosing in elderly and debilitated patients, initially, 0.5 to 2 mg PO b.i.d. or t.i.d.; increase gradually, as needed.Psychotic disordersAdults and children older than age 12: Dosage varies for each patient. Initially, 0.5 to 5 mg PO b.i.d. or t.i.d. Maximum, 100 mg PO daily. Or, 2 to 5 mg lactate IM every 4 to 8 hours, although hourly administration may be needed until control is obtained.Children ages 3 to 12 weighing 15 to 40 kg: Initially, 0.5 mg PO in two or three divided doses daily. May increase dose by 0.5 mg at 5- to 7-day intervals, depending on therapeutic response and patient tolerance. Maintenance dose, 0.05 to 0.15 mg/kg PO daily given in two or three divided doses. Severely disturbed children may need higher doses.Chronic psychosis requiring prolonged therapyAdults: 50 to 200 mg decanoate IM every 4 weeks.Adjust-a-dose: For elderly or debilitated patients, lower initial dose and gradual adjustments are recommended. Recommended initial and maintenance dosage is 10 to 15 times the daily oral dose, administered IM every 4 weeks.Nonpsychotic behavior disordersChildren ages 3 to 12 weighing 15 to 40 kg: 0.05 to 0.075 mg/kg PO daily, in two or three divided doses. Maximum, 6 mg daily. Severely disturbed nonpsychotic or hyperactive children with conduct disorders may only require short-term use.Tourette syndromeAdults: Initially, 0.5 to 5 mg PO b.i.d., t.i.d., or as needed. Up to about 100 mg/day may be needed.Children ages 3 to 12 weighing 15 to 40 kg: 0.05 to 0.075 mg/kg PO daily, in two or three divided doses. Administration POAlert: Haloperidol isn't approved for IV use.Protect drug from light. Slight yellowing of concentrate is common and doesn't affect potency. Discard very discolored solutions.IMProtect drug from light. Slight yellowing of solution is common and doesn't affect potency. Discard very discolored solutions.Use a 21G needle. Maximum volume per injection site shouldn't exceed 3 mL. Give in gluteal muscle by deep IM injection; Z-track techniques are recommended (haloperidol decanoate).When switching from tablets to IM decanoate injection, give 10 to 20 times the oral dose once a month (maximum, 100 mg). If initial dose conversion requires more than 100 mg, give in two injections (100 mg maximum) separated by 3 to 7 days. If patient is elderly or debilitated or if oral haloperidol dose is 10 mg/day or less, initiate dose at 10 to 15 times the daily oral dose. If patient is at high risk for relapse or oral haloperidol dose is greater than 10 mg/day, initiate dose at 20 times the oral daily dose. Action A butyrophenone that probably exerts antipsychotic effects by blocking postsynaptic dopamine receptors in the brain.RouteOnsetPeakDurationPOUnknown2-6 hrUnknownIM (decanoate)Unknown6 daysUnknownIM (lactate)Unknown10-20 minUnknownHalf-life: PO, 14 to 37 hours; IM decanoate, 3 weeks; IM lactate, 20 hours. Adverse Reactions CNS: severe extrapyramidal reactions, dystonia, tardive dyskinesia, NMS, seizures, sedation, drowsiness, lethargy, headache, insomnia, confusion, vertigo, agitation, anxiety, depression, euphoria, restlessness, tonic-clonic seizures, hallucinations, parkinsonian-like syndrome. CV: tachycardia, hypotension, HTN, prolonged QT interval and other ECG changes, torsades de pointes with high doses. EENT: blurred vision, cataracts, retinopathy, oculogyric crisis. GI: dry mouth, anorexia, constipation, diarrhea, nausea, vomiting, dyspepsia. GU: urine retention, menstrual irregularities, priapism. Hematologic: leukopenia, leukocytosis. Hepatic: jaundice. Metabolic: hyperglycemia, hypoglycemia, hyponatremia. Skin: rash, other skin reactions, diaphoresis. Other: gynecomastia. Interactions Drug-drugAnticholinergics: May increase anticholinergic effects and glaucoma. Use together cautiously.Antiparkinsonian drugs (dopamine agonist): May diminish therapeutic effect of both haloperidol and antiparkinsonian drug (dopamine agonist). Avoid using together. If used together can't be avoided, monitor patient for decreased effects of both agents.Azole antifungals, buspirone, macrolides: May increase haloperidol level. Monitor patient for increased adverse reactions; haloperidol dose may need to be adjusted.Beta blockers: May cause an unexpected severe hypotensive reaction. If this occurs, provide supportive treatment.Carbamazepine: May decrease haloperidol level. Monitor patient.CNS depressants: May increase CNS depression. Use together cautiously.Lithium: May cause lethargy and confusion after high doses. Monitor patient.Black Box Warning: Opioid class warning: May cause slow or difficult breathing, sedation, and death. Avoid use together. If use together is necessary, limit dosage and duration of each drug to minimum necessary for desired effect. QT-interval-prolonging drugs: May prolong QT interval. Monitor ECG.Rifampin: May decrease haloperidol level. Monitor patient for clinical effect.Drug-lifestyleAlcohol use, cannabidiol: May increase CNS depression. Discourage use together.Smoking: May decrease haloperidol serum concentration. Monitor therapy. Effects on Lab Test Results May increase LFT values. May decrease sodium level. May increase or decrease glucose level and WBC count. Contraindications & Cautions Contraindicated in patients hypersensitive to drug and in those with dementia with Lewy bodies, Parkinson disease, coma, or CNS depression. Black Box Warning: Opioid class warning: Opioids should only be prescribed with benzodiazepines or other CNS depressants to patients for whom alternative treatment options are inadequate.Use cautiously in elderly and debilitated patients; in patients with history of seizures or EEG abnormalities, prolonged QT interval and other severe CV disorders, allergies, glaucoma, or urine retention; and in those taking anticonvulsants, anticoagulants, antiparkinsonians, or lithium.Use cautiously in patients at risk for falls, including those with diseases or conditions or who are taking drugs that may cause somnolence, orthostatic hypotension, or motor or sensory instability.Decanoate form contains benzyl alcohol.Blood dyscrasias have been reported. Discontinue drug for ANC less than 1,000/mm3 or for leukopenia or agranulocytosis.Dialyzable drug: Unknown.Overdose Signs & Symptoms: Severe extrapyramidal reactions, hypotension, sedation, EEG abnormalities. Pregnancy-Lactation-Reproduction Alert: Antipsychotic use during the third trimester may result in abnormal muscle movements (extrapyramidal symptoms) and withdrawal symptoms in newborns. Use during pregnancy only if clearly needed. Use minimum effective maternal dose. Drug appears in human milk. Breastfeeding isn't recommended. Nursing Considerations Monitor patient for tardive dyskinesia, which may occur after prolonged use. It may not appear until months or years later and may disappear spontaneously or persist for life, despite ending drug. Alert: Watch for signs and symptoms of NMS (extrapyramidal effects, hyperthermia, autonomic disturbance), which is rare but commonly fatal. Alert: Monitor ECG when drug is given in high doses or when patient is taking other QT interval-prolonging drugs because of the increased risk of QT-interval prolongation and torsades de pointes. Black Box Warning: Elderly patients with dementia-related psychosis treated with atypical or conventional antipsychotics are at increased risk for death. Antipsychotics aren't approved for the treatment of dementia-related psychosis.Don't withdraw drug abruptly unless required by severe adverse reactions.Complete fall risk assessments at start of antipsychotic treatment and recurrently for patients on long-term therapy, especially those at increased risk for falls.Esophageal dysmotility and aspiration can occur. Use cautiously in patients at risk for aspiration (those with pneumonia, Alzheimer disease).Look alike-sound alike: Don't confuse Haldol with Halcion or Halog. Patient Teaching Black Box Warning: Opioid class warning: Caution patient or caregiver of patient taking an opioid with a benzodiazepine, CNS depressant, or alcohol to seek immediate medical attention for dizziness, light-headedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.Advise patient to report all adverse reactions.Although drug is the least sedating of the antipsychotics, warn patient to avoid activities that require alertness and good coordination until effects of drug are known. Drowsiness and dizziness usually subside after a few weeks.Advise patient that drug may cause somnolence, orthostatic hypotension, and motor and sensory instability, which may lead to falls.Warn patient to avoid alcohol during therapy.Tell patient to relieve dry mouth with sugarless gum or hard candy.

Phenobarbital

Anticonvulsant Indications: Long-term treatment of generalized tonic-clonic and cortical focal seizures, emergency control of certain acute convulsive episodes (status epilepticus, tetanus, eclampsia, meningitis), and anticonvulsant treatment of generalized tonic-clonic seizures and focal seizures (parenteral). Actions: General CNS depressant, inhibits impulse conduction in the ascending RAS, depresses the cerebral cortex, alters cerebellar function, depresses motor output, and can produce excitation, sedation, hypnosis, anesthesia, and deep coma. Pharmacokinetics: Oral- Onset 30-60 min Duration 10-16hr IM-Onset 10-30 min Duration 4-6hr IV- Onset 5 min Duration 4-6hr T1/2: 79 hours; metabolized in the liver, excreted in the urine. Adverse Effects: Somnolence, insomnia, vertigo, nightmares, lethargy, nervousness, hallucinations, insomnia, anxiety, dizziness, bradycardia, hypotension, syncope, nausea, vomiting, constipation, diarrhea, hypoventilation, respiratory depression, tissue necrosis at injection site, withdrawal syndrome.

Antidepressants Agents Across Lifespan adverse effects

Antidepressant Agents Children Use of antidepressant drugs with children poses a challenge. The response of the child to the drug may be unpredictable, and the long-term effects of many of these agents are not clearly understood. Studies have not shown efficacy in using these drugs to treat depression in children and also indicate that there may be an increase in suicidal ideation and suicidal behavior when antidepressants are used to treat depression in children. Of the tricyclic drugs (TCAs), clomipramine, imipramine, nortriptyline, and trimipramine have established pediatric doses in children older than 6 years. Children should be monitored closely for adverse effects, and dose changes should be made as needed. MAOIs should be avoided in children if at all possible because of the potential for drug-food interactions and the serious adverse effects. The SSRIs and SNRIs can cause serious adverse effects in children. Fluvoxamine and sertraline have established pediatric dose guidelines for the treatment of OCDs. Fluoxetine is widely used to treat depression in adolescents, and a 2000 survey of off-label uses of drugs showed that it was being used in children as young as 6 months. Dosage regimens must be established according to the child's age and weight, and a child receiving an antidepressant should be monitored very carefully. Underlying medical reasons for the depression should be ruled out before antidepressant therapy is begun. Again, these children should be monitored for any suicidal ideation. Adults Adults using these drugs should have medical causes for their depression ruled out before therapy is begun. Thyroid disease, hormonal imbalance, and CV disorders can all lead to the signs and symptoms of depression. The patient needs to understand that the effects of drug therapy may not be seen for 4 weeks and that it is important to continue the therapy for at least that long. These drugs should be used very cautiously during pregnancy and lactation because of the potential for adverse effects on the fetus and possible neurological, cardiac, and respiratory effects on the baby. Use should be reserved for situations in which the benefits to the mother far outweigh the potential risks to the neonate. Older Adults Older patients may be more susceptible to the adverse effects of these drugs, from unanticipated CNS effects to increased sedation, dizziness, and even hallucinations. Doses of all of these drugs need to be reduced and the patient monitored very closely for toxic effects. Safety measures should be provided if CNS effects do occur. Patients with hepatic or renal impairment should be monitored very closely while taking these drugs. Decreased doses may be needed. Because many older patients also have renal or hepatic impairment, they need to be screened carefully. TCAs may exacerbate benign prostate hypertrophy symptoms by decreasing bladder contractions. The adverse effects of TCAs are associated with the effects of the drugs on the central nervous system (CNS) (Fig. 21.2) and on the peripheral nervous system. Sedation, sleep disturbances, fatigue, hallucinations, disorientation, visual disturbances, difficulty in concentrating, weakness, ataxia, and tremors may occur. Use of TCAs may lead to GI anticholinergic effects, such as dry mouth, constipation, nausea, vomiting, anorexia, increased salivation, cramps, and diarrhea. Resultant GU effects may include urinary retention and hesitancy, loss of libido, and changes in sexual functioning. CV effects such as orthostatic hypotension, hypertension, arrhythmias, myocardial infarction, angina, palpitations, and stroke may also pose problems. Miscellaneous reported effects include alopecia, weight gain or loss, flushing, chills, and nasal congestion. These adverse effects may be intolerable to some patients, who then stop taking the particular TCA. Abrupt cessation of all TCAs causes a withdrawal syndrome characterized by nausea, headache, vertigo, malaise, and nightmares.

Fosphenytoin (Cerebyx)

Antiepileptic for Status Epilepticus fosphenytoin sodium faws-FEN-i-toe-in Cerebyx Therapeutic class: Anticonvulsants Pharmacologic class: Hydantoin derivatives Available Forms Injection: 100 mg phenytoin sodium equivalents/2 mL; 500 mg phenytoin sodium equivalents/10 mL vials Indications & Dosages Adjust-a-dose (for all indications): Phenytoin clearance is decreased slightly in elderly patients; lower or less frequent dosing may be required. Status epilepticus Adults: Loading dose, 15 to 20 mg phenytoin sodium equivalent/kg IV at infusion rate of 100 to 150 mg phenytoin sodium equivalent/minute; then 4 to 6 mg phenytoin sodium equivalent/kg/day IV or IM in divided doses as maintenance dose. Children from birth to younger than age 17: Loading dose, 15 to 20 mg phenytoin sodium equivalent/kg IV at 2 mg phenytoin sodium equivalent/minute or 150 mg phenytoin sodium equivalent/minute, whichever is slower; then 2 to 4 mg phenytoin sodium equivalent/kg IV given 12 hours after loading dose, then continued once every 12 hours at 1 to 2 mg phenytoin sodium equivalent/kg/minute or 100 mg/minute, whichever is slower.To prevent and treat seizures during neurosurgery (nonemergent loading or maintenance dosing)Adults: Loading dose, 10 to 20 mg phenytoin sodium equivalent/kg IM or IV at infusion rate not exceeding 150 mg phenytoin sodium equivalent/minute. Maintenance dose is 4 to 6 mg phenytoin sodium equivalent/kg/day IV or IM in divided doses. Children from birth to younger than age 17: Loading dose, 10 to 15 mg phenytoin sodium equivalent/kg IV at 1 to 2 mg phenytoin sodium equivalent/minute or 150 mg phenytoin sodium equivalent/minute, whichever is slower; then 2 to 4 mg phenytoin sodium equivalent/kg IV given 12 hours after loading dose, then continued once every 12 hours at 1 to 2 mg phenytoin sodium equivalent/kg/minute or 100 mg/minute, whichever is slower. Administration IV If rapid phenytoin loading is a main goal, this form is preferred. For status epilepticus, give IV rather than IM because therapeutic phenytoin level occurs more rapidly. For infusion, dilute in D5W or NSS for injection to yield 1.5 to 25 mg phenytoin sodium equivalent/mL. Black Box Warning: Don't give more than 150 mg phenytoin sodium equivalent/minute in adults and 2 mg phenytoin sodium equivalent/kg/minute (or 150 mg phenytoin sodium equivalent/minute) in children because of risk of severe hypotension and cardiac arrhythmias. Careful cardiac monitoring is needed during and after administering IV drug. Although risk of CV toxicity increases with infusion rates above the recommended infusion rate, these events have also been reported at or below the recommended infusion rate. Reducing rate of administration or discontinuing drug may be needed. Maintenance infusion rates in children shouldn't exceed 1 to 2 mg phenytoin sodium equivalent/kg/minute (or 100 mg phenytoin sodium equivalent/minute, whichever is slower).Patients receiving 20 mg phenytoin sodium equivalent/kg at 150 mg phenytoin sodium equivalent/minute typically feel discomfort, usually in the groin. To reduce discomfort, slow or temporarily stop infusion. Monitor patient's ECG, BP, and respirations continuously during maximum phenytoin level—about 10 to 20 minutes after end of fosphenytoin infusion. Severe CV complications are most common in elderly or gravely ill patients. If needed, decrease rate or stop infusion. Store drug under refrigeration. Don't store at room temperature longer than 48 hours. Discard vials that develop particulate matter. Incompatibilities: Other IV drugs. IM Depending on dose ordered, may require two separate IM injections.IM administration generates systemic phenytoin levels similar enough to oral phenytoin sodium to allow essentially interchangeable use. Store drug under refrigeration. Don't store at room temperature longer than 48 hours. Discard vials that develop particulate matter. Action May stabilize neuronal membranes and limit seizure activity either by increasing efflux or decreasing influx of sodium ions across cell membranes in the motor cortex during generation of nerve impulses. Route Onset Peak Duration IV Unknown End of infusion Unknown IM Unknown 30 min Unknown Half-life: Fosphenytoin, 15 minutes; phenytoin, 12 to 29 hours. Adverse Reactions CNS: ataxia, dizziness, somnolence, brain edema, intracranial HTN, agitation, asthenia, dysarthria, extrapyramidal syndrome, fever, headache, hypesthesia, incoordination, increased or decreased reflexes, nervousness, paresthesia, speech disorders, stupor, thinking abnormalities, tremor, vertigo. CV: HTN, hypotension, tachycardia, vasodilation. EENT: nystagmus, amblyopia, deafness, diplopia, tinnitus. GI: constipation, dry mouth, taste perversion, tongue disorder, vomiting. GU: pelvic pain. Metabolic: hypokalemia. Musculoskeletal: back pain, myasthenia. Respiratory: pneumonia. Skin: pruritus, ecchymoses, injection-site reaction and pain, rash. Other: accidental injury, chills, facial edema, infection. Interactions Drug-drug Amiodarone, capecitabine, chloramphenicol, chlordiazepoxide, cimetidine, disulfiram, estrogens, ethosuximide, felbamate, 5-FU, fluconazole, fluoxetine, fluvastatin, fluvoxamine, H2-receptor antagonists, isoniazid, itraconazole, ketoconazole, methylphenidate, miconazole, omeprazole, oxcarbazepine, phenothiazines, salicylates, sertraline, succinimides, sulfonamides, ticlopidine, tolbutamide, topiramate, trazodone, voriconazole, warfarin: May increase phenytoin level and effect. Use together cautiously.Bleomycin, carbamazepine, carboplatin, cisplatin, diazepam, diazoxide, doxorubicin, folic acid, fosamprenavir, methotrexate, nelfinavir, reserpine, rifampin, ritonavir, theophylline, vigabatrin: May decrease phenytoin level. Monitor patient. Cisatracurium, corticosteroids, delavirdine, doxycycline, estrogens, fluconazole, furosemide, hormonal contraceptives, irinotecan, itraconazole, ketoconazole, paclitaxel, pancuronium, paroxetine, posaconazole, quinidine, rifampin, rocuronium, sertraline, teniposide, theophylline, vecuronium, vitamin D, voriconazole, warfarin: May decrease effects of these drugs because of increased hepatic metabolism. Monitor patient closely.Lithium: May increase lithium toxicity. Monitor patient's neurologic status closely. Marked neurologic symptoms have been reported despite normal lithium level.Phenobarbital, valproate sodium, valproic acid: May increase or decrease phenytoin level. May increase or decrease levels of these drugs. Monitor patient.TCAs: May lower seizure threshold and require adjustments in phenytoin dosage. Use together cautiously.Drug-herbSt. John's wort: May decrease phenytoin level. Monitor patient.Drug-lifestyleAlcohol use: Acute intoxication may increase phenytoin level and effect. Discourage use together.Long-term alcohol use: May decrease phenytoin level. Monitor patient and strongly discourage use together. Effects on Lab Test Results May increase alkaline phosphatase, GGT, and glucose levels. May decrease folate, potassium, and T4 levels. May cause falsely low dexamethasone and metyrapone test results. Contraindications & Cautions Contraindicated in patients hypersensitive to drug or its components, phenytoin, or other hydantoins. Contraindicated in patients with a history of prior acute hepatotoxicity attributable to fosphenytoin or phenytoin. Contraindicated in patients with sinus bradycardia, SA block, second- or third-degree AV block, or Adams-Stokes syndrome. Contraindicated in patients taking delavirdine because of potential loss of virologic response and possible resistance to delavirdine or to NNRTIs. Black Box Warning: There is an increased risk of severe hypotension and cardiac arrhythmia (bradycardia, heart block, QT-interval prolongation, ventricular tachycardia, ventricular fibrillation) with IV infusion rate of greater than 150 mg phenytoin sodium equivalent/minute. CV effects can also occur at lower infusion rates; therefore, cardiac monitoring is needed during and after infusion. Reduce rate or discontinue drug as clinically necessary.Use cautiously in patients with porphyria and in those with history of hypersensitivity to similarly structured drugs, such as barbiturates, oxazolidinediones, and succinimide.Alert: If patient develops acute hepatotoxicity, discontinue drug and don't readminister.Alert: Serious and sometimes fatal toxic epidermal necrolysis and SJS have been reported; usually onset of symptoms occurs within 28 days but sometimes later. Discontinue drug at first sign of rash unless rash is clearly not drug related. If rash occurs, evaluate patient for signs and symptoms of DRESS syndrome.Dialyzable drug: Unknown.Overdose Signs & Symptoms: Asystole, bradycardia, cardiac arrest, hypocalcemia, hypotension, lethargy, metabolic acidosis, nausea, syncope, tachycardia, vomiting, death. Pregnancy-Lactation-Reproduction Drug is known to cause birth defects. Use with extreme caution in pregnant women after assessing maternal benefits and fetal risk. Prenatal exposure to phenytoin may increase the risk of congenital malformations and other adverse developmental outcomes. A potentially life-threatening bleeding disorder related to decreased levels of vitamin K-dependent clotting factors may occur in newborns exposed to phenytoin in utero. This drug-induced condition can be prevented with vitamin K administration to the mother before delivery and to the neonate after birth. It isn't known if fosphenytoin appears in human milk but phenytoin does appear in human milk. Weigh benefits of breastfeeding along with the mother's need for drug and potential adverse effects on the breastfed infant. Nursing Considerations Alert: Because of risk of cardiac and local toxicity with IV fosphenytoin administration, use oral phenytoin whenever possible. Most significant drug interactions are those commonly seen with phenytoin. Alert: Drug should always be prescribed and dispensed in phenytoin sodium equivalent units. Don't make adjustments in the recommended doses when substituting fosphenytoin for phenytoin, and vice versa. In status epilepticus, phenytoin may be used as maintenance instead of fosphenytoin, using the appropriate dose. Phosphate load provided by fosphenytoin (0.0037 millimole phosphate/mg phenytoin sodium equivalent) must be taken into consideration when treating patients who need phosphate restriction, such as those with severe renal impairment. Monitor laboratory values. Patients with Chinese ancestry who have tested positive for the allele HLA-B*1502 have a potentially increased risk of serious skin reactions, including SJS and toxic epidermal necrolysis. Monitor these patients carefully. Some patients treated with phenytoin have been shown to metabolize the drug slowly, which appears to be genetically determined. If early signs and symptoms of dose-related CNS toxicity develop, check serum levels immediately. If patient develops exfoliative, purpuric, or bullous rash or signs and symptoms of SLE, SJS, or toxic epidermal necrolysis, stop drug and notify prescriber. If rash is mild (measles-like or scarlatiniform), therapy may resume after rash disappears. If rash recurs when therapy is resumed, further fosphenytoin or phenytoin administration is contraindicated. Document that patient is allergic to drug. Stop drug in patients with acute hepatotoxicity. Doses are usually selected to attain therapeutic serum total phenytoin concentrations of 10 to 20 mcg/mL (unbound phenytoin concentrations of 1 to 2 mcg/mL). Trough levels provide information about clinically effective serum level range and are obtained just before patient's next scheduled dose. After administration, phenytoin levels shouldn't be monitored until conversion to phenytoin is essentially complete—about 2 hours after the end of an IV infusion or 4 hours after IM administration. Interpret total phenytoin levels cautiously in patients with renal or hepatic disease or hypoalbuminemia caused by an increased fraction of unbound phenytoin. It may be more useful to monitor unbound phenytoin levels in these patients. When giving drug IV, monitor patients with renal and hepatic disease because they are at increased risk for more frequent and severe adverse reactions. Monitor glucose level closely in diabetic patients; drug may cause hyperglycemia. Alert: Abrupt withdrawal of drug may precipitate status epilepticus. Look alike-sound alike: Don't confuse Cerebyx with Cerezyme, Celexa, or Celebrex. Patient Teaching Warn patient that sensory disturbances may occur with IV administration. Instruct patient to immediately report adverse reactions, especially rash, palpitations, dyspnea, chest pain, and dizziness. Warn patient not to stop drug abruptly or adjust dosage without discussing with prescriber. Advise female patient of childbearing potential to discuss drug therapy with prescriber if considering pregnancy. Advise female patient of childbearing potential that the benefits of breastfeeding should be weighed along with her need for drug and potential adverse effects on the breastfed infant. Recommend that pregnant patient taking drug enroll in the North American AED Pregnancy Registry (www.aedpregnancyregistry.org or 1-888-233-2334).

