Pharmacology Module 3

Butabital

. Butabital/acetalcystilic acid Generic Name: aspirin/butalbital/caffeine Trade Name: Farbital and Fiorinal Classification: Anelgesic Combination Drug Action: Aspirin reduces pain and inflammation. Caffeine may work by constricting blood vessels that may cause headaches. Butalbital has a depressant effect that reduces anxiety and causes relaxation. Uses: Butalbital is a barbiturate with an intermediate duration of action. Butalbital is often combined with other medications, such as acetaminophen (paracetamol) or aspirin, and is commonly prescribed for the treatment of pain and headache. The various formulations combined with codeine are FDA-approved for the treatment of tension headaches. Butalbital has the same chemical formula as talbutal but a different structure—one that presents as 5-allyl-5-isobutylbarbituric acid General/typical dose range: Adults: 2 tablets at onset, then 1 tablet every 4-6 hours; Butalbital 50 mg/acetaminophen 300 mg/caffeine 40 mg: 1 or 2 capsules orally every 4 hours as needed not to exceed 6 capsules per day; Butalbital 50 mg/acetaminophen 325 mg/caffeine per 15 mL oral liquid: 15 to 30 mL orally every 4 hours as needed not to exceed 90 mL per day children: not recommended. Side Effects: Dizziness; drowsiness; gas; lightheadedness; nausea; vomiting. Contraindications: Coagulation Problems, Acute Alcohol Intoxication, Drug Dependence, Liver Disease, Porphyria Rash, Respiratory Depression, Cardiac Disease, Hypertension, Liver Disease, Seizure Disorders, Pud, Asthma, Gi Toxicity, Renal Dysfunction, Reye's Syndrome, Adrenal Insufficiency, Depression, Hematologic Toxicity, Osteomalacia, Paradoxical Reactions, Cardiotoxicity, Psychiatric Disorders, Renal Dysfunction, Gerd, Anemia, Dialysis, G-6-Pd Deficiency, Hepatotoxicity Drug, Food, Herbal Interactions: Benzodiazepines (eg, chlordiazepoxide), monoamine oxidase (MAO) inhibitors (eg, phenelzine), narcotic analgesics (eg, morphine), sleeping medicines (eg, temazepam), or sodium oxybate (GHB) because they may increase the risk of aspirin/butalbital/caffeine's side effects Anticoagulants (eg warfarin), celecoxib, clopidogrel, heparin, or NSAIDs (eg, ibuprofen) because the risk of serious side effects, such as stomach ulcers and bleeding, may be increased Carbonic anhydrase inhibitors (eg, acetazolamide), insulin, meglitinides (eg, repaglinide), methotrexate, quinolone antibiotics (eg, ciprofloxacin), or valproic acid because the risk of their side effects may be increased by aspirin/butalbital/caffeine Angiotensin-converting enzyme (ACE) inhibitors (eg, lisinopril), antipsychotics (eg, clozapine), beta-blockers (eg, atenolol), corticosteroids (eg, prednisone), doxycycline, estrogens (eg, estradiol), metronidazole, oral contraceptives (eg, norethindrone/ethinyl estradiol), quinidine, probenecid, sulfinpyrazone, theophylline, or tricyclic antidepressants (eg, amitriptyline) because their effectiveness may be decreased by aspirin/butalbital/caffeine Do not use if you are allergic to nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, ibuprofen) or any ingredient in aspirin/butalbital/caffeine, you have Von Willebrand disease, porphyria, or bleeding or blood clotting problems, you are taking sodium oxybate (GHB), heparin, probenecid, or sulfinpyrazone or your child has the flu, chickenpox, or joint problems Patient Instructions/teaching: Take aspirin/butalbital/caffeine by mouth with or without food. If stomach upset occurs, take with food to reduce stomach irritation. Taking it with food may not decrease the risk of stomach or bowel problems (such as bleeding or ulcers) that may occur while taking aspirin/butalbital/caffeine. Talk with your doctor or pharmacist if you experience persistent stomach upset. Do not take aspirin/butalbital/caffeine if it has a strong vinegar-like smell, or if any vinegar smell remains after leaving the bottle open for 10 minutes. If you miss a dose of aspirin/butalbital/caffeine and you are taking it regularly, take it as soon as possible. If several hours have passed or if it is almost time for your next dose, do not double the dose to catch up, unless advised to do so by your doctor. Do not take 2 doses at once. Butalbital-containing drugs (Fiorinal, Fioricent) may need to be tapered slowly because severe problems can develop with abrupt cessation. Serious withdrawal symptoms such as delirium and seizures, can appear without warning. Aspirin/butalbital/caffeine may cause drowsiness or dizziness. These effects may be worse if you take it with alcohol or certain medicines. Use aspirin/butalbital/caffeine with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it. Do not drink alcohol or use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using aspirin/butalbital/caffeine; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness. Serious stomach ulcers or bleeding can occur with the use of aspirin/butalbital/caffeine. Taking it in high doses or for a long time, smoking, or drinking alcohol increases the risk of these side effects. Hormonal birth control (eg, birth control pills) may not work as well while you are using aspirin/butalbital/caffeine. To prevent pregnancy, use an extra form of birth control (eg, condoms). Use aspirin/butalbital/caffeine with caution in the elderly; they may be more sensitive to its effects. Aspirin/butalbital/caffeine should not be used in children younger than 12 years old; safety and effectiveness in these children have not been confirmed. If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using aspirin/butalbital/caffeine while you are pregnant. Aspirin/butalbital/caffeine is not recommended during the last 3 months (third trimester) of pregnancy because it may cause harm to the fetus.

Sumatriptan

. Sumatriptan (p. 1043, 1048) Sumatriptan should be taken after the aura of mirgraine passes because is has been found to be effective only after the headache symptoms appear. Sumpatriptan is available in PO, subcutaneous and intranasal forms. Intranasal has a slower onset than dose SC and is less effective, yet intranasal dosing may be more appealing for children. Do not repeat the dose of medication if patient dose not respond to first dose. Brand Name: Imitrex Generic Name: Sumatriptan Drug Classification: Antimigraine Agent Drug Action: Sumatriptan binds with high affinity to human cloned 5 HT1B/1D receptors. Sumatriptan presumably exerts its therapeutic effects in the treatment of migraine headache through agonist effects at the 5 HT1B/1D receptors on intracranial blood vessels and sensory nerves of the trigeminal system, which result in cranial vessel constriction and inhibition of pro inflammatory neuropeptide release. Uses: Cluster Headaches, Cyclic Vomiting Syndrome, Migraine, New Daily Persistent Headache General/Typical Dose Range: The recommended dose of Sumatriptan tablets is 25 mg, 50 mg, or 100 mg. Doses of 50 mg and 100 mg may provide a greater effect than the 25 mg dose, but doses of 100 mg may not provide a greater effect than the 50 mg dose. Higher doses may have a greater risk of adverse reactions. If the migraine has not resolved by 2 hours after taking Sumatriptan tablets, or returns after a transient improvement, a second dose may be administered at least 2 hours after the first dose. The maximum daily dose is 200 mg in a 24 hour period. Use after Sumatriptan injection: If the migraine returns following an initial treatment with Sumatriptan injection, additional single Sumatriptan tablets (up to 100 mg/day) may be given with an interval of at least 2 hours between tablet doses. The safety of treating an average of more than 4 headaches in a 30 day period has not been established. Dosing in Patients with Hepatic Impairment: If treatment is deemed advisable in the presence of mild to moderate hepatic impairment, the maximum single dose should not exceed 50 mg Side Effects: dizziness, injection site reaction, vertigo, nausea and vomiting, flushing sensation, tingling sensation, and unpleasant taste. Other side effects include: asthenia, burning sensation, chest discomfort, neck pain, neck stiffness, numbness, throat irritation, feeling of heaviness, flushing, sensation of pressure, and sensation of tightness Contraindications: Ischemic coronary artery disease (CAD) (angina pectoris, history of myocardial infarction, or documented silent ischemia) or coronary artery vasospasm, including Prinzmetal's angina. Wolff-Parkinson-White syndrome or arrhythmias associated with other cardiac accessory conduction pathway disorders. History of stroke or transient ischemic attack (TIA) or history of hemiplegic or basilar migraine because these patients are at a higher risk of stroke. Peripheral vascular disease. Ischemic bowel disease. Uncontrolled hypertension. Recent use (i.e., within 24 hours) of ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), or another 5-hydroxytryptamine1 (5-HT1) agonist. Concurrent administration of a monoamine oxidase (MAO)-A inhibitor or recent (within 2 weeks) use of an MAO-A inhibitor. Food, Drug, Herbal Interactions: Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and Sumatriptan tablets within 24 hours of each other is contraindicated. MAO A inhibitors increase systemic exposure by 7 fold. Therefore, the use of Sumatriptan tablets in patients receiving MAO A inhibitors is contraindicated. Because their vasospastic effects may be additive, co-administration of Sumatriptan tablets and other 5 HT1 agonists (e.g., triptans) within 24 hours of each other is contraindicated. Selective Serotonin Reuptake Inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome None of the triptans can be used within 24 h of ergotamine-containing medications or other triptans. Concurrent use of a triptans or use within 2 wk of MAOIs is contraindicated. All triptans interact with SSRIs. Patient Instruction: Sumatriptan is excreted in human milk following subcutaneous administration. Infant exposure to Sumatriptan can be minimized by avoiding breastfeeding for 12 hours after treatment with Sumatriptan tablets. A cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of CAD) prior to receiving Sumatriptan tablets. Sumatriptan tablets may cause serious cardiovascular side effects such as myocardial infarction or stroke. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, irregular heartbeat, significant rise in blood pressure, weakness, and slurring of speech, and should ask for medical advice if any indicative sign or symptoms are observed. Inform patients that anaphylactic/anaphylactoid reactions have occurred in patients receiving Sumatriptan tablets. Such reactions can be life threatening or fatal. Treatment with Sumatriptan tablets may cause somnolence and dizziness; instruct patients to evaluate their ability to perform complex tasks after administration of Sumatriptan tablets. Sumatriptan tablets should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus

Quetiapine

11. Quetiapine-Seroquel 259 A. Drug name: Atypical Antipsychotic. Pregnancy C. B .Action: the atypical APs are thought to block serotonin receptors in the cortex, which blocks the usual ability of serotonin to inhibit the release of dopamine. Thus, more dopamine is released to the prefrontal cortex, which reduces he negative symptoms of schizophrenia. All drugs with antipsychotic properties block dopamine D2receptors, but atypical APs generally have less D2 blockade than the typical APs. Onset = few days - weeks, peak = 1-6 hrs, C.Uses: Psychotic disorders, severe agitation, schizophrenia, acute mania, bipolar maintenance, bipolar depression, adjunct to major depressive disorder anti-depressant treatment. Atypical APs address both the positive and negative symptoms of schizophrenia. D.Gen/typ dose range: Adults: Schizophrenia Initially 25 mg bid, day 1 and increase q d by 25-50 mg in divided doses to target of 300-400 mg/d(divided) by day 4. Then increase by 25-50 mg in 2-d intervals to max 800 mg; lower in the elderly or with hepatic impairment. XR formulation: Initially 300 mg in p.m. (3-4 h before hs), increase by 300 mg/d to range 400-800/d. Mania: 100 mg/d divided, increase by 100 mg/d (divided)to 400 mg by day 4, then 200 mg increments to 800 mg(divided) by day 6. Depression: 50 mg day 1 at hs, then increase by 100 mg qhs until 300 mg on day 4. May increase to 400 mg day 5 and 600 mg day 8 if needed. XR formulation: Mania—300 mg in p.m. day 1, then 600 mg in p.m. day 2. Day 3titrate to effective dose (range 400-800) Depression—50 mg day 1, 100 mg day 2, 200 mg day 3, and300 mg day 4 Give evening dose 3-4 h before hs. E.SE/ADR: seizures, weight gain, diabetes, hyperprolactinemia, dizziness, somnolence, orthostatic hypotension, tachycardia, sleep disturbance, constipation, and rhinitis. Atypical APS have less risk for EPSs, TD, and elevation of prolactin levels. F.Contraindication: pregnancy, lactation, young children, hypersensitivity. Caution in renal/hepatic disease, geriatric require low dose. G.F/D/H interacs: Glucocorticoids = decreased antipsychotic effect. Phenytoin = increased toxicity of phenytoin; decreased antipsychotic effect. Erythromycin, ketoconazole, itraconazole, fluconazole = Increased effect of antipsychotics. Rifampin, SSRIs = Decreased effect of antipsychotics. Carbamazepine = Increased toxicity of carbamazepine. Cimetidine = Increased effect of antipsychotics. Ciprofloxacin (Cipro) = Potent 1A2 inhibitor. Antihypertensive = Hypotension H.Pt. instruct: Alert the patient to avoid the use of alcohol or other CNS depressants. Advise of the potential for significant weight gain and in-crease in triglycerides, and assist the client in modifying diet and exercise regimes to counter these undesirable effects. I. Monitoring: unhealthy weight gain, which leads to a metabolic syndrome (abdominal obesity, high blood pressure, high cholesterol levels, and insulin resistance). Before starting any atypical antipsychotic, patients should be assessed for waist circumference, body mass index (BMI), blood pressure (BP), fasting plasma glucose, and lipid profile. The practitioners should recheck BMI monthly and order laboratory work-ups at 3 months. After 3 months, the BMI should be checked quarterly and BP, laboratory work-ups, and waist circumference annually.

Acetaminophen

28. Acetaminophen Generic: Acetaminophen Trade: Tylenol Class: Analgesics Action: Produce analgesia by inhibiting prostaglandin and other substances that sensitize pain receptors. Drug may relieve fever through central action in the hypothalamic heat-regulating center. Uses: Mild pain or fever, arthritis General/Typical Dose Range: Adults and children >14 - 325-650mg Q4-6hrs or 1gram TID. Children- 10-15mg/kg/dose Q4hr. May be given rectally, dosing adults & children vary. Adults do not exceed 3g/day, Children all ages not to exceed 5 doses in 24hrs. May be given IV as well, however, many associated ADR and side effects. Side effects/ADR: PO- N/V/D, IV- hypertension, tachycardia, constipation, oliguria, hemolytic anemia, leukopenia, pancytopenia, neutropenia, jaundice, hypoglycemia, hypokalemia, hypomagnesemia, extremity pain, abnormal breath sounds, dyspnea, hypoxia, pulmonary edema, pleural effusion, wheezing, rash. Contraindications: black box warning: can cause acute liver failure, may require liver transplant or cause death. Most cases of liver failure result in doses greater than 4000mg/day often as a result of taking multiple products containing acetaminophen. May cause potentially fatal skin reactions: SJS, toxic epidermal necrolysis, acute generalized exanthematous pustulosis. Do not use in pt with severe hepatic impairment or severe active liver disease. Use caution in pt with long term alcohol use. Food, Drug, Herbal Interactions: Drug to Drug- bartbiturates, carbamazepine, hydantoins, rifampin, sulfinpyrazone, busulfan, cholestyramine, dasatinib, dofetilide, Isoniazid, lamotrigine, methemoglobinemia associated agents, probenecid, warfarin. Drug to Herb- St. Johns Wort, watercress. Drug to Food- Caffeine, alcohol. Patient Instructions/Teaching: Do not give to children under 2 unless directed by provider. Only intended for short term use, see provider is giving longer than 5 days in children and 10 days in adults. BLACK BOX: many OTC meds contain acetaminophen and should be counted when calculating total daily dose. Not for marked fever (>103.1). Long term use can result in liver damage, excessive alcohol use will increase this risk. Contact dr with s&s of liver damage. May breast feed. Stop immediately if rash develops.

