Pharm 2 Test 1

Drug Interactions - Opioid Agonists

CNS depressants - benzo (valium), alcohol and barbiturates Anticholinergic drugs Hypotensive drugs - exacerbate effect Monoamine oxidase inhibitors Agonist-antagonist opioids Opioid antagonists Other interactions

Adverse Effects of Benzodiazepines

CNS depression Anterograde amnesia Sleep driving and other complex sleep-related behaviors. Paradoxical effects Respiratory depression Abuse Use in pregnancy and lactation Other adverse effects - Occasional reactions include weakness, headache, blurred vision, vertigo, nausea, vomiting, epigastric distress, and diarrhea. Neutropenia and jaundice occur rarely. Rarely, benzodiazepines may cause severe allergic reactions, including angioedema and anaphylaxis.

Drugs for Alzheimer's Disease

Cholinesterase Inhibitors: *Donepezil (Aricept) - Mild to Severe AD *Rivastigmine (Exelon) - Mild to Moderate AD *Galantamine (Razadyne, Reminyl) - Mild to Moderate AD N-methyl-D-aspartate (NMDA) Antagonist *Memantine (Namenda, Ebixa) - Moderate to Severe AD Although these drugs produced statistically significant symptomatic improvement in clinical trials, benefits in most patients are marginal. The major known risk factor for AD is advancing age.

Drug Management of Status Epilepticus

Continuous series of tonic-clonic seizures that lasts 20 to 30 minutes Goals of treatment Maintain ventilation Correct hypoglycemia Terminate seizures Benzodiazepine lorazepam is recommended for first-line management Diazepam, which is also a benzodiazepine, may be used if lorazepam is not readily available Initiate or continue long-term suppression drugs such as phenytoin [Dilantin] or fosphenytoin [Cerebyx]

Adaptation of the cns to prolonged drug exposure

Decreased Side Effects *Exposure over time decreases the intensity of side effects - example initial sedation with phenobarbital Tolerance *Decreased response occurring in the course of prolonged drug use Physical Dependence *A state in which abrupt discontinuation of drug use will precipitate a withdrawal syndrome *The withdrawal reaction continues until adaptive changes have had time to revert, restoring the CNS to its pre-treatment / pre-drug state