Anxiolytic and Hypnotic Agents

Anxiolytics = Prevent feelings of tension, nervousness, fear Sedatives = Calm and make patients unaware of the environment Hypnotics = Cause sleep Anxiolytic and Hypnotic Agents Children Use of anxiolytic and hypnotic drugs with children is challenging. The response of the child to the drug may be unpredictable; inappropriate aggressiveness, crying, irritability, and tearfulness are common. Using good sleep hygiene measures is the preferred approach to insomnia in children. Of the benzodiazepines, only chlordiazepoxide, clonazepam, clorazepate, midazolam, and diazepam have established pediatric dosages. Some of the others are used in pediatric settings; dosage may be calculated using age and weight. The barbiturates, being older drugs, have established pediatric dosages. These drugs must be used with caution because of the often unexpected responses. Children must be monitored very closely for CNS depression and excitability. The antihistamines diphenhydramine and promethazine are more popular for use in helping to calm children and to induce rest and sleep. Care must be taken to assess for possible dried secretions and effects on breathing. Dosage must be calculated carefully. Adults Adults using these drugs for the treatment of insomnia need to be cautioned that they are for short-term use only. The reason for the insomnia should be sought (e.g., medical, hormonal, or anxiety problems). Other methods for helping to induce sleep—established routines, quiet activities before bed, a back rub, or warm bath—should be encouraged before drugs are prescribed. Adults receiving anxiolytics also may need referrals for counseling and diagnosis of possible causes. Adults should be advised to avoid driving and making legal decisions when taking these drugs. Liver function should be evaluated before and periodically during therapy. These drugs are contraindicated during pregnancy and lactation because of the potential for adverse effects on the fetus and possible sedation of the baby. The antihistamines, which have not been associated with congenital malformations, may be the safest to use, with caution, if an anxiolytic or hypnotic drug must be used. Older Adults Older patients may be more susceptible to the adverse effects of these drugs, from unanticipated CNS effects to increased sedation, dizziness, and even hallucinations. This is a major safety concern with this group. Dosages of all of these drugs should be reduced, and the patient should be monitored very closely for toxic effects and to provide safety measures if CNS effects do occur. Baseline liver and renal function tests should be performed, and these values should be monitored periodically for any changes that would indicate a need to decrease dosage further or to stop the drug. Nondrug measures to reduce anxiety and to help induce sleep are important with older patients. The patient should be screened for physical problems, neurological deterioration, or depression, which could contribute to the insomnia or anxiety.

Independent Nursing Actions for Muscle Relaxer

Apply Ice to numb and heat to relax the muscle when it comes to spasms. Ice immediately following injury up to 24 hours then start alternating with heat/ice. RICE Other measures in addition to these drugs should be used to alleviate muscle spasm and pain. These include rest of the affected muscle, ice for acute injuries to decrease inflammation, and compression and elevation to decrease swelling. Heat applications have been showed to increase blood flow to the area and remove the pain-causing chemicals. Physical therapy is helpful to facilitate the return of the muscle to normal tone and activity. Anti-Inflammatory agents, including nonsteroidal anti-inflammatory drugs (NSAIDs), are also often used to decrease pain if the underlying problem is related to injury or inflammation.

Ethosuximide (Zarontin)

Approved for: -Absence Side effects: -Nausea, sedation, BM suppression, rash The most common adverse effects associated with benzodiazepines relate to CNS depression and its effects on body function: depression, confusion, drowsiness, lethargy, fatigue, constipation, dry mouth, anorexia, cardiac arrhythmias and changes in blood pressure, urinary retention, and loss of libido. Benzodiazepines may be associated with physical dependence and withdrawal syndrome, especially with rapid reduction in dose. Brand Names: US Zarontin Brand Names: Canada Zarontin What is this drug used for? It is used to help control certain kinds of seizures. What do I need to tell the doctor BEFORE my child takes this drug? If your child is allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell the doctor about the allergy and what signs your child had. This drug may interact with other drugs or health problems. Tell the doctor and pharmacist about all of your child's drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe to give this drug with all of your child's other drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor. What are some things I need to know or do while my child takes this drug? Tell all of your child's health care providers that your child is taking this drug. This includes your child's doctors, nurses, pharmacists, and dentists. Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles. If seizures are worse or not the same after starting this drug, talk with the doctor. Do not stop giving this drug to your child all of a sudden without calling the doctor. Your child may have a greater risk of seizures. If your child needs to stop this drug, you will want to slowly stop it as told by the doctor. Very bad and sometimes deadly blood cell problems may happen. Your child will need to have blood tests while taking this drug. Talk with the doctor. Tell the doctor right away if your child has any signs of infection. Have blood work checked as you have been told by the doctor. Talk with the doctor. Talk with your child's doctor before your child uses marijuana, other forms of cannabis, or prescription or OTC drugs that may slow your child's actions. Alcohol may interact with this drug. Be sure your child does not drink alcohol. Take care of your child's teeth. See a dentist often. If your child is pregnant or breast-feeding a baby: This drug may cause harm to the unborn baby if your child takes it during pregnancy. If your child is pregnant or gets pregnant while taking this drug, call the doctor right away. Tell the doctor if your child is breast-feeding a baby. You will need to talk about any risks to the baby. What are some side effects that I need to call my child's doctor about right away? WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child's doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect: Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat. Signs of lupus like a rash on the cheeks or other body parts, sunburn easy, muscle or joint pain, chest pain or shortness of breath, or swelling in the arms or legs. Fever, chills, or sore throat; any unexplained bruising or bleeding; or feeling very tired or weak. Feeling confused, not able to focus, or change in behavior. Hallucinations (seeing or hearing things that are not there). Bad dreams. Trouble sleeping. Change in balance. Trouble walking. Pinpoint red spots on the skin. Change in eyesight. Gum changes. Like other drugs that may be used for seizures, this drug may rarely raise the risk of suicidal thoughts or actions. The risk may be higher in people who have had suicidal thoughts or actions in the past. Call the doctor right away about any new or worse signs like depression; feeling nervous, restless, or grouchy; panic attacks; or other changes in mood or behavior. Call the doctor right away if any suicidal thoughts or actions occur. A very bad skin reaction (Stevens-Johnson syndrome/toxic epidermal necrolysis) may happen. It can cause very bad health problems that may not go away, and sometimes death. Get medical help right away if your child has signs like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in the mouth, throat, nose, or eyes. A very bad and sometimes deadly effect has happened in people taking drugs for seizures like this drug. Call the doctor right away if your child has swollen glands; fever; rash; chest pain; not able to pass urine or change in how much urine is passed; or signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes. What are some other side effects of this drug? All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child's doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away: Feeling dizzy, sleepy, tired, or weak. Headache. Hiccups. Diarrhea, upset stomach, or throwing up. Not hungry. Stomach pain or cramps. Weight loss. These are not all of the side effects that may occur. If you have questions about side effects, call your child's doctor. Call your child's doctor for medical advice about side effects. You may report side effects to your national health agency. How is this drug best given? Give this drug as ordered by your child's doctor. Read all information given to you. Follow all instructions closely. All products: Keep giving this drug to your child as you have been told by your child's doctor or other health care provider, even if your child feels well. Do not change the dose or stop your child's drug. This could cause seizures. Talk with your child's doctor. Liquid: Measure liquid doses carefully. Use the measuring device that comes with this drug. If there is none, ask the pharmacist for a device to measure this drug. What do I do if my child misses a dose? Give a missed dose as soon as you think about it. If it is close to the time for your child's next dose, skip the missed dose and go back to your child's normal time. Do not give 2 doses at the same time or extra doses. How do I store and/or throw out this drug? All products: Store at room temperature in a dry place. Do not store in a bathroom. Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets. Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area. Liquid: Do not freeze. Protect from light. General drug facts If your child's symptoms or health problems do not get better or if they become worse, call your child's doctor. Do not share your child's drug with others and do not give anyone else's drug to your child. Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child's doctor, nurse, pharmacist, or other health care provider. If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Therapeutic Action and Indications of Dopaminergic Agents

Arrange to decrease dose or discontinue the drug if dry mouth becomes so severe that swallowing becomes difficult. Provide sugarless lozenges to suck and frequent mouth care to help with this problem. Give drug with caution and arrange for a decrease in dose in hot weather or with exposure to hot environments because patients are at increased risk for heat prostration because of decreased ability to sweat. Give drug with meals if GI upset is a problem, before meals if dry mouth is a problem, and after meals if drooling occurs and the drug causes nausea to facilitate compliance with drug therapy. Monitor bowel function and institute a bowel program if constipation is severe. Ensure that the patient voids before taking the drug; monitor urinary output and palpate for bladder distention and residual urine if urinary retention is a problem. Establish safety precautions if CNS or vision changes occur to prevent patient injury. Provide thorough patient teaching about topics such as the drug name and prescribed dose, measures to help avoid adverse effects, warning signs that may indicate problems, and the need for periodic monitoring and evaluation to enhance patient knowledge about drug therapy and to promote compliance. Offer support and encouragement to help the patient cope with the progressive nature of the disease and long-term drug regimen.

Immune Sera

As explained earlier, passive immunity can be achieved by providing preformed antibodies to a specific antigen. These antibodies are found in immune sera, which may contain antibodies to toxins, venins, bacteria, viruses, or even red blood cell antigenic factors. The term immune sera is usually used to refer to sera that contain antibodies to specific bacteria or viruses. The term antitoxin refers to immune sera that have antibodies to very specific toxins that might be released by invading pathogens. The term antivenin is used to refer to immune sera that have antibodies to venom that might be injected through spider or snake bites. These drugs are used to provide early treatment following exposure to known antigens. They are very specific for antigens to which they can respond (Table 18.2). Therapeutic Actions and Indications Immune sera are used to provide passive immunity to a specific antigen, which could be a pathogen, venom, or toxin. They also may be used as prophylaxis against specific diseases after exposure in patients who are immunosuppressed. In addition, immune sera may be used to lessen the severity of a disease after known or suspected exposure (see Fig. 18.1 for sites of action of immune sera and antitoxins). Table 18.2 lists the various available immune sera, antitoxins, and antivenins, as well as usual indications. Pharmacokinetics No pharmacokinetic data are available for these biologicals. Contraindications and Cautions Immune sera are contraindicated in patients with a history of severe reaction to any immune sera or to products similar to the components of the sera to prevent potential serious hypersensitivity reactions. They should be used with caution during pregnancy because of potential risk to the fetus, in patients with coagulation defects or thrombocytopenia, or in patients with a known history of previous exposure to the immune sera because increased risk of hypersensitivity reaction occurs with each use. Adverse Effects Adverse effects can be attributed either to the effect of immune sera on the immune system (rash, nausea, vomiting, chills, fever) or to allergic reactions (chest tightness, falling blood pressure, difficulty breathing). Local reactions, such as swelling, tenderness, pain, or muscle stiffness at the injection site, are very common (Fig. 18.2).

Nursing Considerations for Patients Receiving Neuromuscular Junction Blocking Agents

Assessment: History and Examination Assess for contraindications or cautions: Any known allergies to these drugs to avoid hypersensitivity reactions; impaired liver or kidney function, which might interfere with metabolism or excretion of the drug; myasthenia gravis, which may be exacerbated by the use of this drug; impaired cardiac or respiratory function, which may be worsened due to the drug's effect on respiratory muscles and changes in perfusion; personal or family history of malignant hyperthermia, which may increase the patient's risk for this condition; fractures, which might lead to additional trauma with administration of succinylcholine; narrow-angle glaucoma because an increase in intraocular pressure can occur with succinylcholine; paraplegia, which might lead to potassium imbalance with administration of succinylcholine; and current status of pregnancy or lactation. Perform a physical assessment to establish baseline status before beginning therapy and evaluation for any potential adverse effects. Assess the patient's neurological status, including level of orientation, affect, reflexes, pupil size and reactivity, and muscle tone and response, to monitor drug effects and recovery. Monitor respiratory rate and auscultate lung sounds for evidence of adventitious sounds to evaluate effects on respiratory muscles and monitor for adverse reactions. Monitor vital signs, including temperature, pulse rate, and blood pressure, to identify changes. Auscultate the abdomen for evidence of bowel sounds to monitor effects on GI muscles and recovery. Inspect the skin for color and evidence of pressure areas or breakdown, which could result when movement ceases. Monitor the results of laboratory tests, including liver function tests, to determine the need for possible dose adjustment and serum electrolyte levels to determine potential cautions to the use of the drugs. Refer to the "Critical Thinking Scenario" for a full discussion of nursing care for an elderly patient who is receiving succinylcholine. Nursing Diagnoses Nursing diagnoses related to drug therapy may include the following: Impaired gas exchange related to depressed respirations Impaired skin integrity related to immobility from prolonged drug effects Impaired verbal communication related to effects on muscle activity Fear related to paralysis Risk of injury related to loss of muscle control Pain related to prolonged muscle contraction with succinylcholine use Deficient knowledge regarding drug therapy Planning The patient will receive the best therapeutic effect from the drug therapy. The patient will have limited adverse effects to the drug therapy. The patient will have an understanding of the drug therapy, adverse effects to anticipate, and measures to relieve discomfort and improve safety. Implementation with Rationale Be aware that administration of the drug should be performed by trained personnel (usually an anesthesiologist) because of the potential for serious adverse effects and the need for immediate ventilatory support. Ensure that emergency supplies and equipment are readily available to maintain airway and provide mechanical ventilation. Do not mix the drug with any alkaline solutions such as barbiturates because a precipitate may form, making it inappropriate for use. Test patient response and recovery periodically if the drug is being given over a long period to maintain mechanical ventilation. Discontinue the drug if response does not occur or is greatly delayed. Monitor patient temperature for prompt detection and treatment of malignant hyperthermia; have dantrolene readily available for treatment of malignant hyperthermia if it should occur. Arrange for a small dose of a nondepolarizing NMJ blocker before the use of succinylcholine to reduce the adverse effects associated with muscle contraction. Ensure that a cholinesterase inhibitor is readily available to overcome excessive neuromuscular blockade caused by nondepolarizing NMJ blockers. Have a peripheral nerve stimulator on standby to assess the degree of neuromuscular blockade, if appropriate. Provide comfort measures to help the patient tolerate drug effects, such as pain relief as appropriate; reassurance, support, and orientation for conscious patients unable to move or communicate; skin care and turning to prevent skin breakdown; and supportive care for emergencies such as hypotension and bronchospasm. Monitor patient response closely (blood pressure, temperature, pulse, respiration, reflexes) to determine effectiveness; expect dose adjustment to ensure the greatest therapeutic effect with minimal risk of toxicity. Provide thorough patient preoperative teaching about this drug because most patients who receive the drug will be receiving teaching about a particular procedure and will be unconscious when the drug is given. Teaching includes drug to be given, method for administration, effects of the drug (i.e., what to expect), and safety precautions. Offer support and encouragement to help the patient to cope with drug effects. Evaluation Monitor patient response to the drug (adequate muscle paralysis). Monitor for adverse effects (respiratory depression, hypotension, bronchospasm, GI slowdown, skin breakdown, fear related to helplessness and inability to communicate). Evaluate effectiveness of the teaching plan (the patient can relate anticipated effects of the drug and the recovery process). Monitor the effectiveness of comfort measures and compliance with the regimen. Key Points Nondepolarizing NMJ blockers prevent ACh from exciting the muscle, and paralysis ensues because the muscle cannot respond. Depolarizing NMJ blockers cause muscle paralysis by acting like ACh. They excite (depolarize) the muscle and prevent repolarization and further stimulation. There is only one drug available in this class.

Rocuronium (Zemuron)

Non-depolarizing neuromuscular blocker agent Rapid onset:Preferred for rapid intubation; short outpatient surgical procedures. No known effect on pain perception or consciousness, may be associated with pulmonary hypertension, use caution with hepatic impairment

Nursing consideration for Patients Receiving Immune Stimulants

Nursing Considerations for Patients Receiving Immune Stimulants Assessment: History and Examination Assess for contraindications and cautions: Known allergies to any of these drugs or their components to prevent hypersensitivity reactions, current status related to pregnancy or lactation to avoid serious adverse effects on the fetus or baby, and history of hepatic, renal, or cardiac disease; bone marrow depression; leukemic states; and CNS disorders, including seizures, all of which could be exacerbated by the effects of these drugs. Perform a physical assessment to determine baseline status before beginning therapy and for any potential adverse effects: Inspect for the presence of any skin lesions to detect early dermatological effects, obtain weight to monitor for fluid retention, monitor temperature to detect any infection, check heart rate and rhythm and blood pressure to monitor for any cardiac effects of the drug, and assess level of orientation and reflexes to evaluate CNS effects of the drug. Obtain a baseline electrocardiogram if appropriate to evaluate cardiac function and monitor adverse effects of the drugs. Assess patient's renal and liver function, including renal and liver function tests, to determine the appropriateness of therapy and to determine the need for possible dose adjustment and toxic drug effects. Monitor the results of laboratory tests such as complete blood count (CBC) to identify changes in bone marrow function. Nursing Diagnoses Nursing diagnoses related to drug therapy might include the following: Acute pain related to CNS, GI, and flu-like effects Imbalanced nutrition: Less than body requirements related to flu-like effects Anxiety related to diagnosis and drug therapy Deficient knowledge regarding drug therapy Planning The patient will receive the best therapeutic effect from the drug therapy. The patient will have limited adverse effects to the drug therapy. The patient will have an understanding of the drug therapy, adverse effects to anticipate, and measures to relieve discomfort and improve safety. Implementation with Rationale Arrange for laboratory tests before and periodically during therapy, including CBC and differential, to monitor for drug effects and adverse effects. Administer drug as indicated; instruct the patient and a significant other if injections are required to ensure that the drug will be given even if the patient is not able to administer it. Monitor for severe reactions, such as severe hypersensitivity reactions, and arrange to discontinue the drug immediately if they occur. Arrange for supportive care and comfort measures for flu-like symptoms (e.g., rest, environmental control, acetaminophen) to help the patient cope with the drug effects. Ensure that the patient is well hydrated during therapy to prevent severe adverse effects. Instruct female patients in the use of barrier contraceptives to avoid pregnancy during therapy because of the potential for adverse effects on the fetus. Offer support and encouragement to deal with the diagnosis and the drug regimen. Provide patient teaching about measures to avoid adverse effects, warning signs of problems, and proper administration technique. Evaluation Monitor patient response to the drug (improvement in condition being treated). Monitor for adverse effects (flu-like symptoms, GI upset, CNS changes, bone marrow depression). Evaluate the effectiveness of the teaching plan (patient can name drug, dosage, adverse effects to watch for, specific measures to avoid adverse effects). Monitor the effectiveness of comfort measures and compliance with the regimen.