Codeine, Tylenol # 3

39. Codeine (Tylenol #3) a. Drug name: trade and generic: i. Tylenol with codeine # 4 ii. Tylenol with codeine # 3 iii. Acetaminophen/codeine b. Drug classification: analgesic/antitussive combos; opioid combos, opiod agonist c. Drug action: i. Tylenol: analgesic action is unknown, antipyretic, direct action on the hypothalamus ii. Codeine: opiate action by binding to various opioid receptors producing analgesia, sedation and antitussive effects (opioid agonist) 1. Onset: 10-30 min 2. Peak: 0.5-1h 3. Duration: 4-6 h 4. Half-life: 3h 5. Excretion: Urine d. Uses: pain control, cough suppressant, secondary, fever control from tylenol e. Dose: i. Adults: 1. Pain, mild -moderate: 15-60 mg codeine PO q4-6 h prn; use lowest effective dose, do not exceed 1g, 4h and 4g/day of acetaminophen, 360 mg/day codeine from all sources (the same for all following doses) 2. Cough: 30 mg codeine PO q 4-6 h prn, MAX 120 mg/day codeine, use lowest effective dose, shortest tx duration, same acetaminophen guidelines 3. Renal dosing and hepatic dosing: not defined, but consider lower dose with renal impairment and/or hepatic impairment ii. Pediatric dosing: 1. Pain, 7-12 yo: 15-30 mg codeine PO q 4-6 hours prn: MAX 60 mg/dose codeine; alt 0.5-1 mg/kg codeine PO 4-6 hours prn 2. Pain, 13-17 yo: 15-60 mg codeine PO q4-6 h; MAX 60 mg/dose codeine; alt 0.5-1 mg/kg codeine PO q4-6h; 3. Cough, 6-11 yo: 1-1.5 mg/kg/day codeine PO divdied q 4-6 h; MAX 60 mg/dose codeine 4. Cough, 12 yo and older: 30 mg codeine PO q 4-6 hours; MAX 120 mg /day codeine f. Side effects/ADR: i. ADR: CNS depression, respiratory depression, hepatotoxicity, paralytic ileus, biliary spasm, ICP increase, hemolytic anemia, pancytopenia, thrombocytopenia, leukopenia, neutropenia, hypersensitivity reaction, anaphylaxis, skin reaction, dependency/abuse, adrenal insufficiency, withdrawal symptoms with abrupt D/C after long-term use, analgesic-associated nephropathy (chronic use) ii. Side effects: Lightheadedness, dizziness, sedation, constipation, nausea/vomiting, abdominal pain, rash, pruritus, urinary retention, urinary retention, euphoria, dysphoria g. Contraindications: Hypersensitivity to drug/class, respiratory depression, paralytic ileus, post-tonsillectomy or adenoidectomy use (peds pts), avoid abrupt withdrawal in long-term use, caution if hypersensitivity, caution if G6PD deficiency, caution in ped patients, caution in elderly or debilitated pts, ultra-rapid CYP2D6 metabolizer, severe renal or hepatic impairment, caution with long-term use in sleep apnea, CNS depression, CNS depressant use, alcohol use, hx of drug or alcohol abuse, head injury, increased ICP, seizure disorder, acute abdomen, GI/GU obstruction, hypothyroidism, adrenal insufficiency, biliary disease, urethral stricture, prostate hypertrophy h. Interactions for codeine: i. CNS depressants, alcohol, hypnotics, barbiturates, benzos, antipsychotics-additive CNS depression ii. Cimetidine, hydantoins, rifampin, droperidol, charcoal, nicotine-decreased effect of opioid, increased dose of opioid may be necessary iii. Carbamazepine, warfarin, MAOs, furazolidone, nitrous oxide-decreased effect of interacting drug, monitor blood levels when possible iv. Acetaminophen interaction characteristics: CYP2E1 substrate, affected by delayed gastric emptying, analgesic associated nephropathy, methemoglobinemia v. Herbs: black cohash, german cohash, Siberian ginseng, goldenseal, passionflower (caution advised with all of these herbs) vi. Food: Caution with potassium supplements, read above i. Patient Education: i. taper gradually with long-term use ii. Potential for physical dependence and pt should use for relief of acute, severe pain iii. Long-term for chronic pain can result in tolerance and hypersensitivity to pain iv. Avoid concurrent use of opioids with alcohol and/or CNS depressents v. Avoid using acetaminophen with combination opioids vi. May cause drowsiness and patients should not use when physical alertness is required, such as driving vii. Change position slowly to minimize postural hypotension viii. May cause constipation, so increase daily fiber and fluid intake ix. Opioid may be taken with food to avoid nausea x. Controlled substances: advise to be careful of possible theft or use by unauthorized agents

Remeron

42. Remeron/Mirtazapine (p. 253) This drug has less sexual, GI and anxiogenic side effects. Unfortunately, it also blocks histamine which can lead to weight gain and drowsiness at some doses. This may be an advantage for treatment in patients who are depressed with sleeping difficulties or weight loss. Mirtazapine does not have the anti-muscarinic side effects of NNSRIs. Generic Name: Mirtazapine Brand Name: Remeron, Remeron Soltabs Classification: Antidepressant, Norepinephrine-and Serotonin-Specific Agonist Drug Action: Mirtazapine is a unique antidepressant used to treat anxiety and depression. It is a 5HT agonist and reuptake inhibitor that block sthe reuptake of NE and the somato-dendritic reuptake of5HT available for release from the presynaptic neuron and more NE available in the synaptic cleft. Mirtazapine specifically blocks the 5HT2 and 5HT3 receptors. Uses: Mirtazapine is used to treat major depressive disorder. It may also be used in patients who have sleep disorders. General/typical dose range: Initial dose: 15 mg orally once a day at bedtime. Maintenance dose: 15 to 45 mg per day. Side Effects: drowsiness, dizziness; strange dreams; vision changes; dry mouth; constipation; increased appetite; or weight gain. Contraindications: The use of monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders with Mirtazapine Tablets or within 14 days of stopping treatment with Mirtazapine Tablets are contraindicated because of an increased risk of serotonin syndrome. The use of Mirtazapine Tablets within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated. Starting Mirtazapine Tablets in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome Food, Drug, Herbal: Cimetidine (Tagamet); diazepam (Valium); ketoconazole; St. John's wort; tramadol; tryptophan (sometimes called L-tryptophan); medicine to treat mood disorders, thought disorders, or mental illness - such as lithium, other antidepressants, or antipsychotics; migraine headache medicine - sumatriptan, zolmitriptan, and others; or seizure medicine - carbamazepine, phenytoin. Patient Instructions/teaching: Avoid drinking alcohol. It may increase certain side effects of Remeron. Remeron may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Remeron is usually taken once a day at bedtime. Take the regular Remeron tablet with water. To take the Remeron SolTab orally disintegrating tablet: Keep the tablet in its blister pack until you are ready to take it. Open the package and peel back the foil. Do not push a tablet through the foil or you may damage the tablet. Use dry hands to remove the tablet and place it in your mouth. Do not swallow the tablet whole. Allow it to dissolve in your mouth without chewing. If desired, you may drink liquid to help swallow the dissolved tablet. It may take up to several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve after 4 weeks of treatment. Do not stop using Remeron suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using mirtazapine.

Celebrex

43. Celebrex a. Drug name: i. Brand: Celebrex ii. Generic: Celecoxib iii. Drug class: NSAIDs b. Action of drug: COX 2 selective drug/inhibitor and does not inhibit COX-1. Less risk of GI bleeding, but still at risk for CV problems. i. Onset: unknown ii. Peak: 3 h iii. Duration: 12-24 h iv. Protein binding: 97.5% v. Bioavailability: unknown vi. Half-life: 11h vii. Metabolism: liver (CYP450: 2C9) viii. Elimination: 25 in the urine and 57% in the feces c. Uses: Anti-inflammatory activity, analgesia relief of mild to moderate pain, antipyretic, not used for anti-platelet therarpy since this activity only exists while the NSAID is in the blood, osteoarthritis, juvenile idiopathic arthritis, rheumatoid arthritis d. Dosage: i. Dosage form: 1. Capsules: 100, 200, 400 mg 2. Children: JIA: >10 to <25kg = 50 mg bid; >25 kg: 100 mg bid 3. Adults: a. Acute pain: 400 mg at first, followed by 200 mg bid b. OA: 200 mg daily c. RA: 100 to 200 mg bid e. SE/ADR: i. SE: HA, dyspepsia, URI, diarrhea, abdominal pain, n/v, rash, flatulence, peripheral edema, dizziness, ALT AST elevated, BUN elevated, fever in peds, cough in peds, arthralgia in peds, photosensitivity, delayed ovulation, ii. ADR: GI bleed, GI perf/ulcer, MI, stroke, thromboembolism, HTN, CHF, renal papillary necrosis, nephrotoxicity, hepatotoxicity, hypersensitivity, anaphylaxis, bronchospasm, exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, drug rxn w/eosinophilia and systemic sx, anemia, blood dyscrasias f. Contraindications: i. hypersens to drug/class/compon, sulfonamides, aspirin triad, pregnancy starting at 30 wk gestation, CABG surgery periop use, GI bleeding, ii. Caution with alcohol use, elderly or debilitated patients, smoker, poor CYP2C9 metabolizer, renal or hepatic impairment, asthma, recent MI, CV dz, cardiac dz risk, HTN, CHF, fluid retention, GI bleeding or ulcer hx, dehydration, prolonged use, systemic onset JIA, female pts trying to conceive g. Interactions: i. Anticoagulents: may prolong PT, avoid coadministration, monitor PT and patients, instruct patients to watch for bleeding ii. Beta Adrenergic blockers: Antihypertensive effect impaired; sulindac and naproxen do not affect atenolol; select appropriate drug match iii. Hydantoins: serum levels of phenytoin increased, resulting in increased pharmacological and toxic effects of phenytoins, if used together, monitor blood levels and adjust accordingly iv. Lithium: serum lithium levels increased, sulindac has no effect; monitor serum levels v. Loop diuretics: decreased effect of loop diuretics, avoid concurrent use or select different diuretic vi. Probenicid: may increase conc. And tox. Risk of NSAIDS, avoid concurrent use vii. Salicilates: dec. plasma conc. Of NSAIDS, avoid concurrent use viii. Drugs contraindicated: cidofovir, ketorlac, thioridazine ix. Herbs: caution with willow bark (may inc. risk of GI bleed with additive effects, willow bark may contain salicylates) x. Food h. Patient Education: i. Administration: 1. A missed dose should be taken as soon as pt remembers unless it is almost time for next dose 2. Drugs taken more than once a day should be taken within 1 to 2 hours of scheduled time 3. Doses should not be doubled 4. Taking the higher dose than prescribed does not increase effectiveness and may increase ADRs 5. For some NSAIDS, there is a prescribed length of time which the drug may not be taken 6. Take the drug with food or a full glass of water, remain upright position for 15 to 30 min to reduce GI discomfort and ADR 7. Remind patients to avoid aspirin, alcohol, and other GI irritants ii. Adverse Reactions: 1. Instruct on ADR and what to do if one occurs 2. Contact provider with coffee ground emesis or black-stool 3. Notify provider with skin rash, itching, weight gain, edema, or persistent headache. 4. May cause drowsiness, so pt should avoid activities that require mental alertness until response to drug is known

Cymbalta

44. Cymbalta a. Name i. Brand: Cymbalta ii. Generic: Duloxetine iii. Classification: serotonin-norepinephrine reuptake inhibitors or SNRIs, subclasses fibromyalgia, other analgesics, other neurologics b. Drug action: i. Indications: depression, diabetic neuropathy, fibromyalgia, anxiety ii. Metabolism: liver extensively; CYP450: 1A2, 2D6 substrate iii. Excretion: urine 70% (<1% unchanged) feces 20% iv. Half life: 12h v. Mechanism of action: exact mechanism unknown, inhibits norepinephrine and serotonin reuptake c. Uses: depression, diabetic neuropathy, fibromyalgia, anxiety d. Doses: i. Adults: 40 mg - 60 mg/d max 60 mg, 60 mg for neuropathy and fibromyalgia ii. Dosage forms: tablets 20, 30, 60 mg e. SE/ADR i. ADR: suicidality, depression exacerbation, hypomania/mania, serotonin syndrome, abnormal bleeding, alt. Plt fxn, anaphylaxis/anaphylactoid reaction, steven-johnson syndrome, erythema multiforme, angle-closure glaucoma, seizures, hyponatremia, SIADH, urinary retention, hepatotoxicity, orthostatic hypotension, syncope, extrapyramidal sx, hypertensive crisis, arrhythmias, withdrawal with abrupt d/c ii. SE: nausea, HA, xerostomia, wt loss, abdominal pain, somnolence, fatigue, constipation, anorexia, insomnia, vomiting, dizziness, vomiting, diarrhea, diaphoresis, erectile dysfunction, agitation, oropharyngeal pain, libido decrease blurred vision, tremor, anxiety, anorgasmia, yawning, dyspepsia, ejaculatory dysfunction, BP elevation, palpitations, urinary hesitancy, ALT and AST elevation f. Contraindications: i. Contraindicated: hypersens to drug/class/compn, CrCl <30, hepatic impairment, alcohol abuse, avoid abrupt withdrawal ii. Caution: smoking habit changes, pts <25 yo, elderly pts, pregnancy in 3rd trimester, bleeding risk, hypomania or mania hx, GI motility disorder, glaucoma (angle closed), sz hx, volume depletion, HTN g. Interactions i. Drugs that inhibit CYP450 2D6 ii. Drugs that inhibit 1A2: quinolone antibiotics and fluxovamine iii. Frequent alcohol: no interaction but may cause liver function issues iv. Drugs that inhibit CYP3A4 (ketoconazole) v. Interaction characteristics: antiplatelet effects, CNS depression, hyponatremia, lowers sz threshold, serotonergic effects vi. Herbs: willow bark (synergistic effects, may inc. bleeding risk and may contain salicylates), St John's Wort (may inc. risk of seritonin syndrome with additive effects), red clover (combo may inc. risk of bleeding with a synergistic effect), krill oil (may incr. Risk of bleeding with synergistic effect); horse chestnut seed (bleeding risk), ginko (bleeding), ginger (bleeding), garlic (bleeding), fenugreek, german chamomile vii. Food: omega 3 acid: (antiplatelet and may inc. risk of bleeding with synergistic effect), green tea (inc. risk of bleeding with synergistic effect), flaxseed (bleeding), fish oils (bleeding) h. Patient education: i. Written description of side effects and ways to relieve them ii. Women of childbearing age need to report if they are pregnant and need to be tapered off of med, esp. in 3rd trimester iii. Do not stop abruptly. Dose must be tapered to avoid withdrawal iv. Refills should be requested to allow sufficient time to avoid running out

Gabapentin

45. Gabapentin a. Name i. Generic: gabapentin ii. Brand: neurontin, gralise iii. Class: neuroleptics, seizure disorders, anticonvulsants, antiepileptic drugs b. Action i. Metabolism: not metabloized ii. Excretion: urine 100% iii. Mechanism of action: exact mechanism unknown, blocks voltage -dependent calcium channels modulating, excitatory neurotransmitter release iv. Half life: 5-7 h v. Onset: no info vi. Peak: 2-2.5 h vii. Duration: no info c. Uses: partial seizures in children and adults, post-herpetic neuralgia, neurpathic pain in adults d. Dosage: i. Epilepsy 1. Adults and Children >12 yr: starting dose is 300 mg TID. This may be increased using 300 or 400 mg capsules, or 600 or 800 mg tablets tid up to 1800 mg/day. Dosages up to 2400 mg/day have been well tolerated in clinical studies. The max time between doses in the tid schedule should not exceed 12 h. 2. Children 3-12 yr: start dose should range from 10-15 mg/kg/d in 3 divided doses, and the effective dose should be reached by upward titration over a period of approximately 3 d. The effective dose of gabapentin in patients 5yr of age and older is 25-35 mg/kg/d and given in divided doses (tid). Dosages up to 50 mg/kg/d have been well tol. in long-term study. Max time interval between doses should not exceed 12 h. ii. Postherpetic neuralgia: Adults: therapy is initiated as a single dose on day 1, 600 mg/d on day 2 (divided BID), and 900 mg/d on day 3 (divided tid). The dose can be subsequently be titrated up as needed for pain relief to a daily dose of 1800 mg (divided tid). iii. Available forms 1. Capsules 100, 300, 400 mg 2. Oral solutions: 50 mg/mL 3. Tablets: 300 mg, 600 mg 4. ER tabs: 300 mg, 600 mg e. SE/ADR i. SE: dizziness, somnolence, ataxia, fatigue, fever, peripheral edema, nystagmus, n/v, hostility in peds, tremor, diplopia, asthenia, dirrhea, infection, xerostomia, emotional lability in peds, amblyopia, HA, constipation, hyperkinesia in peds, abnormal thinking, wt gain, dysarthria, dyspepsia, amnesia, back pain, depression, impotence ii. ADR: depression, suicidality, erythema multiforme, steven-johnson syndrome, drug rxn with eosinophilia with systemic sx, anaphylaxis, angioedema, rhabdomyolysis, withdrawal sz or symptoms with abrupt d/c f. Contraindications i. Contraindicated: hypersens to drug/class/compon, avoid abrupt withdrawal, ii. Caution with renal impairment, depression or hx, CNS depressant use, alcohol use, or drug abuse, pregnancy category C, excreted in milk, risk of suicidal thoughts and neuropsychiatric side effects in peds pts g. Interactions i. Gabapentin and other AEDs, no interaction ii. Coadministered with Naproxen: incr. absorption of gabapentin 12-15% iii. Gabapentin may incr. The effects of alcohol and other CNS depressants iv. Gabapentin may cause a false positive urinary protein level with the N-Multistik SG test h. Patient education i. Administration: 1. Patients taking AEDs that affect GABA should take meds exactly as prescribed to maintain consistent therapeutic levels. 2. Missing a dose can cause incr. In seizures 3. Withdrawal sz may occur if med abruptly d/c'd; therefore pts need to be warned to take meds as scheduled and to not stop without discussing cessation with provider ii. Adverse reactions 1. Warn about possible neuropsychiatric adverse drug reactions, including behavioral changes, suicidal thoughts and action 2. Any changes should be reported to provider immediately 3. Pt should be warned about possible somnolence, dizziness, or balance issues when starting this med iii. Lifestyle management 1. Patients with sz should get enough sleep and exercise 2. Avoid stress that may trigger sz