Major Nursing Implications in Administration of POAs

Dosage must be individualized. High doses are required for patients with a low tolerance to pain or with extremely painful disorders. Patients with sharp, stabbing pain need higher doses than patients with dull pain. Older adults generally require lower doses than younger adults. Neonates require relatively low doses because their blood-brain barrier is not fully developed. For all patients, dosage should be reduced as pain subsides. Outpatients should be warned not to increase dosage without consulting the prescriber. Before an opioid is administered, respiratory rate, blood pressure, and pulse rate should be determined. The drug should be withheld and the prescriber notified if respiratory rate is below 12 breaths/min, if blood pressure is significantly below the pretreatment value, or if pulse rate is significantly above or below the pretreatment value. As a rule, opioids should be administered on a fixed schedule—not PRN. With a fixed schedule, medication is given before intense pain returns. As a result, the patient is spared needless discomfort. Furthermore, anxiety about recurrence of pain is reduced. If breakthrough pain occurs, supplemental doses of a short-acting preparation should be given. Therapeutic Goal Relief or prevention of moderate to severe pain while causing minimal respiratory depression, constipation, urinary retention, and other adverse effects. Baseline Data Pain Assessment. Assess pain before administration and 1 hour later. Determine the location, time of onset, and quality of pain (eg, sharp, stabbing, dull). Also, assess for psychologic factors that can lower pain threshold (anxiety, depression, fear, anger). Because pain is subjective and determined by multiple factors (eg, cultural influences, patient expectations, associated disease), there is no reliable objective method for determining how much discomfort the patient is experiencing. Ultimately, you must rely on your ability to interpret what patients have to say about their pain. When listening to patients, be aware that a few may claim discomfort when their pain is under control, and others may claim to feel fine when they actually hurt. Vital Signs. Before administration, determine respiratory rate, blood pressure, and pulse rate. Identifying High-Risk Patients All opioids are contraindicated for premature infants (both during and after delivery). Morphine is contraindicated following biliary tract surgery. Meperidine is contraindicated for patients taking MAOIs. Use opioids with caution in patients with head injury, profound CNS depression, coma, respiratory depression, pulmonary disease (eg, emphysema, asthma), cardiovascular disease, hypotension, reduced blood volume, benign prostatic hypertrophy, urethral stricture, and liver impairment. Caution is also required when treating infants, older-adult or debilitated patients, and patients receiving MAOIs, CNS depressants, anticholinergic drugs, and hypotensive agents. In addition, use opioids with caution in patients deemed at high risk of opioid abuse. Implementation: Administration Routes Oral, IM, IV, subQ, rectal, epidural, intrathecal, transdermal (fentanyl), and transmucosal (fentanyl). Routes for specific opioids are shown in Tables 28-5 and 28-6. Dosage General Guidelines. Adjust dosage to meet individual needs. Higher doses are required for patients with low pain tolerance or with especially painful conditions. Patients with sharp, stabbing pain need higher doses than patients with dull, constant pain. Older-adult patients generally require lower doses than younger adults. Neonates require relatively low doses because the blood-brain barrier is poorly developed. For all patients, dosage should be reduced as pain subsides. Oral doses are larger than parenteral doses. Check to ensure that the dose is appropriate for the intended route. Tolerance may develop with prolonged treatment, necessitating dosage escalation. Warn outpatients not to increase dosage without consulting the prescriber. Dosage in Patients with Cancer. Treatment of cancer pain is done long term. The objective is to maximize comfort. Physical dependence is a minor concern. Cancer patients should receive opioids on a fixed schedule around-the-clock—not PRN. If breakthrough pain occurs, fixed dosing should be supplemented PRN with a short-acting opioid. Because of tolerance to opioids or intensification of pain, dosage escalation may be required. Hence, patients should be reevaluated on a regular basis to determine if pain control is adequate. Discontinuing Opioids. Although significant dependence in hospitalized patients is rare, it can occur. To minimize symptoms of abstinence, withdraw opioids slowly, tapering the dosage over 3 days. Warn outpatients against abrupt discontinuation of treatment. Administration Before administration, determine respiratory rate, blood pressure, and pulse rate. Withhold medication and notify the prescriber if respiratory rate is at or below 12 breaths/min, if blood pressure is significantly below the pretreatment value, or if pulse rate is significantly above or below the pretreatment value. As a rule, opioids should be administered on a fixed schedule, with supplemental doses as needed. Perform IV injections slowly (over 4 to 5 minutes). Rapid injection may produce severe adverse effects (profound hypotension, respiratory arrest, cardiac arrest) and should be avoided. When making an IV injection, have an opioid antagonist (eg, naloxone) and facilities for respiratory support available. Perform injections (especially IV) with the patient lying down to minimize hypotension. Warn patients using fentanyl patches to avoid exposing the patch to direct heat (eg, heating pad, hot tub) because doing so can accelerate fentanyl release. Warn patients not to crush or chew controlled-release oxycodone [OxyContin] tablets. Warn patients using morphine/naltrexone [Embeda] not to crush or chew the capsules or to drink alcohol, because these actions can accelerate absorption of morphine from the product. Instruct patients using tramadol ODTs [Rybix ODT] to place the tablet on the tongue until it dissolves (about 1 minute), and then swallow with or without water. Opioid agonists are regulated under the Controlled Substances Act and must be dispensed accordingly. All pure agonists are Schedule II substances, except hydrocodone (Schedule III). Concern for Opioid Abuse as a Factor in Dosage and Administration Although opioids have a high potential for abuse, abuse is rare in the clinical setting. Consequently, when balancing the risk of abuse against the need to relieve pain, do not give excessive weight to concerns about abuse. The patient must not be allowed to suffer because of your unwarranted fears about abuse and dependence. Although abuse is rare in the clinical setting, it can occur. To keep abuse to a minimum: (1) screen patients for abuse risk, (2) exercise clinical judgment when interpreting requests for opioid doses that seem excessive, (3) use opioids in the lowest effective doses for the shortest time required, (4) reserve opioid analgesics for patients with moderate to severe pain, and (5) switch to a nonopioid analgesic when the intensity of pain no longer justifies an opioid. Responses to analgesics can be reinforced by nondrug measures, such as positioning the patient comfortably, showing concern and interest, and reassuring the patient that the medication will provide relief. Rest, mood elevation, and diversion can raise pain threshold and should be promoted. Conversely, anxiety, depression, fatigue, fear, and anger can lower pain threshold and should be minimized. Ongoing Evaluation and Interventions Evaluating Therapeutic Effects Evaluate for pain control 1 hour after opioid administration. If analgesia is insufficient, consult the prescriber about an increase in dosage. Patients taking opioids chronically for suppression of cancer pain should be reevaluated on a regular basis to determine if dosage is adequate.