Nursing Considerations for Patients Receiving Vaccines

Nursing Considerations for Patients Receiving Vaccines Assessment: History and Examination Assess for contraindications or cautions: Known allergies to any vaccines or to the components of the one being used to prevent hypersensitivity reactions; current status related to pregnancy, which is a contraindication to the use of vaccines; recent administration of immune globulin or blood products, which could alter the response to the vaccine; history of immune deficiency, which could alter immune reactions; and evidence of acute infection, which could be exacerbated by the introduction of other antigens. Perform a physical assessment to determine baseline status before beginning therapy and for any potential adverse effects: Inspect for the presence of any skin lesions to monitor for hypersensitivity reactions; check temperature to monitor for possible infection; monitor pulse, respirations, and blood pressure; auscultate lungs for adventitious sounds; and assess level of orientation and affect to monitor for hypersensitivity reactions to the vaccine. Evaluate the range of motion of the extremity to be used for vaccine administration to assure adequate blood flow to deal with the antigen and inflammatory reaction. Assess tissue perfusion to establish a baseline to monitor for potential hypersensitivity reactions. Nursing Diagnoses Nursing diagnoses related to drug therapy might include the following: Acute pain related to injection, gastrointestinal (GI), and flu-like effects Ineffective tissue perfusion if severe reaction occurs Deficient knowledge regarding drug therapy Planning The patient will receive the best therapeutic effect from the drug therapy. The patient will have limited adverse effects to the drug therapy. The patient will have an understanding of the drug therapy, adverse effects to anticipate, and measures to relieve discomfort and improve safety. Implementation with Rationale Do not use to treat acute infection; a vaccine is only used to prevent infection with future exposures. Do not administer if the patient exhibits signs of acute infection or immune deficiency because the vaccine can cause a mild infection and can exacerbate acute infections. Do not administer if the patient has received blood, blood products, or immune globulin within the last 3 months because a severe immune reaction could occur. Arrange for proper preparation and administration of the vaccine; check on the timing and dose of each injection because dose, preparation, and timing vary with individual vaccines. Maintain emergency equipment on standby, including epinephrine, in case of severe hypersensitivity reaction. Arrange for supportive care and comfort measures for flu-like symptoms (rest, environmental control, acetaminophen) and for injection discomfort (local heat application, anti-inflammatories, resting arm) to promote patient comfort. Do not administer aspirin to children for the treatment of discomforts associated with the immunization. Aspirin can mask warning signs of Reye syndrome, a potentially serious disease. Provide thorough patient teaching, including measures to avoid adverse effects, warning signs of problems, and the need to keep a written record of immunizations, to increase knowledge about drug therapy and to increase compliance with the drug regimen. Provide a written record of the immunization, including the need to return for booster immunizations and timing of the boosters, if necessary, to increase patient compliance with medical regimens. Evaluation Monitor patient response to the drug (prevention of disease, appropriate antibody titer levels). Monitor for adverse effects (flu-like symptoms; GI upset; local pain, swelling, nodule formation at the injection site). Evaluate the effectiveness of the teaching plan (patient can name drug, dosage, adverse effects to watch for; has written record of immunizations; can state when to return for the next immunization or booster if needed). Monitor the effectiveness of comfort measures and adherence to the regimen. See "Critical Thinking Scenario" for additional information on educating a parent about vaccines.

Immune System Response

Calor (heat)- Caused by increased blood flow Tumor (swelling)- Caused by fluid that leaks into the tissues Rubor (Redness)- Caused by the increase in blood flow due to vasodilation Dolor (pain)- Caused by the activation of pain fibers

Morphine

Children The safety and effectiveness of most of these drugs have not been established in children. If a child older than 12 years of age requires a skeletal muscle relaxant after an injury, metaxalone has an established pediatric dosage. Other agents have been used with adjustments to the adult dosage based on the child's age and weight. Baclofen is often used to relieve the muscle spasticity associated with cerebral palsy. A caregiver needs intensive education in the use of the intrathecal infusion pump and how to monitor the child for therapeutic as well as adverse effects. Methocarbamol is the drug of choice if a child needs to be treated for tetanus. Dantrolene is used to treat upper motor neuron spasticity in children. The dosage is based on body weight and increases over time. The child should be screened regularly for CNS and GI (including hepatic) toxicity. Botulinum toxins are not approved for use in children. The use of these neurotoxins in children has been associated with the development of botulism. Adults Adults being treated for acute musculoskeletal pain should be cautioned to avoid driving and to take safety precautions against injury because of the related CNS effects, including dizziness and drowsiness. Rest of the muscle, heat, massage, and physical therapy are key components to recovery from any muscular injury or pain. Adults complaining of muscle spasm pain that may be related to anxiety often respond effectively to diazepam, which is a muscle relaxant and anxiolytic. Women of childbearing age should be advised to use contraception when they are taking these drugs. If a pregnancy does occur or is desired, they need counseling about the potential for adverse effects. Women who are nursing should be encouraged to find another method of feeding the baby because of the potential for adverse drug effects on the baby. Females who are over 35 years of age have an increased risk for the hepatotoxicity associated with dantrolene and should be monitored closely for any change in hepatic function and given written information about the prodrome syndrome that often occurs with the hepatic toxicity. Older Adults Older patients are more likely to experience the adverse effects associated with these drugs—CNS, GI, and cardiovascular. Because older patients often also have renal or hepatic impairment, they are also more likely to have toxic levels of the drug related to changes in metabolism and excretion. Carisoprodol is the centrally acting skeletal muscle relaxant of choice for older patients and for those with hepatic or renal impairment. If dantrolene is required for an older patient, lower doses and more frequent monitoring are needed to assess for potential cardiac, respiratory, and liver toxicity. Older women who are receiving hormone replacement therapy are at the same risk for development of hepatotoxicity as premenopausal women and should be monitored accordingly. SAFETY ALERT! morphine hydrochloride MOR-feenDoloralmorphine sulfateArymo ER, Duramorph PF, Infumorph, Kadian, M-Ediat, M-Eslon, MorphaBond, Morphine LP Epidural, MS Contin, MS.IR, Statex, Statex DPSTherapeutic class: Opioid analgesicsPharmacologic class: OpioidsControlled substance schedule: II Available Forms morphine hydrochloride Syrup: 1 mg/mL∗; 5 mg/mL∗ morphine sulfate Capsules (extended-release microgranules [M-Eslon]) : 10 mg; 15 mg; 30 mg; 60 mg; 100 mg; 200 mg Capsules (extended-release pellets) : 30 mg; 45 mg; 60 mg; 75 mg; 90 mg; 120 mg Capsules (extended-release pellets [Kadian]) : 10 mg; 20 mg; 30 mg; 40 mg; 50 mg; 60 mg; 70 mg; 80 mg; 100 mg; 130 mg; 150 mg; 200 mg Capsules (immediate-release [M-Ediat]): 5 mg; 10 mg; 20 mg; 30 mg Drops (Statex): 20 mg/mL; 50 mg/mL Injection with preservative: 0.5 mg/mL; 1 mg/mL; 2 mg/mL; 5 mg/mL; 10 mg/mL; 15 mg/mL; 50 mg/mL Injection without preservative (Duramorph, Infumorph): 0.5 mg/mL; 1 mg/mL; 10 mg/mL; 25 mg/mL ampules Injection without preservative (Carpuject and prefilled syringes and vials): 2 mg/mL; 4 mg/mL; 8 mg/mL; 10 mg/mL; 15 mg/mL Oral solution: 10 mg/5 mL; 20 mg/5 mL; 20 mg/mL (concentrate); 100 mg/5 mL (concentrate) Suppositories: 5 mg; 10 mg; 20 mg; 30 mg Syrup (Statex): 1 mg/mL; 5 mg/mL; 10 mg/mL Tablets: 5 mg; 10 mg; 15 mg; 20 mg; 25 mg; 30 mg; 50 mg Tablets (extended-release) : 15 mg; 30 mg; 60 mg; 100 mg; 200 mg Tablets (extended-release, abuse deterrent) : 15 mg; 30 mg; 60 mg; 100 mg Indications & Dosages Alert: Initiate dosing for each patient individually and use the lowest effective dosage for the shortest duration consistent with individual treatment goals.Moderate to severe painAdults: Initially, 10 mg (based on 70 kg individual) IM or 0.1 to 0.2 mg/kg IV every 4 hours p.r.n. Or, 15 to 30 mg (immediate-release tablets) PO, or 10 to 20 mg (oral solution) PO, or 10 to 20 mg PR every 4 hours p.r.n.For extended-release tablet, give 15 or 30 mg PO every 8 to 12 hours.For epidural injection, give 5 mg by epidural catheter; then, if pain isn't relieved adequately in 1 hour, give supplementary doses of 1 to 2 mg at intervals sufficient to assess effectiveness. Maximum total epidural dose shouldn't exceed 10 mg/24 hours.For intrathecal injection, a single dose of 0.2 to 1 mg may provide pain relief for 24 hours (only in the lumbar area). Don't repeat injections.Moderate to severe pain requiring continuous, around-the-clock oral opioidAdults: For patients receiving other oral morphine formulations, may convert to extended-release capsules by administering patient's total daily oral morphine dose as extended-release capsules once daily (Kadian) or by administering one-half of patient's total daily oral morphine dose b.i.d. (Kadian capsules, MS Contin tablets, Arymo ER tablets). Patients 24-hour morphine requirement may also be divided every 8 hours and given as MS Contin tablets or Arymo ER tablets. Initial dosage in opioid-naive or opioid-nontolerant patients is 15 mg (Arymo ER tablets) PO every 8 or 12 hours. Don't give Kadian more frequently than every 12 hours. MS Contin shouldn't be used more frequently than every 8 hours. Administration POBlack Box Warning: Take care when administering morphine oral solution to avoid dosing errors because of confusion among different concentrations and between milligrams and milliliters, which could result in accidental overdose and death. Take care to ensure the proper dose is communicated and dispensed.Black Box Warning: Oral solutions of various concentrations and an intensified oral solution (20 mg/mL) are available. Carefully note strength given. The 20-mg/mL concentration is indicated for use only in opioid-tolerant patients because of the risk of fatal respiratory depression in opioid-naive patients. It's packaged with a calibrated oral syringe for accurate dosing.Black Box Warning: Instruct patient to swallow extended-release or long-acting morphine sulfate oral formulations whole, without crushing, chewing, or dissolving, which may cause rapid, uncontrolled release and absorption of a potentially fatal dose of morphine. If necessary, capsules (Kadian) may be carefully opened and entire contents poured into cool, soft foods such as applesauce and swallowed immediately without chewing.Give morphine sulfate without regard to food.May give Kadian capsules through a gastrostomy tube; flush tube with water, sprinkle contents of capsules in 10 mL of water, and flush through tube.IVFor continuous infusion, mix drug with D5W to yield 0.1 to 1 mg/mL, and give by a continuous infusion device.In adults with severe, chronic pain, maintenance IV infusion is 0.8 to 80 mg/hour; sometimes higher doses are needed.Make sure an opioid antagonist is immediately available before administering IV.Black Box Warning: Infumorph and Duramorph are supplied in sealed ampules. Treat accidental dermal exposure to these drugs by removing contaminated clothing and rinsing affected area with water.Black Box Warning: Inspect parenteral drug products for particulate matter before opening the amber ampule and again for color after removing contents from ampule. Don't use if solution in the unopened ampule contains a precipitate that doesn't disappear upon shaking. After removal, don't use unless solution is colorless or pale yellow.Incompatibilities: None listed by manufacturer. Consult a drug incompatibility reference for more information.IMDocument injection site.Store injection solution at room temperature and protect from light.Black Box Warning: Solution may darken with age. Don't use if injection is darker than pale yellow, discolored, or contains precipitate.Epidural/intrathecalDocument injection site; limit to lumbar area.Alert: Intrathecal dosage is usually one-tenth that of epidural dosage.Verify proper placement of needle or catheter in the intrathecal or epidural space before injecting drug.Black Box Warning: Inspect for particulate matter and discoloration before administration. Don't use if it's darker than pale yellow, discolored in any other way, or contains a precipitate.Store injection solution at room temperature until ready to use; discard unused portion.Protect from light; don't freeze or heat sterilize.RectalRefrigeration of rectal suppository isn't needed. Action Unknown. Binds with opioid receptors in the CNS, altering perception of and emotional response to pain.RouteOnsetPeakDurationPO30 min1-2 hr3-5 hrPO (extended-release)1-2 hr3-4 hr8-24 hrIV5-10 min20 min4-5 hrIM10-30 min30-60 min4-5 hrPR20-60 min20-60 min3-7 hrEpidural15-60 min15-60 min24 hrIntrathecal15-60 min30-60 min24 hrHalf-life: Immediate release, 2 to 4 hours; extended release, 11 to 24 hours. Adverse Reactions CNS: dizziness, drowsiness, headache, euphoria, light-headedness, nightmares, sedation, somnolence, seizures, depression, hallucinations, nervousness, physical dependence, syncope, anxiety. CV: bradycardia, cardiac arrest, shock, HTN, hypotension, tachycardia, palpitations, peripheral circulatory collapse, peripheral edema, chest pain, syncope. EENT: miosis, blurred vision. GI: constipation, nausea, vomiting, anorexia, biliary tract spasms, dry mouth, ileus, flatulence, abdominal pain. GU: urine retention. Hematologic: thrombocytopenia, anemia, leukopenia. Respiratory: apnea, respiratory arrest, respiratory depression. Skin: diaphoresis, edema, pruritus, skin flushing, pain at injection site. Other: decreased libido. Interactions Drug-drugAlvimopan: May enhance adverse/toxic effects of alvimopan. Alvimopan is contraindicated in patients receiving therapeutic doses of opioids for more than 7 consecutive days immediately before alvimopan initiation. Consider therapy modification.Black Box Warning: Benzodiazepines, CNS depressants: May cause slow or difficult breathing, sedation, and death. Avoid use together. If use together is necessary, limit dosage and duration of each drug to the minimum necessary for desired effect. Cimetidine: May increase respiratory and CNS depression when given with morphine sulfate. Monitor patient closely.General anesthetics, hypnotics, MAO inhibitors, other opioid analgesics, TCAs: May cause respiratory depression, hypotension, profound sedation, or coma. Use together with caution, reduce morphine dose, and monitor patient response.Alert: Serotonergic drugs (amoxapine, antiemetics [dolasetron, granisetron, ondansetron, palonosetron], antimigraine drugs, buspirone, cyclobenzaprine, dextromethorphan, linezolid, lithium, MAO inhibitors, maprotiline, methylene blue, mirtazapine, nefazodone, SSNRIs, SSRIs, TCAs, trazodone, tryptophan, vilazodone): May increase risk of serotonin syndrome. Use together cautiously and monitor patient for serotonin syndrome.Drug-herbAlert: St. John's wort: May increase risk of serotonin syndrome. Use together cautiously and monitor patient for serotonin syndrome.Drug-lifestyleBlack Box Warning: Alcohol use: May cause additive CNS effects and fatal overdose. Warn patient to avoid alcohol and products containing alcohol. Effects on Lab Test Results May increase amylase level. May decrease Hb level (morphine sulfate). May decrease platelet count. May cause abnormal LFT values (morphine sulfate). Contraindications & Cautions Contraindicated in patients hypersensitive to drug and in those with conditions that would preclude IV administration of opioids (acute bronchial asthma or upper airway obstruction). Black Box Warning: Opioids should only be prescribed with benzodiazepines or other CNS depressants to patients for whom alternative treatment options are inadequate.Black Box Warning: Use of extended-release or long-acting morphine sulfate forms may increase the risk of addiction, abuse, and misuse, even at recommended doses, and has a greater risk of overdose and death. Reserve their use for patients for whom alternative treatment options are ineffective, not tolerated, or are otherwise insufficient to provide adequate pain management.Black Box Warning: Accidental ingestion of even one dose of extended-release or long-acting forms of morphine sulfate, especially by children, can result in a fatal overdose. Keep out of reach of children.Alert: Drug may lead to a rare but serious decrease in adrenal gland cortisol production.Alert: Drug may cause decreased sex hormone levels with long-term use.Alert: Patients are at increased risk for oversedation and respiratory depression if they snore or have a history of sleep apnea, haven't used opioids recently or are first-time opioid users, have increased opioid dosage requirements or opioid habituation, have received general anesthesia for longer lengths of time or received other sedating drugs, have preexisting pulmonary or cardiac disease, or have thoracic or other surgical incisions that may impair breathing. Monitor patients carefully.Contraindicated in patients with GI obstruction.Use with caution in elderly or debilitated patients and in those with head injury, increased ICP, seizures, chronic pulmonary disease, prostatic hyperplasia, severe hepatic or renal disease, acute abdominal conditions, hypothyroidism, Addison disease, and urethral stricture.Use with caution in patients with circulatory shock, biliary tract disease, CNS depression, toxic psychosis, acute alcoholism, delirium tremens, and seizure disorders.Dialyzable drug: Yes.Overdose Signs & Symptoms: Miosis, CNS depression, respiratory depression, apnea, flaccid skeletal muscles, bradycardia, hypotension, circulatory collapse, cardiac arrest, respiratory arrest, death. Pregnancy-Lactation-Reproduction Alert: Carefully weigh risks and benefits of using drug in pregnant women. Drug should be used in pregnancy only if need for opioid analgesia clearly outweighs potential risks to the fetus. Black Box Warning: Prolonged use of opioids during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If opioid use is required for a prolonged period, apprise pregnant patient of risk to the neonate and ensure appropriate treatment will be available.Because of the potential for serious adverse reactions in breastfeeding infants, including respiratory depression, sedation, and possibly withdrawal symptoms upon cessation of morphine to the mother, patient should discontinue breastfeeding or discontinue drug, taking into account importance of drug to the mother.If morphine use is necessary in a breastfeeding patient, use cautiously. Limit use and supplement with nonopioid agents. Monitor infant for increased sleepiness, difficulty feeding or breathing, and limpness. Nursing Considerations Black Box Warning: Assess each patient's risk of addiction, abuse, or misuse before prescribing extended-release or long-acting forms of morphine sulfate, and monitor all patients regularly for development of these behaviors.Black Box Warning: Monitor patients for respiratory depression, especially during initiation of extended-release or long-acting morphine sulfate or after a dosage increase. Serious, life-threatening, or fatal respiratory depression may occur.Alert: If patient is taking opioids with serotonergic drugs, watch for signs and symptoms of serotonin syndrome (agitation, hallucinations, rapid HR, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, diarrhea), especially at start of treatment and at dosage increases. Signs and symptoms may occur within several hours of coadministration but may also occur later, especially after dosage increase. Discontinue the opioid, serotonergic drug, or both if serotonin syndrome is suspected.Alert: Monitor patient for signs and symptoms of adrenal insufficiency (nausea, vomiting, loss of appetite, fatigue, weakness, dizziness, low BP). Perform diagnostic testing if adrenal insufficiency is suspected. If adrenal insufficiency is confirmed, treat with corticosteroids and wean patient off opioids if appropriate. Discontinue corticosteroids when clinically appropriate.Alert: Monitor patient for signs and symptoms of decreased sex hormone levels (low libido, erectile dysfunction, amenorrhea, infertility). If signs and symptoms occur, evaluate patient and obtain lab testing.Alert: Carefully monitor vital signs, pain level, respiratory status, and sedation level in all patients receiving opioids, especially those receiving IV drugs, even those given postoperatively.Reassess patient's level of pain at least 15 and 30 minutes after giving parenterally and 30 minutes after giving orally.Alert: Extended-release capsules aren't for use on an as-needed basis.Black Box Warning: Keep opioid antagonist (naloxone) and resuscitation equipment available.Monitor circulatory, respiratory, bladder, and bowel functions carefully. Drug may cause hypotension, urine retention, nausea, vomiting, ileus, or altered level of consciousness regardless of the route.Alert: Intrathecal dosage is usually one-tenth of epidural dosage.Black Box Warning: Life-threatening respiratory depression may occur with morphine use, even when drug has been used as recommended and not misused or abused. Proper dosing and titration are essential, and morphine should only be prescribed by health care providers knowledgeable in the use of potent opioids for management of long-term pain. Monitor patients for respiratory depression, especially during initiation of morphine or after a dosage increase. Instruct patients to swallow morphine capsule whole; Kadian capsule can be opened and contents sprinkled on applesauce and swallowed without chewing. Crushing, dissolving, or chewing pellets within the capsule can cause rapid release and absorption of a potentially fatal dose of morphine.If respirations drop below 12 breaths/minute, withhold dose and notify prescriber.Black Box Warning: Morphine has an abuse liability similar to other opioid analgesics and may be misused, abused, or diverted.Alert: Extended-release tablets and capsules aren't for use on an as-needed basis for mild or acute pain or for postoperative pain, unless patient has already been receiving long-term opioid therapy before surgery or if postoperative pain is expected to be moderate to severe and persist for an extended period.Preservative-free preparations are available for epidural and intrathecal use.Epidural administration has been associated with less potential for immediate or late adverse effects than intrathecal administration; use epidural route whenever possible.A constant IV infusion of naloxone, 0.6 mg/hour, for 24 hours after intrathecal injection may be used to reduce potential adverse effects.Black Box Warning: When the epidural or intrathecal route is used, observe patients in a fully equipped and staffed environment for at least 24 hours after the initial dose.Black Box Warning: Infumorph isn't recommended for single-dose IV, IM, or subcut administration.Black Box Warning: Improper or erroneous substitution of Infumorph 200 or 500 (10 or 25 mg/mL, respectively) for regular Duramorph (0.5 or 1 mg/mL) is likely to result in serious overdose, leading to seizures, respiratory depression, and possibly fatal outcome.When drug is given epidurally, monitor patient closely for respiratory depression up to 24 hours after the injection. Check respiratory rate and depth every 30 to 60 minutes for 24 hours. Watch for pruritus and skin flushing.Morphine is drug of choice in relieving MI pain; may cause transient decrease in BP.An around-the-clock regimen best manages severe, chronic pain. Verify patient has a breakthrough pain medication prescribed in addition to the around-the-clock medication.Morphine may worsen or mask gallbladder pain.Constipation is commonly severe with maintenance dose. Ensure that stool softener or stimulant laxative is ordered.Taper morphine sulfate therapy gradually when stopping therapy.Black Box Warning: Each ampule of Infumorph and Duramorph contains a large amount of a potent opioid that has been associated with abuse and dependence among health care providers. Due to the limited indications for this product, risk of overdose, and risk of its diversion and abuse, special measures should be taken to control this product within the hospital or clinic. Infumorph and Duramorph should be subject to rigid accounting, rigorous control of wastage, and restricted access.Black Box Warning: Accidental consumption of morphine, especially by children, can result in a fatal overdose of morphine.Alert: Don't stop drug abruptly; withdraw slowly and individualize gradual taper plan to prevent signs and symptoms of withdrawal, worsening pain, and psychological distress in physically dependent patients. Refer to manufacturer's label for specific tapering instructions.Alert: When tapering opioids, monitor patient closely for signs and symptoms of opioid withdrawal (restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, mydriasis, irritability, anxiety, insomnia, backache, joint pain, weakness, abdominal cramps, anorexia, nausea, vomiting, diarrhea, increased BP or HR, increased respiratory rate), which may indicate a need to taper more slowly. Also monitor patient for suicidal thoughts, use of other substances, and mood changes.Look alike-sound alike: Don't confuse morphine with hydromorphone. Don't confuse MS Contin with Oxycontin. Patient Teaching Black Box Warning: Caution patient or caregiver of patient taking an opioid with a benzodiazepine, CNS depressant, or alcohol to seek immediate medical attention for dizziness, light-headedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.Alert: Explain assessment and monitoring process to patient and family. Instruct them to immediately report difficulty breathing or other signs or symptoms of a potential adverse opioid-related reaction.Alert: Encourage patient to report all medications being taken, including prescription and OTC medications and supplements.Warn patient that morphine can cause constipation.Alert: Caution patient to immediately report signs and symptoms of serotonin syndrome, adrenal insufficiency, and decreased sex hormone levels.When drug is used after surgery, encourage patient to turn, cough, deep-breathe, and use incentive spirometer to prevent lung problems.Caution ambulatory patient about getting out of bed or walking. Warn outpatient to avoid driving and other potentially hazardous activities that require mental alertness until drug's adverse CNS effects are known.Black Box Warning: Drinking alcohol or taking drugs containing alcohol while taking extended-release capsules may cause additive CNS effects and potentially fatal overdose. Warn patient to read labels on OTC drugs carefully for alcohol content and not to use alcohol in any form.Tell patient to swallow morphine sulfate whole or to open capsule and sprinkle beads or pellets on a small amount of applesauce immediately before taking.Black Box Warning: Tell patient to keep morphine oral preparations out of the reach of children. In case of accidental ingestion, advise patient to seek emergency medical help immediately.Alert: Counsel patient not to discontinue opioids without first discussing with prescriber the need for a gradual tapering regimen.Alert: Warn patient not to crush, break, or chew extended-release forms.