Haldol

9. Haldol 256 A. Drug name: haloperidol-Haldol, Nonphenothiazine typical Antipsychotic. Pregnancy C B. Action: The typical APs block D2 receptors in the basal ganglia, hypothalamus, limbic system, brainstem, and medulla and reduce the positive symptoms of schizophrenia. Clinical effectiveness occurs when 60% to 70% of D2 receptors are blocked. Too much dopamine blockade, however, leads to symptoms resembling those of parkinsonism. Prolactin elevation appears beyond 72% D2 occupancy. As D2occupancy nears 78%, extrapyramidal symptoms (EPSs) are more prominent. Onset = 2hrs, Peak = 2-6 hrs, duration= 8-12hrs, halfe life = 21-24 hr, excreted in urine. C. Uses: Psychosis, schizophrenia, manic state, acute severe agitation. Typical APs, addresses only positive symptoms of schizophrenia, are less effective in treating the negative symptoms of schizophrenia, such as flat affect, decreased motivation, withdrawal from interpersonal relationships, and poor grooming and hygiene. D. Gen/typ dose range: Adults: 0.5-5 mg 2-3 times daily to usual maximum dose of 30 mg/d; some adults require 100 mg/d IM: 2-5 mg; may repeat after 60 min; substitute with oral as soon as feasible. First oral dose should be administered 12-24 h following last IM dose. Decanoate: Deep IM every 4 wk; initial dose 10-15 times oral dose not to exceed 100 mg. Older adults: Lower doses and slower titration . Children:0.05-15 mg/kg/d; may give in divided doses E. SE/ADR: A life-threatening adverse reaction is neuroleptic malignant syndrome (NMS), characterized by fever up to 107°F, elevated pulse, diaphoresis, rigidity, stupor or coma, and acute renal failure. EPSs are among the most troublesome side effects and include pseudo parkinsonism (shuffling, pill-rolling, cog-wheeling, tremors, drooling, rigidity), akathisia (restlessness), dystonia (involuntary, painful movements), and tardive dyskinesia (TD) (involuntary buccolingual movements, difficulty speaking and swallowing, which may be irreversible). Other side effects are sedation, weight gain, anticholinergic effects, photosensitivity, reduction of seizure threshold, orthostatic hypotension, sexual dysfunction, galactorrhea, and amenorrhea. F. Contraindication: narrow-angle glaucoma, bone marrow depression, severe liver or cardio-vascular disease. use cautiously in the presence of CNS tumors, epilepsy, diabetes mellitus, respiratory disease, and prostatic hypertrophy. Safety is not established in pregnancy and lactation. All antipsychotic medications now have an FDA Black-Box Warning regarding increased mortality in elderly patients with dementia-related psychosis and are not approved G. F/D/H interacs: CNS depression with concomitant use of CNS depressants. There may be additive hypotension with antihypertensive. Nicotine = decrease antipsychotic level. SSRIs = increase AP level. TCAs = increased sedation, risk of seizures, anticholinergic effect, serum levels of TCA, risk of arrhythmias. Diazoxide = hyperglycemia. Trazodone = increased hypotension. Phenytoin = increased toxicity of phenytoin. Hypoglycemics = decreased diabetic control. Dopaminergics = Antagonize antipsychotic effect. Beta blockers = increased effect of both drugs. Anticholinergics = Increased anticholinergic effect; increased risk of hyperthermia. Lithium, antacids, cimetidine = Decreased antipsychotic effect, ncreased risk of neurotoxicity and EPS. H. Pt. instruct: Anticipate the need for refills before the patient runs out of medication. Teach the patient to avoid sudden withdrawal of the medication because EPSs can occur. Emphasize that it is important to take the medication as prescribed, because non-compliance is the leading cause of increased symptoms and hospitalization. Advise the patient to report any side effects of EPSs, TD, or NMS. Advise the patient to rise slowly to minimize orthostatic hypotension. Caution the patient to avoid taking alcohol or other CNS depressants concurrently with these drugs and to avoid driving or other activities requiring alertness, because medication may cause drowsiness. Advise the patient to wear sunscreen and protective clothing because photosensitivity and changes in skin pigmentation may occur. I. Monitoring: The motor function of individuals taking typical antipsychotics should be routinely assessed with the Abnormal Involuntary Movement Scale (AIMS) to detect early EPS. Typical APs may elevate prolactin levels because dopamine, which inhibits prolactin, is blocked. Patients should be monitored for the consequences of chronic prolactin elevation, such as galactorrhea, gynecomastia, amenorrhea, and sexual dysfunction.

Triamincinolone

Generic: Triamcinolone Trade: Kenalog Class: Corticosteroids Action: Decrease inflammation by stabilizing leukocyte lysosomal membranes, suppresses immune response, stimulates bone marrow, influences protein, fat and carbohydrate metabolism. Uses: Adrenocortical insufficiency, Rheumatic disorders, Systemic Lupus Erythematosus, other inflammatory diseases or for immunosuppression. General/Typical Dose Range: adults- 4-12mg/d PO in single or divided doses. Children- 117mcg/kg/d in single or divided doses. Side Effects/ADR: Muscle & skin- atrophy, thinning of skin, alopecia, acneiform eruptions, poor healing, purpura, striae, hirsutism and desquamation. Myopathy is also seen with marked muscle wasting. Long term effects include truncal obesity, buffalo hump and moon faces. Skeletal- osteoporosis, muscle weakness, growth suppression in children. CNS- euphoria, insomnia, psychotic behavior, pseudotumor cerebri, seizures, vertigo, headache, paresthesia. CV- heart failure, arrhythmias, thromboembolism, hypertension, edema. EENT- cataracts, glaucoma. GI- peptic ulceration, pancreatitis, GI irritation, increased appetite, nausea, vomiting. GU- menstrual irregularities, increased urine calcium level. Metabolic- Hypokalemia, hypocalcemia, hyperglycemia, carbohydrate intolerance, hypercholesterolemia. Other- Cushingcoid state, susceptibility to infection, acute adrenal insufficiency. Contraindication: Pt with hypersensitivity to drug, those with systemic fungal infection, those with immunosuppressive doses together with live virus vaccines. Use caution with pt with recent MI, GI ulcer, renal disease, hypertension, osteoporosis, DM. Food, Drug, Herbal interactions: Drug-Drug: NSAIDS, other GI irritants, Insulin, Hypoglycemics(oral). Patient Instruction/Teaching: Do not stop medication abruptly without Dr consent. Take medication with food. Teach signs and symptoms of early adrenal insufficiency. Warn patient about long term therapy effects (moon face, buffalo hump, etc.), periodic eye exams with long term therapy, avoid exposure to infection and notify provider if exposure occurs. Notify prescriber of sudden weight gain or swelling. Tell patient to notify prescriber of any ophthalmic signs and symptoms.

Anti-epileptic Drugs

Seizures are the result of the abnormal discharge of neurons. Anything that disrupts the stability of the neuron may trigger abnormal activity and seizures. May factors may precipitate seizures including hyperventilation, sleep deprivation, sensory stimuli, emotional stress, and hormonal changes. Antiepileptic drugs (AEDs) that affect gamma aminobutyric acid or GABA include benzos, gabapentin, topamax, and Gabitral. These may be used for pain treatment including neuropathic pain (gabapentin) and migraine (Topamax). The mechanism of action is not well understood. Gabapentin is thought to be a GABA analogue that binds to unknown receptors in the brain; it does not bind to GABA receptors, nor does it mimic GABA.

Trazodone

Trazodone is an SARI. On rare occasions traodone has been associated with priapism and anticholinergic side effects. Not recommended as first-line antidepressant due to potential side effects of sedation and orthostatic hypotension. Generic Name: Trazodone Brand Name: Oleptro, Desyrel, Desyrel Dividose Classification: Seotonin Agonist Reuptake Inhibitors Drug Action: Trazodone works to inhibit the reuptake of 5HT but also blocks the postsynaptic 5HT receptor subtype. With long term use, this drug has the ability to increase serotonin release through the desensitization of 5HT receptors. Uses: Trazodone is primarily used for the treatment of depression. It is sometimes prescribed as a sedative, and also is used in combination with other drugs for the treatment of panic attacks, aggressive behavior, agoraphobia, and cocaine withdrawal General/typical dose range: Adults: 50-400 mcg/d; increase in 50 mcg increments every 3-4 d; take with food; dispenses in 50, 300, 150, 300 mg tablets Immediate-release tablets: Initial dose: 150 mg per day in divided doses. Maintenance dose: May be increased by 50 mg per day every 3 to 4 days. The maximum dose for outpatients usually should not exceed 400 mg per day in divided doses. Inpatients may be given up to but not in excess of 600 mg per day in divided doses. Trazodone should be taken shortly after a meal or light snack. Extended-release tablets: Recommended starting dose: 150 mg once daily Maintenance dose: The dose may be increased by 75 mg/day every three days (for example, start 225 mg on day 4 of therapy). Maximum daily dose: 375 mg Trazodone extended-release tablets should be taken orally at the same time every day, in the late evening preferably at bedtime, on an empty stomach. Once an adequate response has been achieved, dosage may be gradually reduced, with subsequent adjustment depending on therapeutic response. Side Effects: Dry mouth, muscle or bone pain, trouble sleeping, trouble remembering, drowsiness, dizziness; vision changes; constipation, altered sense of taste. On rare occasions has contributed to anticholinergic side effects and priapism. May cause sedation or orthostatic hypotension. Contraindications: History of suicidal thoughts or feelings Food, Drug, Herbal: Ask your doctor before taking a nonsteroidal anti-inflammatory drug (NSAID) for pain, arthritis, fever, or swelling. This includes aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib (Celebrex), diclofenac, indomethacin, meloxicam, and others. Using an NSAID with this medicine may cause you to bruise or bleed easily. Do not use trazodone if you have taken an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, and tranylcypromine. After you stop taking trazodone, you must wait at least 14 days before you start taking an MAOI. Taking this medicine with other drugs that make you sleepy can worsen this effect. Ask your doctor before taking trazodone with a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures. Do not take medication with heart rhythm medicine--amiodarone, disopyramide, dofetilide, dronedarone, flecainide, ibutilide, quinidine, sotalol; or medicine to treat a psychiatric disorder--chlorpromazine, haloperidol, pimozide, thioridazine. Patient Instructions/teaching: Do not drink alcohol. Trazodone can increase the effects of alcohol, which could be dangerous. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall. Trazodone may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Some young people have thoughts about suicide when first taking an antidepressant. Your doctor will need to check your progress at regular visits while you are using trazodone. Your family or other caregivers should also be alert to changes in your mood or symptoms. Taking an SSRI antidepressant during pregnancy may cause serious lung problems or other complications in the baby. However, you may have a relapse of depression if you stop taking your antidepressant. Tell your doctor right away if you become pregnant while taking trazodone. Do not start or stop taking this medicine during pregnancy without your doctor's advice. It is not known whether trazodone passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby. Do not give this medicine to anyone younger than 18 years old without the advice of a doctor. Trazodone is not approved for use in children.

Pregabalin

pregabalin (Lyrica): A relative of gabapentin, it may be better, and can be given twice a day. Some believe that it is more effective against seizures than is gabapentin. Pregabalin has no drug interactions, no liver metabolism, no protein binding, and similar side effects to gabapentin. Typical adult dose is 150 - 600 mg bid. I usually start my patients with 50 mg daily, adding 50 mg each week on a twice a day basis until taking 300 - 600 mg per day. This is slower than the package insert suggested starting dose, but avoid sedation. Pregabalin often is used also for chronic pains of certain types. See information on Lyrica.

Allopurionol

• Trade name: Zyloprim • Generic name: Allopurinol • Class: Antigout agent (xanthine oxidase inhibitors) • Action: Acts directly on purine metabolism, reducing the production of uric acid without disrupting the biosynthesis of vital purines. Inhibits xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine and zanthine to uric acid. • Uses: Preventative drug of choice for patients with urinary caliculi, chronic tophaceous gout, or high serum uric acid levels. Also used for hyperuricemia associated with tx of malignancy. • General/typical dose range: typical: 100-300mg/day po qd (100mg po qd with renal insufficiency). Extra info: 100mg/day to 800mg/day depending on patient status; 200-300mg/d for mild gout, 400-600mg/d for moderately severe tophaceous gout. Doses > 800mg/d must be divided; chemo related hyperuricemia: 600-800mg/day PO x2-3 days & consume high levels of fluid; recurrent calcium oxalate caliculi: 200-300mg/day to prevent recurrent stones. Pediatrics: 10mg/kg/day in 2-3 divided doses for hyperuricemia associated with malignancy, & younger children given 150mg/d in 3 divided doses. • Side effects/ADR: Allopurinol hypersensitivity syndrome = fever, rash, eosinophilia, hepatitis, progressive renal insufficiency, and may be fatal!; drowsiness, dizziness, GI upset, hypersensitivity, Stevens-Johnson syndrome, toxic epidermal necrolytis, hepatotoxicity, may cause urine crystals (intake 3000ml/day of fluid) • Contraindications: severe hepatic dysfunction; concurrent use with uricosuric agents, thiopurines, ACE inhibitors, and with thiazide diuretics (with thiazide diuretics, either don't use together or monitor for hypersensitivity) • Food/drug/herbal interactions: -ACE inhibitors: high r/o hypersensitivity -Aluminum salts: decreased effectiveness of allopurinol -Ampicillin: rate of ampicillin induced rash much higher -Anticoagulants: anticoagulant effect enhanced (NOT warfarin though) -Cyclophosphamide: myelosuppression; increased bleeding -Theophylline: theophylline clearance decreased w/ large doses of allopurinol, increased toxicity risk -Thiazide diuretics: increased incidence of hypersensitivity rxns -Thiopurines: increase in toxic effect of thiopurines -Uricosuric agents: uricosuric agents that increase excretion of urate also likely to increase excretion of oxypurinol and lower degree of inhibition of xanthine oxidase; avoid concurrent use! • Patient instructions/teaching: a week or more of treatment may be necessary before the full effects can be seen, take exactly as prescribed, do not d/c without discussing with provider, don't stop preventative medication during an acute attack, avoid ETOH, and have an alkaline diet. Will monitor serum uric acid level at baseline and after 1-3 weeks of therapy and then periodically throughout therapy. Monitor liver and renal fx at baseline and periodically with allopurinol. Reduce consumption of animal protein, sodium, refined sugars, oxalate rich foods, excessive calcium intake, and increase intake of oral fluids and dietary fiber. There will be a fall in serum and urinary uric acid levels in 2-3 days. Urine must remain alkaline (administer sodium bicarb or K+ citrate) in conjunction with therapy. Allopurinol is good for patients that overproduce uric acid. With allopurinol, if the dosing schedule is once daily, it should not be taken until the next day if miss a dose. If the dosing schedule is >1x/day, the next dose should be up to 300mg.

Alprazolam

A. Alprazolam -Xanax and Lorazepam -Ativan A. Note: first name is generic, 2nd is brand. Pregnancy category D, Schedule IV. Xanax and Ativan are short acting benzos more likely to cause dependence because of their high potency and rapid, short term action . withdrawal occur 1 -2 days after the last dose of short-acting benzos B.Action: increase the action of GABA, an inhibitory neurotransmitter, thereby decreasing the effect of neuronal excitation. Benzos bind to the benzodiazepine receptor within the GABA receptor. C.Uses: short term treatment of Anxiety/panic disorder. For long term treatment consider SSRIs first, if the benzodiazepine is necessary, then clonazepam is preferred due to its long half-life and daily dosing ability. Additional uses are muscle relaxant, paranesthesia sedation, acute agitation, dystonia, emergency treatment of uncontrollable seizures, and restless leg syndrome, chemo nausea/vomiting, irritable bowel syndrome, use in alcohol withdrawal and delirium tremens because they have cross-sensitivity with alcohol and act as an anticonvulsant. D. SE/ADR: CNS depression, drowsiness, impaired cognition, potential for cardiac and respiratory depression, especially in combination with other CNS depressants. Paradoxical anxiety, agitation, and acute rage may occur with benzodiazepines. E. Contraindication:. Pregnancy, lactation, hepatic and renal disease, and not recommended for children younger than 6 years. Other contraindications are hypersensitivity to benzodiazepines and acute narrow-angle glaucoma. Geriatric patients generally should not be prescribed benzodiazepines; if they are prescribed, they should be in very low doses due to their decreased rate of metabolism and consequent potential for accumulation. These drugs are not the treatment of choice for depression or psychosis or in the absence of anxiety signs and symptoms. Gradually tapered than abruptly discontinued because of the risk of severe withdrawal symptoms. One strategy for tapering is to decrease the dose by 0.5 mg per week, and then by 0.25 mg per week for the last few weeks. Another is to substitute a long-acting benzodiazepine such as clonazepam in an equivalent dose for a short-acting one and then titrate down. F. Pt. instruct: Advise the patient to avoid alcohol. Patients should also be advised to report ocular pain or changes in vision immediately. G. Monitring: Increased blood levels of TCAs and digitalis may occur with concurrent use of benzodiazepines and should be monitored. Specific Differences Dosing: Dosing: Anxiety: 0.25-0.5 mg tid, maximum 4 mg/d . Panic disorder: 0.5 mg tid, titrate q 3-4 d to 1-10 mg/d (mean 5-6 mg/d. tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg. Orally disintegrating tablets: 0.25 mg Onset =intermediate 1-2 h, Peak =1-2h, duration =intermediate up to 24 hr, half life = 8-37 hr. excreted thru urine Interacts with Cimetidine oc, disulfiram, omeprazole and macrolide antibiotics = increases effect Grapefruit juice= decrease metabolism and increase effect Ketoconazole = concurrent use contraindicated.