Drug Interactions of Cholinesterase Inhibitors

Drugs that block cholinergic receptors can reduce therapeutic effects *First generation antihistamines, *Tricyclic antidepressants, *Conventional antipsychotics can reduce therapeutic effects, and should be avoided.

Adverse Effects of Centrally Acting Muscle Relaxants

Hepatic toxicity Physical dependence Abstinence syndrome Adverse effects: Generalized CNS depression Hepatic toxicity *Tizanidine [Zanaflex] and metaxalone [Skelaxin] can cause damage *Chlorzoxazone [Paraflex] can cause hepatitis and necrosis Physical dependence Abstinence syndrome Other adverse effects

Advantage of New AED - Levetiracetam (Keppra) - Page 231

In contrast to other AEDs, levetiracetam does not impair speech, concentration, or other cognitive functions. Unlike most other AEDs, levetiracetam does not interact with other drugs. It does not alter plasma concentrations of oral contraceptives, warfarin, digoxin, or other AEDs. These benefits are primarily attributable to the fact that levetiracetam is not metabolized by P450 isoenzymes. Broad spectrum of antiseizure activity Bipolar disorder Adverse effects Dizziness, diplopia, blurred vision, nausea, vomiting, and headache Severe skin reactions Aseptic meningitis Risk for suicide

Pharmacokinetics of Antagonists

Naloxone may be administered IV, IM, or subQ. After IV injection, effects begin almost immediately and persist about 1 hour. Following IM or subQ injection, effects begin within 2 to 5 minutes and persist several hours. Elimination is by hepatic metabolism. The half-life is approximately 2 hours. Naloxone cannot be used orally because of rapid first-pass inactivation.

Adverse Effects of Nonergot DA Receptor agonist - Pramipexole

Nausea, dizziness, daytime somnolence, insomnia, constipation, weakness, and hallucinations. Combined with levodopa 50% experience orthostatic hypotension and hallucinations double. Also impulse control disorders. (Burchum 183-184)

Levodopa - dopamine replacement

Only given in combination with carbidopa or carbidopa/entacapone Highly effective, but benefits diminish over time Orally administered, rapid absorption from small intestine Food delays absorption *Neutral amino acids compete with levodopa for *intestinal absorption and for transport across blood-brain barrier *High-protein foods will reduce therapeutic effects

Patient Teaching with Traditional AEDs

Patients should be informed that gastric upset can be reduced by administering phenytoin with or immediately after a meal. Patients using the oral suspension should shake it well before dispensing, since failure to do so can result in uneven dosing. (Burchum 223)

Antidepressants

Primarily used to relieve symptoms of depression Can also help patients with anxiety disorders Not indicated for uncomplicated bereavement ***Pharmacotherapy - Primary therapy****

Opioid Analgesics, Opioid Antagonists, & Centrally Acting Analgesics

Pure Opioid Agonists Morphine Agonist-Antagonist Opioids Pentazocine Pure Opioid Antagonists Naloxone (Burchum 261)

Safety Alert - Anticholinergic Drugs

Safety Alert Beers Criteria Anticholinergic drugs have been designated as potentially inappropriate for use in geriatric patients. The anticholinergics most commonly prescribed for management of Parkinson's disease are benztropine [Cogentin] and trihexyphenidyl. (Burchum 187)

Adverse Effects of Agonist-Antagonist Opioids

Same as morphine, however agonist-antagonist drugs increase cardiac work, so it should be avoided in patients who have had a myocardial infarction.