Carisoprodol (Soma)

Influenza vaccine

Contraindication: Eggs, LAIV, Immunocompromised, <2y.o., chronic disease. All adults are advised to be immunized yearly with an influenza vaccine and once with a pneumococcal pneumonia vaccine and the pneumococcal 13-valent vaccine. These vaccines provide some protection against diseases that can prove dangerous for people with chronic lung, CV, or endocrine disorders. The influenza vaccine changes yearly, depending on predictions of which flu strain might be emergent in that year. The pneumonia vaccine contains 23 strains and is believed to offer lifetime protection. Older patients are at greater risk for severe illness from influenza and pneumococcal infections. The yearly flu shot and the pneumococcal and pneumococcal 13-valent vaccines should be stressed for this group.

Dantrolene (Dantrium) Contraindications and Cautions

Dantrolene is contraindicated in the presence of any known allergy to the drug to prevent hypersensitivity reactions. It is also contraindicated in the following conditions: Spasticity that contributes to locomotion, upright position, or increased function, which would be lost if that spasticity were blocked; active hepatic disease, which might interfere with metabolism of the drug and because of known liver toxicity; and lactation because the drug may cross into breast milk and cause adverse effects in the infant. The botulinum toxins are contraindicated in the presence of allergy to any component of the drug to prevent hypersensitivity reactions or with active infection at the site of the injection because injecting the drug could aggravate the infection. Caution should be used with dantrolene in women and in all patients older than 35 years because of increased risk of potentially fatal hepatocellular disease (Box 25.2); in patients with a history of liver disease or previous dysfunction, which could make the liver more susceptible to cellular toxicity; in patients with respiratory depression, which could be exacerbated by muscular weakness; in patients with cardiac disease because cardiac muscle depression may be a risk; and during pregnancy because of the potential for adverse effects on the fetus. Caution should be used with the botulinum toxins with any peripheral neuropathic disease; with neuromuscular disorders, which could be exacerbated by the effects of the drug; in children because it is not approved for use in children and severe effects including botulism have been reported; with pregnancy and lactation because the potential effects on the fetus or baby are not known; and with any known cardiovascular disease because of the potential changes in tissue perfusion and risk of systemic absorption.

Nursing considerations and teaching needs for patients receiving psychotherapeutic agents.

Do not allow patient to crush or chew sustained release capsules, which will speed up their absorption and may cause toxicity. If administering parenteral forms, keep patient recumbent for 30 minutes to reduce the risk of orthostatic hypotension. Consider warning patient or patient's guardians about the risk of development of tardive dyskinesias with continued use so they are prepared for that neurological change. Caution patient/guardians about the risk of gynecomastia when using these drugs to prevent undue stress. Monitor CBC to arrange to discontinue the drug at signs of bone marrow suppression. Monitor blood glucose levels with long-term use to detect the development of glucose intolerance. Arrange for gradual dose reduction after long-term use. Abrupt withdrawal has been associated with gastritis, nausea, vomiting, dizziness, arrhythmias, and insomnia. Provide positioning of legs and arms to decrease the discomfort of dyskinesias. Provide sugarless candy and ice chips to increase secretions and frequent mouth care to prevent dry mouth from becoming a problem. Encourage patient to void before taking a dose if urinary hesitancy or retention is a problem. Provide safety measures such as side rails and assistance with ambulation if CNS effects or orthostatic hypotension occurs to prevent patient injury. Provide for vision examinations to determine ocular changes and arrange appropriate dose change. Provide thorough patient teaching, including drug name, prescribed dosage, measures for avoidance of adverse effects, cautions that it may take weeks to see the desired clinical effects, warning signs that may indicate possible problems, and the need for monitoring and evaluation to enhance patient knowledge about drug therapy and to promote compliance. (Refer to "Critical Thinking Scenario.") Warn the patient that urine may have a pink to reddish-brown color. Offer support and encouragement to help the patient to cope with the drug regimen.

Fluoxetine (Prozac)

FLUoxetine hydrochloride floo-OX-e-teen Prozac, Sarafem Therapeutic class: Antidepressants Pharmacologic class: SSRIs Available Forms Capsules (delayed-release) : 90 mg Capsules (pulvules): 10 mg; 20 mg; 40 mg Oral solution: 20 mg/5 mL Tablets: 10 mg; 15 mg; 20 mg; 60 mg Indications & Dosages Adjust-a-dose (for all indications): For patients with renal or hepatic impairment and those taking several drugs at the same time, reduce dose or increase dosing interval. Depression, OCD (excluding Sarafem)Adults: Initially, 20 mg PO in the morning; increase dosage after several weeks based on patient response. Doses over 20 mg/day can be given once daily in the morning or divided into b.i.d. dosing (morning and noon). Maximum daily dose is 80 mg. Children ages 7 to 17 (OCD): 10 mg PO daily. After 2 weeks, increase to 20 mg daily. Dosage range is 20 to 60 mg daily. In lower weight children, initially 10 mg/day. Consider additional dosage increases after several more weeks if insufficient clinical improvement is observed. Dosage range of 20 to 30 mg/day is recommended.Children ages 8 to 18 (depression): 10 mg PO once daily for 1 week; then increase to 20 mg daily. Due to higher plasma levels in lower weight children, the starting and target dose in this group may be 10 mg/day. Consider a dosage increase to 20 mg/day after several weeks if insufficient clinical improvement is observed. Maintenance therapy for depression in stabilized patients (not for newly diagnosed depression)Adults: 90 mg Prozac Weekly PO once weekly. Start once-weekly doses 7 days after the last daily dose of Prozac 20 mg. Short-term and long-term treatment of bulimia nervosa (excluding Sarafem)Adults: 60 mg PO daily in the morning. For some patients, it may be advisable to titrate up to this target dose over several days.Short-term treatment of panic disorder with or without agoraphobia (excluding Sarafem)Adults: 10 mg PO once daily for 1 week, then increase dose as needed to 20 mg daily. Maximum daily dose is 60 mg. Depressive episodes associated with bipolar I disorder (with olanzapine)Adults: 20 mg PO with 5 mg PO olanzapine once daily in the evening. Dosage adjustments can be made based on efficacy and tolerability within ranges of fluoxetine 20 to 50 mg and olanzapine 5 to 12.5 mg. Children ages 10 to 17: Initially, 20 mg PO with 2.5 mg olanzapine PO once daily in evening. Dosage adjustments can be made based on efficacy and tolerability. Safety of doses above 12 mg olanzapine with 50 mg fluoxetine hasn't been evaluated in pediatric clinical studies. Premenstrual dysphoric disorder Adults: 20 mg Sarafem PO daily continuously (every day of the menstrual cycle) or intermittently (20 mg daily starting 14 days before the anticipated onset of menstruation through first full day of menses and repeating with each new cycle). Maximum daily dose, 80 mg PO.Treatment-resistant depression Adults: 20 mg PO with 5 mg PO olanzapine once daily in the evening. Dosage adjustments can be made based on efficacy and tolerability within ranges of fluoxetine 20 to 50 mg and olanzapine 5 to 20 mg. Administration PO Give drug without regard for food. Avoid giving drug in the afternoon, whenever possible, because doing so commonly causes nervousness and insomnia.Delayed-release capsules must be swallowed whole; don't crush or open. Action Thought to be linked to drug's inhibition of CNS neuronal uptake of serotonin.RouteOnsetPeakDurationPOUnknown6-8 hr Unknown Half-life: Acute administration, 1 to 3 days; long-term administration, 4 to 6 days. Adverse Reactions CNS: nervousness, somnolence, anxiety, insomnia, headache, drowsiness, tremor, dizziness, asthenia, abnormal thinking, fatigue, fever, emotional lability. CV: palpitations, hot flashes, prolonged QT interval. EENT: nasal congestion, pharyngitis, sinusitis. GI: nausea, diarrhea, dry mouth, anorexia, dyspepsia, constipation, abdominal pain, vomiting, flatulence, increased appetite, taste perversion. GU: sexual dysfunction, decreased libido, micturition disorder. Metabolic: weight loss, hyponatremia. Musculoskeletal: muscle pain. Respiratory: URI, cough. Skin: rash, pruritus, diaphoresis. Other: flulike syndrome, chills. Interactions Drug-drug Amphetamines, antiemetics, antipsychotics, buspirone, dextromethorphan, dihydroergotamine, lithium salts, meperidine, opioids, other SSRIs or SSNRIs (duloxetine, venlafaxine), TCAs, tramadol, trazodone, tryptophan: May increase the risk of serotonin syndrome. Avoid combinations of drugs that increase the availability of serotonin in the CNS; monitor patient closely if used together.Antiplatelet agents, aspirin, NSAIDs: May increase risk of bleeding. Use together cautiously.Benzodiazepines, lithium, TCAs: May increase levels of these drugs, resulting in additional CNS effects. Monitor patient closely.Beta blockers, carbamazepine, flecainide, vinblastine: May increase levels of these drugs. Monitor drug levels and monitor patient for adverse reactions.Cyclosporine: May increase renal toxicity of cyclosporine. Monitor patient carefully for cyclosporine toxicity.Cyproheptadine: May reverse or decrease fluoxetine effect. Monitor patient closely.Dextromethorphan: May cause unusual side effects such as visual hallucinations. Advise use of cough suppressant that doesn't contain dextromethorphan while taking fluoxetine.Highly protein-bound drugs: May increase level of fluoxetine or other highly protein-bound drugs. Monitor patient closely.Insulin, oral antidiabetics: May alter glucose level and antidiabetic requirements. Adjust dosage.Linezolid, methylene blue: May cause serotonin syndrome. Use extreme caution and monitor closely.MAO inhibitors (phenelzine, selegiline, tranylcypromine): May cause serotonin syndrome and signs and symptoms resembling NMS. Avoid using at the same time and for at least 5 weeks after stopping fluoxetine.Phenytoin: May increase phenytoin level and risk of toxicity. Monitor phenytoin level and adjust dosage.Pimozide, thioridazine: May increase levels of these drugs, increasing risk of serious ventricular arrhythmias and sudden death. Don't use together and don't use thioridazine for at least 5 weeks after stopping fluoxetine.Tamoxifen: May decrease tamoxifen plasma level, leading to breast cancer recurrence. Monitor patient carefully.Triptans: May cause weakness, hyperreflexia, incoordination, rapid changes in BP, nausea, and diarrhea. Monitor patient closely, especially at the start of treatment and when dosage increases.Warfarin: May increase risk for bleeding. Monitor PT and INR.Drug-herbKava kava, St. John's wort, tryptophan, valerian: May increase sedative and hypnotic effects; may cause serotonin syndrome. Discourage use together.Drug-lifestyleAlcohol use: May increase CNS depression. Discourage use together. Effects on Lab Test Results May decrease sodium level. Contraindications & Cautions Contraindicated in patients hypersensitive to drug, with pimozide, and within 14 days of stopping an MAO inhibitor intended to treat psychiatric disorders. MAO inhibitors shouldn't be started within 5 weeks of stopping fluoxetine. Avoid using thioridazine with fluoxetine or within 5 weeks after stopping fluoxetine. Black Box Warning: Drug may increase the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder or other psychiatric disorder.Black Box Warning: Fluoxetine is approved for use in children with major depressive disorder and OCD. Fluoxetine isn't approved for use in children younger than age 7. Sarafem isn't approved for use in children.Alert: Concomitant use with linezolid or methylene blue can cause serotonin syndrome (fever, mental status changes, muscle twitching, excessive sweating, shivering or shaking, diarrhea, loss of coordination). Use drug with linezolid or methylene blue only for life-threatening or urgent conditions when the potential benefits outweigh the risks of toxicity.Use cautiously in patients at high risk for suicide and in those with history of diabetes mellitus, seizures, mania, or hepatic, renal, or CV disease.Dialyzable drug: No.Overdose Signs & Symptoms: Nausea, seizures, somnolence, tachycardia, vomiting, coma, delirium, ECG abnormalities, hypotension, mania, NMS-like reactions, pyrexia, stupor, syncope. Pregnancy-Lactation-Reproduction Use cautiously in pregnant women and only if benefit justifies possible risk to the fetus. Drug appears in human milk. Use in breastfeeding women isn't recommended. Nursing Considerations Alert: If linezolid or methylene blue must be given, fluoxetine must be stopped and patient monitored for serotonin toxicity for 5 weeks or until 24 hours after final dose of linezolid or methylene blue, whichever comes first. Treatment with fluoxetine may be resumed 24 hours after final dose of linezolid or methylene blue. Use antihistamines or topical corticosteroids to treat rashes or pruritus. Watch for weight change during therapy, particularly in underweight or bulimic patients. Record mood changes. Watch for suicidal tendencies. Drug has a long half-life; monitor patient for adverse effects for up to 2 weeks after drug is stopped. Monitor patient for serotonin syndrome, particularly when drug is used in combination with other serotonergic agents. Alert: Combining triptans with an SSRI or an SSNRI may cause serotonin syndrome or NMS-like reactions. Serotonin syndrome may be more likely to occur when starting or increasing the dose of triptan, SSRI, or SSNRI. Monitor blood glucose level (in diabetic patients) and liver and renal function (baseline and as clinically indicated). Obtain ECG and monitor periodically in patients with risk factors for QT-interval prolongation and ventricular arrhythmia. Monitor mental status for depression, suicidal ideation (especially at beginning of therapy and with dosage changes), anxiety, social functioning, mania, or panic attacks. Observe for signs or symptoms of serotonin syndrome, akathisia, or sleep disturbances. When discontinuing drug, taper dosage over 2 weeks to 1 month to avoid withdrawal syndrome. Look alike-sound alike: Don't confuse fluoxetine with fluvoxamine or fluvastatin. Don't confuse Prozac with Proscar or Prilosec. Patient Teaching Black Box Warning: Advise family and caregivers to carefully observe patient for worsening suicidal thinking or behavior.Alert: Teach patient to recognize and immediately report symptoms of serotonin toxicity (fever, mental status changes, muscle twitching, excessive sweating, shivering or shaking, diarrhea, loss of coordination).Tell patient to avoid taking drug in the afternoon whenever possible because doing so commonly causes nervousness and insomnia.Drug may cause dizziness or drowsiness. Warn patient to avoid driving and other hazardous activities that require alertness and good psychomotor coordination until effects of drug are known.Tell patient to consult prescriber before taking other prescription or OTC drugs.Advise patient that full therapeutic effect may not be seen for 4 weeks or longer.

Hydantoin

Hydantoins are generally contraindicated in the presence of allergy to any of these drugs to avoid hypersensitivity reactions. Many of these agents are associated with specific birth defects and should not be used in pregnancy or lactation unless the risk of seizures outweighs the potential risk to the fetus. In such cases, the mother should be informed of the potential risks. The risk of taking a woman with a seizure disorder off an antiepileptic drug that has stabilized her condition may be greater than the risk of the drug to the fetus. Discontinuing the drug could result in status epilepticus, which has a high risk of hypoxia for the mother and the fetus. Research has not been able to show the effects of even a minor seizure during pregnancy on the fetus, making it important to prevent seizures during pregnancy if at all possible. Women of childbearing age should be urged to use barrier contraceptives while taking these drugs. If a pregnancy does occur, the woman should receive educational materials and counseling. Caution should be used with elderly or debilitated patients who may respond adversely to the CNS depression and with patients who have impaired renal or liver function that may interfere with drug metabolism and excretion. Patients with hepatic impairment are at risk for increased toxicity from phenytoin. Caution should be used when giving ethotoin to diabetic patients and patients with severe cardiovascular problems. Patients receiving fosphenytoin intravenously require careful monitoring of their cardiovascular status during the infusion period. Some potentially serious name confusion has occurred with fosphenytoin (Box 23.4). Other contraindications include coma, depression, or psychoses, which could be exacerbated by the generalized CNS depression.

Balsalazide (Colazal)

IBD Management - Salicylate Derivative Anti Inflammatory agents not only because of their ability to block the inflammatory response but also because of their antipyretic (fever-blocking) and analgesic (pain-blocking) properties. hey were extracted from willow bark, poplar trees, and other plants by ancient peoples to treat fever, pain, and what we now call inflammation. Dosage 3 750mg capsules PO tid for 8 weeks Usual Indications- Treatment of mildly to moderate acute ulcerative colitis. Actions: Inhibits the synthesis of prostaglandins; blocks the effects of pyrogens at the hypothalamus; inhibits platelet aggregation by blocking thromboxane A2. T1/2: 15 minutes to 12 hours; metabolized in the liver and excreted in the urine. Adverse Effects: Nausea, vomiting, heartburn, epigastric discomfort, occult blood loss, dizziness, tinnitus, acidosis. Absorbed directly in the stomach Peaks with 5 minutes to 30 minutes Metabolized in the liver and excreted in the urine Crosses Placenta and enters breast milk Contraindications-known allergy to drug or other NSAIDs, Impaired Renal Function, Chickenpox or Influenza

Phenelzine (Nardil)