Amitriptiline

Amitriptline (p. 245, 902, 1045, 1059, 1060) This drug has been used for post-traumatic tension-type headaches as well as for the nonspecific symptoms, such as irritability, dizziness, depression, fatigue and insomnia. Contraindicated in patients with narrow angle glaucoma, urinary retention, pregnancy, breast feeding, concurrent use of MAOIs (within 14 days) and suicidal patients. Brand Name: Vanatrip, Elavil, Endep Generic Name: Amitriptyline Drug Classification: Tricyclic antidepressants Action: Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Use: Amitriptyline is used to treat symptoms of depression and depression. Dose: Outpatients: Usual dose: 75 mg orally per day in divided doses; this may be increased to a total of 150 mg per day if needed Alternate dose: 40 to 100 mg orally as a single dose at bedtime; this may be increased by 25 or 50 mg as needed at bedtime to a total of 150 mg per day Maximum dose: 150 mg orally per day Inpatients: Initial dose: 100 mg orally per day Maintenance dose: 40 to 100 mg orally as a single dose at bedtime Maximum dose: 300 mg orally per day Dosage should be reduced to the lowest amount that will maintain relief of symptoms, when satisfactory improvement has been obtained.Dose increases should preferably be made in the late afternoon or at bedtime due to the sedative effect. The full therapeutic effect may take as long as 30 days to develop. Maintenance therapy should be continued for 3 months or longer to lessen the possibility of relapse. Side Effects: constipation, diarrhea; nausea, vomiting, upset stomach; mouth pain, unusual taste, black tongue; appetite or weight changes; urinating less than usual; itching or rash; breast swelling (in men or women); or decreased sex drive, impotence Contraindications: Do not use if you have recently had a heart attack. Food, Drug, Herbal: Do not use amitriptyline if you have used an MAO inhibitor in the past 14 days, such as isocarboxazid, linezolid, methylene blue injection, phenelzine, rasagiline, selegiline, or tranylcypromine. Dangerous side effects or death can occur when alcohol is combined with amitriptyline. Patient Instruction: Before taking amitriptyline, tell your doctor if you have used an "SSRI" antidepressant in the past 5 weeks, such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem, Symbyax), fluvoxamine (Luvox), paroxetine (Paxil), or sertraline (Zoloft). You may have thoughts about suicide when you first start taking an antidepressant such as amitriptyline, especially if you are younger than 24 years old. Your doctor will need to check you at regular visits for at least the first 12 weeks of treatment. Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself. It is not known whether amitriptyline will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. Amitriptyline can pass into breast milk and may harm a nursing baby. You should not breast-feed while you are using amitriptyline. Amitriptyline is not approved for use by anyone younger than 12 years old. t may take up to 4 weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve. If you need surgery, tell the surgeon ahead of time that you are using amitriptyline. You may need to stop using the medicine for a short time. Do not stop using amitriptyline suddenly, or you could have unpleasant withdrawal symptoms. Ask your doctor how to safely stop using amitriptyline. This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert. Avoid exposure to sunlight or tanning beds. Amitriptyline can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Prednisone

Generic: Prednisone Trade: Prednicolone Class: Corticosteroid Action: Decreases inflammation, mainly by stabilizing leukocyte lysosomal membranes; suppresses immune response; stimulates bone marrow; and influences protein, fat and carbohydrate metabolism. Uses: Adrenocortical insufficiency, inflammation, immunosuppression, nephrotic syndrome. General/Typical Dose Range: Adults- 5-60mg/d PO in single or divided doses. Children- 0.14-2mg/kg/d PO in 4 divided doses. Side Effects/ADR: Muscle & skin- atrophy, thinning of skin, alopecia, acneiform eruptions, poor healing, purpura, striae, hirsutism and desquamation. Myopathy is also seen with marked muscle wasting. Long term effects include truncal obesity, buffalo hump and moon faces. Skeletal- osteoporosis, muscle weakness, growth suppression in children. CNS- euphoria, insomnia, psychotic behavior, pseudotumor cerebri, seizures, vertigo, headache, paresthesia. CV- heart failure, arrhythmias, thromboembolism, hypertension, edema. EENT- cataracts, glaucoma. GI- peptic ulceration, pancreatitis, GI irritation, increased appetite, nausea, vomiting. GU- menstrual irregularities, increased urine calcium level. Metabolic- Hypokalemia, hypocalcemia, hyperglycemia, carbohydrate intolerance, hypercholesterolemia. Other- Cushingcoid state, susceptibility to infection, acute adrenal insufficiency. Contraindications: Pt with hypersensitivity to drug, those with systemic fungal infection, those with immunosuppressive doses together with live virus vaccines. Use caution with pt with recent MI, GI ulcer, renal disease, hypertension, osteoporosis, DM. Food, Drug, Herbal interactions: Drug-Drug: NSAIDS, other GI irritants, Insulin, Hypoglycemics(oral). Patient Instruction/Teaching: Do not stop medication abruptly without Dr consent. Take medication with food. Teach signs and symptoms of early adrenal insufficiency. Warn patient about long term therapy effects (moon face, buffalo hump, etc.), periodic eye exams with long term therapy, avoid exposure to infection and notify provider if exposure occurs. Notify prescriber of sudden weight gain or swelling.

NDRI

NDRI- (Norepinephrine-Dopamine Reuptake Inhibitors) pg. 904 -Only NDRI available in the US. -Due to the short half-life, more than one dose per day may impact on sleep. If second dose is required, does no later than 5 hrs before bedtime. Use of the slow releases preparation or extended release facilitates once a day dosing.

NSAIDS

NSAIDS are typically used for inflammation, pain, and fever treatment. Advantages include affordable treatment in addition to less reliance on opioids (that carry the risk of physical abuse). NSAIDS are among the most widely used OTC medications. Aspirin and other salicylates are members of this class. The inflammatory response occurs due to cellular destruction, resulting in the release of chemical mediators, including histamine, prostaglandins, leukotrienes, cytokines, oxygen radicals, and enzymes. The enzymes lipo-oxygenase are needed to produce these mediators. Though the mechanism of action of NSAIDs is not completely known, the major mechanism is thought to include inhibition of cyclo-oxygenase activity and prostaglandin synthesis. Two cyclo-oxygenase isoenzymes have been identified including COX-1 and COX-2. COX-1 is expressed systemically and synthesized continuously so that it is present all the time in all tissues and cells, especially platelets, endothelial cells, the GI tract, the renal microvasculature, glomeruli, and collecting ducts. COX-1 is responsible for part of homeostatsis including platelet aggregation, the regulation of blood flow, to the kidney and stomach, and regulation of gastric acid secretion esp. In the stomach. Inhibition by NSAIDS accounts for side effects or ADR. COX 2 is an inducible enzyme that is synthesized mainly in response to pain and inflammation. However, there is some synthesis in the kidneys, brain, and bone, female reproductive system, and GI tract. NSAIDS Anti-inflammatory activity, analgesia relief of mild to moderate pain, antipyretic, not used for anti-platelet therapy since this activity only exists while the NSAID is in the blood.

Opioid analgesics

Opioid analgesics are the next step in treating pain when nonopioid drugs are not effectively treating it. Opioids alter perception of pain and the response to painful stimuli. Most of the drugs are schedule II narcotics under federal law. State laws vary on allowing NPs to prescribe. Opioids may be classified as agonists, mixed agonists-antagonists, or partial agonists. Opioids interact with mu, kappa, delta, or sigma receptor, producing both desired and adverse effects of opioids. Primary receptors associated with analgesia are the mu and kappa receptors. Activation of these receptors is thought to create an analgesic effect by inhibiting adenyl cyclase activity, which results in a reduction of intracellular cyclic adenosine monophosphate. In addition to analgesia, activation of mu receptors may cause euphoria, physical dependence, and respiratory depression. Activation of kappa may cause miosis, sedation, and respiratory depression. Mixed agonists-antagonists can cause withdrawal symptoms when given to narcotic-dependent individuals because of their preference at specific opioid receptor sites.

SNRI

SNRI (pg. 903) ADR-similar to that of SSRIs. Common side effects insomnia and elevated blood pressure. Lethal in overdose, and limiting the quantity prescribed is warranted.

Gabapentin

gabapentin (Neurontin): Gabapentin has the reputation of being a safe but not particularly powerful AED. The effectiveness criticism probably is because it is often prescribed at too low a dose. The drug probably works by influencing transport of GABA and effects on calcium channels. It has no drug interactions, is not metabolized in the liver and it does not bind to blood proteins. Side effects are unsteadiness, weight gain, fatigue, dizziness. Typical adult dose is 300-600 mg three times a, but doses can be up to 1200 mg three times a day. I often start at 300 mg per day, sometimes in one dose or with 100 mg pills, and increase over a month or two to the full dose. Gabapentin often is used also for chronic pains of certain types. See information on gabapentin here.

Lacosamide

lacosamide (Vimpat): Lacosamide is a new (2009) antiepileptic drug , for partial and secondarily generalized seizures. It is chemically related to the amino acid, serine. Vimpat blocks sodium channels (but in a different way from other seizure medicines), and this block reduces brain excitability. Side effects include dizziness, headache, nausea or vomiting, double vision, fatigue, memory or mood problems. Vimpat may affect the internal organs, blood counts or heart rhythm, but these potentially serious side effects are infrequent. The recommended starting dose is 50 mg twice daily, increased each week by an extra 100 mg, to the recommended maintenance dosage of 100-200 mg twice a day. See information on Vimpat.

Lamotrigine

lamotrigine (Lamictal): A broad-spectrum alternative to VPA, with a better side effect profile. However, LTG may not be as effective for myoclonic seizures. Lamotrigine works by several mechanisms including blocking release of glutamate, the brain's main excitatory neurotransmitter. It has the usual side effects of dizziness and fatigue, usually mild cognitive (thinking) impairment. Severe medical side effects are unusual. The practical side effect issue is rash, occurring in several percent of people who take it, especially if the dose is increased too fast. Therefore, it takes a couple of months to get up to the typical adult dose of 200 mg twice a day. I usually start my patients at low doses, adding one 25 mg pill daily each week on a two-times-a-day schedule until taking 100 mg twice a day. If there is no rash at that time, one is unlikely. I then switch my patients to 100 mg pills and increase to 200 mg twice a day over the next few weeks. This is slower than the package insert suggested starting dose, however, a slow starting dose is especially important if the patient also takes valproic acid (Depakote), to reduce risk for rash. Lamotrigine is also used for mood stabilization. See information on Lamictal.

Levetriacetam

levetiracetam (Keppra): Levetiracetam is one of the more used medicines in seizure clinics because it probably is effective for a broad-spectrum of seizures types, has a relatively low incidence of causing thinking/memory problems, and can be started at 500 mg twice a day, which is an effective dose. It has no drug interactions, is not metabolized in the liver and it does not bind to blood proteins. The most common side effects are dizziness, fatigue, insomnia, but the more troublesome problem can be irritability and mood changes. This may occur to some degree in up to a third of those taking the medicine. A typical adult dose is 500 - 1500 mg twice a day. I usually start my patients with 250 mg twice a day and increase the next week to 500 mg twice a day, then the next week to 1000 mg in the am plus 500 mg in the pm, then the week after to 1000 mg twice a day. This is slower than the package insert suggested starting dose. See information on Keppra.

Lorazepam

lorazepam (Ativan): Lorazepam is similar to clonazepam in dosage and action, but it is not as long-acting. It is usually used as a 'rescue medication' for patients who frequently have clusters of seizures. It works reasonably quickly when taken orally and anti-seizure effect lasts for 2-6 hours. Typical adult dose is 0.5-2.0 mg orally or as needed. A lorazepam concentrate, 2 mg per ml, can be taken as 1 ml liquid under the tongue in urgent situations.

Methylphenitade

methylphenidate (Ritalin) • Trade name: Ritalin • Generic name: Methylphenidate (Schedule II drug) • Class: Stimulants • Action: see dextroamphetamine above • Uses: ADHD, narcolepsy • General/typical dose range: 10-30mg/day in 2-3 divided doses (max 60 mg/day in divided doses). Children > 6 y/o: 5mg bid AC and at lunch, with increase of 5-10mg at weekly intervals; (max is same as adults). With children, stop if no improvement in 4 weeks. • Side effects/ADR: see dextroamphetamine above • Contraindications: see dextroamphetamine above • Food/drug/herbal interactions: see dextroamphetamine above • Patient instructions/teaching: see dextroamphetamine above

Oxycarbezine

oxcarbazepine (Trileptal): Slightly different from carbamazepine, it is at least as effective, and may have fewer side effects, except for more risk for low blood sodium (hyponatremia). It is more expensive than generic carbamazepine. A typical adult dose is 600 mg twice a day. I start my patients with 150 mg twice a day, and increase by 150 mg daily each week. This is slower than the package insert suggested starting dose. An immediate switch from carbamazepine to full-dose oxcarbazepine is possible in some cases. See information on Trileptal.

Phenobarbital

phenobarbital (Luminal): The old-timer: very inexpensive and effective in a single daily dose. Phenobarbital increases the effect of GABA, the main inhibitory neurotransmitter in the brain. Watch for sedation, thinking/memory problems and depression. Phenobarbital can cause long-term bone problems. Phenobarbital is mildly addictive and requires slow withdrawal. During pregnancy, there is a significant rate of birth defects. Typical adult dose is around 100 mg per day. I start my patients with 30 mg pills, 2 or 3 at bedtime, to allow for future dosage flexibility. The target serum level is 10-40 mcg per ml. See information on phenobarbital.

Phenytoin

phenytoin (Dilantin): The most used AED by general physicians in the US, less so by epilepsy doctors, because of the side effects. Phenytoin alters brain cell sodium channels, which has the effect of limiting rapid firing of the brain cells. It is inexpensive. Common side effects are unsteadiness and moderate cognitive problems. There are long-term potential cosmetic (body/face hair growth, skin problems), and bone problems (osteoporosis). Phenytoin causes a rash rate of a few percent, sometimes even the dangerous rash called Stevens-Johnson syndrome. Typical adult dose is 300-400 mg per day, usually with 100 mg pills. Phenytoin can be started quickly in an emergency with intravenous administration, or a large dose of capsules if an immediate effect is required. Small changes in phenytoin dose can cause large changes in serum drug levels, so the blood levels can be hard to regulate. The target serum level is 10-20 mcg per ml. See information on phenytoin.

Rufinamide

rufinamide (Banzel, Inovelon in Europe): Banzel is approved for add-on treatment of children age 4 and older and adults with the Lennox Gastaut Syndrome (see http://www.epilepsy.com/EPILEPSY/epilepsy_lennoxgastaut ). This syndrome can include seizure types such as atonic (drop) seizures, tonic (stiffening) seizures, myoclonic (brief jerking) seizures, or staring (absence) seizures, as well as partial seizures. Banzel works on sodium channels in brain cells, in a way to make them less excitable. Common side effects include headache, dizziness, fatigue and sleepiness, double vision and tremor (trembling). People who have the "short QT syndrome," a rare heart rhythm irregularity, should not take Banzel. The drug comes as 200 and 400 mg tablets. Children will usually be started at doses of approximately 10 mg/kg/day administered in two equally divided doses. Dosing can increase by adding additional 10 mg/kg amounts every two days, until the child is taking 45 mg/kg/day or a maximum of 3200 mg/day, divided into two doses each day. See information on Banzel.

Topiramate

topiramate (Topamax): A good broad-spectrum AED (i.e., treats all types of seizures). Topiramate has several mechanisms, including blocking the enzyme carbonic anhydrase, which affects the acidity of brain tissue. More acidity (to a point) suppresses seizures. Side effects include thinking and memory problems in about 1/3rd, renal stones in 1-2%, rare cases of glaucoma (increased eye pressure) and weight loss. Typical adult dose is 150-200 mg twice a day. I usually start my patients with one 25 mg pill daily, adding another pill each week on a two-times-a-day schedule until taking 100 mg twice a day. If there are no significant side effects, I then switch my patients to 100 mg pills and increase to 200 mg twice a day over the next few weeks. Topiramate also is used for migraine headache prevention. See information on Topamax

Valproic acid

valproic acid (Depakote): This is the standard broad-spectrum AED (treats all types of seizures) and no other AED is more effective for generalized seizure types. VPA has effects on GABA (at least in very high doses), and a neurotransmitter called NPY to block seizures, and maybe also on calcium channels. VPA has significant side effects: weight gain, tremor, hair loss, GI upset, blood count decreases, hepatic or pancreatic injury, bone weakness over time (osteoporosis), birth defects in up to 10% (folic acid can help to prevent them). Typical adult dose is 250 mg - 500 mg three times a day, but dose can be higher. An extended release form can be taken once a day. See information on valproic acid.

Vigabratin

vigabatrin (Sabril): At time of this writing, vigabatrin is approved in the US, but official package insert information has not become available. Vigabatrin is a "designer drug," made to block metabolism of GABA, the brain's main inhibitory neurotransmitter. Sabril has been used for over a decade in many countries, and it is effective for partial seizures, with or without secondary generalization. It also may be very effective for infantile spasms, a serious type of seizures in young children. Release in the US was delayed because the drug is toxic to the retina of the eye in up to 30% of people who take it long-term. This toxicity can result in permanent loss of peripheral vision. Regular vision testing is recommended for all people on this drug. A typical regimen begins with 500 mg twice a day, and can increase over a month or two to 1500 mg twice a day.