Safety Alert and Adverse Effects for Serotonin Receptor Agonists

Serotonin receptor agonists can cause vasoconstriction and coronary vasospasm. These drugs should not be administered to patients with coronary artery disease, current symptoms of angina, or uncontrolled hypertension. Serotonin agonists are going to cause a release in serotonin, if Pt is on another serotonin drug the Pt is at risk for serotonin syndrome = a medical emergency. Don't use with SSRIs Adverse effects: *Chest symptoms *Transient "heavy arms" or "chest pressure" experienced by 50% of users *Coronary vasospasm *Rare angina as a result of vasospasm *Teratogenesis *Vertigo, malaise, fatigue, and tingling sensations *Very bad taste when taken in intranasal form

Drug Interactions for Serotonin Receptor Agonists

Sumatriptan (Imitrex), other triptans, and ergot alkaloids (eg, ergotamine, dihydroergotamine) all cause vasoconstriction. Accordingly, if one triptan is combined with another or with an ergot alkaloid, excessive and prolonged vasospasm could result. Accordingly, sumatriptan should not be used within 24 hours of an ergot derivative or another triptan.

Drugs for Headaches

To abort an ongoing attack *Aspirin-like drugs, opioid analgesics, and migraine-specific drugs *Nonspecific analgesics Opioid analgesics (for example, butorphanol, meperidine) *Migraine-specific drugs *Serotonin1B/1D receptor agonists *Ergot alkaloids To prevent attacks from occurring *Beta blockers, tricyclic antidepressants, and antiepileptic drugs

Therapeutic Effects of Drugs for Spasticity

Treatment of spasm Physical measures *Immobilization of affected muscle *Cold compresses *Whirlpool baths *Physical therapy Spasticity associated with multiple sclerosis, cerebral palsy, and spinal cord injury

Mechanism of Action of NMDA receptor antagonist

modulates the effects of glutamate, the major excitatory transmitter in the CNS at NMDA receptors, which are believed to play a critical role in learning and memory. Under pathologic conditions, there is slow but steady leakage of glutamate from the presynaptic neuron and surrounding glia. As a result, the channel in the NMDA receptor is kept open, thereby allowing excessive influx of calcium. High intracellular calcium has two effects: 1. Impaired learning and memory 2. Neurodengeration (too much intracellular calcium is toxic)

Safety Alert - Suicide Risk

Antidepressants may increase the risk of suicide in depressed patients, especially during the early phase of treatment. The risk of antidepressant-induced suicide is greatest among children, adolescents, and young adults. Patients starting treatment or changing doses must be monitored closely for suicidal behavior. ***Hospitalization - concrete plan***

Safety Alert - Formulations of Gabapentin

Additional Formulations of Gabapentin Two forms of gabapentin are not currently indicated for management of epilepsy and, therefore, should not be confused with the form of gabapentin known as Neurontin. • Gabapentin ER [Gralise] is approved for management of postherpetic neuralgia. • Gabapentin enacarbil [Horizant], a prodrug form of gabapentin, is approved for treatment of moderate to severe restless legs syndrome. Owing to differences in pharmacokinetics, these forms of gabapentin are not interchangeable with each other or with Neurontin. (Burchum 230)

Drugs for Epilepsy

Drugs for Epilepsy - Suppress discharge of neurons within a seizure focus Suppress propagation of seizure activity from the focus to other areas of the brain How antiepileptic drugs work: Suppression of sodium influx Suppression of calcium influx Promotion of potassium efflux Blockade of receptors for glutamate Potentiation of GABA Traditional Agents **Phenytoin (dilantin)** - partial and tonic-clonic seizures Carbamazepine Valproic acid **Ethosuximide - Drug of choice for absence seizures Phenobarbital Diazepam (IV) Newer Agents **Oxcarbazepine - Indicated for monotherapy and adjunctive therapy of partial seizures in adults and children; Clinically significant hyponatremia (sodium concentration below 125 mmol/L) Lamotrigine Do not stop drugs spontaneously, taper off. Epilepsy: Group of disorders characterized by excessive excitability of neurons in the central nervous system Can produce a variety of symptoms that range from brief periods of unconsciousness to violent convulsions May also cause problems with learning, memory, and mood

Adverse Effects of Cholinesterase Inhibitors

From slides: By elevating acetylcholine in the periphery - Cholinergic Side Effects: *GI - nausea, vomiting, dyspepsia, diarrhea often occur ***Dizziness and Headache are also common**** *Bronchoconstriction - r/t elevation of ach at the synapses in the lungs ***Bradycardia leading to fainting, falls, fall-related fractures, & pacemaker placement - uncommon but a serious concern****