If TCAs are given with cimetidine, fluoxetine, or ranitidine, an increase in TCA levels results with an increase in both therapeutic and adverse effects, especially anticholinergic conditions. Patients should be monitored closely, and appropriate dose reductions should be made. Other drug combinations may also pose problems. The combination of TCAs and oral anticoagulants leads to higher serum levels of the anticoagulants and increased risk of bleeding. Blood tests should be done frequently, and appropriate dose adjustments in the oral anticoagulant should be made. If TCAs are combined with sympathomimetics or clonidine, the risk of arrhythmias and hypertension is increased. This combination should be avoided, especially in patients with underlying CV disease. The combination of TCAs with MAOIs leads to a risk of severe hyperpyretic crisis with severe convulsions, hypertensive episodes, and death. This combination should be avoided. Although TCAs and MAOIs have been used together in selected patients who do not respond to a single agent, the risk of severe adverse effects is very high. phenelzine sulfate FEN-el-zeenNardilTherapeutic class: AntidepressantsPharmacologic class: MAO inhibitors Available Forms Tablets: 15 mg Indications & Dosages Depression clinically characterized as atypical, nonendogenous, or neurotic in patients who failed to respond to other therapy Adults: Initially, 15 mg PO t.i.d. Increase to at least 60 mg/day as tolerated. Many patients don't show a clinical response until treatment at 60 mg has continued for at least 4 weeks. May increase to maximum dosage of 90 mg/day to achieve clinical response. After maximum benefit has been achieved, slowly reduce dosage over several weeks as tolerated. Maintenance dose may be as low as 15 mg daily or 15 mg every other day. Continue as long as required. Administration POMay give without regard for meals.Store at 59° to 86° F (15° to 30° C). Action MAO inhibitors increase the concentration of epinephrine, norepinephrine, and serotonin in storage sites throughout the CNS and inhibit MAO, theoretically producing antidepressant activity.RouteOnsetPeakDurationPOUnknown43 minUnknownHalf-life: 11.6 hours. Adverse Reactions CNS: sleep disturbances, hypersomnia, drowsiness, dizziness, headache, tremors, twitching, myoclonic movements, hyperreflexia, weakness, fatigue. CV: orthostatic hypotension, edema. GI: dry mouth, nausea, diarrhea, abdominal pain, constipation. GU: ejaculation disturbance, erectile dysfunction, urine retention, anorgasmia. Hepatic: elevated transaminase levels. Metabolic: weight gain. Interactions Drug-drugAntihypertensives (beta blockers, thiazide diuretics): May increase risk of exaggerated hypotensive effects. Use together cautiously.Antiparkinsonians (levodopa, rasagiline): May increase risk of hypertensive crisis. Use together is contraindicated. Allow at least 14 days to elapse between stopping rasagiline and starting phenelzine.Atomoxetine: May increase effects of atomoxetine and risk of serious or fatal reactions. Use together is contraindicated.Barbiturates: May increase risk of hypnosis. Reduce barbiturate dosage if used together.Bupropion, buspirone: May increase risk of adverse effects and HTN. Use together is contraindicated. At least 14 days should elapse between bupropion or buspirone and initiation of phenelzine.Carbamazepine, cyclobenzaprine: May increase risk of hypertensive crisis, severe seizures, coma, or circulatory collapse. Don't give phenelzine with or within 10 days of discontinuing carbamazepine or cyclobenzaprine.Catechol-O-methyltransferase inhibitors (entacapone, tolcapone): May increase risk of excessive sympathetic stimulation. Use together isn't recommended.CNS depressants (meperidine), dextromethorphan: May cause excitation, seizures, delirium, hyperpyrexia, circulatory collapse, coma, and death. Use together is contraindicated.CNS stimulants (amphetamines, cocaine, dexmethylphenidate, epinephrine, methylphenidate, norepinephrine): May increase risk of hypertensive crisis. Use together is contraindicated.Cocaine, general anesthesia, local anesthetics containing sympathomimetic vasoconstrictors: May increase hypotensive effects. Discontinue phenelzine at least 10 days before elective surgery.Dibenzazepine derivatives (amitriptyline, amoxapine, carbamazepine, clomipramine, desipramine, doxepin, imipramine, maprotiline, mirtazapine, nortriptyline, perphenazine and amitriptyline, protriptyline, trimipramine): May increase risk of adverse drug interactions if used concurrently or if therapy is initiated within less than 10 days of each other. Inform patient of risk and monitor patient carefully.Diethylpropion: May increase risk of diethylpropion toxicity (headache, fever, elevated BP, bradycardia). Avoid use together.Fentanyl: May increase risk of respiratory, cardiac, and CNS reactions. Allow at least 14 days to elapse between use of phenelzine and initiation of fentanyl.Hypoglycemics (insulin, nateglinide, repaglinide, sulfonylureas): May potentiate hypoglycemic effects of these drugs. Use together cautiously. Lower hypoglycemic doses may be needed.Linezolid, methylene blue: May increase risk of serotonin syndrome. Don't use together. If urgent treatment with linezolid or methylene blue is needed, discontinue phenelzine and monitor patient for serotonin syndrome for 2 weeks or until 24 hours after last dose of linezolid or methylene blue.MAO inhibitors (isocarboxazid, methyclothiazide, procarbazine, tranylcypromine): May increase risk of hypertensive crisis, seizures, fever, marked sweating, excitation, delirium, tremor, coma, and circulatory collapse. Concomitant use is contraindicated. Allow 14 days between phenelzine dose and another MAO inhibitor.OTC drugs (antiappetite medications, asthma inhalant medications, cold and cough preparations [including those containing dextromethorphan], energy-producing products, hay fever medications, L-tryptophan-containing preparations, nasal decongestants [tablets, drops, spray], sinus medications, weight-reducing preparations): May precipitate hypertensive crisis or other serious symptoms. Avoid use together.Phenylalanine: May increase risk of hypertensive reaction. Use together is contraindicated.Selective 5-HT receptor agonists (rizatriptan, sumatriptan): May increase risk of prolonged vasospastic reactions and serotonin syndrome. Use together isn't recommended.Selective norepinephrine reuptake inhibitors (duloxetine, milnacipran): May cause additive effects and severe CNS toxicity. Use together is contraindicated.Serotoninergic drugs (citalopram, dexfenfluramine, fluoxetine, fluvoxamine, paroxetine, sertraline, venlafaxine), trazodone: May increase risk of serotonin syndrome. Concomitant use is contraindicated. At least 14 days should elapse between serotoninergic drug and phenelzine; however, 5 weeks should elapse between stopping fluoxetine and starting phenelzine.TCAs (amitriptyline, nortriptyline), tetracyclic antidepressants (maprotiline, mirtazapine): May cause serious or fatal reactions (hyperthermia, rigidity, delirium, coma). Use together is contraindicated. Don't give phenelzine with or within 10 days after stopping tetracyclic antidepressant or TCA.Tetrabenazine: May cause severe toxicity (confusion, restlessness, behavior changes). Use together is contraindicated.Tramadol: May increase risk of respiratory, cardiac, and CNS reactions, and reduce seizure threshold. Avoid use together.Drug-herbGinseng: May increase risk of adverse effects. Use together cautiously.Drug-foodAlert: Any spoiled or improperly refrigerated, handled, or stored protein-rich foods (such as dairy products, fish, and meats, including foods that may have undergone protein changes by aging, pickling, fermentation, or smoking to improve flavor); broad bean pods (fava bean pods); caffeine, chocolate (excessive amounts); cheese (aged varieties); foods high in tyramine or dopamine (such as dry sausage [including Genoa salami, hard salami, pepperoni, Lebanon bologna], liver, pickled herring); meat extract; sauerkraut; yeast extract (including brewer's yeast in large quantities); yogurt: May increase risk of hypertensive crisis. Use together is contraindicated.Drug-lifestyleAlert: Alcohol, alcohol-free and reduced-alcohol beer and wine products: May increase risk of hypertensive crisis. Use together is contraindicated. Effects on Lab Test Results May elevate serum transaminase levels. May decrease WBC counts. Contraindications & Cautions Black Box Warning: Short-term studies of major depressive disorder and other psychiatric disorders found that antidepressants increase the risk of suicidal thinking and suicidal behavior in children, adolescents, and young adults. Patients of all ages should be monitored appropriately for clinical worsening, suicidality, or changes in behavior. Drug isn't approved for use in children.Contraindicated in patients hypersensitive to drug or its components.Alert: Drug isn't recommended for depressive reactions for which other antidepressants may be effective. Drug should be reserved for patients who can be closely supervised and who haven't responded satisfactorily to drugs more commonly used for depression. Drug shouldn't be the initial therapy for depression.Drug is associated with orthostatic hypotension, hypertensive crisis (sometimes fatal), organ dysfunction, serotonin syndrome, myoclonus, and weight gain.Drug is contraindicated in patients with cerebrovascular defects or CV disorders (including HF); pheochromocytoma, severe renal impairment or renal disease, or liver disease; in those with abnormal LFT values; and in patients undergoing elective surgery.Drug isn't indicated for bipolar depression. Before starting drug, screen patients to rule out bipolar disorder as a reason for depression.Withdrawal syndrome can occur 24 to 72 hours after drug is withdrawn abruptly. Signs and symptoms include nightmares, agitation, psychosis, and seizures. Avoid abrupt withdrawal; if withdrawal signs and symptoms occur, drug may need to be reinstituted, then titrated downward cautiously.Drug can reduce the seizure threshold in patients with epilepsy.Use cautiously in patients with diabetes mellitus. Drug may increase insulin sensitivity and lower patient requirements for insulin or oral hypoglycemics.Use cautiously in elderly patients. Drug's effects may become more pronounced in these patients. Start dosing at low end of dosing range.Dialyzable drug: Unknown.Overdose Signs & Symptoms: Hypertensive crisis, death, drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonus, rigidity, seizures, coma, rapid or irregular pulse, HTN, hypotension and vascular collapse, precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, cool and clammy skin. Pregnancy-Lactation-Reproduction Safe use during pregnancy hasn't been established. Use in pregnant women only if benefit outweighs fetal risk. Safe use during breastfeeding hasn't been established. Consider the risks and benefits before use in breastfeeding women. Nursing Considerations Monitor patient (even if normotensive) for orthostatic hypotension. Reduce dosage if hypotension occurs. Alert: Most important reaction associated with drug is hypertensive crisis, which can be fatal. Stop drug if any of the following occur: occipital headache that may radiate frontally, palpitations, neck stiffness or soreness, nausea or vomiting, sweating (sometimes with fever and sometimes with cold, clammy skin), photophobia, tachycardia or bradycardia, constricting chest pain, and dilated pupils. Discontinue drug if hypertensive crisis occurs. Start therapy to lower BP; give phentolamine 5 mg IV slowly to avoid producing an excessive hypotensive effect. Manage fever through external cooling. Other symptomatic and supportive measures may be desirable in particular cases. Alert: Intracranial bleeding, sometimes fatal, has been reported in association with the paradoxical increase in BP. Monitor BP closely to detect evidence of any pressor response. Don't rely solely on BP readings, but observe patient frequently. Immediately discontinue drug if palpitations or frequent headaches occur during therapy as these signs may be prodromal of a hypertensive crisis. If patient needs to change antidepressant, allow for a 10- to 14-day washout period based on specific antidepressants used before or after phenelzine therapy. For fluoxetine, washout period should be 5 weeks after fluoxetine is stopped. Monitor patient with seizure disorders. Drug may decrease seizure threshold. Monitor patients for hypomania and agitation, especially those taking higher-than-recommended doses or after long-term therapy. Black Box Warning: Monitor patient for clinical worsening, suicidality, and unusual behavior changes (anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia [psychomotor restlessness], hypomania, mania), especially during first few months of therapy and when dosage is increased or decreased. If these signs or symptoms occur or worsen, consider changing therapeutic regimen.If patient requires elective surgery using general anesthesia, stop drug 10 days before procedure.Abruptly discontinuing or interrupting antidepressant therapy has been associated with a discontinuation syndrome (nausea, vomiting, diarrhea, headaches, light-headedness, dizziness, diminished appetite, sweating, chills, tremors, paresthesia, fatigue, somnolence, sleep disturbances [vivid dreams, insomnia]). Patient Teaching Black Box Warning: Alert family and caregivers of patient being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, to the need for daily monitoring to detect emergence of agitation, irritability, unusual behavior changes, and suicidality. Advise them to immediately report such symptoms to prescriber.Instruct patient to seek immediate emergency care if signs and symptoms of hypertensive crisis occur, such as severe headache, palpitations, neck stiffness or soreness, nausea or vomiting, sweating (sometimes with fever and sometimes with cold and clammy skin), sensitivity to light, changes in HR, constricting chest pain, or dilated pupils.Caution patient to keep all follow-up visits with prescriber as scheduled and to contact prescriber between visits as needed, especially for concerns about signs and symptoms.Teach patient to alert prescriber immediately if other drugs, supplements, or OTC products have been added to the drug regimen. Caution patient not to take any OTC medications without first consulting prescriber.Tell patient not to discontinue drug without discussing with prescriber.Teach patient about low-tyramine diets and the need to follow a low-tyramine diet at all times.Teach patient with diabetes that drug can lower requirements for insulin or oral hypoglycemics.Warn patient to discuss breastfeeding with prescriber.Tell patient to avoid alcohol use.Remind female patient of childbearing potential to contact prescriber if she becomes pregnant or is planning to become pregnant during therapy.

Immune Modulators

Immune Modulators Children Most of the drugs that affect the immune system are not recommended for use in children or have not been tested in children. The exceptions—interferon alfa-2b, azathioprine, raxibacumab, cyclosporine, tacrolimus, and palivizumab—should be used cautiously, monitoring the child frequently for infection, GI, renal, hematological, or CNS effects. The immune suppressants (azathioprine, cyclosporine, and tacrolimus) are usually needed in higher doses for children than for adults to achieve the same therapeutic effect. Protecting the child from infection and injury is a very important part of the care of a child taking an immune modulator. This can be a great challenge with an active child. Adults Both the adult patient who is receiving a parenteral immune modulator and a significant other should learn the proper technique for injection, disposal of needles, and special storage precautions for the drug. It is important to stress ways to avoid exposure to infection and injury to prevent further complications. The patient should be encouraged to seek regular follow-up and medical care. Immune modulators are contraindicated during pregnancy and lactation because of the potential for adverse effects on the fetus or neonate and complications for the mother. Women of childbearing age should be advised to use barrier contraceptives while taking these drugs and, if breast-feeding, should be counseled to find another method of feeding the baby. Some of these drugs impair fertility, and the patient should be advised of this fact before taking the drug. Older Adults Older patients may be more susceptible to the effects of the immune modulators, partly because the aging immune system is less efficient and less responsive. These patients need to be monitored closely for infection, GI, renal, hepatic, and CNS effects. Baseline renal and liver function tests can help to determine whether a decreased dosage will be needed before beginning therapy. Because these patients are more susceptible to infection, they need to receive extensive teaching about ways to avoid infection and injury sites on noninvaded cells to produce antiviral proteins, which prevent viruses from entering the cell. In addition, interferons have been found to inhibit tumor growth and replication, to stimulate cytotoxic T-cell activity, and to enhance the inflammatory response. Of interest, interferon gamma-1b also acts like an interleukin, stimulating phagocytes to be more aggressive. See Table 17.1 for usual indications for each interferon.

immunity

Immunity is a state of relative resistance to a disease that develops after exposure to the specific disease-causing agent. People are not born with immunity to diseases, so they must acquire immunity by stimulating B-cell clones to form plasma cells and then antibodies. Active immunity occurs when the body recognizes a foreign protein and begins producing antibodies to react with that specific protein or antigen. After plasma cells are formed to produce antibodies, specific memory cells that produce the same antibodies are created. If the specific foreign protein is introduced into the body again, these memory cells react immediately to release antibodies. This type of immunity was always thought to be lifelong, but it was discovered that patients who had been immunized against smallpox often had no antibodies to smallpox after many years. It is thought that the eradication of the disease has resulted in no stimulation of the memory cells, and after a prolonged period with no stimulation, perhaps the memory cells no longer produce antibodies. Passive immunity occurs when preformed antibodies are injected into the system and react with a specific antigen. These antibodies come from animals that have been infected with the disease or from humans who have had the disease and have developed antibodies. The circulating antibodies act in the same manner as those produced from plasma cells, recognizing the foreign protein and attaching to it, rendering it harmless. Unlike active immunity, passive immunity is limited. It lasts only as long as the circulating antibodies last because the body does not produce its own antibodies. In some cases, the host human responds to the circulating injected antibodies, which are foreign proteins to the host's body, by producing its own antibodies to the injected antibodies. This results in serum sickness, a massive immune reaction manifested by fever, arthritis, flank pain, myalgia, and arthralgia.

interferon alfa-2b

Immunostimulant Indications: Hairy cell leukemia, malignant melanoma, AIDS-related Kaposi sarcoma, chronic hepatitis B and C, follicular lymphoma, intralesional treatment of condylomata acuminata in patients 18 years of age or older. Actions: Inhibits the growth of tumor cells and enhances the immune response. Pharmacokinetics: Route: IM, subcutaneous Onset: Rapid Peak: 3-12hr Route: IV Onset: Rapid Peak: End of Infusion T1/2: 2 to 3 hours, metabolized in the kidney, excretion is unknown. Adverse Effects: Dizziness, confusion, rash, dry skin, anorexia, nausea, bone marrow suppression, flu-like syndrome.

Lidocaine

Indications: Infiltration anesthesia, peripheral and sympathetic nerve blocks, central nerve blocks, spinal and caudal anesthesia, topical anesthetic for skin or mucous membrane disorders. Actions: Blocks the generation and conduction of action potentials in sensory nerves by reducing sodium permeability, reducing the height and rate of rise of the action potential, increasing the excitation threshold, and slowing the conduction velocity. Pharmacokinetics: IM-Onset 5-10min Peak 5-15min Duration 2hr Topical-Onset Not generally absorbed systemically T1/2: 10 minutes, then 1.5 to 3 hours; metabolized in the liver, excreted in the urine. Adverse Effects: Headache, backache, hypotension, urinary retention, urinary incontinence, pruritus, seizures; when locally applied, burning, stinging, swelling, tenderness.

Sumatriptan (Imitrex)

Indications: Treatment of acute migraine; treatment of cluster headaches (subcutaneous route). Actions: Binds to serotonin receptors to cause vasoconstrictive effects on cranial blood vessels. Pharmacokinetics: Nasal Spray- Onset Varies Peak 5-20min Duration Unknown Oral-Onset 1-1.5hr Peak 2-4hr Duration Up to 24 hr Subcutaneous-Onset Rapid Peak 1-5hr Duration Up to 24hr T1/2: 115 minutes; metabolized in the liver, excreted in the urine. Adverse Effects: Dizziness, vertigo, weakness, myalgia, blood pressure alterations, tightness or pressure in the chest, injection site discomfort, tingling, burning sensations. SUMAtriptan succinate sue-mah-TRIP-tanImitrex, Imitrex STATdose, Onzetra Xsail, Zembrace SymTouchTherapeutic class: Antimigraine drugsPharmacologic class: Serotonin 5-HT1 receptor agonists Available Forms Injection: 4 mg/0.5 mL; 6 mg/0.5 mL prefilled syringes; 6 mg/0.5 mL vials; 3 mg/0.5 mL; 6 mg/0.5 mL single-dose autoinjector; prefilled-syringe Injection (needle-free): 4 mg/0.5 mL; 6 mg/0.5 mL jet-injector Nasal powder: 11 mg (base)/disposable nosepiece Nasal solution: 5 mg/0.1 mL; 20 mg/0.1 mL Tablets : 25 mg; 50 mg; 100 mg (base) Indications & Dosages Acute migraine attacks (with or without aura) Adults: 1 to 6 mg subcut depending on product; maximum dose is 12 mg in 24 hours, separated by at least 1 hour. Or 25 to 100 mg PO, initially. If desired response isn't achieved in 2 hours, may give second dose of 25 to 100 mg. Additional doses may be used in at least 2-hour intervals. Maximum daily oral dose, 200 mg.For nasal spray, give 5 mg, 10 mg, or 20 mg once in one nostril; may repeat once after 2 hours, for maximum daily dose of 40 mg.For nasal powder, one 11 mg nosepiece in each nostril (22 mg total), using the Xsail breath-powered delivery device. If desired response isn't achieved in 2 hours, or migraine returns after a transient improvement, may give second dose of 22 mg. Maximum recommended dose within 24 hours is two doses (44 mg/4 nosepieces) or one dose of 22 mg and one dose of another sumatriptan product, separated by at least 2 hours.Adjust-a-dose: In patients with mild to moderate hepatic impairment, the maximum single oral dose shouldn't exceed 50 mg.Cluster headache (except Zembrace)Adults: 6 mg subcut. Maximum recommended dose is two 6-mg injections in 24 hours, separated by at least 1 hour. Administration POGive drug without regard for food.Give drug whole; don't crush or break tablet.SubcutaneousRedness or pain at injection site should subside within 1 hour after injection.Use injection site with adequate skin and subcutaneous tissue thickness to accommodate length of needle.Use only the abdomen or thigh for needle-free injection system.Intranasal sprayHave patient blow nose before use.Give medication on inhalation in one nostril, while blocking the other nostril.Intranasal powderUse with the Xsail device only; insert disposable nosepiece into the device body.Pierce capsule inside nosepiece by pressing and releasing the white piercing button one time on the device body.Insert nosepiece into one nostril, ensuring a tight seal; rotate device, place mouthpiece into mouth, and blow forcefully through mouthpiece for 2 to 3 seconds to deliver powder into the nasal cavity.Remove and discard nosepiece; repeat in other nostril, using a second nosepiece. Action May act as an agonist at serotonin receptors on extracerebral intracranial blood vessels, which constricts the affected vessels, inhibits neuropeptide release, and reduces pain transmission in the trigeminal pathways.RouteOnsetPeakDurationPO30 min2-21/2 hrUnknownSubcut10 min12 minUnknownIntranasal spray15-30 min5-23 minUnknownIntranasal powderUnknown45 minUnknownHalf-life: About 2 hours; intranasal, about 3 hours. Adverse Reactions CNS: dizziness, vertigo, drowsiness, headache, anxiety, malaise, fatigue. CV: atrial fibrillation, ventricular fibrillation, ventricular tachycardia, coronary artery vasospasm, transient myocardial ischemia, MI, pressure or tightness in chest. EENT: discomfort of throat, nasal cavity or sinus, mouth, jaw, or tongue; altered vision. GI: abdominal discomfort, dysphagia, diarrhea, nausea, vomiting, unusual or bad taste (nasal spray). Musculoskeletal: myalgia, muscle cramps, neck pain. Respiratory: upper respiratory tract inflammation and dyspnea (PO). Skin: injection-site or application-site reaction, tingling, diaphoresis, flushing. Other: warm or hot sensation, burning sensation, heaviness, pressure or tightness, tight feeling in head, cold sensation, numbness. Interactions Drug-drugAntipsychotics, metoclopramide, serotonin modulators: May enhance adverse or toxic effect of other serotonin modulators, increasing risk of serotonin syndrome. Monitor therapy.Ergot and ergot derivatives, other 5-HT1 agonists: May prolong vasospastic effects. Don't use within 24 hours of sumatriptan therapy.MAO inhibitors: May reduce sumatriptan clearance. Use with or within 2 weeks of MAO inhibitor is contraindicated.Methylene blue, SSRIs: May cause serotonin syndrome. Monitor patient closely for weakness, hyperreflexia, and incoordination if use together can't be avoided.Drug-herbSt. John's wort: May increase serotonin levels. Use together cautiously. Effects on Lab Test Results May increase liver enzyme levels. Contraindications & Cautions Contraindicated in patients with hypersensitivity to drug or its components and in those with history, symptoms, or signs of ischemic cardiac, cerebrovascular (such as stroke or TIA), or peripheral vascular syndromes (such as ischemic bowel disease); hemiplegic or basilar migraine; significant underlying CV diseases, including angina pectoris, MI, and silent myocardial ischemia; Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders; uncontrolled HTN; or severe hepatic impairment. Contraindicated within 24 hours of another 5-HT agonist or drug containing ergotamine and within 2 weeks of MAO inhibitor. Use cautiously in patient with risk factors for CAD, such as postmenopausal women, men older than age 40, or patients with HTN, hypercholesterolemia, obesity, diabetes, smoking, or family history of CAD. Dialyzable drug: Unknown. Pregnancy-Lactation-Reproduction There are no adequate studies in pregnant women. Use only if potential benefit justifies potential risk to the fetus. Drug appears in human milk after subcut administration. Refer to individual manufacturer's instructions regarding breastfeeding. Some manufacturers don't recommend breastfeeding and other sources note that patient doesn't have to discontinue breastfeeding. Nursing Considerations Alert: When giving drug to patient at risk for CAD, give first dose in presence of other medical personnel. Rarely, serious adverse cardiac effects can follow administration. Alert: Combining drug with an SSRI or an SSNRI may cause serotonin syndrome. Symptoms include restlessness, hallucinations, loss of coordination, fast heartbeat, rapid changes in BP, increased body temperature, hyperreflexia, nausea, vomiting, and diarrhea. Serotonin syndrome may occur when starting or increasing the dose of drug, SSRI, or SSNRI. Monitor patient for seizures. Seizures have been reported in patients with and without a history of seizures. After subcut injection, most patients experience relief in 1 to 2 hours. Look alike-sound alike: Don't confuse sumatriptan with somatropin. Patient Teaching Inform patient that drug is intended only to treat migraine attacks, not to prevent them or reduce their occurrence. If patient is pregnant or may become pregnant, tell her not to use drug but to discuss with prescriber the risks and benefits of using drug during pregnancy. Tell patient that drug may be taken at any time during a migraine attack, as soon as signs or symptoms appear. Review information about drug's injectable form, which is available in a spring-loaded injector system for easier patient use. Make sure patient understands how to load the injector, give the injection, and dispose of used syringes. Teach patient to select subcut administration sites with adequate subcutaneous tissue thickness. Teach patient using intranasal powder how to use Xsail device correctly. Teach patient to blow nose before using nasal spray. Patient should block other nostril while inhaling gently during administration and should keep head upright and breathe gently for 10 to 20 seconds after dose is given. Alert: Tell patient to report all adverse reactions and to immediately report persistent or severe chest pain. Warn patient to stop using drug and to call prescriber if pain or tightness in the throat, wheezing, heart throbbing, rash, lumps, hives, or swollen eyelids, face, or lips develop.