Zonisamide

zonisamide (Zonegran): Zonisamide is rather similar in its coverage and side effects to topiramate, except glaucoma is not usually listed. Some find less cognitive impairment than with topiramate but this is individual and dose-dependent. Typical adult dose is 100-300 mg twice a day. I usually start my patients with one 25 mg pill daily, adding 25 mg each week on a two-times-a-day schedule until taking 100 mg twice a day. If there are no significant side effects, I then switch my patients to 100 mg pills and increase to 200 mg twice a day over the next few weeks. See information on zonisamide.

Phentermine

• Trade name: Adipex-P, Suprenza • Generic name: Phentermine • Class: Anorexiant • Action: stimulate satiety centers in hypothalamus & limbic region; raises levels of leptin • Uses: Short-term (8-12 weeks, MAX 6 months) adjunctive treatment of exogenous obesity, approved for use if BMI >/= 30 or BMI >/= 27 who have an obesity related condition (HTN, DM, CAD). Note: phentermine is a schedule IV drug. • General/typical dose range: 15-30mg PO 1-2hr before or after breakfast • Side effects/ADR: CNS overstimulation, pulmonary htn (rare), regurgitant cardiac valcular disease, urticarial headache, agitation, confusion, insomnia, dizziness, hypertension, palpitations, arrhythmias, dry mouth, mydriasis, dysuria, constipation, vomiting, diarrhea, impotence. Pts that take high doses for extended period may experience dizziness, fatigue, and depression if the drug is suddenly withdrawn • Contraindications: Avoid with patients with h/o cardiovascular disease, substance abuse history (cocaine, meth, etc.), and diabetics who are difficult to monitor. Avoid use w/ MAOIs: hypertensive crisis, pregnancy • Food/drug/herbal interactions: SSRIs: serotonin syndrome; MAOIs: hypertensive crisis; Alcohol: CNS depression; Phenothiazines: psychosis; Insulin/sulfonylureas: altered requirements r/o hypoglycemia; Guanethidine: antagonoization of effect; Furazolidone: serotonin syndrome; lithium toxicity, Be careful when use w/ SSRIs: serotonin syndrome; patients w/ DM experience altered insulin or oral hypoglycemic dosage requirements; MAOIs: hypertensive crisis, Adrenergic blockers, insulin, sylfonylureas, & phenothiazines may be antagonized during anorexiant administration • Patient instructions/teaching: High risk of tolerance/dependence.

Paroxetine

•Paxil Action- Blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane enhancing the actions of serotonin on 5HT1A autoreceptors. • Uses - Anxiety, Depression, PTSD, OCD, PMDD. No approved for use in children due to lack of effectiveness. • General/typical dose range -20 mg/day Max: 50 mg/day • Side effects/ADR - Reproductive-Teratogenicity. Hema-abnormal bleeding or altered platelet functions. MUSC-Back pain, myalgia, myopathy. Neuro-Paresthesia, tremor. CNS: serotonin syndrome, decreased libido, headache, insomnia, worsening depression, increased suicidal risk extrapyramidal symptoms. CV: HTN. • Contraindications-Abrupt withdrawal, Pregnancy • Food, drug, herbal interactions- MAO inhibitors Patient instructions/teaching- Do no stop antidepressant without first consulting to a physician-Risk of Serotonin syndrome. Monitor for worsening, suicidality, or unusual changes in behavior.

Febuxostat

. Febuxostat • Trade name: Uloric • Generic name: Febuxostat • Class: Antigout • Action: Inhibits xanthine oxidase • Uses: treat hyperuricemia in patients with gout. • General/typical dose range: start at 40mg PO once daily. If uric acid levels not <6mg/dl after 2 weeks, increase dose to 80mg once daily. • Side effects/ADR: liver fx abnormalities, nausea, arthralgia, rash, MI, stroke, GI upset. Note: give this drug with gout flare prophylaxis such as NSAID or colchicine during tx initiation of anti-hyperuricemic agents. Febuxostat can cause increase in cardiovascular thrombolytic events (higher rate seen than with allopurinol) • Contraindications: hypersensitivity, asymptomatic uricemia, do not use concurrently in drugs metabolized by xanthine oxidase (theophylline, mercaptopurine, azathioprine) as toxicity can occur. • Food/drug/herbal interactions: causes increased plasma levels in drugs that are metabolized by xanthine oxidase: theophylline, mercaptopurine, azathioprine • Patient instructions/teaching: goal is serum uric acid level of <6mg/dl, may take 2 weeks of more to see effect, take exactly as prescribed, do not d/c without discussing with provider, don't stop preventative medication during an acute attack, ensure adequate fluid intake, avoid ETOH, and have an alkaline diet. Will monitor serum uric acid level at baseline and after 1-3 weeks of therapy and then periodically throughout therapy. Renal dose adjustment can be made based on CrCl. AST/ALT may be increased with this medication (monitor LFTs at 2 months, 4 months, and periodically thereafter). Can be taken without regard to food. Febuxostat good for patients that overproduce uric acid.

Amitriptyline:

1. Amitriptyline: Elavil. Tricyclic anti-depressant (TCAs) The TCAs act on the neurotransmitters serotonin and norepinephrine by inhibiting their reuptake at the presynaptic neuron. However they also act on histamine (contributing to drowsiness and weight gain) and acetylcholine. Used for the treatment of depression and insomnia, obsessive compulsive disorder.. Contraindicated with cardiovascular disorders. All anti -depressants carry a black box warning regarding increased risk of suicidal though and behavior. Dosage 75mg/d n divided doses to max of 150mg/d. May give entire dose at bedtime. Hospitalized patients may require 200-300mg/d. The most significant drug interactions are those that increase plasma level of the TCA \and thereby increase the risk of cardiotoxicity as with SSRIs, cannabis and sympathometics. ADR include anticholinergic side effects such as dry mouth, constipation, urinary hesitancy or retention, blurred vision, sedation, orthostatic hypotension weight gain, nausea and vomiting, gynecomastia and changes in libido. Pt's newly prescribed to TCA should be cautioned about safety in a situation in which mental alertness is required until full effect of drug has been determined. Steady state can usually be achieved in 5 days. Use in extreme caution or not at all with the elderly. Orthostatic hypotension contributes to falls. Pt teaching avoid hazardous activities or using heavy machinery if drowsy. Suck sugarless candy or chew gum for dry mouth. Increase fluids and fiber for constipation.

Amantadine

12. Amantadine Symmetrel A.Drug name: Dopaminergic, Pregnancy C B.Action: Amantadine releases dopamine from storage. Onset = 48h, Peak = 4 hr, half life = 18-24hr. C.Uses: Parkinson's disease; drug-induced EPS; parkinsonism syndrome following carbon monoxide poisoning D.Gen/typ dose range: Adults:100-200 mg bid; may increase to maximum of 400 mg/d in divided doses after several weeks without response after lower dose. In conjunction with levodopa: 100 mg qd bid. Capsules: 100 mg Syrup: 50 mg/5 mL. E.SE/ADR: Nausea and vomiting, dizziness, postural hypotension, abdominal pain, dyspepsia, constipation, dry mouth, depression, insomnia, confusion, and hallucinations. F.Contraindication : Renal impairment should be carefully assessed before using amantadine because it is excreted unchanged through the kidneys, hypersensitivity, use cautiously in patients with a history of cardiac, psychiatric, or ulcer disease. Dopaminergics are Pregnancy Categories B and C; their safety of use during lactation and in children has not been determined. G.F/D/H interacs : MAOIs, TCAs, opioids = hypertensive crisis. Oral contraceptive = Decreased effectiveness of oral contraceptives. H.Pt. instruct: Advise the patient to exercise care when changing position to prevent postural hypotension and to avoid hazardous activities if drowsy or dizzy. Explain that gastric irritation maybe decreased by taking medication with food . I. Monitoring: Monitor the effectiveness of the drug in managing parkinsonism symptoms. Assess for the "on-off" phenomenon in which symptoms suddenly worsen or improve. Monitor hepatic and renal function in patients on long-term therapy.

Buspirone

14. Buspirone-Buspar pg 269 A.Drug name: Serotonergic anxiolytic (member of the azapirones) . preg. Cat. B. exert effects without the CNS depression and sedation of barbiturates and benzodiazepines but also without the anticonvulsant or muscle-relaxant qualities. Buspirone has little risk of dependence and few drug interactions, and it is considered relatively safe, even in high doses. B.Action: binds to the serotonin-1A (5-HT 1a) presynaptic and postsynapticreceptors. At the presynaptic 5-HT 1a receptor, buspirone is a full agonist, that is, it contributes to the channel's opening and permitting serotonin binding, thereby inhibiting neuron firing. Buspirone also is a partial agonist at the postsynaptic5-HT 1a receptors. When there is an excess of serotonin, buspirone acts as an antagonist, but in a deficit state such as is presumed in anxiety and depression, it acts as an agonist. Increase norepinephrine metabolism in the brain. Has no effect on GABA receptors. It takes 1-2 wks for onset, and up to 6 wks for max effect. Peaks in circulation 0.7 to 1.5 hrs and has an intermediate effect. It is a CYP450 3A4 enzyme substrate. C.Uses: Anxiety D.Gen/typ dose range: usual dose is 15 mg/per day (7.5 mg BID). Initially, the patient takes 5 mg 2 or 3 times a day for 4 days; then the dose is increased by 5 mg each dose to a maximum dose of 60 mg per day. It is available in 5, 10, and 15 mg tablets, E.SE/ADR: lightheadedness, headache, nausea, insomnia, dry mouth, nervousness. Akathisia and involuntary movements are rare. F.Contraindication: hypersensitivity, severe hepatic/renal. Panic disorder due to prolonged onset and exacerbating panic. Lactation. G.F/D/H interacs. Interaction with MAOIs and SSRIs = can cause serotonin syndrome with symptoms of nausea, diarrhea, chills, sweating, elevated temperature and blood pressure, agitation ataxia, coma, and death. Haloperidol = increased serum levels of haloperidol due to competition for metabolism. Trazodone = increased ALT (alanine transaminase). Drugs that inhibit CYP3A4 (erythromycin, ketoconazole, nefazodone, intraconazole, ritonavir) and grapefruit juice = may increase serum levels of buspirone. Drugs that induce CYP3A4 (rifampin, dexamethasone, phenytoin, phenobarbital, carbamazepine) = decrease buspirone levels. H.Pt. instruct: advise the patient to try the medication and observe the effects, especially drowsiness, before engaging in activities requiring mental or physical alertness. The patient also needs to be told of the prolonged onset and be offered nonpharmacological strategies for anxiety management during this time. Monitoring: no monitoring.

Valproic acid

15. Valproic acid -Depakene • Trade name: Depakene • Generic name: Valproic acid • Class: Anticonvulsant (also approved as mood stabilizer in the 90's) • Action: Inhibits enzymes that catabolize GABA or block the reuptake of GABA into glia and nerve endings, resulting in increased brain concentrations of GABA, an inhibitory neurotransmitter in the CNS. • Uses: Complex partial, petit mal, absence seizure epilepsy; mania • General/typical dose range: 750-3000mg/day initially in divided dose, then once daily at bedtime if side effects are tolerable (max. daily dose is 60mg/kg/day). • Side effects/ADR: Pregnancy category D (causes neural tube defects); most adverse effects are transient (GI distress, heartburn, & CNS depression). Decreased mental alertness when initiating treatment; uncommon side effects: decreased platelet aggregation, bone marrow suppression, hepatoxicity, liver failure. • Contraindications: significant hepatic impairment • Food/drug/herbal interactions: -CNS depressants: increased sedation/disorientation -Anticoagulants: increased bleeding time -Anticonvulsants: increase plasma level of anticonvulsant & decrease valproate efficacy -TCAs, barbituates, diazepam, ethosuximide: increased blood level and increased risk of cardiotoxicity -Clonazepam: increased risk of absence seizures -Lithium: increased tremors -Typical antispychotics: increased risk of neurotoxicity, sedation, EPS -Antiviral: decreased valproate level -Cimetidine, salicylates, rifampin, erythromycin: increased plasma level and half-life of valproate Lamotrigine: decreased valproic levels, increased lamotrigine levels • Patient instructions/teaching: Avoid potentially dangerous sitations until the effects of the drug can be assessed (initiation of treatment can cause decreased mental alertness). Diabetics can show falsely positive ketone urine tests. Plasma levels will need to be assessed to help guide dosage adjustments. Warn patients about easy bruising and delayed clotting initially. Patients prone to falls must notify PCP and family right away. Do not d/c drug abruptly

Lithium Carbonate

2. Lithium Carbonate: lithobid. Mood stabilizer Mechanism of action not completely understood. It is thought that Lithium might replace sodium during depolarization in neuronal pathways. Used to treat manic phase of bipolar disorders and prevention of manic episodes. Dosage for acute mania is 600mg TID or 900mg BID extended release. Maintenance is 300mg tid or 450mg bid controlled -release. Lithium is one of the few psychopharmacological agents that is not metabolized by the liver and essentially is excreted into the urine unchanged. For this reason kidney function is critical in the use of lithium. Narrow therapeutic to toxic level index. Toxicity includes tremors, vomiting, diarrhea and confusion. Baseline chemistry should include creatinine, BUN, and TSH levels. Lithium should not be used with pregnant of lactating women. There is a 10% chance of fetal abnormalities if used during first trimester. The relationship between sodium, lithium and body fuid is inverse in that when sodium and fluids are depleted (vomiting, heavy sweating, diuretic use), the level of lithium is increased. The reverse is also true. The reason for most drug interactions with Lithium are altering fluid balance and lithium concentration. Blood levels should be obtained 14days after beginning treatment and 14 days after every dosage change. Pt's should be advised on the extent of monitoring. Education on fluid and electrolyte balance. Adequate sodium intake.

Probenecid

24. Probenecid Generic: Probenecid Trade: Probalan Class: Uricosurics Action: Blocks renal tubular reabsorption of uric acid, increasing excretion, and inhibits active renal tubular secretion of many weak organic acids, such as PCN and cephalosporins. Uses: Adjunct to PCN therapy, Alternative therapy for uncomplicated Gonorrhea, Hyperuricemia of gout/gouty arthritis. General/Typical Dose Range: Gout- 250mg-500mg; Gonorrhea- 1gram in conjunction with PCN. Side Effects/ADR: CNS-fever, headache, dizziness. CV- flushing. GI- anorexia, N/V, sore gums. GU- urinary frequency, renal colic, nephritic syndrome, costovertebral pain. Hematologic: aplastic anemia, hemolytic anemia, anemia. Hepatic: hepatic necrosis. Skin: dermatitis, pruritis. Other: worsening of gout, hypersensitivity, reactions including anaphylaxis. Contraindications: Pt hypersensitive to drug and those with uric acid kidney stonesor blood dyscrasias; Pt with acute gout attack and children under 2. Use caution with peptic ulcer or renal impairment. Use caution with sulfa allergy. Use during pregnancy only when benefits outweigh risks. Food, Drug, Herbal Interactions: Drug-Drug: Acyclovir, cephalosporins, clofibrate, dapsone, indomethacin, ketamine, lorazepam, meclofenamate, penicillin, rifampin, sulfanomides, thiopental. Allopurinal, methotrexate, nitrofurantoin, Nsaids, Salicylates, Sulfonylureas, zidovudine. Drug-Food: Alcohol may increase urate level. Patient Instruction/Teaching: Instruct patient to take drug regularly to prevent recurrence. Regular visits are needed to monitor uric acid and dosage adjustments as needed. Lifelong therapy may be needed with hyperuricemia. With gout avoid ASA, may use acetaminophen for pain. Drink at least 6-8 glasses of water a day. Avoid alcohol. With gout limit intake of high purine foods. Because it may be prescribed in adjunct to antibiotic, pt should complete all meds as prescribed.

Sulfinpyrazone

25. Sulfinpyrazone Generic: Sulfinpyrazone Trade: Anturane Class: Uricosuric Drug Action: Inhibit renal tubular reabsorption of urate and thus increase the renal excretion of uric acid and decrease serum uric acid levels. Also, completely inhibits platelet prostaglandin synthesis, which prevents platelet aggregation and gives the drug an antithrombotic effect. Uses: Prevent gout flares General/Typical Dose Range: 200mg-400mg in two divided doses Side Effects/ADR: GI- N/V/D Contraindications: Should be used with caution in renal pts. Use with caution in people with peptic ulcer disease or spastic colon. Should be avoided with suspected Sulfa allergy. Only used in pregnancy when benefits outweigh the risks to the fetus. Food, Drug, Herbal Interaction: Drug-Drug: Acetaminophen, oral anticoagulants, Niacin, Salicylates, Theophylline, Tolbutamide, Verapamil. Patient Instructions/Teaching: Take drug exactly as prescribed. Take missed doses as soon as remembered. Keep appointments with PCP to monitor renal function and dose adjustments. Education on diet to reduce available urates. Drink plenty of fluids, avoid alcohol.