Therapeutic Uses of Amantadine

From slides: May help reduce levodopa - induced dyskinesias Book: Amantadine [Symmetrel] was developed as an antiviral agent (see Chapter 93), and was later found effective in PD. Possible mechanisms include inhibition of dopamine uptake, stimulation of dopamine release, blockade of cholinergic receptors, and blockade of glutamate receptors. Responses develop rapidly—often within 2 to 3 days—but are much less profound than with levodopa or the dopamine agonists. Furthermore, responses may begin to diminish within 3 to 6 months. Accordingly, amantadine is not considered a first-line agent. However, the drug may be helpful for managing dyskinesias caused by levodopa. (Burchum 187)

Managing Breakthrough Pain

Increase opioid dosage, NSAIDS won't work. Patients may experience transient episodes of moderate to severe breakthrough pain Access to rescue medication *Strong opioid with rapid onset and short duration *Immediate-release oral morphine *Transmucosal fentanyl [Abstral, Actiq, Fentora, Onsolis, Subsys] *Fentanyl nasal spray [Lazanda]

Pharmacology Aids to Smoking Cessation

Nicotine-Based Products: *Nicotine patch [Nicotrol, NicoDerm CQ] *Nicotine gum [Nicorette, others] *Nicotine lozenge [Nicorette Lozenge, Thrive *Nicotine nasal spray [Nicotrol NS] *Nicotine inhaler [Nicotrol Inhaler, Nicorette Inhaler image Nicotine-Free Products: *Varenicline *Bupropion

Therapeutic Uses for Dantrolene

Spasticity associated with multiple sclerosis, cerebral palsy, and spinal cord injury Malignant hyperthermia *Potentially fatal condition caused by succinylcholine and general anesthetics

Adverse Effects of Traditional AEDs (Antiepileptic Drugs)

Slides (phenytoin/dilantin): Nystagmus Sedation Ataxia Diplopia Cognitive impairment Gingival hyperplasia Skin rash Effects in pregnancy Cardiovascular effects Gingival hyperplasia: Swelling, tenderness, and bleeding of the gums Gingivectomy Folic acid (0.5 mg/day) may prevent gum overgrowth Risk can be minimized by good oral hygiene, including dental flossing and gum massage From Book: Adverse Effects Effects on the CNS. Although phenytoin acts on the CNS in a relatively selective fashion to suppress seizures, the drug can still cause CNS side effects—especially when dosage is excessive. At therapeutic levels (10 to 20 mcg/mL), sedation and other CNS effects are mild. At plasma levels above 20 mcg/mL, toxicity can occur. Nystagmus (continuous back-and-forth movements of the eyes) is relatively common. Other manifestations of excessive dosage include sedation, ataxia (staggering gait), diplopia (double vision), and cognitive impairment. Gingival Hyperplasia. Gingival hyperplasia (excessive growth of gum tissue) is characterized by swelling, tenderness, and bleeding of the gums. In extreme cases, patients require gingivectomy (surgical removal of excess gum tissue). Gingival hyperplasia is seen in about 20% of patients who take phenytoin. Can risk be reduced? Yes. Evidence indicates that supplemental folic acid (0.5 mg/day) may prevent gum overgrowth. In addition, risk can be minimized by good oral hygiene, including dental flossing and gum massage. Patients should be taught these techniques and encouraged to practice them. Dermatologic Effects. Between 2% and 5% of patients develop a morbilliform (measles-like) rash. Rarely, morbilliform rash progresses to much more severe reactions: Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN). According to a 2008 alert from the FDA, the risk of developing SJS/TEN may be increased by a genetic mutation known as human leukocyte antigen (HLA)-B*1502, which occurs almost exclusively in people of Asian descent. However, data in support of this association are preliminary; until more is known, phenytoin should not be prescribed for patients known to have this mutation. Effects in Pregnancy. Phenytoin is a teratogen. It can cause cleft palate, heart malformations, and fetal hydantoin syndrome, characterized by growth deficiency, motor or mental deficiency, microcephaly, craniofacial distortion, positional deformities of the limbs, hypoplasia of the nails and fingers, and impaired neurodevelopment. Because of these effects, phenytoin is classified in FDA Pregnancy Risk Category D, and hence should be used during pregnancy only if safer alternatives are not effective and if the benefits of seizure control are deemed to outweigh the risk to the fetus. Phenytoin can decrease synthesis of vitamin K-dependent clotting factors, and can thereby cause bleeding tendencies in newborns. The risk of neonatal bleeding can be decreased by giving prophylactic vitamin K to the mother for 1 month before and during delivery, and to the infant immediately after delivery. Cardiovascular Effects. When phenytoin is administered by IV injection (to treat SE), cardiac dysrhythmias and hypotension may result. These dangerous responses can be minimized by injecting phenytoin slowly and in dilute saline solution (see the Safety Alert). (Burchum 222-223)