Mental Disorders and Their Classifications

Mental disorders were once attributed to environmental influences and life experiences such as poor parenting or trauma. Mental disorders are now thought to be caused by some inherent dysfunction within the brain that leads to abnormal thought processes and responses. Most theories attribute these disorders to some sort of chemical imbalance in specific areas within the brain. Diagnosis of a mental disorder is often based on distinguishing characteristics as described in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition, text revision (DSM-IV-TR). Because no diagnostic laboratory tests are available, patient assessment and response must be carefully evaluated to determine the basis of a particular problem. Selected disorders are discussed here. Schizophrenia, the most common type of psychosis, can be debilitating and prevents affected individuals from functioning in society. Characteristics of schizophrenia include hallucinations, paranoia, delusions, speech abnormalities, and affective problems. This disorder, which seems to have a strong genetic association, may reflect a fundamental biochemical abnormality. Bipolar disorder involves extremes of depression alternating with hyperactivity and excitement. This condition may reflect a biochemical imbalance followed by overcompensation on the part of neurons and their inability to reestablish stability. Narcolepsy is characterized by daytime sleepiness and sudden periods of loss of wakefulness. This disorder may reflect problems with stimulation of the brain by the reticular activating system (RAS) or problems with response to that stimulation. Attention deficit disorders involve various conditions characterized by an inability to concentrate on one activity for longer than a few minutes and a state of hyperkinesis. These conditions are usually diagnosed in school-aged children but can occur in adults.

nonbarbiturate anesthetics Contraindications and Cautions

Methohexital cannot come in contact with silicone (rubber stoppers and disposable syringes often contain silicone) because it will cause an immediate breakdown of the silicone. As a result, it poses special problems, and special precautions must be taken. This drug should not be used until the anesthesiologist and staff are ready and equipped for intubation and respiratory support because of the rapid onset and because these drugs can cause respiratory depression and apnea. This drug should not be used during pregnancy or lactation unless the benefit clearly outweighs the potential risk to the fetus or neonate because of the CNS-depressive effects of these drugs

Pharmacokinetics Methohexital

Methohexital has a rapid onset of action and a recovery period that is usually 3 to 4 minutes. This drug is lipophilic. It is dissolved and rapidly absorbed through the lipid blood-brain barrier and diffuses into the brain rapidly.

Pentazocine (Talwin)

Narcotic agonists-antagonists are contraindicated in the presence of any known allergy to any narcotic agonist-antagonist to avoid hypersensitivity reactions. Nalbuphine should not be given to patients who are allergic to sulfites to avoid a cross-hypersensitivity reaction. Caution should be used in cases of physical dependence on a narcotic because a withdrawal syndrome may be precipitated; the narcotic antagonistic properties can block the analgesic effect and intensify the pain. Narcotic agonists-antagonists may be desirable for relieving chronic pain in patients who are susceptible to narcotic dependence, but extreme care must be used if patients are switched directly from a narcotic agonist to one of these drugs. Caution should also be exercised in the following conditions: chronic obstructive pulmonary disease or other respiratory dysfunction, which could be exacerbated by respiratory depression; acute myocardial infarction (MI), documented coronary artery disease (CAD), or hypertension, which could be exacerbated by the cardiac stimulatory effects of these drugs; and renal or hepatic dysfunction, which could interfere with the metabolism and excretion of the drug. Pentazocine must be administered cautiously to patients with known heart disease because the drug may cause cardiac stimulation, including arrhythmias, hypertension, and increased myocardial oxygen consumption, which could lead to angina, MI, or heart failure. There are no adequate studies regarding their effects during pregnancy. They should be used during pregnancy only if the benefit to the mother clearly outweighs the risk to the fetus because of potential adverse effects on the neonate, including respiratory depression. They are used to relieve pain during labor and delivery, which provides short-term exposure to the fetus. They are known to enter breast milk and should be used with caution during lactation because of the potential for adverse effects on the baby. Pentazocine(pen TAZ oh seen) Brand Names: US Talwin [DSC] Brand Names: Canada Talwin Warning This drug is a strong pain drug that can put your child at risk for addiction, abuse, and misuse. Misuse or abuse of this drug can lead to overdose and death. Talk with your child's doctor. Your child will be watched closely to make sure your child does not misuse, abuse, or become addicted to this drug. This drug may cause very bad and sometimes deadly breathing problems. Call the doctor right away if your child has slow, shallow, or trouble breathing. The chance of very bad and sometimes deadly breathing problems may be greater when your child first starts this drug or anytime the dose is raised. Talk with your child's doctor. Even one dose of this drug may be deadly if it is taken by someone else or by accident, especially in children. If this drug is taken by someone else or by accident, get medical help right away. Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets. This drug has an opioid drug in it. Severe side effects have happened when opioid drugs were used with benzodiazepines, alcohol, marijuana or other forms of cannabis, or prescription or OTC drugs that may cause drowsiness or slowed actions. This includes slow or troubled breathing and death. Benzodiazepines include drugs like alprazolam, diazepam, and lorazepam. Benzodiazepines may be used to treat many health problems like anxiety, trouble sleeping, or seizures. If you have questions, talk with the doctor. Many other drugs interact with this drug. These drugs can raise the chance of side effects as well as very bad and sometimes deadly breathing problems. Talk with the doctor and pharmacist to make sure that it is safe for your child to use this drug with all of his/her other drugs. Be sure your child does not drink alcohol or use products that have alcohol. Unsafe and sometimes deadly effects may happen. Get medical help right away if your child does not respond, answer, or react like normal; feels very sleepy or dizzy; passes out; or will not wake up. If your child is pregnant: Using this drug for a long time during pregnancy may lead to withdrawal in the newborn baby. This can be life-threatening. Talk with the doctor. What is this drug used for? It is used to ease pain. It may be given to your child for other reasons. Talk with the doctor. What do I need to tell the doctor BEFORE my child takes this drug? If your child is allergic to this drug; any part of this drug; or any other drugs, foods, or substances. Tell the doctor about the allergy and what signs your child had. If your child has any of these health problems: Lung or breathing problems like asthma, trouble breathing, or sleep apnea; high levels of carbon dioxide in the blood, or stomach or bowel block or narrowing. If your child has taken certain drugs for depression or certain other health problems in the last 14 days. This includes isocarboxazid, phenelzine, or tranylcypromine. Very high blood pressure may happen. If your child is taking any of these drugs: Linezolid or methylene blue. If your child is taking any of these drugs: Buprenorphine, butorphanol, or nalbuphine. This is not a list of all drugs or health problems that interact with this drug. Tell the doctor and pharmacist about all of your child's drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe to give this drug with all of your child's other drugs and health problems. Do not start, stop, or change the dose of any drug your child takes without checking with the doctor. What are some things I need to know or do while my child takes this drug? Tell all of your child's health care providers that your child is taking this drug. This includes your child's doctors, nurses, pharmacists, and dentists. Have your child avoid tasks or actions that call for alertness until you see how this drug affects your child. These are things like riding a bike, playing sports, or using items such as scissors, lawnmowers, electric scooters, toy cars, or motorized vehicles. To lower the chance of feeling dizzy or passing out, have your child rise slowly if your child has been sitting or lying down. Have your child be careful going up and down stairs. If your child is allergic to sulfites, talk with your child's doctor. Some products have sulfites in them. If your child has been taking this drug for a long time or at high doses, it may not work as well and your child may need higher doses to get the same effect. This is known as tolerance. Call the doctor if this drug stops working well. Do not give more than ordered. Long-term or regular use of opioid drugs like this drug may lead to dependence. Lowering the dose or stopping this drug all of a sudden may cause a greater risk of withdrawal or other severe problems. Talk to your child's doctor before you lower the dose or stop giving this drug. You will need to follow the doctor's instructions. Tell your child's doctor if your child has more pain, mood changes, thoughts of suicide, or any other bad effects. Do not give this drug with other strong pain drugs or pain patches without talking to your child's doctor first. This drug may raise the chance of seizures in some people, including people who have had seizures in the past. Talk to the doctor to see if your child has a greater chance of seizures while taking this drug. Very bad skin problems have happened where the shot was given. Talk with the doctor. If your child is pregnant or breast-feeding a baby: This drug may cause harm to the unborn baby if your child takes it during pregnancy. If your child is pregnant or gets pregnant while taking this drug, call the doctor right away. Tell your child's doctor if your child is breast-feeding a baby. This drug passes into breast milk and may harm your child's baby. What are some side effects that I need to call my child's doctor about right away? WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your child's doctor or get medical help right away if your child has any of the following signs or symptoms that may be related to a very bad side effect: Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat. Trouble breathing, slow breathing, or shallow breathing. Feeling very sleepy. Noisy breathing. Breathing problems during sleep (sleep apnea). Very bad dizziness or passing out. Feeling confused. Mood changes. Seizures. Very bad constipation. Very bad belly pain. Irritation where the shot is given. A severe and sometimes deadly problem called serotonin syndrome may happen if your child takes this drug with certain other drugs. Call your child's doctor right away if your child has agitation; change in balance; confusion; hallucinations; fever; fast or abnormal heartbeat; flushing; muscle twitching or stiffness; seizures; shivering or shaking; sweating a lot; severe diarrhea, upset stomach, or throwing up; or severe headache. Taking an opioid pain drug like this drug may lead to a rare but very bad adrenal gland problem. Call your child's doctor right away if your child has very bad dizziness or passing out, very bad upset stomach or throwing up, or if your child feels less hungry, very tired, or very weak. Long-term use of an opioid drug may lead to lower sex hormone levels. Call your child's doctor if your child has a lowered interest in sex, fertility problems, no menstrual period (females), or change in sex ability (males). What are some other side effects of this drug? All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your child's doctor or get medical help if any of these side effects or any other side effects bother your child or do not go away: Dizziness. Feeling sleepy. Upset stomach or throwing up. Constipation. These are not all of the side effects that may occur. If you have questions about side effects, call your child's doctor. Call your child's doctor for medical advice about side effects. You may report side effects to your national health agency. How is this drug best given? Give this drug as ordered by your child's doctor. Read all information given to you. Follow all instructions closely. It is given as a shot into a muscle, vein, or into the fatty part of the skin. What do I do if my child misses a dose? This drug is given on an as needed basis. Do not give to your child more often than told by the doctor. How do I store and/or throw out this drug? If you need to store this drug at home, talk with your child's doctor, nurse, or pharmacist about how to store it. General drug facts If your child's symptoms or health problems do not get better or if they become worse, call your child's doctor. Do not share your child's drug with others and do not give anyone else's drug to your child. Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets. Throw away unused or expired drugs. Do not flush down a toilet or pour down a drain unless you are told to do so. Check with your pharmacist if you have questions about the best way to throw out drugs. There may be drug take-back programs in your area. Some drugs may have another patient information leaflet. If you have any questions about this drug, please talk with your child's doctor, nurse, pharmacist, or other health care provider. A drug called naloxone can be used to help treat an overdose of this drug. Your child's doctor may order naloxone for you to keep while your child takes this drug. If you have questions about how to get or use naloxone, talk with your child's doctor or pharmacist. If you think there has been an overdose, call your poison control center or get medical care right away even if naloxone has been used. Be ready to tell or show what was taken, how much, and when it happened.

Outline the nursing considerations and teaching needs for patients receiving anxiolytic or hypnotic agent.

Provide comfort and safety measures, small meals, drugs with food if GI upset occurs, bowel program as needed; taper dosage after long-term use; reduce dosage if other medications include narcotics; lower dose with renal or hepatic impairment. Provide support and reassurance to deal with drug effects. Provide patient teaching regarding drug, dosage, adverse effects, safety precautions, and unusual symptoms to report.

Flumazenil (Romazicon)

Reversal Agent for Benzo Therapeutic class: Benzodiazepine antagonists Pharmacologic class: Antidotes Available Forms Injection: 0.1 mg/mL in 5-mL and 10-mL multiple-dose vials Indications & Dosages Complete or partial reversal of sedative effects of benzodiazepines after anesthesia (adults) or conscious sedation (adults and children) Adults: Initially, 0.2 mg IV over 15 seconds. If patient doesn't reach desired level of consciousness after 45 seconds, repeat dose. Repeat at 1-minute intervals, if needed, until cumulative dose of 1 mg has been given (first dose plus four more doses). Most patients respond after 0.6 to 1 mg of drug. In case of resedation, dosage may be repeated after 20 minutes, but never give more than 1 mg at any one time or exceed 3 mg in any 1 hour. Children age 1 year and older: 0.01 mg/kg (up to 0.2 mg) IV over 15 seconds. If patient doesn't reach desired level of consciousness after 45 seconds, repeat dose. Repeat at 1-minute intervals, if needed, until cumulative dose of 0.05 mg/kg or 1 mg, whichever is lower, has been given (first dose plus four more doses).Suspected benzodiazepine overdose Adults: Initially, 0.2 mg IV over 30 seconds. If patient doesn't reach desired level of consciousness after 30 seconds, give 0.3 mg over 30 seconds. If patient still doesn't respond adequately, give 0.5 mg over 30 seconds. Repeat 0.5-mg doses, as needed, at 1-minute intervals until cumulative dose of 3 mg has been given. Most patients with benzodiazepine overdose respond to cumulative doses between 1 and 3 mg; rarely, patients who respond partially after 3 mg may need additional doses, up to 5 mg total. If patient doesn't respond in 5 minutes after receiving 5 mg, sedation is unlikely to be caused by benzodiazepines. In case of resedation, may repeat dose after 20 minutes, but never give more than 1 mg (give as 0.5 mg/minute) at any one time or exceed 3 mg in any 1 hour. Administration IVStore drug in vial until use.Make sure airway is secure and patent.Compatible solutions include D5W, lactated Ringer injection, and NSS.To minimize pain at injection site, inject drug over 15 to 30 seconds into large vein through free-flowing solution.Monitor patient for signs and symptoms of extravasation.Drug is stable in a syringe for 24 hours.Incompatibilities: None listed by manufacturer. Consult a drug incompatibility reference for more information. Action Competitively inhibits the actions of benzodiazepines on the GABA-benzodiazepine receptor complex.RouteOnsetPeakDurationIV1-2 min6-10 min1 hr (variable range: 19-50 min)Half-life: Adults: 40 to 80 minutes (terminal); children: 20 to 75 minutes (terminal). Adverse Reactions CNS: dizziness, headache, seizures, agitation, emotional lability, anxiety, nervousness, tremor, insomnia, vertigo, fatigue, malaise, paresthesia. CV: arrhythmias, cutaneous vasodilation, palpitations, flushing. EENT: abnormal or blurred vision, lacrimation, dry mouth. GI: nausea, vomiting. Respiratory: dyspnea, hyperventilation. Skin: diaphoresis. Other: pain at injection site. Interactions Drug-drug Antidepressants, drugs that may cause seizures or arrhythmias: May increase risk of seizures or arrhythmias. Don't use flumazenil when overdose involves more than one drug, especially when seizures (from any cause) are likely. Effects on Lab Test Results None reported. Contraindications & Cautions Contraindicated in patients hypersensitive to flumazenil or benzodiazepines, in those with evidence of serious TCA overdose, and in those who have received benzodiazepines to treat a potentially life-threatening condition such as status epilepticus. Use cautiously in patients with head injury, psychiatric disorders, or alcohol dependence. Use cautiously in patients at high risk for developing seizures and in those who have recently received multiple doses of a parenteral benzodiazepine, who display signs of seizure activity, or who may be at risk for benzodiazepine dependence, such as ICU patients. Dialyzable drug: No. Overdose Signs & Symptoms: Anxiety, agitation, increased muscle tone, hyperesthesia, seizures. Pregnancy-Lactation-Reproduction There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if benefit outweighs risk to the fetus. It isn't known if drug appears in human milk. Use cautiously in breastfeeding women. Nursing Considerations Monitor patient closely for resedation, respiratory depression, or other residual effects that may occur after reversal of benzodiazepine effects; drug's duration of action is the shortest of all benzodiazepines. Length of monitoring period depends on specific drug being reversed. Monitor patient closely after doses of long-acting benzodiazepines such as diazepam, or after high doses of short-acting benzodiazepines such as 10 mg of midazolam. In most cases, severe resedation and respiratory depression are unlikely in patients who fail to show signs of resedation 2 hours after a 1-mg dose. Repeat doses of flumazenil in patients with liver disease should be reduced in size or frequency because flumazenil clearance is reduced to 40% to 60% of normal in patients with mild to moderate hepatic disease and to 25% of normal in patients with severe hepatic dysfunction; dose of flumazenil used for initial reversal of benzodiazepine effects isn't affected. Black Box Warning: Monitor patients for seizures, especially those who have been on benzodiazepines for long-term sedation or in overdose cases in which patients are showing signs of serious TCA overdose. Practitioners should individualize flumazenil dosage and be prepared to manage seizures. Patient Teaching Warn patient not to perform hazardous activities within 24 hours of procedure because of the risk of residual sedative effects of the benzodiazepine. Tell patient to avoid alcohol, CNS depressants, and OTC drugs for 24 hours and to report all adverse reactions. Give family necessary instructions and provide patient with written instructions. Patient may not be able to recall information given after the procedure; drug doesn't reverse amnesic effects of benzodiazepines. Do not administer these drugs intra-arterially because serious arterio-spasm and gangrene could occur. Monitor injection sites carefully for local reactions. Do not mix IV drugs in solution with any other drugs to avoid potential drug-drug interactions. Give parenteral forms only if oral forms are not feasible or available, and switch to oral forms as soon as possible to avoid serious reactions or adverse effects. Give IV medications slowly because rapid administration may cause cardiac problems. Provide standby life support facilities in case of severe respiratory depression or hypersensitivity reactions. Taper dose gradually after long-term therapy, especially in patients with epilepsy. Acute withdrawal may precipitate seizures or cause withdrawal syndrome in these patients. Provide comfort measures to help patients tolerate drug effects, including small, frequent meals; access to bathroom facilities; bowel program as needed; consuming food with the drug if GI upset is severe; and environmental control, safety precautions, orientation, and appropriate skin care as needed. Provide thorough patient teaching, including drug name, prescribed dosage, measures for avoidance of adverse effects, and warning signs that may indicate possible problems. Instruct patients about the need for periodic monitoring and evaluation to enhance patient knowledge about drug therapy and to promote compliance. Offer support and encouragement to help the patient cope with the diagnosis and the drug regimen. Provide comfort and safety measures, small meals, drugs with food if GI upset occurs, bowel program as needed; taper dosage after long-term use; reduce dosage if other medications include narcotics; lower dose with renal or hepatic impairment. Provide support and reassurance to deal with drug effects. Provide patient teaching regarding drug, dosage, adverse effects, safety precautions, and unusual symptoms to report.