Phenytoin

3. Phenytoin: Dilantin. Hydantoins. First line treatment of choice for tonic-clonic and partial complex seizures also the leasy sedating and most commonly used drug to treat seizure disorders. Theraputic plasma level is 10-20 mcg/mL. Works by stabilizing neuronal membranes and decreasing seizure activity by increasing efflux of sodium ions across cell membranes in the motor cortex. Metabolized in the liver: strong CYP 2C6 effects. Levels will increase with cimetidine, diazepam, acute alcohol intake, valporic acid, ibuprofen and allopurinol and will decrease with barbituates, antacids, calcium and chronic alcohol use. Never give IV or IM in primary care setting. Black box warning for IV administration due to cardiovascular reactions with too rapid IV med administration. Dosing: initial Po dose 1g divided in 3 doses then after 24hrs 300mg /d in one extended release dose. Children 4-8mg/kg/d in divided doses. Concurrent administration causes decreased effect of carbamazepine, estrogens, acetaminophen, corticosteroids, levodopa, sulfonylureas, cardiac glycosides. Many ADRs. Most common are nystagmus, dizziness, pruritis, paresthesia, headache, somnolence, ataxia, confusion. CV: hypotension, tachycardia. GI: N/V, anorexia, constipation dry mouth, gingival hyperplasia. GU: urinary retention, urinary discoloration.

Aspirin

31. Aspirin (Classification-Salicylates) • Action-Inhibit prostaglandin formation • Uses-Fever, pain, inflammation, antiplatelet • General/typical dose range-325-650mg PO q 4 hrs; Max: 4 g/day • Side effects/ADR-GI-bleeding, hepatotoxicity, Reye Syndrome. CNS-intracranial hemorrhage, seizures, coma • Contraindications -Bleeding disorders or thrombocytopenia, Children(Viral infection with or without fever in children and teenagers for the risk of Reye's syndrome), Pregnancy, Renal dysfunction • Food, drug, herbal interactions- Drug interaction-heparin, warfarin, or thrombolytic agent. Increase bleeding-cefamandole, cefoperazone, cefotetan, valprioc acid, or plicamycin. Enhance activity of penicillins, phenytoin, methotrexate, valprioc acid, sulfonyluresas, and sulfonamides. Antagonize the beneficial effects of probenecid or sulfinpyrazone and blunt therapeutic responses to diuretics, antihypertensive, and some NSAIDs. Glucocorticoids decrease serum salicylate levels. Foods that contain salicylate-spices high in salicylate-curry, paprika, licorice, Benedictine liqueuer, prunes, raisins, tea, and gherkins. Foods that acidify the urine may increase serum salicylate levels, and those that alkalinize the urine may have the opposite effect. • Patient instructions/teaching- if changes in behavior with nausea and vomiting occur, d/c immediately as can be an early sign of Reye's syndrome D/c if appearance of skin rash or any other sign of hypersensitivity like anaphlactoid reactions Restrict use in patients with prior hx of peptic ulcer disease, blood thinners, or steroid use Do consume alcohol or smoke Stop use immediately if experience bloody vomit, bloody or black stools, stomach pain that does not get better, redness or swelling, ringing in the ears, or loss of hearing. Ch. 29

Fluoxetine

32. fluoxetine- Prozac (Classification-SSRI) Does not require gradual and slow tapering b/c of its long half-life and active metabolites. A single does as the last step in tapering off other SSRIS is helpful in avoiding withdrawal symptoms. • Action-Blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane enhancing the actions of serotonin on 5HT1A autoreceptors. • Uses-Anxiety and Depression Children-Major depression in children 8-17years and effective in treating OCD in children 7-17yrs. • General/typical dose range-20-80 mg/day. Max: 80 mg/day • Side effects/ADR-CNS: serotonin syndrome, decreased libido, headache, insomnia, worsening depression, increased suicidal risk extrapyramidal symptoms. CV: HTN. Metabolic-hyponatremia, hypoglycemia • Contraindications- Concomitant use with or within 21 days of discontinuing therapy with MAO inhibitors and other serotonergic drugs. Co-administration with pimozide Concomitant use with or within 5 weeks of d/c therapy with thioridazine • Food, drug, herbal interactions - MAO inhibitors • Patient instructions/teaching- Monitor for worsening, suicidality, or unusual changes in behavior. If taken for 5 weeks, do not drastically stop medication due to risk of serotonin syndrome-agitation, anxiety, bad dreams, dizziness, diarrhea, nausea, vomiting, flu like symptoms, and electric shock symptoms.

Sertraline

33. Sertraline- Zoloft (Classification-SSRI) • Action- Blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane enhancing the actions of serotonin on 5HT1A autoreceptors. • Uses -Anxiety, Depression, PTSD,OCD, PMDD. Children-OCD 6-17yrs. But not for depression or panic disorder. • General/typical dose range-50-200 mg PO qd Max: 200 mg PO qd • Side effects/ADR- CNS: serotonin syndrome, decreased libido, headache, insomnia, worsening depression, increased suicidal risk extrapyramidal symptoms. CV: Hypotension, syncope, increased coagulation time, arrhythmias. Metabolic-hyponatremia, hypoglycemia DERM: Stevens Johnson Syndrome • Contraindications - MAO inhibitor use within 14 days Concurrent Disulfiram use (oral sol) Concurrent use of pimozide • Food, drug, herbal interactions -MAO inhibitors • Patient instructions/teaching- Monitor for worsening, suicidality, or unusual changes in behavior. If taken for 5 weeks, do not drastically stop medication due to risk of serotonin syndrome-agitation, anxiety, bad dreams, dizziness, diarrhea, nausea, vomiting, flu like symptoms, and electric shock symptoms

Escitalopram

35. Escitalopram (Lexapro) (Classification-SSRI) • Action- Blocks the reuptake of serotonin at the serotonin reuptake pump of the neuronal membrane enhancing the actions of serotonin on 5HT1A autoreceptors. • Uses-Major depressive disorder, anxiety disorders, OCD. • General/typical dose range-10-40 mg/day • Side effects/ADR-CV: Neonatal persistent pulmonary htn (>20 wk gestation). Met:SIADH, abn. Bleeding/altered platelet function. MISC-influenza, fatigue, increased sweating, withdrawal syndrome, neonatal serotonin syndrome(3rd trimester), neonatal withdrawal (3 trimester) , serotonin syndrome Contraindications- hypersensitivity to citalopram Concurrent use or use within 14 days of discontinuing MAO inhibitors Concomitant use in patients taking pimozide Co-administration with serotonin precursors (such as tryptophan) No approved for use in pediatric patients <12 yrs of age Food, drug, herbal interactions-MAO inhibitors Patient instructions/teaching- Monitor for emergence of agitation, irritability, unusual changes in behavior, emergence of suicidality. SNRI (pg. 903) ADR-similar to that of SSRIs. Common side effects insomnia and elevated blood pressure. Lethal in overdose, and limiting the quantity prescribed is warranted.

Venlafaxine

36. Venlafaxine-Effexor(Classification-SNRI) Action-Block the reuptake of NE and 5HT, thus permitting greater availability of these neurotransmitters to bind with the respective receptors in the brain. Uses-depression General/typical dose range-ER- 75-225 mg PO daily. Immediate Release-37.5-75 mg PO daily Side effects/ADR -CNS-decreased libido, insomnia, headache. GI-nausea, appetite changes. CV-hypertension, tachycardia, arrhythmias. MISC-Neuroleptic malignant syndrome, Serotonin syndrome, withdrawal syndrome Contraindications-Concurrent MAO inhibitor therapy Cisapride, dronedarone, non-selective MAOIs, phenothiazines. Not approved for use in pediatric patients. Food, drug, herbal interactions -MAOIs Patient instructions/teaching-Monitor for emergence of agitation, irritability, unusual changes in behavior, and emergence of suicidality.

Duloxetine

37. Duloxetine-Cymbalta (Classification-SSNRI) • Action- Block the reuptake of NE and 5HT, thus permitting greater availability of these neurotransmitters to bind with the respective receptors in the brain. • Uses-depression and treatment of diabetic neuropathy • General/typical dose range-40-60 mg/day Max: 120 mg/day Side effects/ADR -MISC-pyrexia, decreased weight and appetite. GI-hepatotoxicity Contraindications- MOA inhibitor use within 14 days before or 5 days after Hepatic impairment Uncontrolled angel closure glaucoma Alcohol abuse End stage renal disease • Food, drug, herbal interactions-MAO inhibitors • Patient instructions/teaching-close supervision for clinical worsening.

Buproprion

38. Bupropion-Wellbutrin(Classification-NDRI) • Action-Increase NE and DA by weakly inhibiting their neuronal reuptake. Uses- Major depressive disorder, seasonal affective disorder, and an adjunct to smoking cessation. • General/typical dose range-150-450 mg/day • Side effects/ADR- CNS: increase of seizures with high doses. (Stay within the 450mg total daily dose). Migraine headache, agitation. CV: htn, hypotension, syncope, arrhythmias. EENT: elevated IOP. GI: hepatotoxicity, dry mouth, nausea. DERM: Stevens Johnson syndrome • Contraindications- Avoided in patients at risk for seizures. Lower incidence of sexual side effects due to lack of direct effects on seroternergic neurotransmission. Not effective in treating anxiety b/c they actually exacerbate anxiety and agitation. Dose dependent increased risk for seizures in patients with eating disorders or those with chronic medical conditions that require the use of diuretics. Concurrent use of MAOI within 14 days. • Food, drug, herbal interactions- MAOIs • Patient instructions/teaching- Close monitoring for any worsening depression, suicide risk etc.

Topiramate

4. Topiramite: Topamax: GABA effecting drugs.(AED). GAGA is not metabolized. Excreted unchanged in urine. Topiramate not effected by food administration. Can treat and prevent seizures. It can also prevent migraine headaches. Will not treat headache once it has begun. Decrease serum bicarbonate can lead to metabolic acidosis. Can cause acute myopia and angle closure glaucoma. Any eye pain or blurred vision should be reported immediately. Drink plenty of liquids to prevent kidney stones and electrolyte imbalances. Do not discontinue abruptly. Dosing starts at 25mg bid and then increases 25mg weekly for 4 to 6 weeks.

Hydrocodone/acetaminophen

40. Hydrocodone/acetaminophen a. Name i. Brand: hycet, lorcet, lorcet-plus, lortab, maxidone, norco, vicodin, vicodin, ES, Vicodin HP, Zamicet, Zydone, ii. Generic: hydrocodone/acetaminophen b. Drug class: opioid combos, opioid agonist c. Mechanism of action: binds to various opioid receptors, producing analgesia and sedation (opioid agonist) d. Uses: pain control e. Dosing: i. Adult: pain, moderate-moderate severe. 2.5-10 mg hydrocodone PO q4-6h prn, do not exceed 1 g/4h and 4g/day acetaminophen, taper gradually to D/C if long-term use, no renal dosing/hepatic dosing but decrease dose with impairment ii. Pediatric 1. 2 yo and older <50 kg, moderate-mod. Severe pain, 0.1-0.15 mg/kg hydrocodone PO q4-6h prn, elixir contains 7% alcohol, do not exceed 75 mg/kg/day acetaminophen 2. 2 yo and older, >50 kg, 2.5-10 mg hydrocodone PO q 4-6 hours prn, do not exceed 1g/4h and 4g/day acetaminophen f. Contraindications: hypersensitivity to drug/class/compon., avoid abrupt d/c, caution in elderly, debilitated patients, renal impairment, hepatic impairment, if hx of drug abuse or alcohol abuse, CNS depressant use, pulmonary impairment, sleep apnea, head injury, ICP increases, acute abdomen, hypothyroidism, addison's disease, prostatic hypertrophy, urethral stricture, G6PD deficiency g. Interactions: i. Acetaminophen interaction characteristics: CYP2E1 substrate, affected by delayed gastric emptying, analgesic associated nephropathy, methemoglobinemia ii. CNS depressants, alcohol, hypnotics, barbiturates, benzos, antipsychotics-additive CNS depression iii. Cimetidine, hydantoins, rifampin, droperidol, charcoal, nicotine-decreased effect of opioid, increased dose of opioid may be necessary iv. Carbamazepine, warfarin, MAOs, furazolidone, nitrous oxide-decreased effect of interacting drug, monitor blood levels when possible h. Contraindicated: cisapride, dronedarone, pimozide, thioridazine i. Patient instructions: do not stop without speaking with doctor with long-term use due to risk of withdrawal, same education as number 1

Moprhine

41. Morphine a. Name i. Brand: Avinza, Kadian, MS Contin, Oramorph SR, Roxanol, Duramorph, Infumorph, MSIR, OMS concentrate, MS/L, RMS, Astramorph PF ii. Generic: morphine sulfate b. Drug classification: opioid agonists c. Drug action: binds to various opioid receptors, producing analgesia and sedation i. Onset: 15-60 min ii. Peak: 0.5-1h iii. Duration: 3-7h iv. Half-life: 1.5-2h v. Metabolized: liver vi. Excretion: Urine d. Uses: pain, heart attack, angina, pulmonary edema e. General/typical dosage range: i. Adult dosing: 1. PO: 10-30 mg q4h 2. Controlled release: 30 mg q8h; do not crush or chew 3. SC/IM: 5-20 mg/70 kg q4h 4. IV: 2.5-15 mg/70kg in 4-5 mL of water for injection over 4-5 min 5. Continuous IV infusion: 0.1-1 mg/mL in 5% dextrose 6. Rectal: 10-20 mg q 4h ii. Children 1. SC, IM: 0.1-0.2 mg/kg to maximum of 15 mg q 4 h iii. Forms 1. Capsule: 30, 45, 60, 75, 90, 120 mg 2. Oral solution: 1mg/mg 3. Tablet: 15, 30 mg 4. ER tablet: 15, 30, 60 100, 200 mg 5. Injection: 0.5 mg/mL f. Side Effects/ADR: 1. Side effects: somnolence, constipation, n/v, dizziness, diaphoresis, dysphoria,euphoria, diaphoresis, HA, edema, abdominal pain, prurititis, flushing, xerostomia, asthenia, parasthesia, urinary retention, libido decrease, miosis 2. ADR: respiratory arrest, apnea, resp. depression, circulatory depression, severe hypotension, shock, paralytic ileus, ICP increase, seizures, biliary spasm, bradycardia, anaphylaxis, dependency, abuse, adrenal insufficiency, opioid-induced androgen deficiency (long-term use), withdrawal sx if abrupt d/c (prolonged or long-term use. ii. Contraindications/Cautions: hypersensitivity to drug/class/components, respiratory depression, acute or severe asthma, paralytic ileus, GI obstruction or stricture, coma or impaired consciousness, circulatory shock, labor and delivery (PO form), premature labor (injectable form), <24 h postop in opioid naïve patients, ER form; avoid abrupt withdrawal in long-term use, caution in elderly and debilitated patients, renal or hepatic impairment, pulmonary impairment, sleep apnea with long-term use, CNS depression, CNS depressant use, alcohol use, ICP increase, seizure disorder, hypovolemia, GI motility disorder, acute pancreatitis or biliary disease, prostatic hypertrophy, urethral stricture, substance abuse hx, mental illness hx iii. Interactions: see interactions for 1 iv. Patient Education: do not crush, chew, dissolve extended release tabs, do not stop abruptly without, see interactions for 1

Oxycodone

42. Oxycodone: a. Name i. Generic: oxycodone ii. Brand: Oxaydo, oxecta, Oxycontin, Oxyfast, Roxycodone, Xtampza ER b. Drug action: Opioid agonist i. Onset: 15-30 min ii. Peak: 1h iii. Duration: 4-6 h iv. Half life: not listed v. Excreted in urine c. Uses: moderate to moderately severe pain d. General/typical dosage range: i. Adults: 2.5 to 5 mg ii. Children: 0.1-0.2 mg/kg/dose q 4-6 hours prn iii. Forms: 1. Capsule: 5, 7.5 mg 2. Oral solution: 5 mg/5mL iv. SE and ADRs 1. Side effects: same as number 1 2. ADR: Same as number 1 v. Contraindications: Same as number 1 and other opiates vi. Food drug interactions: same as number 1 vii. Patient instructions: same as number 1 e. Interactions: i. Concomitant use with CYP450 3A4 inhibitors or d/c of CYP450 3A4 inducers may increase oxycodone conc. Which may increase or prolong adverse effects including fatal respiratory depression, monitor pt ii. Same interactions as other opioids first listed in number 1