Adverse Effects of Ergot Alkaloids - Ergotamine

The drug can stimulate the chemoreceptor trigger zone, causing nausea and vomiting in about 10% of patients, thereby augmenting nausea and vomiting caused by the migraine itself. Concurrent treatment with metoclopramide or a phenothiazine antiemetic (eg, prochlorperazine) can help reduce these responses. Other common side effects include weakness in the legs, myalgia, numbness and tingling in the fingers and toes, angina-like pain, and tachycardia or bradycardia.

Benefit of Benzodiazepines during Withdrawal - Page 418-419

They are safe. In patients with severe alcohol dependence, benzodiazepines can stabilize vital signs, reduce symptom intensity, and decrease the risk of seizures and delirium tremens.

Adverse Effects of Adjuvant Medications for Pain: Hydroxyzine

Increases/compounds constipation.

Patient Education for Zolpidem (Ambien) - Page 378

patients should be warned against combining zolpidem with alcohol and all other drugs that depress CNS function..

Therapeutic Uses for Benzodiazepines

(1) anxiety, (2) insomnia, and (3) seizure disorders. In addition, they are used as preoperative medications and to treat muscle spasm and withdrawal from alcohol. Although all benzodiazepines share the same pharmacologic properties, and therefore might be equally effective for all applications, not every benzodiazepine is actually employed for all potential uses. The principal factors that determine the actual applications of a particular benzodiazepine are (1) the pharmacokinetic properties of the drug itself and (2) research and marketing decisions of pharmaceutical companies. Specific applications of individual benzodiazepines are shown in Table 34-2.

Drug Interactions for Lithium

****Diuretics - reduce sodium and increase the risk of lithium toxicity. Toxicity can occur because, in the presence of low sodium, renal excretion of lithium is reduced, causing lithium levels to rise. Nonsteroidal anti-inflammatory drugs Anticholinergic drugs

Adverse Effects of Tricyclic Antidepressants

****Orthostatic hypotension*** ****Cardiac toxicity** Anticholinergic effects Diaphoresis Sedation Seizures Hypomania TCAs are no longer 1st line treatment and are going out of use due to adverse effects. OD can be deadly

Patient and Family Education for SSNRIs - Venlafaxine [Effexor]

***Serious reactions if combined with MAOIs*** ***Neonatal withdrawal syndrome*** Warn patients not to discontinue treatment once mood has improved, since doing so could lead to relapse. Abrupt discontinuation can cause an intense withdrawal syndrome. Symptoms include anxiety, agitation, tremors, headache, vertigo, nausea, tachycardia, and tinnitus. Worsening of pretreatment symptoms may also occur. Withdrawal symptoms can be minimized by tapering the dosage over 2 to 4 weeks. Inform patients about possible sexual dysfunction (anorgasmia, impotence, decreased libido), and encourage them to report problems. Inform patients about possible dizziness and fatigue when using SSRIs, and advise them to exercise caution while performing hazardous tasks (eg, driving). Inform patients about the risk of rash and instruct them to notify the prescriber if one develops. Alert patients to the sequelae of bruxism (headache, jaw pain, and dental problems, such as cracked fillings). MAOIs should be withdrawn at least 14 days before starting venlafaxine. When switching from venlafaxine to an MAOI, venlafaxine should be discontinued 7 days before starting the MAOI.