Vaccine Schedule

See Table 18.1 in book page 314

Anatomy of the Brain Figure

See page 334 Fig 19.7

Auranofin (Ridaura)

Some patients with rheumatic inflammatory conditions do not respond to the usual anti-inflammatory therapies, and their conditions worsen despite weeks or months of standard pharmacological treatment. Some of these patients respond to treatment with gold salts, also known as chrysotherapy, in which gold is taken up by macrophages, which then inhibit phagocytosis; it is reserved for use in patients who are unresponsive to conventional therapy and can be very toxic. The gold salt available for use is auranofin (Ridaura). auranofin or-RAIN-oh-finRidauraTherapeutic class: AntiarthriticsPharmacologic class: Gold compounds Available Forms Capsules: 3 mg Indications & Dosages RA in patients with an insufficient response to or intolerance of an adequate trial of doses of one or more NSAIDs Adults: 3 mg PO b.i.d. or 6 mg PO once daily. After 6 months, may increase to 3 mg PO t.i.d. If response is inadequate after 3 months of 9 mg/day, stop use. Administration POGive drug without regard for food. Action Probably acts by inhibiting sulfhydryl systems, which alters cellular metabolism. May also alter enzyme function and immune response and suppress phagocytic activity.RouteOnsetPeakDurationPO3-6 mo2 hrProlongedHalf-life: 21 to 31 days. Adverse Reactions EENT: conjunctivitis. GI: stomatitis, glossitis, dysgeusia, metallic taste, dyspepsia, abdominal pain, nausea, vomiting, anorexia, flatulence, constipation, diarrhea. GU: acute renal failure, nephrotic syndrome, glomerulonephritis, hematuria, proteinuria. Hematologic: aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, eosinophilia, anemia. Skin: rash, pruritus, dermatitis, exfoliative dermatitis, urticaria, erythema, alopecia. Interactions Drug-drugPhenytoin: May increase phenytoin blood level. Watch for toxicity. Effects on Lab Test Results May increase alkaline phosphatase, ALT, and AST levels. May decrease Hb level and hematocrit. May increase eosinophil count. May decrease granulocyte, platelet, and WBC counts. Contraindications & Cautions Contraindicated in patients with history of severe gold toxicity or toxicity from previous exposure to other heavy metals and in those with necrotizing enterocolitis, pulmonary fibrosis, exfoliative dermatitis, bone marrow aplasia, or severe hematologic disorders. Use cautiously with other drugs that cause blood dyscrasias. Use cautiously in patients with rash, history of bone marrow depression, or renal, hepatic, or inflammatory bowel disease. Dialyzable drug: Unknown. Overdose Signs & Symptoms: Encephalopathy, peripheral neuropathy. Pregnancy-Lactation-Reproduction There are no adequate and well-controlled studies in pregnant women. Use during pregnancy isn't recommended. Breastfeeding during therapy isn't recommended. Nursing Considerations Black Box Warning: Monitor patient for signs and symptoms of gold toxicity, such as platelet count below 150,000/mm3, fall in Hb, granulocyte count less than 1,500/mm3, leukopenia (WBC count less than 4,000/mm3), proteinuria, hematuria, pruritus, rash, stomatitis, or persistent diarrhea. Drug should only be prescribed after lab results have been reviewed. Prescriber should have experience with chrysotherapy and be thoroughly familiar with toxicities and benefits of the drug.Alert: Monitor patient's urinalysis results monthly. If proteinuria or hematuria is detected, stop drug because these may indicate development of nephrotic syndrome or glomerulonephritis, and notify prescriber.Monitor renal function test and LFT results. Patient Teaching Tell patient to continue other drug therapies if prescribed. Remind patient to see prescriber for monthly platelet counts. Suggest that patient have regular urinalysis. Black Box Warning: Explain possibility of adverse reactions to patient before start of therapy; tell patient to promptly report signs and symptoms of toxicity.Tell patient to keep taking drug if mild diarrhea occurs but to immediately report blood in stool. Diarrhea is the most common adverse reaction.Advise patient to report rash or other skin problems and to stop drug until reaction subsides. Itching may precede dermatitis; consider itchy skin eruptions during drug therapy to be a reaction until proven otherwise.Inform patient that inflammation of the mouth may be preceded by a metallic taste; tell patient to notify prescriber if this occurs. Promote careful oral hygiene during therapy.Advise patient to report unusual bleeding or bruising.Inform patient that beneficial effect may be delayed for 3 to 4 months and up to 6 months in some patients. If response is inadequate and maximum dose has been reached, expect prescriber to stop drug.

Therapeutic Actions and Indications Tricyclic Antidepressants

The TCAs inhibit presynaptic reuptake of the neurotransmitters 5HT and NE, which leads to an accumulation of these neurotransmitters in the synaptic cleft and increased stimulation of the postsynaptic receptors. The exact mechanism of action in decreasing depression is not known but is thought to be related to the accumulation of NE and 5HT in certain areas of the brain. TCAs are indicated for the relief of symptoms of depression. The sedative effects of these drugs may make them more effective in patients whose depression is characterized by anxiety and sleep disturbances. Some are effective for treating enuresis in children older than 6 years (see Box 21.1). Some of these drugs are being investigated for the treatment of chronic, intractable pain. In addition, the TCAs are anticholinergic. Clomipramine is now also approved for use in the treatment of obsessive-compulsive disorders (OCDs).

Adverse Effects with antipsychotic drugs

The adverse effects associated with the antipsychotic drugs are related to their dopamine-blocking, anticholinergic, antihistamine, and alpha-adrenergic activities. The most common CNS effects are sedation, weakness, tremor, drowsiness, extrapyramidal side effects, pseudoparkinsonism, dystonia, akathisia, tardive dyskinesia, and potentially irreversible neuroleptic malignant syndrome (Box 22.5; Fig. 22.2). Anticholinergic effects include dry mouth, nasal congestion, flushing, constipation, urinary retention, impotence, glaucoma, blurred vision, and photophobia. Blocking of dopamine leads to an increase in prolactin levels and subsequent gynecomastia (breast development and occasionally milk production). This can be a concern, especially for male patients taking these drugs and they should be advised of that possibility. CV effects, which are probably related to the dopamine-blocking effects, include hypotension, orthostatic hypotension, cardiac arrhythmias, congestive heart failure, and pulmonary edema. Several of these agents (thioridazine, mesoridazine, ziprasidone) are associated with prolongation of the QTc interval, which could lead to serious or even fatal cardiac arrhythmias. Patients receiving these drugs should have a baseline and periodic electrocardiogram (ECG) during therapy. All of the atypical antipsychotics include warnings that there is a risk for the development of diabetes mellitus and weight gain when these drugs are used (Fig. 22.3). Ziprasidone has been associated with serious to fatal skin reactions and the systemic symptoms of DRESS (drug reaction with eosinophilia and systemic symptoms). Consequently, when patients are maintained on any of the atypical antipsychotics, they should be monitored regularly for the signs and symptoms of diabetes mellitus.

Succinylcholine Adverse Effects

The adverse effects of succinylcholine are the same as those for nondepolarizing NMJ blockers. In addition, succinylcholine is associated with muscle pain related to the initial muscle contraction reaction. A nondepolarizing NMJ blocker may be given first to prevent some of these contractions and the associated discomfort. Aspirin also alleviates much of this pain after the procedure. Malignant hyperthermia, which may occur in susceptible patients, is a serious condition characterized by massive muscle contraction, sharply elevated body temperature, severe acidosis, and if uncontrolled death (Fig. 28.4). This reaction is most likely with succinylcholine, and treatment involves dantrolene (see Chapter 25) to inhibit the muscle effects of the NMJ blocker

Amitriptyline (Elavil)

The tricyclic antidepressants (TCAs), including the amines, secondary amines, and tetracyclics, all reduce the reuptake of 5HT and NE into nerves. Because all TCAs are similarly effective, the choice of TCA depends on individual response to the drug and tolerance of adverse effects. A patient who does not respond to one TCA may respond to another drug from this class. amitriptyline hydrochloride a-mih-TRIP-ti-leenElavilTherapeutic class: AntidepressantsPharmacologic class: TCAs Available Forms Tablets: 10 mg; 25 mg; 50 mg; 75 mg; 100 mg; 150 mg Indications & Dosages Depression (outpatients) Adults: 75 mg PO daily in divided doses. Or, 50 to 100 mg PO daily as single dose at bedtime or in divided doses. May increase by 25 to 50 mg, as needed, to a total of 150 mg/day. Make increases preferably in late afternoon or at bedtime. Continue for at least 3 months. Maintenance, 40 to 100 mg daily.Elderly patients and adolescents: 10 mg PO t.i.d. plus 20 mg at bedtime daily.Depression (hospitalized patients)Adults: Initially, 100 mg PO daily. If necessary, gradually increase to 200 to 300 mg daily. Maintenance dose is 40 to 100 mg daily. Continue for at least 3 months. Administration POGive drug without regard for food.Give higher doses in late afternoon or at bedtime to minimize daytime sedation. Action Unknown. A TCA that increases the amount of norepinephrine, serotonin, or both in the CNS by blocking their reuptake by the presynaptic neurons.RouteOnsetPeakDurationPOUnknown2-5 hrUnknownHalf-life: 13 to 36 hours. Adverse Reactions CNS: stroke, seizures, coma, ataxia, tremor, peripheral neuropathy, anxiety, insomnia, restlessness, drowsiness, dizziness, weakness, fatigue, headache, extrapyramidal reactions, hallucinations, delusions, disorientation. CV: orthostatic hypotension, tachycardia, heart block, arrhythmias, MI, ECG changes, HTN, edema, palpitations, syncope. EENT: blurred vision, mydriasis, increased IOP, tinnitus. GI: dry mouth, nausea, vomiting, anorexia, epigastric pain, diarrhea, constipation, paralytic ileus. GU: urine retention, altered libido, erectile dysfunction. Hematologic: agranulocytosis, thrombocytopenia, leukopenia, eosinophilia. Metabolic: hypoglycemia, hyperglycemia. Skin: rash, urticaria, photosensitivity reactions, diaphoresis. Other: hypersensitivity reactions. Interactions Drug-drugBarbiturates: May increase amitriptyline metabolism. Consider therapy modification.Cimetidine: May decrease TCA metabolism. Monitor therapy.CNS depressants: May enhance CNS depression. Avoid using together.Disulfiram: May increase pharmacologic effects of amitriptyline. May cause acute organic brain syndrome. Monitor patient. Stop amitriptyline or decrease amitriptyline dosage if an interaction is suspected.Epinephrine, norepinephrine: May increase hypertensive effect. Use together cautiously.Fluoxetine, fluvoxamine, hormonal contraceptives, paroxetine, sertraline: May increase TCA level. Consider therapy modification.Linezolid, methylene blue: May cause serotonin syndrome. Avoid combination.MAO inhibitors: May cause severe excitation, hyperpyrexia, or seizures, usually with high doses. Avoid using within 14 days of MAO inhibitor therapy.Quinolones: May increase the risk of life-threatening arrhythmias. Monitor therapy.Drug-herbSAM-e, St. John's wort, yohimbe: May cause serotonin syndrome and decrease amitriptyline level. Discourage use together.Drug-lifestyleAlcohol use: May enhance CNS depression. Discourage use together.Smoking: May lower drug level. Watch for lack of effect.Sun exposure: May increase risk of photosensitivity reactions. Advise patient to take precautions. Effects on Lab Test Results May increase or decrease glucose level. May increase eosinophil count and LFT values. May decrease granulocyte, platelet, and WBC counts. Contraindications & Cautions Contraindicated in patients hypersensitive to drug, in those who have received an MAO inhibitor within the past 14 days, and in the acute MI recovery phase. Alert: Concomitant use with linezolid or methylene blue can cause serotonin syndrome (fever, mental status changes, muscle twitching, excessive sweating, shivering or shaking, diarrhea, loss of coordination). Use drug with linezolid or methylene blue only for life-threatening or urgent conditions when the potential benefits outweigh the risks of toxicity. Black Box Warning: Drug isn't approved for use in children younger than age 12.Use cautiously in patients with history of seizures, urine retention, angle-closure glaucoma, or increased IOP; in those with hyperthyroidism, CV disease, diabetes, or impaired liver function; and in those receiving thyroid drugs.Use cautiously in elderly patients and in patients with suicidal ideation.Use cautiously in those receiving electroconvulsive therapy.Dialyzable drug: No.Overdose Signs & Symptoms: Cardiac arrhythmias, severe hypotension, seizures, CNS depression, coma, impaired myocardial contractility, confusion, disturbed concentration, transient visual hallucinations, dilated pupils, disorders of ocular motility, agitation, hyperactive reflexes, polyradiculoneuropathy, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia. Pregnancy-Lactation-Reproduction There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if potential benefit outweighs potential risk to the fetus. Drug appears in human milk. Patient should discontinue breastfeeding or discontinue drug. Nursing Considerations Black Box Warning: Drug may increase the risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder or other psychiatric disorder. Don't use in children younger than age 12.Alert: If linezolid or methylene blue must be given, amitriptyline must be stopped and patient should be monitored for serotonin toxicity for 2 weeks, or until 24 hours after the last dose of methylene blue or linezolid, whichever comes first. Treatment with amitriptyline may be resumed 24 hours after last dose of methylene blue or linezolid.Amitriptyline has strong anticholinergic effects and is one of the most sedating TCAs. Anticholinergic effects have rapid onset even though therapeutic effect is delayed for weeks.Elderly patients may have an increased sensitivity to anticholinergic effects of drug; sedating effects of drug may increase the risk of falls in this population.If signs or symptoms of psychosis occur or increase, expect prescriber to reduce dosage. Record mood changes. Monitor patient for suicidal tendencies and allow only minimum supply of drug.Because patients using TCAs may suffer hypertensive episodes and arrhythmias during surgery, stop drug gradually several days before surgery.Monitor glucose level.Watch for nausea, headache, and malaise after abrupt withdrawal of long-term therapy; these symptoms don't indicate addiction.Don't withdraw drug abruptly.Look alike-sound alike: Don't confuse amitriptyline with nortriptyline or aminophylline. Don't confuse Elavil with Eldepryl or enalapril. Patient Teaching Black Box Warning: Advise family and caregivers to closely observe patient for increased suicidal thinking and behavior.Alert: Teach patient to recognize and immediately report symptoms of serotonin toxicity (fever, mental status changes, muscle twitching, excessive sweating, shivering or shaking, diarrhea, loss of coordination).Advise patient to take full dose at bedtime when possible; however, caution patient that morning orthostatic hypotension may occur.Tell patient to avoid alcohol during drug therapy.Advise patient to consult prescriber before taking other drugs.Warn patient to avoid activities that require alertness and psychomotor coordination until CNS effects of drug are known. Drowsiness and dizziness usually subside after a few weeks.Inform patient that dry mouth may be relieved with sugarless hard candy or gum. Saliva substitutes may be useful.Advise patient to use a sunblock, wear protective clothing, and avoid prolonged exposure to strong sunlight.Warn patient not to stop drug abruptly.Advise patient that it may take as long as 30 days to achieve full therapeutic effect.

Contraindications and Cautions of Vaccines

The use of vaccines is contraindicated in the presence of immune deficiency because the vaccine could cause disease and the body would not be able to respond as anticipated if it is in an immunodeficient state, during pregnancy because of potential effects on the fetus and on the success of the pregnancy, in patients with known allergies to any of the components of the vaccine (refer to each individual vaccine for specifics, sometimes including eggs, where some pathogens are cultured), or in patients who are receiving immune globulin or who have received blood or blood products within the last 3 months because a serious immune reaction could occur. Caution should be used any time a vaccine is given to a child with a history of febrile convulsions or cerebral injury or in any condition in which a potential fever would be dangerous. Caution also should be used in the presence of any acute infection.

Describe the function of the cerebral cortex, cerebellum, hypothalamus, thalamus, midbrain, pituitary gland, medulla, spinal cord, and reticular activating system. Intellectual and Emotional Functions.

The way that the cerebral cortex uses sensory information is not clearly understood, but research has demonstrated that the two hemispheres of the brain process information in different ways. The right side of the brain is the more artistic side, concerned with forms and shapes, and the left side is more analytical, concerned with names, numbers, and processes. Why the two hemispheres are different and how they develop differently is not known. When learning takes place, distinct layers of the cerebral cortex are affected, and an actual membrane change occurs in a neuron to store information in the brain permanently. Learning begins as an electrical circuit called an engram, a reverberating circuit of action potentials that eventually becomes a long-term, permanent memory in the presence of the proper neurotransmitters and hormones. Scientists do not understand exactly how this happens, but it is known that the nerve requires oxygen, glucose, and sleep to process an engram into a permanent memory, and during that processing, structural changes occur to the cells involved in the engram. This reverberating circuit is responsible for short-term memory. When patients have a decreased blood supply to the brain, short-term memory may be lost, and they are not able to remember new things. This happens because the engram requires a constant supply of oxygen and glucose to maintain that electrical circuit and if it cannot be maintained it is lost. Because they are unable to remember new things, the brain falls back on long-term, permanent memory for daily functioning. For example, a patient may be introduced to a nurse and have no recollection of the nurse 2 hours later and yet be able to recall the events of several years ago vividly. Several substances appear to affect learning. Antidiuretic hormone, which is released during reactions to stress, is one such substance. Although too much stress prevents learning, feeling slightly stressed may increase a person's ability to learn. A patient who is a little nervous about upcoming surgery, for example, seems to display a better mastery of facts about the surgery and postoperative procedures than a patient who is very stressed and scared or one who appears to show no interest or concern. Oxytocin is another substance that seems to increase actual learning. Because childbirth is the only known time that oxytocin levels increase, the significance of this is not understood. Nurses who work with maternity patients should know that women in labor will very likely remember the smallest details about the whole experience and should use whatever opportunity is made available to do teaching. In addition, the limbic system appears to play an important role in how a person learns and reacts to stimuli. The emotions associated with a memory as well as with the present have an impact on stimulus response. The placebo effect is a documented effect of the mind on drug therapy. If a person perceives that a drug will be effective, it is much more likely to actually be effective. This effect, which uses the actions of the cerebrum and the limbic system, can have a tremendous impact on drug response. Events that are perceived as stressful by some patients may be seen as positive by other patients.

Clinically Important Drug-drug Interactions for NSAIDs

There is an increased risk of bleeding with oral anticoagulants because of effects on the liver; of toxicity with chronic ethanol ingestion because of toxic effects on the liver; and of hepatotoxicity with barbiturates, carbamazepine, hydantoins, or rifampin. These combinations should be avoided, but if they must be used, appropriate dose adjustment should be made and the patient should be monitored closely.

Depolarizing Neuromuscular Junction Blocker

There is only one agent classified as a depolarizing NMJ blocker: succinylcholine (Anectine, Quelicin).

Benztropine (Cogentin)

Tx: Parkinson's Class: anticholinergic AE: TACHYCARDIA, blurred vision, dry eyes Indications: Adjunctive therapy for Parkinson disease, relief of symptoms of extrapyramidal disorders (parkinsonism) that accompany neuroleptic therapy. Actions: Acts as an anticholinergic, principally in the CNS, returning balance to the basal ganglia and reducing the severity of rigidity, akinesia, and tremors; peripheral anticholinergic effects help to reduce drooling and other secondary effects of parkinsonism. Pharmacokinetics: Oral-Onset 1hr Peak Unknown Duration 6-10hr IM,IV-Onset 15min Peak Unknown Duration6-10hr T1/2: Unknown, metabolized in the liver. Adverse Effects: Disorientation, confusion, memory loss, nervousness, light-headedness, dizziness, depression, blurred vision, mydriasis, dry mouth, constipation, urinary retention, urinary hesitation, flushing, decreased sweating.

NSAIDs

Use of any other immunosuppressant drugs with TNF blockers increases the risk of serious infections and cancer. Live vaccines should not be given while on these drugs What are nonsteroidal antiinflammatory drugs? — Nonsteroidal antiinflammatory drugs, also called "NSAIDs," are medicines that relieve pain and reduce inflammation. They are one of the most commonly used kinds of medicines. NSAIDs can help people who have conditions that cause ongoing pain, such as arthritis. They can also help people heal more quickly after an injury. But NSAIDs can cause problems of their own, so it's important to take the lowest dose you need for the shortest time. You can buy many NSAIDs without a prescription, including aspirin, ibuprofen (sample brand names: Advil, Motrin), and naproxen (brand name: Aleve). These same NSAIDs can also be prescribed by a doctor, usually at a higher strength. Plus, there are many other prescription-strength NSAIDs. Are all NSAIDs the same? — Yes and no. All NSAIDs work on the same chemical process in the body, but they do it in different ways. Some NSAIDs need to be taken more often during the day than others to work for certain kinds of pain. And some are more likely than others to cause certain side effects. Are NSAIDs safe for everyone? — No. People with certain medical conditions should avoid NSAIDs or use them with care. Talk with your doctor if you use NSAIDs without a prescription (called "over-the-counter") on a regular basis to be sure they are safe for you. If you have an ulcer in your stomach or intestine or you have ever had bleeding in the gut, ask your doctor if NSAIDs are safe for you. Your doctor might suggest that you take an NSAID along with a medicine that can protect your stomach and intestines. That's because NSAIDs can damage your stomach or intestines. If you have heart disease or ever had a stroke, ask your doctor if it is safe to take an NSAID. NSAIDs can increase the risk of heart attack, heart failure, and stroke. This is especially true for people who already have heart disease or risk factors like high blood pressure. But if your doctor prescribes low-dose aspirin to prevent heart attacks or stroke, you should take it as directed. At low doses, aspirin can actually protect you from these problems. If you have kidney disease, heart failure, or cirrhosis, avoid NSAIDs completely. NSAIDs can make heart failure, kidney disease, and cirrhosis worse. If you take medicines called diuretics (also called "water pills"), ask your doctor if NSAIDs are safe for you. NSAIDs can cause kidney problems in people taking diuretics or certain other medicines to control blood pressure. This can happen in people with very mild kidney disease or in older people. If you have high blood pressure, ask your doctor if NSAIDs are safe for you. NSAIDs can raise blood pressure even in people who are taking medicine for high blood pressure. Experts recommend that people with high blood pressure who need NSAIDs take the lowest possible dose for the shortest amount of time. If you have any disorders that increase the risk of bleeding, ask your doctor if NSAIDs are safe for you. If you are having surgery, ask your doctor if you should stop taking NSAIDs. Most people need to stop NSAIDs at least several days to a week before surgery to lower the risk of bleeding. Most people who take aspirin need to stop taking it a full week before surgery. If you are pregnant, avoid NSAIDs during the last 3 months of pregnancy. They are probably safe to use when breastfeeding, but check with your doctor or nurse if you are breastfeeding. If you take any other prescription or non-prescription medicines, or you take any herbal medicines, ask your doctor or pharmacist if NSAIDs are safe for you. This is especially important if you take: Blood thinners, such as warfarin (brand name: Coumadin) or heparin Phenytoin (brand names: Dilantin, Phenytek), a medicine used to prevent seizures Cyclosporine, a medicine given to people who have had an organ transplant What side effects can NSAIDs cause? — In most cases, NSAIDs cause no side effects. The side effects they do cause can include: Stomach upset, ulcers, and bleeding - NSAIDs can cause stomach upset. If you take them regularly for a long time, NSAIDs can also cause ulcers or bleeding in the stomach or intestines. Liver damage - Long-term use of NSAIDs, especially at high doses, can harm the liver. Kidney damage - Using NSAIDs, even for a short time, can harm the kidneys. They are especially risky in people who already have kidney disease. Ringing in the ears - Ringing in the ears (tinnitus) is common in people who take high doses of aspirin. It can also happen in people who take other NSAIDs. The ringing usually goes away when they take a lower dose. What happens if I take more than the recommended dose? — Taking more than the recommended dose of an NSAID might not cause serious problems. But it could make side effects much more likely without helping your symptoms very much. On the other hand, taking too much aspirin or acetaminophen (sample brand name: Tylenol) can be harmful or even cause death. Anybody who takes too much of any medicine at once should call a doctor or the Poison Control Hotline (1-800-222-1222). If the person is not breathing or is not conscious, call for an ambulance (in the US and Canada, dial 9-1-1).