Propanolol

46. Propranolol (p. 191 - 195, 330, 332, 346, 893, 1044, 1050, 1180) Interacts with Acetaminophen, Gabapentin, Haloperidol, Loop Diurectis, Phenothiazines, warfarin. Propranolol in doses of 20 to 80 mg 3 to 4 times daily has proved effective in reducing the incidence of migraine headache in some patients. If a satisfactory response to the maximum dose of the medication is not obtained within 4 to 6 weeks, the drug should be gradually withdrawn. Propranolol is used for several arrhythmias. Indications include PSVT: atrial fibrillation, tachycardias associated with digitalis toxicity, excessive catecholamines, thyroid disorders (inhibits peripheral conversion of T4 to T3). Start with a trial of 3 months. As improve, this needs to be tapered slowly (over week) if discontinued. Interacts with many drugs including cimetidine, oral contraceptives, calcium channel blockers. A pulse below 50 or systolic BP below 100 in the adult suggests that maximum dosage has been reached. Treatment should be reassessed every 6 months. Adverse effects include fatigue, lethargy and depression. Not tolerated well by athletes. Pregnancy category C. Brand Name: Inderal, Innopran and Hemangeol Generic Name: Propranolol Drug Classification: Group II antiarrhythmics, Non-cardioselective beta blockers Action: Propranolol is a non-selective beta blocker; that is, it blocks the action of epinephrine (adrenaline) and norepinephrine (noradrenaline) at both β1- and β2-adrenergic receptors. Uses: Propranolol is used to treat tremors, angina (chest pain), hypertension (high blood pressure), heart rhythm disorders, and other heart or circulatory conditions. It is also used to treat or prevent heart attack, and to reduce the severity and frequency of migraine headaches. Dose: Initial dose: Immediate-release: 40 mg propranolol orally 2 times a day Sustained-release: 80 mg orally once a day XL sustained-release: 80 mg orally once a day at bedtime Maintenance dose: Immediate-release: 120 to 240 mg orally per day Sustained-release: 120 to 160 mg orally per day XL sustained-release: 80 to 120 mg orally once a day at bedtime Maximum dose: IR/SR: 640 mg orally per day XR: 120 mg orally per day Uses: Propranolol is used to treat tremors, angina (chest pain), hypertension (high blood pressure), heart rhythm disorders, and other heart or circulatory conditions. It is also used to treat or prevent heart attack, and to reduce the severity and frequency of migraine headaches. Emangeol (propranolol oral liquid 4.28 milligrams) is given to infants who are at least 5 weeks old to treat a genetic condition called infantile hemangiomas. Hemangiomas are caused by blood vessels grouping together in an abnormal way. These blood vessels form benign (non-cancerous) growths that can develop into ulcers or red marks on the skin. Hemangiomas can also cause more serious complications inside the body (in the liver, brain, or digestive system). Side Effects: nausea, vomiting, diarrhea, constipation, stomach cramps; decreased sex drive, impotence, sleep problems (insomnia); or tired feeling. Contraindications: You should not use this medicine if you have asthma, very slow heart beats, or a serious heart condition such as "sick sinus syndrome" or "AV block" (unless you have a pacemaker). Also contraindicated in CHF, asthma, COPD, PVD, diabetes, depression, Wolff-Parkinson-White syndrome. Food, Drugs, Herbal: Avoid drinking alcohol. It may increase your blood levels of propranolol. warfarin, Coumadin, Jantoven; amitriptyline, clomipramine, desipramine, imipramine, and others; drugs to treat high blood pressure or a prostate disorder - doxazosin, prazosin, terazosin; heart or blood pressure medicine - amiodarone, diltiazem, propafenone, quinidine, verapamil, and others; NSAIDs (nonsteroidal anti-inflammatory drugs) - aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others; or steroid medicine - prednisone and others; other antidepressants; cimetidine; heart rhythm medicine such as flecainide, propafenone, quinidine, and others; or medicine to treat mental illness. Patient Instruction: Adults may take propranolol with or without food, but take it the same way each time. Take propranolol at the same time each day. Do not crush, chew, break, or open an Your blood pressure will need to be checked often. If you need surgery, tell the surgeon ahead of time that you are using propranolol. You may need to stop using the medicine for a short time. Do not skip doses or stop using propranolol suddenly. Stopping suddenly may make your condition worse. Follow your doctor's instructions about tapering your dose. This medicine can cause unusual results with certain medical tests. Tell any doctor who treats you that you are using propranolol. If you are being treated for high blood pressure, keep using propranolol even if you feel well. High blood pressure often has no symptoms. You may need to use blood pressure medicine for the rest of your life. Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall. When beta-blockers are abruptly discontinued, exacerbations of angina pectoris and myocardial infarction have occurred. When this drug is chronically administered, particularly in patients with ischemic heart disease, the dose should be reduced gradually over a period of 1 to 2 weeks and patients should be monitored. If angina markedly worsens or acute coronary insufficiency develops, therapy should be temporarily reinstated unstable angina should be managed. Patients should be warned not to abruptly discontinue therapy without physician advice.

Anti-epileptics

48. Review Anti-Epileptics Review pages 227 - 245 and 1045 - 1046. AEDs are thought to work on migraines in a fashion similar to their effect on seizures. The AEDs decrease brain excitability by increasing the threshold for activation of the brainstem areas that are thought to be important for initiating migraine. The AEDs that are used for this include divalproex, gabapentin, and topiramate. Every medicine has a brand and a generic name. The generic usually is cheaper, sometimes by quite a lot. For medicines introduced in recent years, patent (or "market exclusivity") protection may block the sale of generic versions. A generic medicine usually works well, but it may not generate the same blood levels as does the brand name or an alternative generic medicine. Therefore, with changes of pill manufacturers, the blood levels can change. This may produce breakthrough seizures or side effects. The most important concern when taking generic drugs is to be sure the tablets are made by the same manufacturer for each refill. Switching from one generic manufacturer to another could result in different amount of active drug in each pill. The current author supports the right of the patient and doctor to know about medication substitution and consider whether generic substitution is safe. Starting schedule: Many AEDs have to be started slowly to minimize side effects, event though this delays helping the seizures. The titration (starting) schedules are those of the author, and may be slower than is the schedule recommended in the package insert. Dosages are all for adults. Children are treated on the basis of their weight (mg per kg dosing basis). Monotherapy: Some AEDs have approval for monotherapy (to be used alone) and others only as adjunctive (add-on) therapy to another AED. This reflects what testing evidence has been presented to the FDA - not all AEDs have gone through the required two clinical studies to show effectiveness in monotherapy. AEDs not proven effective in monotherapy still probably work well as single medications and are used that way by epilepsy doctors on a case-by-case basis where the benefit seems to exceed the risk. Side effects: Every seizure medicine can sometimes cause side effects of fatigue, dizziness, unsteadiness, blurry vision, stomach upset, headaches, and reduced resistance to colds, memory and thinking problems. Weight gain tends to occur with valproic acid (Depakote), gabapentin (Neurontin), pregabalin (Lyrica) and carbamazepine (Tegretol, Carbatrol). Weight loss tends to occur with topiramate (Topamax), zonisamide (Zonegran) and felbamate (Felbatol). These are not mentioned separately in each section, unless they are especially common with the medicine. Detailed information is provided by the pharmacy as a package insert for new prescriptions and refills. Effects on internal organs: All seizure medicines can cause problems with blood counts (white cells, red cells and platelets), or liver or other internal organs, so doctors usually order blood tests to screen for these problems. Blood can be tested when starting a medicine to get a baseline, after a few months on the drug, every few months to yearly thereafter, then at individually determined times. The package insert often has recommendations, but there are no universal rules about when to test blood. All seizure medicines can produce either mild or severe allergic reactions. One, called the hypersensitivity syndrome, produces fever, rash, fluid accumulation, swollen lymph nodes, possible liver injury and confusion Suicide warning: The US FDA has required a suicide warning on all seizure medications as a general class. All people taking them should be aware of and report any serious depression or suicidal thinking to their doctor, but the actual risk for suicide due to AEDs is quite low. Mechanism: Mechanisms of action in the brain for antiepileptic drugs are described in simple form: most AEDs have multiple mechanisms of action to block seizures. Not a cure: Although AEDs are called "antiepileptic," they do not cure epilepsy, but just suppress seizures while the medications are in the body. Individual Antiepileptic Drugs (AEDs), alphabetically: carbamazepine (Tegretol, Carbatrol): A favorite partial seizure medicine in the developed world. Carbamazepine affects sodium channels, and inhibits rapid firing of brain cells. Long-acting forms such as Carbatrol or Tegretol-XR can be given once a day. Potential side effects include GI upset, weight gain, blurred vision, low blood counts, low blood sodium (hyponatremia). Carbamazepine causes a rash rate of a few percent, sometimes even the dangerous rash called Stevens-Johnson syndrome. People of Asian descent with HLA-B*1502 antigen are more at risk. Typical adult dose is 400 mg tid. I start my patients with 200 mg bid and each week, and increase by 200 mg daily to about 400 mg three times a day. View information on Carbamazepine here and information about Carbatrol here. clonazepam (Klonopin): Clonazepam is a member of the drug class known as benzodiazepines, to which diazepam (Valium), lorazepam (Ativan), clorazepate (Tranxene), alprazolam (Xanax) also belong. Benzodiazepines are used as anti-seizure drugs, sedatives, tranquilizers and muscle relaxants. Benzodiazepines increase the effectiveness of GABA, the brain's main inhibitory neurotransmitter. Clonazepam is more long-acting against seizures than are diazepam or lorazepam. Side effects of clonazepam include sedation, thinking/memory impairment, mood changes, addiction. More so than most, its effects wear off over time. A typical adult dose is 0.5-1.0 mg three times a day. I usually start my patients with 0.5 mg at night, and if they are not too sleepy the next day, increase to 0.5 mg twice a day. A week later, if seizures persist, I will increase to 0.5 mg three times a day. See information on Clonazepam here.

Levetiractem

5. Levetiracetam: Keppra. Antiepileptic. Unique drug class of its own because it is chemically unrelated to other AEDs. Mechanism of action unknown. May inhibit burst firing. Used as an adjunct therapy in the treatment of partial onset seizures in children and adults. Dosing initially 100mg/d given as a twice daily dose of 500mg.increase daily dose q 2 weeks by increments of 1000mg/day to max of 300mg/d. The only absolute contraindications to the use of Keppra is sensitivity to the drug. Monitor for suicidal thoughts, depression and behavioral or mood changes. Not many drug interactions because Keppra is unbound. Half-life is 7 hours and is 68% eliminated renally

Carbamezine

6. Carbamazine-Tegretol: Iminostilbenes. Action unknown but thought to work on sodium channels, slowing influx of sodium in the cortical neurons and slowing spread of abnormal activity. Iminostilbens derivatives used to treat epilepsy, bipolar effective disorder, aggressive and assaultive behavior, and some neuralgias. Typical dose range in adults and children > 12 200mg Bid increased in weekly intervals to max of 1,00mg/D. Children <12 start at 100mg BID to max of 1,00mg. ADR include black box warning for Steven-Johnson syndrome and toxic epidermal necrosis I patients of Chinese ethnicity. Black box also since can depress the bone marrow and lead to leukopenia, thrombocytopenia, agranulocytosis and aplastic anemia. Baseline testing should include CBC, liver function test, with initial frequent follow up decreasing to every 3 to 4 months. Most serious drug interactions increase plasma levels of carbamazepine to potentially toxic levels such as propoxyphene, hydantoins, cimetidine, erythromycin, clarithromycin. Grapefruit juice increases serum levels and effects of carbamazepine. Pt's should be instructed to report skin lesions, bruising, fever or sore throat and drug should be stopped. Food may help increase absorption. Drug may be sedating so care should be exercised when mental and physical alertness is required for safety.

Ethosuximide

7. Ethosuximide: Zarontin: Succinimides: For treatment of absence seizures (petit mal seizures) in children and adults. An anticonvulsant which works by decreasing nerve impulse and transmission in the motor cortex. Typical dosing for adults and children > 6yrs is 500mg daily or 250mg BID: may increase by 250mg every 4-7 days to max of 1.5g?d. Most common ADR's with succinimides are GI distress which can be alleviated by taking med with food or milk. Most serious drug interactions are those that cause CNS depression, such as alcohol, opioid agonists, and benzos and CNS depressants. Pt teaching should include avoiding alcohol, monitor for behavioral changes, harmless changes in urine color may occur. Withdrawal of medication with precipitate absence seizures.

Lamotrigine

8. Lamotrigine: Lamictal. Anti-epileptic Used as adjunctive therapy in adults and children age 2 or older in the treatment of partial seizures, primary generalized tonic-clonic seizures, and generalized seizures associated with Lennox-Gastaut syndrome. Lamotrigine is approved for maintenance treatment of bipolar 1 disorder to delay occurrence of mood episode in adults age 18 and older. The target dosing is 200mg/d..100mg/d in patients taking valproate and 400mg/d in patients not taking valproate and taking either carbamazepine, phenytoin, phenobarbital, primidone. Rifmpin (ABX used to treat tuberculosis and other infections) decreases lamotrigine levels by 40%. Oral contraceptives decrease lamotrigine concentrations by 50%.The most concerning interaction with lamotrigine is with valproate. When administered concurrently with lamotrigine there is increased risk of life threatening rash, such as Steven -Johnson developing. Valproate also increases lamotrigine levels by 2 fold. There is a black box warning regarding serious life threatening rashes (S-JS). Once again suicidal thoughts and behavior and mood changes. Tablets should not be crushed and chewed. There is a chewable tablet that may be dissolved in water or juice. Life style management for patients who experience seizures should include good sleep and exercise and avoid of stressful situations that may trigger seizures.

Zolpidem

A. Drug Name: Zolpidem- Ambien and Eszopiclone- Lunesta. Schedule IV, Pregnancy C. B. Action: causes CNS depression by binding to GABA, but not at the benzodiazepine site. Rapidly absorbed through the oral admin and are protein bound. Zolpiderm is 92% preotien bound. Short half lives and short duration. Peak onset is 0.5-1hr. C. Uses : sedation and inducing sleep D. SE/ADR: headache, mild transient anterograde amnesia, dizziness, somnolence, and nausea. Abnormal behaviors such as "sleep driving" or worsening of depression may occur. Women are more sensitive to the effects of zolpidem and should be prescribed lower doses than men. Schedule IV drugs and all exhibit withdrawal symptoms when used chronically and abruptly discontinued. Mild cataplexy, including periods of leg weakness lasting seconds to minutes, may occur day or night. Sleep paralysis, the inability to move or speak, may occur for up to several minutes during the sleep-wake transition. E. Contraindication: pregnancy, lactation, not approved for children. No sleeping medication should be used acutely beyond 3 weeks or chronically beyond 3 months without careful evaluation of the treatment plan. F. F/D/H interacs: nonbenzodiazepine drugs have an additive effect with CNS depressants including benzodiazepines and alcohol. Drugs that induce CYP450 3A4 (cimetidine, phenytoin, rifampin, and carbamazepine) will decrease the blood levels of these hypnotics. Drugs that inhibit CYP450 3A4 (ketoconazole, clarithromycin, erythromycin, and protease in-hibitors) will increase the blood levels of these hypnotics. G. Pt. instruct: rapid onset and the patient should be warned to take within 30 minutes of bedtime. advised to take these drugs immediately be-fore bedtime and to get at least 6 hours of sleep. use caution if driving a vehicle or operating hazardous machinery until they know what effect the drug has for them. should not combine these drugs with over-the-counter sleeping aids or alcohol. H. Monitoring: No specific monitoring Specific Differences Zolpiderm-Ambien Dosing: 5mg for elderly and women. 10mg for men. Ambein CR is 12.5mg for men and 6.5mg for elderly. Sublingual is for middle of the night wakening, max dose 1.75mg for women and elderly and 3.5mg for men. Eszopiclone- Lunesta Dosing: 2-3mg daily, elderly is 1-2mg

SNRIs

Antidepressants include the class of serotonin-norepinephrine reuptake inhibitors or SNRIs. These are used to treat depression and sometimes fibromyalgia. Cymbalta blocks the serotonin and norepinephrine transporters, thereby inhibiting the reuptake of the neurotransmitter and increasing the availability to bind with the postsynaptic receptors. Cymbalta appears to be more potent and equal serotonin and norepinephrine reuptake inhibitor than venlafaxine

Atomoxetine

Atomoxetine-Strattera • Trade name: Strattera • Generic name: Atomoxitine • Class: Norepinephrine Reuptake Inhibitor (available as an alternative to stimulants for ADHD) • Action: Selectively inhibits presynaptic norepinephrine transport • Uses: ADHD • General/typical dose range: PO adults and children >70 kg: start w/ 40mg/day and increase dose every 3 days to target 80mg. After 2-4 weeks, dose may be increased to 100mg/day. If <70kg start PO 0.5 mg/kg/day, increase after a minimum of 3 days to PO 1.2mg/kg/day in single dose or 2 evenly divided doses, max amt is 1.4mg/kg/day or 100mg/day, whichever is less. • Side effects/ADR: monitor for suicidality especially in children, behavior changes, mood swings, insomnia, nausea, vomiting, dizziness, GI upset, rash, dry mouth, impotence, increased menstrual cramps, htn, orthostatic hypotension, Raynaud's, long QT, dry mouth, constipation, urinary retention, decreased appetite, angioneurotic edema • Contraindications: hypersensitivity, use of MAOIs w/i 14 days, narrow angle glaucoma, cardiac structure abnormalities, cardiomyopathy, severe arrhythmias, severe CAD, hx pheochromocytoma. • Food/drug/herbal interactions: fluoxetine, paroxetine, quinidine: increases plasma levels of Strattera. Interacts w/ MAOIs. • Patient instructions/teaching: consume with or without food, can be discontinued without being tapered, not intended to be opened and should be taken whole, monitor for behavior changes or suicidality.

SSRI

Ch. 29 SSRI-(pg. 251) orally and absorbed thru GI tract. Peak plasma levels 1-8hrs. Metabolized by liver (CYP450 system) Contraindication-limited to hypersensitivity to any of the drugs and concurrent or within 14 Days of the administration of an MAOI. Used cautiously in patients with severe hepatic or renal impairment and should be avoided in the first and last trimesters of pregnancy. Adverse Effect-Serotonin syndrome (nausea, diarrhea, chills, sweating, hyperthermia, hypertension, myoclonic jerking, tremor, agitation, ataxia, disorientation, confusion, delirium. Can progress to coma and death. Contraindications: Concomitant use of St. John's wort and or SAMe (S-adenosylmethionine) may contribute to serotonin syndrome. SSRIs should not be prescribed with TCAs and require washout between drugs. Uses-OCD, depressive, anxiety, panic disorders, bulimia, premenstrual dysphoric disorder, PTSD. Off label uses include the treatment of anorexia, depressive phase of bipolar disorder, chronic headaches and other types of pain impulse control disorders and trichotillomania. Monitor during first 2-3 weeks including regular assessments of suicidal thinking. Should be at least one telephone contact on weekly basis. Patient Education-May take drug as long at 3-4 weeks for full therapeutic benefits become evident and that the initial adverse reactions commonly including nausea, intermittent, light headedness, sedation, muscle restlessness, and sleep disruptions should be minor and transient. Drugs can initially be sedating

Colchicine

Colchicine Generic: Colchicine Trade: Colcrys Class: Antigout Action: Not completely known, involves a reduction in lactic acid produced by leukocytes, reducing uric acid deposits and phagocytosis, thereby decreasing the inflammatory process. Uses: Prevention of Gout flares, Gout flares, Familial Mediterranean Fever (FMF), Acute Pericarditis, Recurrent Pericarditis, Behcet Syndrome. General/Typical Dose Range: 0.6mg-1.8mg Side Effects/ADR: CNS-fatigue, headache. EENT-pharyngolaryngeal pain. GI-N/V/D. Hematologic: aplastic anemia, granulocytopenia, leukopenia, pancytopenia, thrombocytpomepia. Other- gout Contraindication: Pt with serious CV, GI, renal or hepatic impairment and those taking P-glycoprotein inhibitors or strong CYP3A4 inhibitors. Use caution with hematologic disorders due to myelosuppression. Use only during pregnancy when the benefit to patient outweighs risk to fetus. Drug does appear in breast milk. Food, Drug, Herbal interactions: Drug to drug- acidifying agent may inhibit action of colchicine. Alkalyzing agent may increase action of colchicine. CNS depressants may increase sensitivity to drug. Digoxin HMG-CoA reductase inhibitors (atorvastatin, simvastatin) may increase risk of myopathy or rhabdomyolysis. CYP3A4 inhibitors may increase colchicine level. Drug to Food- Grapefruit, grapefruit juice may increase drug level. Patient Teaching: Teach patient to avoid grapefruit and grapefruit juice while taking this drug. Advise females not to breast feed and use alternative method for feeding baby. Advise to report muscle pain, weakness, tingling or numbness in fingers or toes. Unusual bleeding, increased infections, severe diarrhea, vomiting, or cyanosis, patient should discontinue drug.

Salicylates

Contraindications-used cautiously for patient with hepatic impairment due to reversible hepatic encephalophy occurring even after therapeutic doses for RA. -Caution in those with renal insufficiency. Salicylates may cause patient decrease in renal function and aggravate chronic kidney diseases. Magnesium salicylates are contraindicated in the presence of renal insufficiency b/c kidney cannot eliminate the magnesium causing hypermagnesemia. -Used with caution in presence of gout-low doses-decrease urate excretion and raise serum uric acid levels. High doses-uricosuric effect; however, are rarely tolerate at this high of a dose. -Ingestion during pregnancy-produce anemia in mother and increase the risk for postpartum hemorrhage. Inhibition of prostaglandin synthesis may cause constriction of the ductus arteriousus and other possible untoward effect in the fetus. Especially do not us during last trimester of pregnancy. -Aspirin should not be used in children. ADR-GI irritation and bleeding. Prolonged use -iron deficiency anemia. -Hypersensitivity-more common in patients with asthma, nasal polyps, or chronic urticarial. -Ototoxic at increased blood levels. D/c if dizziness, tinnitus, or impaired hearing develops. Temp. Hearing loss disappears gradually when the drug is stopped -TX of toxicity -induction of emesis or gastric lavage. Activated charcoal. Hemodialysis is reserved for those patients with severe poisoning.

Dexmaphetamine

Dexamphetamine • Trade name: Dexedrine • Generic name: Dextroamphetamine • Class: Stimulants (Schedule II drug) • Action: CNS stimulants are sympathomimetic amines that act as dopamine agonists and indirectly release and prevent the reuptake of dopamine, serotonin, and norepinephrine in presynaptic nerve endings. This action stimulates the cerebral cortex, brainstem, and reticular activating system and appears to stimulate the reward center in the brain. • Uses: ADHD, narcolepsy, exogenous obesity • General/typical dose range: 10mg daily; may increase by 10mg increments every week to max of 30mg/day; give individual doses at 4-6 hour intervals. Children age 3-5: 2.5mg/day; increase by 2.5mg daily at weekly intervals to range of 0.1-0.5mg/kg/day; give in the AM. Children > 5 y/o: 5mg 1-2x/day; may increase in 5mg increments weekly to max of 40mg/day; usual range is 0.1-0.5mg/kg/day. • Side effects/ADR: insomnia, weight loss, growth retardation in children, tachycardia, palpitations, restlessness, irritability, euphoria, headache, blurred vision, tremor, increased libido with impaired ability, htn, arrhythmias. Some pts may experience paradoxical drowsiness, peripheral vasculopathy • Contraindications: atherosclerotic and symptomatic heart disease, htn, hyperthyroidism, hypersensitivity to sympathomimetic amines, glaucoma, motor tics, agitation, hx drug abuse, and during or w/I 14 days of use of an MAOI, pregnancy, • Food/drug/herbal interactions: MAOIs (increased risk of hypertensive crisis), CNS depressants and alkalinizing agents (decreased effect of stimulant), Antidepressants (increased effect of antidepressant, especially w/ TCAs; increased risk of cardiotoxicity in children), Guanethidine (increased hypotensive effect), Hypoglycemic agents (increased glucose lability and decreased control), Acidifying agents (decreased effect of stimulant), Phenytoin (increased plasma level of phyenytoin), warfarin and anticonvulsants (increased effect of these meds) • Patient instructions/teaching: may cause insomnia, take no closer than 6 hours before bedtime. Consider drug holidays in children to prevent growth retardation and maintain records of growth and weight. Avoid driving until effects of med are known due to possibility of dizziness. Abrupt cessation may cause fatigue and depression. To reduce anorexia and growth retardation in children, give these meds after meals. High abuse potential. Report to provider any numbness, pain, skin color change, or sensitivity to temperature in fingers or toes. Avoid ETOH

Ergotamine

Ergotamine (p. 1041, 1056, 1057) Ergotamine causes a clear pharmacological dependence and withdrawal. When a patient has analgesic-rebound headache, other headache therapies used for acute or preventative therapy may be resistant to treatment. This medication can harm an unborn baby or a nursing baby. Do not take ergotamine if you are pregnant or breast-feeding. Brand Name: Ergomar Generic Name: Ergotamine Drug Classification: Antimigraine Agent Drug Action: Ergotamine shares structural similarity with neurotransmitters such as serotonin, dopamine, and epinephrine and can thus bind to several receptors acting as an agonist. The anti-migraine effect is due to constriction of the intracranial extracerebral blood vessels through the 5-HT1B receptor, and by inhibiting trigeminal neurotransmission by 5-HT1D receptors. Ergotamine also has effects on the dopamine and norepinephrine receptors. Its side effects are due mainly to its action at the D2 dopamine and 5-HT1A receptors. Uses: Ergotamine is used to treat acute cluser headaches (sublingual 2 mg administered at onset of headache). Ergotamine is used to treat a migraine type headache. This medication will only treat a headache that has already begun. It will not prevent migraine headaches or reduce the number of attacks. Ergotamine may also be administered in a 2 mg dose given before bed if nocturnal attacks occur frequently. General/Typical Dose: Initial dose: 2 mg under the tongue given as quickly as possible after the first symptom of headache. Another 2 mg tablet may be taken at 30 minute intervals if necessary, but dosage must not exceed three tablets in any 24-hour period. Total weekly dosage should not exceed five tablets (10 mg). Ergotamine sublingual tablets should not be used for chronic daily administration. Side Effects: May cause severe nausea and vomiting. May also cause dizziness, spinning sensation, weakness or mild itching. Contraindications: Contraindicated in pregnancy, lactation, CAD, PVD. Food, Drug, Herbal Interactions: Do not take ergotamine within 24 hours before or after using another migraine headache medicine, including: dihydroergotamine (D.H.E. 45, Migranal), caffeine and ergotamine (Cafergot, Ercaf, Wigraine), ergonovine (Ergotrate), methylergonovine (Methergine), methysergide (Sansert); or almotriptan (Axert), eletriptan (Relpax), frovatriptan (Frova), naratriptan (Amerge), sumatriptan (Imitrex), rizatriptan (Maxalt, Maxalt-MLT), or zolmitriptan (Zomig). conivaptan (Vaprisol), imatinib (Gleevec), isoniazid (for treating tuberculosis), or nefazodone (an antidepressant); diclofenac (Arthrotec, Cataflam, Voltaren, Flector Patch, Solareze); clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin), or telithromycin (Ketek); clotrimazole (Mycelex Troche), itraconazole (Sporanox), ketoconazole (Extina, Ketozole, Nizoral, Xolegal), or voriconazole (Vfend); heart or blood pressure medication such as diltiazem (Cardizem, Dilacor, Tiazac), nicardipine (Cardene), quinidine (Quin-G), or verapamil (Calan, Covera, Isoptin, Verelan); or HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), fosamprenavir (Lexiva), indinavir (Crixivan), nelfinavir (Viracept), saquinavir (Invirase, Fortovase), or ritonavir (Norvir). birth control pills; zileuton (Zyflo); cold or allergy medications; nicotine (Nicoderm, Nicorette); diet pills, stimulants, or medication to treat ADHD (such as Ritalin or Adderall); an antidepressant such as fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), nefazodone (Serzone), paroxetine (Paxil), sertraline (Zoloft), and others; an antibiotic such as metronidazole (Flagyl); clotrimazole (Mycelex Troche), fluconazole (Diflucan), or other antifungal medication; nitroglycerin or other nitrate medicines such as isosorbide (Isordil, Dilatrate, Imdur, Monoket); or heart or blood pressure medication such as atenolol (Tenormin), carvedilol (Coreg), labetalol (Normodyne, Trandate), metoprolol (Lopressor, Toprol), nadolol (Corgard), propranolol (Inderal, InnoPran), sotalol (Betapace), and others. Grapefruit and grapefruit juice may interact with ergotamine and lead to potentially dangerous effects. Discuss the use of grapefruit products with your doctor. Do not increase or decrease the amount of grapefruit products in your diet without first talking to your doctor. Patient Instruction/Teaching: Ergotamine causes a clear pharmacological dependence and withdrawal. When a patient has analgesic-rebound headache, other headache therapies used for acute or preventative therapy may be resistant to treatment This medication can harm an unborn baby or a nursing baby. Do not take ergotamine if you are pregnant or breast-feeding. This medication can harm an unborn baby or a nursing baby. Do not take ergotamine if you are pregnant or breast-feeding. Take the first dose of ergotamine as soon as you notice headache symptoms, or after an attack has already begun. Place 1 ergotamine tablet under your tongue. If your headache does not completely go away, you may take a second tablet after at least 30 minutes have passed, and a third tablet if needed after another 30 minutes have passed (a total of 3 tablets). If you still have migraine symptoms after taking a total of 3 tablets, call your doctor. Do not take more than a total of 3 tablets in any 24-hour period. Do not take more than a total of 5 tablets over a period of 7 days. Take the first dose of ergotamine as soon as you notice headache symptoms, or after an attack has already begun. Place 1 ergotamine tablet under your tongue. If your headache does not completely go away, you may take a second tablet after at least 30 minutes have passed, and a third tablet if needed after another 30 minutes have passed (a total of 3 tablets). If you still have migraine symptoms after taking a total of 3 tablets, your doctor. Do not take more than a total of 3 tablets in any 24-hour period. Do not take more than a total of 5 tablets over a period of 7 days.

Gabapentin

Gabapentin-Neurontin • Trade name: Neurontin • Generic name: Gabapentin • Class: Anticonvulsants; Gamma-aminobutyric acid (GABA) Analogs • Action: GABA analogue that binds to unknown receptors in the brain; it does NOT bind to GABA receptors NOR does it mimic GABA: inhibits sodium channels and affects amino acid transport in CNS. • Uses: Epilepsy (efficacy for partial and secondary generalized seizures, alone or as add on agent); postherpetic neuralgia • General/typical dose range: -For partial seizures: start at 300mg/day tid; range: 900-1800mg/day PO divided 3x/day -Post herpetic neuralgia: 300mg PO day 1, 300mg PO bid day 2, 300 mg PO tid day 3; may titrate upward as needed up to 600mg tid -Pediatric dosing: 3-4 y/o: usual dose 40mg/kg/day PO divided tid; 5-12 y/o usual dose 25-35mg/kg/day PO divided tid; > 12 y/o: 900-1800 mg/day PO divided tid **Doses should not be more than 12 hours apart**, **Renal insufficiency will require dosage adjustments** • Side effects/ADR: in pediatrics, side effects have included behavior problems, hostility, changes in school performance, hyperkinesias. Could cause risk of suicidal behavior and ideations. Most common CNS adverse effects are somnolence and dizziness. Less common CNS adverse events are ataxia and abnormal thinking. Watch for peripheral edema. • Contraindications: hypersensitivity • Food/drug/herbal interactions: Increases effects of alcohol and other CNS depressants. • Patient instructions/teaching: do not abruptly d/c the drug for r/o withdrawal seizures, monitor for worsening of depression, suicidal thoughts, or changes in behavior. Take med exactly as prescribed, as missing doses can cause an increase in seizures. Get adequate sleep and exercise and avoid stressful situations that can target seizures. 1st line tx for elderly.

Ibuprofen

Generic: Ibuprofen Trade:Advil, Motrin Class: NSAID Action: Inhibits prostaglandin synthesis to produce anti-inflammatory, analgesic and antipyretic effects. Uses: Arthritis, mild to moderate pain, fever, migraine, muscle strain, primary dysmenorrhea. General/Typical Dosing Range: Adults- 1.2-3.2g/day in 3 or 4 divided doses. Children- 30-70mg/kg/d in 3-4 divided doses. Not given to children <6 months. Side Effects/ADR: Dizziness, headache, nervousness, N/V/D, tinnitus, abd pain, acute renal failure, hematuria, cystitis, agranulocytosis, aplastic anemia, leukopenia, pancytopenia, thrombocytopenia, prolonged bleeding time. Hypokalemia, Hypoglycemia, rash. Contraindication: Not to be used in pt with angioedema, BLACK BOX: not to be given to pt for treatment of perioperative pain in CABG surgery. Risks with pregnancy avoid late in pregnancy. Use caution with elderly with GI issues, renal problems or coagulation defects. Avoid in pt with lupus. Food, Drug, Herbal Interactions: Anticoagulants, antihypertensives, furosemide, thiazide diuretics. Aspirin, corticosteroids, Biphosphinates, Cyclosporine, Digoxin, lithium, oral anticoagulants, Methotrexate. Drug to Herb- Dong-Quia, feverfew, garlic, ginger, ginko biloba, horse chestnut, red clover. Drug to lifestyle- Alcohol, sun exposure. Patient Instructions/Teaching: Take medication with meals to prevent GI upset. Do not exceed 1.2g daily for adults & children >12yrs or 30mg/kg for children 6m to 11 years. Do not give to children <6months. May take 2-4 weeks for therapeutic effect of arthritis pain. Use caution with alcohol, ASA and steroids. Teach s&s of bleeding. Wear sunscreen.

Naproxen

Generic: Naproxen Trade: Aleve Class: NSAID Action: Inhibit prostaglandin synthesis to produce anti-inflammatory, analgesic, and antipyretic effects. Uses: Acute Gout, Acute tendonitis, bursitis, pain, primary dysmenorrhea, arthritic pain, episodic migraine prevention. General/Typical Dosing Range: 250-500mg BID up to 1.5g/d for limited periods. Side Effects/ADR: no significant adverse drug reactions specific to naproxen N/V/D, dizziness, edema, tinnitus, auditory/visual disturbances, ecchymoses, increased bleeding time, dyspnea, diaphoresis, pruritis, Contraindication: BLACK BOX: may increase risk of thrombotic event, MI, or stroke, GI bleed. May signs of infection with antipyretic effect. Pt with renal disease, avoid in pregnancy especially late and while breast feeding. Food, Drug, Herbal interactions: ACE inhibitors, diuretics, antihypertensives, ASA, steroids, Digoxin, Lithium, Loop and thiazide diuretics, Methotrexate, oral anti-coagulants, alfalfa, anise, bilberry, dong quai, feverfew, garlic, ginger, white willow, alcohol. Patient Instruction/Teaching: Do not take more than 660mg/24hrs. take with food. Make take 2-4 weeks for arthritic pain relief. S&S of Gi bleed. Caution with use of other NSAIDs. Warn pt of activities requiring mental alertness.

Lorazepam: anxiety only

Initial dose: 2-3 mg/d divided bid or tid,increase to usual range of 2-6 mg/d Elderly: 1-2 mg/d in divided doses. Short-term insomnia due to anxiety: 2-4 mg at bedtime. Tablets: 0.5, 1, 2 mg Intensol solution: 2 mg/mLInjection: 2 or 4 mg/mL Onset = intermediate, peak = 2-4 h, duration= intermediate, half life = 10-20 h. excreted thru urine. Valproate =decreased metabolism and increased effect. May need less dose.