Gardacil vaccine

VACCINE TO PROTECT AGAINST CERVICAL CANCER In 2006, the U.S. Food and Drug Administration approved the first vaccine to protect against cancer caused by a virus. Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States. The Centers for Disease Control and Prevention estimates that 6 million Americans become infected with genital HPV each year and that half of the sexually active men and women become infected at some time during their lifetime. Most of the time the body's defense system will clear the virus, but some types of HPV can be more virulent. There are many types of HPV; some cause genital warts, and others are known to cause abnormal cells on the lining of the cervix, which can lead to cervical cancer years later. The vaccine Gardasil is effective against HPV types 16 and 18 (which account for 70% of cervical cancers) and against types 6 and 11 (which are responsible for 90% of genital warts). The vaccine is recommended for both girls and women aged 9 to 26 years and boys and men aged 9 to 26 years. Studies have shown that it is only effective if it is given before HPV infection occurs, so it is best given before the person becomes sexually active. The vaccine is given as a series of three injections. The second injection is given about 2 months after the first, and the last injection is given about 6 months later. It is not yet known whether a booster injection will be needed later and its effects if given inadvertently to a pregnant woman. Side effects that have been reported include the usual flu-like symptoms seen with immunization and pain at the injection site. The vaccine is not without controversy. It costs approximately $200 for the three-shot series, making it an expensive injection. In February 2007, the governor of Texas issued an executive order mandating that the vaccine be given to all schoolgirls entering the sixth grade. A group resenting the mandate for a vaccine sued, and the order was overruled. New Hampshire and Alaska have adopted voluntary programs that supply the vaccine free of charge to girls 11 to 18 years (New Hampshire) or 9 to 18 years (Alaska). Those debating the use of the drug cite the potential for preventing more than 9,700 new cases and 3,700 deaths from cervical cancer every year, whereas others question the long-term effects and effectiveness of the vaccine, stating that it is poor judgment to mandate something with such a short track record. Others fear that women who have had the vaccine will stop getting an annual pelvic exam and Pap smear, which is still needed because cervical cancer can be caused by other factors. Others fear that the protection offered by the vaccine will lead to earlier or more frequent sexual activity among women who have had the vaccination. Controversy regarding the vaccine is not as heated now, but there is still research on going regarding the risk-benefit ratio, especially due to the high cost of the vaccine that may prohibit the vaccines' use in diverse and low-resource populations. This is the first vaccine to protect against cancer, and it is hoped that more such vaccines will be developed in the future. The willingness of parents to listen to the pros and cons and accept the need for this vaccine will have a big impact on the success of this and other such vaccines

Vaccines and Biological Weapons

Vaccines and Biological Weapons The events of September 11, 2001, and the subsequent war on terrorism have heightened awareness of several diseases that might be in development as biological weapons. Anthrax, plague, tularemia, smallpox, botulism, and a variety of viral hemorrhagic fevers are all considered to be likely biological warfare weapons. Anthrax A vaccine is available in the United States made from inactivated cell-free filtrate of an avirulent strain of the anthrax bacillus. It is available only for military use. Active production stopped in 1998, but production and supply issues were made high priorities. Ciprofloxacin and, in sensitive cases, doxycycline and penicillins are effective in treating postexposure cases. The vaccine is given and repeated in 2 and 4 weeks, along with the appropriate antibiotic, to patients who have been exposed. The monoclonal antibody, raxibacumab, was approved in 2014 and is specific to the anthrax bacillus and is used for treatment postexposure, along with standard antibiotic therapy. Plague Plague is easily spread from person to person and, without treatment, can progress rapidly to respiratory failure and death. There is currently no vaccine for plague; a whole-cell vaccine that was used for many years is no longer available. Research is ongoing using a pneumonic plague vaccine that has successfully protected animals. Several drugs have been found to be lifesaving with plague—streptomycin, doxycycline, ciprofloxacin, and chloramphenicol. Smallpox Smallpox was considered eradicated since no new cases had been seen in 20 years. Smallpox is highly transmissible and has a 30% mortality rate in unvaccinated people. Immunization against smallpox ended in the 1970s. There is now a vaccine, which is given to military personnel and people thought to be at high risk. It is currently thought that the vaccine is no longer effective after 20 years, although there is no definite evidence that previously vaccinated people have no protection. The smallpox vaccine uses live virus, placed in punctures made in the skin. After exposure, vaccination given within the first 3 to 4 days can prevent the disease. If it has been 7 days or longer since exposure, the vaccine and a vaccinia immune globulin should be used, if any are available. So far, no drugs are thought to be effective in treating smallpox. Early studies have, however, shown cidofovir to be effective in vitro. Tularemia Tularemia in an aerosolized form can cause systemic and respiratory illness with a 35% mortality rate. It is not passed from person to person. There is no vaccine available, but doxycycline and ciprofloxacin can be used after exposure, and gentamicin has been effective after symptoms appear. Botulism Botulism, produced by Clostridium botulinum, can be aerosolized or used to contaminate food. The toxin it produces causes cranial nerve palsies that can result in muscle paralysis and respiratory failure. A botulinum toxoid is available through the Centers for Disease Control and Prevention for the military and high-risk workers. Antitoxin is also available for patients with specific exposures, and research is ongoing with an equine antitoxin effective against all seven serotypes of botulism that is thought to cause fewer hypersensitivity reactions than what is currently available. Viral Hemorrhagic Fever Lassa, Marburg, Junin, and Ebola viruses cause hemorrhagic fevers with mortality rates as high as 90%. No vaccines are currently available for these agents, although the U.S. Army has had success with a vaccine for Junin. Ribavirin has been effective in some cases of Lassa fever and has been effective orally for postexposure prophylaxis. It is being studied for effectiveness with these other viruses. Currently, there is no established treatment, and this area is one of the highest priorities for combating possible biological warfare. The outbreak of Ebola in Africa in 2014 and return of infected workers to the United States brought a great deal of attention to this problem. Many drug companies are working to find a treatment for these viral infections.

Vaccines and Autism

Vaccines do not cause autism The Immunization Safety Review Committee Board of Health Promotion and Disease Prevention of the Institute of Medicine under the auspices of the Centers for Disease Control and Prevention and the National Institutes of Health has concluded that there is no evidence to support a linkage between the use of measles, mumps, and rubella (MMR) vaccine and the development of autism (a psychiatric neurological impairment affecting children and marked by deficits in communication and social attachment). The original research by Andrew Wakefield supporting a link was published in the British Medical Journal in 1996. With more study since that time, the BMJ has disclaimed this study as fraud and continues to report, as late as 2011, more evidence of fraudulent information that was published in that original article. The media, however, continue to pursue this possible connection, raising concerns for parents about the use of vaccines in children. Among materials studied by the Institute of Medicine were questionnaires about reported symptoms and the timing of the vaccination and Vaccine Adverse Event Reporting System reports. The information obtained will help determine a need for other research, and it will also be used to educate parents. Parents can be referred to www.cdc.gov; click on vaccine safety to get current information and to review the research that has been done.

Autoimmune Disease

a condition in which the immune system mistakenly attacks itself, targeting the cells, tissues, and organs of a person's own body. Doesn't recognize it's own cells

Reticular Activating System (RAS)

a dense network of neurons found in the core of the brain stem; it arouses the cortex and screens incoming information Extreme sedation results in further central nervous system (CNS) depression and sleep, or hypnosis. Hypnotics are used to help people fall asleep by causing sedation. Drugs that are effective hypnotics act on the reticular activating system (RAS) and block the brain's response to incoming stimuli. Hypnosis, therefore, is the extreme state of sedation, in which the person no longer senses or reacts to incoming stimuli.

B cells

a lymphocyte not processed by the thymus gland, and responsible for producing antibodies. B cells are found throughout the MPS in groups called clones. B cells are programmed to identify specific proteins, or antigens. They provide what is called humoral immunity (Fig. 15.4). When a B cell reacts with its specific antigen, it changes to become a plasma cell. Plasma cells produce antibodies, or immunoglobulins, which circulate in the body and react with this specific antigen when it is encountered. This is a direct chemical reaction. When the antigen and antibody react, they form an antigen-antibody complex. This new structure reveals a new receptor site on the antibody that activates a series of plasma proteins in the body called complement proteins

Acetylcholine (ACh)

a neurotransmitter involved in learning, memory and muscle movement Acetylcholine, which communicates between nerves and muscles, is also important as the preganglionic neurotransmitter throughout the autonomic nervous system and as the postganglionic neurotransmitter in the parasympathetic nervous system and in several pathways in the brain.

Acetaminophen (Tylenol)

analgesic/antipyretic (non-NSAID) Indications: Treatment of mild to moderate pain, fever, or signs and symptoms of the common cold or flu; musculoskeletal pain associated with arthritis and rheumatic disorders. Actions: Acts directly on the hypothalamus to cause vasodilation and sweating, which will reduce fever; mechanism of action as an analgesic is not understood. Pharmacokinetics: Route- Oral Onset- Varies Peak- 0.5-2hr Duration- 3-6hr Route- IV Onset- Beginning of Infusion Peak- End of Infusion Duration- 4-6hr T1/2: 1 to 3 hours; metabolized in the liver and excreted in the urine. Adverse Effects: Rash, fever, chest pain, liver toxicity and failure, bone marrow suppression

Ergot Derivatives

cause constriction of cranial blood vessels and decrease the pulsation of cranial arteries Combining triptans with ergot-containing drugs results in a risk of prolonged vasoactive reactions. There is a risk of severe adverse effects if these drugs are used within 2 weeks after discontinuation of a MAOI because of the increased vasoconstrictive effects that occur. If triptans are to be given, it is imperative that the patient has not received an MAOI in more than 2 weeks

DTaP vaccine

contains diphtheria toxoid, acellular pertussis (whooping cough), and tetanus toxoid Making a comeback in California

Levodopa

dopamine precursor (converted by dopa decarboxylase) Use = first line for Parkinson's *SE: dyskinesia/sporadic mvmts, cardiac arrhythmias (d/t peripheral conversion) Also, get predictable wearing-off phenomenon and unpredictable "off/on" phenomenon Don't take B6/multivitamin bc -->increased levodopa peripheral metabolism Indications: Treatment of parkinsonism and Parkinson disease. Actions: Precursor of dopamine, which is deficient in parkinsonism; crosses the blood-brain barrier, where it is converted to dopamine and acts as a replacement neurotransmitter; effective for 2 to 5 years in relieving the symptoms of Parkinson disease. Pharmacokinetics: Oral-Onset Varies Peak 0.5-2hr Duration 5hr T1/2: 1 to 3 hours; metabolized in the liver, excreted in the urine. Adverse Effects: Adventitious movements, ataxia, increased hand tremor, dizziness, numbness, weakness, agitation, anxiety, anorexia, nausea, dry mouth, dysphagia, urinary retention, flushing, cardiac irregularities. Arrange to decrease dose or discontinue the drug if dry mouth becomes so severe that swallowing becomes difficult. Provide sugarless lozenges to suck and frequent mouth care to help with this problem. Give drug with caution and arrange for a decrease in dose in hot weather or with exposure to hot environments because patients are at increased risk for heat prostration because of decreased ability to sweat. Give drug with meals if GI upset is a problem, before meals if dry mouth is a problem, and after meals if drooling occurs and the drug causes nausea to facilitate compliance with drug therapy. Monitor bowel function and institute a bowel program if constipation is severe. Ensure that the patient voids before taking the drug; monitor urinary output and palpate for bladder distention and residual urine if urinary retention is a problem. Establish safety precautions if CNS or vision changes occur to prevent patient injury. Provide thorough patient teaching about topics such as the drug name and prescribed dose, measures to help avoid adverse effects, warning signs that may indicate problems, and the need for periodic monitoring and evaluation to enhance patient knowledge about drug therapy and to promote compliance. Offer support and encouragement to help the patient cope with the progressive nature of the disease and long-term drug regimen.

Narcotic Agonists Antagonists

drugs that react at some opioid receptor sites to stimulate their activity and at other opioid receptor sites to block activity The narcotic agonists-antagonists (see Table 26.1) stimulate certain opioid receptors but block other such receptors. These drugs, which have less abuse potential than the pure narcotic agonists, exert a similar analgesic effect as morphine. Like morphine, they may cause sedation, respiratory depression, and constipation. They have also been associated with more psychotic-like reactions, and they may even induce a withdrawal syndrome in patients who have been taking narcotics for a long period. Available narcotic agonists-antagonists include buprenorphine (Buprenex), butorphanol (generic), nalbuphine (generic), and pentazocine (Talwin).

Hypnotics

drugs used to induce sleep Extreme sedation results in further central nervous system (CNS) depression and sleep, or hypnosis. Hypnotics are used to help people fall asleep by causing sedation. Drugs that are effective hypnotics act on the reticular activating system (RAS) and block the brain's response to incoming stimuli. Hypnosis, therefore, is the extreme state of sedation, in which the person no longer senses or reacts to incoming stimuli.

Hageman factor

first factor activated when a blood vessel or cell is injured; starts the cascading reaction of the clotting factors, activates the conversion of plasminogen to plasmin to dissolve clots, and activates the kinin system responsible for activation of the inflammatory response Hageman factor activates kallikrein, a substance found in the local tissues, which causes the precursor substance kininogen to be converted to bradykinin and other kinins. Bradykinin was the first kinin identified and remains the one that is best understood. Bradykinin causes local vasodilation and changes in capillary permeability, which brings more blood to the injured area and allows white blood cells to escape into the tissues. It also stimulates nerve endings to cause pain, which alerts the body to the injury. Bradykinin also causes the release of arachidonic acid from the cell membrane. Arachidonic acid is the precursor to many substances called autacoids, including cyclooxygenase, prostacyclin, and thromboxane. These substances act like local hormones that cause an effect in the immediate area and then are broken down. These autacoids include the following: Prostaglandins, some of which augment the inflammatory reaction and some of which block it. Cyclooxygenase, which is involved in inflammation and various protective actions in the body. Leukotrienes, some of which can cause vasodilation and increased capillary permeability, and some of which can block the reactions. Thromboxanes, which cause local vasoconstriction and facilitate platelet aggregation and blood coagulation.

Adverse effects of Antidepressants

insomnia, weight gain, sexual dysfunction/inability to reach orgasm The adverse effects associated with SSRIs, which are related to the effects of increased 5HT levels, include CNS effects such as headache, drowsiness, dizziness, insomnia, anxiety, activation of mania/hypomania, tremor, agitation, and seizures. GI effects such as nausea, vomiting, diarrhea, dry mouth, anorexia, constipation, and changes in taste often occur as do GU effects, including painful menstruation, cystitis, sexual dysfunction, urgency, and impotence. Respiratory changes may include cough, dyspnea, upper respiratory infections, and pharyngitis. SSRIs may also cause serious intraocular pressure changes if used in patients with untreated narrow-angle glaucoma. Other reported effects are sweating, rash, fever, and pruritus. Recent studies have linked the incidence of suicidal ideation and suicide attempts to the use of these drugs in pediatric patients and adolescents (Box 21.3).

Methocarbamol (Robaxin)

methocarbamol meth-oh-KAR-ba-malRobaxin, Robaxin-750Therapeutic class: Skeletal muscle relaxantsPharmacologic class: CNS depressants Available Forms Injection: 1,000 mg/10-mL vials Tablets: 500 mg; 750 mg Indications & Dosages As adjunct to rest, physical therapy, and other measures for relief of discomfort associated with acute, painful musculoskeletal conditions Adults and children older than age 16: Initially 1,500 mg PO q.i.d. for first 48 to 72 hours. For severe conditions, may increase up to 8,000 mg/day PO in divided doses. For maintenance therapy, give 1,000 mg PO q.i.d or 1,500 mg PO t.i.d or 750 mg PO every 4 hours. Or, initially 1,000 mg IM or IV every 8 hours, with maximum dose of 3,000 mg/day for no more than 3 consecutive days. May repeat course of therapy after drug-free interval of 48 hours.Adjust-a-dose: Adjust dosage and frequency of injection based on severity of the condition and therapeutic response. For moderate symptoms, one dose of 1 g IV or IM may be adequate.Tetanus, in addition to standard treatmentAdults: Initially, 1,000 to 2,000 mg injected into tubing of previously inserted indwelling needle. An additional 1,000 or 2,000 mg may be added to the infusion bottle so that a total of up to 3,000 mg is given as the initial dose. May repeat initial dosage every 6 hours until administration via NG tube is possible.Children: Initially, give minimum dose of 15 mg/kg or 500 mg/m2 IV; may repeat every 6 hours if needed. Maximum dose is 1.8 g/m2/day IV for 3 consecutive days. Administration POMay crush tablets and mix with food or liquid or suspend in water or saline for NG tube administration.Store at room temperature (68° to 77° F [20° to 25° C]).IVMay give solution undiluted directly into vein at a maximum rate of 3 mL/minute (one 10-mL vial in approximately 3 minutes).May add solution to IV drip of NSS or D5W. One 10-ml vial as a single dose shouldn't be diluted to more than 250 mL for IV infusion. After mixing with IV infusion fluids, don't refrigerate.Alert: Use caution to prevent vascular extravasation of this hypertonic solution, which may result in thrombophlebitis.Store at room temperature (68° to 77° F [20° to 25° C]).Incompatibilities: None listed by manufacturer. Consult a drug incompatibility reference for more information.IMInject no more than 5 mL (one-half vial) into each gluteal region. May repeat injections at 8-hour intervals. Action Action not established. Drug is a CNS depressant. It has no direct action on the contractile mechanism of striated muscle, the motor end plate, or the nerve fiber.RouteOnsetPeakDurationPO30 min1-2 hrUnknownIVUnknownUnknownUnknownIMUnknownUnknownUnknownHalf-life: 1 to 2 hours. Adverse Reactions CNS: fever, headache, amnesia, confusion, dizziness or light-headedness, drowsiness, insomnia, sedation, seizures, syncope, vertigo. CV: bradycardia, flushing, hypotension, thrombophlebitis. EENT: diplopia, nystagmus, blurred vision, conjunctivitis, nasal congestion. GI: dyspepsia, metallic taste, nausea, vomiting. Hematologic: leukopenia. Hepatic: jaundice. Musculoskeletal: mild muscular incoordination. Skin: pruritus, rash, urticaria. Other: hypersensitivity reaction, anaphylactic reaction, angioneurotic edema, pain and sloughing at injection site. Interactions Drug-drugCNS depressants: May enhance adverse effects of both drugs. Use cautiously together.Magnesium sulfate: May enhance CNS depressant effects. Use cautiously together.Black Box Warning: Opioid class warning: Opioids: May cause slow or difficult breathing, sedation, and death. Avoid use together. If use together is necessary, limit dosage and duration of each drug to minimum necessary for desired effect. Psychotropics: May enhance adverse effects of methocarbamol. Use cautiously together.Pyridostigmine: May inhibit therapeutic effect of pyridostigmine. Use cautiously together in patients with myasthenia gravis receiving anticholinesterase agents.SSRIs: May increase risk of SSRI adverse effects, especially psychomotor impairment. Use cautiously together.Drug-herbKava kava: May enhance CNS depressant effect of methocarbamol. Discourage use together.Drug-lifestyleAlcohol use, cannabis: May enhance CNS depressant effect of methocarbamol. Discourage use together. Effects on Lab Test Results May cause a color interference in certain screening tests for 5-hydroxyindoleacetic acid (5-HIAA) using nitrosonaphthol reagent and in screening tests for urinary vanillylmandelic acid (VMA) using Gitlow method. Contraindications & Cautions Contraindicated in patients hypersensitive to drug or its components. Black Box Warning: Opioid class warning: Opioids should only be prescribed with benzodiazepines or other CNS depressants to patients for whom alternative treatment options are inadequate.Injectable formulation is contraindicated in patients with known or suspected renal impairment because of presence of polyethylene glycol 300.Use injectable formulation cautiously in patents with suspected or known seizure disorders.Use cautiously in patients with myasthenia gravis receiving anticholinesterase agents as drug may inhibit the effect of pyridostigmine bromide.Use cautiously in patients with cirrhosis as drug elimination may be reduced.Use in children only for treatment of tetanus.Dialyzable drug: Unknown.Overdose Signs & Symptoms: Nausea, drowsiness, blurred vision, hypotension, seizures, coma, death. Pregnancy-Lactation-Reproduction Fetal and congenital abnormalities have been reported after in utero exposure to drug. Don't give drug to women who are pregnant or may become pregnant unless benefits outweigh risks. It isn't known if drug appears in human milk. Use cautiously in breastfeeding women. Nursing Considerations Patient should remain in a recumbent position during and for at least 10 to 15 minutes after injection to minimize CV adverse effects. If patient develops CV adverse effects during infusion (bradycardia, flushing, hypotension, syncope, thrombophlebitis), epinephrine, injectable steroids, and/or injectable antihistamines may be given. If during IM injection blood is aspirated into syringe, the blood may be injected with drug or injection may be stopped when plunger reaches the blood. Closely watch for seizures in patients receiving injectable form. Overdose most frequently occurs in conjunction with alcohol or other CNS depressant use. Look alike-sound alike: Don't confuse Robaxin with ribavirin or Skelaxin. Patient Teaching Caution patient that drug may cause drowsiness or dizziness, impairing the ability to perform hazardous tasks, including driving a motor vehicle or operating machinery. Patient should avoid these activities until drug's effects are known. Black Box Warning: Opioid class warning: Caution patient or caregiver of patient taking an opioid with a benzodiazepine, CNS depressant, or alcohol to seek immediate medical attention for dizziness, light-headedness, extreme sleepiness, slowed or difficult breathing, or unresponsiveness.Advise patient to avoid alcohol and products containing alcohol while taking drug.Teach patient about adverse reactions and to report them to prescriber.Advise patient that lab tests will be performed regularly to assess liver and kidney function during maintenance therapy.Tell female patient of childbearing potential to notify prescriber about planned, suspected, or known pregnancy.Advise female patient to consult prescriber if she plans to breastfeed during therapy.

Skin

primary defense for the body against pathogens and infection/first line of deffense

Pharmacology

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