Contraindications for Bupropion (Wellbutrin)

***Should not be used in patients with psychotic disorders.*** ***Seizures - Read page 356 MAOIs can increase the risk of bupropion toxicity Contraindicated in patients with a history of hypersensitivity to bupropion or any inactive ingredients in the formulations. Delayed hypersensitivity reactions, consisting of arthralgia, myalgia, fever and rash have been reported in association with bupropion and may resemble serum sickness. Anaphylactoid/anaphylactic reactions and Stevens-Johnson syndrome have also been reported.

Pain Management in Patients with Cancer

ASK about pain regularly Assess pain systematically BELIEVE the patient and family in their reports of pain and what relieves it CHOOSE pain control options appropriate for the patient, family, and setting DELIVER interventions in a timely, logical, coordinated fashion EMPOWER patients and their families. Enable patients to control their treatment to the greatest extent possible Drug therapy: Nonopioid analgesics *Nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen Opioid analgesics *Oxycodone, fentanyl, and morphine Adjuvant analgesics *Amitriptyline, carbamazepine, and dextroamphetamine World Health Organization analgesic ladder: Step 1: Mild to moderate pain Nonopioid analgesics NSAIDs and acetaminophen Step 2: More severe pain Add an opioid analgesic, oxycodone, or hydrocodone Step 3: Severe pain Substitute a powerful opioid such as morphine or fentanyl

Adverse Effects and Toxicity of Pure Opioid Agonists

Activate mu receptors and kappa receptors Can produce: Respiratory depression constipation Orthostatic hypotension Euphoria Sedation Physical depression Urinary Retention Cough Suppression Biliary Colic Emesis Elevation of Intracranial Pressure Miosis Birth Defects Toxicity clinical manifestations: Classic triad - Coma, Respiratory Depression, Pinpoint Pupils Treatment Ventilatory support and administer Antagonist: Naloxone [Narcan] General guidelines Monitor vital signs before giving and Give on a fixed schedule

Contraindications for Nonopioid Analgesic Administration

Acute renal failure and bleeding. Chemo affects platelet count and their ability to increase count. Don't want to increase the risk for bleeding.

Adverse Effects of Dopamine Replacement - Levodopa/Carbidopa

Adverse Effects Most side effects of levodopa are dose dependent. Older-adult patients, who are the primary users of levodopa, are especially sensitive to adverse effects. Nausea and Vomiting. Most patients experience nausea and vomiting early in treatment. The cause is activation of dopamine receptors in the chemoreceptor trigger zone (CTZ) of the medulla. Nausea and vomiting can be reduced by administering levodopa in low initial doses and with meals. (Food delays levodopa absorption, causing a decrease in peak plasma drug levels and a corresponding decrease in stimulation of the CTZ.) However, since administration with food can reduce therapeutic effects by decreasing levodopa absorption, administration with meals should be avoided if possible. Giving additional carbidopa (without levodopa) can help reduce nausea and vomiting. Why carbidopa helps is unknown. Dyskinesias. Ironically, levodopa, which is given to alleviate movement disorders, actually causes movement disorders in many patients. About 80% develop involuntary movements within the first year. Some dyskinesias are just annoying (eg, head bobbing, tics, grimacing), whereas others can be disabling (eg, ballismus, a rapid involuntary jerking or flinging of proximal muscle groups, or choreoathetosis, a slow involuntary writhing movement). These dyskinesias develop just before or soon after optimal levodopa dosage has been achieved. Dyskinesias can be managed in three ways. First, the dosage of levodopa can be reduced. However, dosage reduction may allow PD symptoms to reemerge. Second, we can give amantadine (see below), which can reduce dyskinesias in some patients. If these measures fail, the only remaining options are surgery and electrical stimulation. Cardiovascular Effects. Postural hypotension is common early in treatment. The underlying mechanism is unknown. Hypotension can be reduced by increasing intake of salt and water. An alpha-adrenergic agonist can help too. Conversion of levodopa to dopamine in the periphery can produce excessive activation of beta1 receptors in the heart. Dysrhythmias can result, especially in patients with heart disease. Psychosis. Psychosis develops in about 20% of patients. Prominent symptoms are visual hallucinations, vivid dreams or nightmares, and paranoid ideation (fears of personal endangerment, sense of persecution, feelings of being followed or spied on). Activation of dopamine receptors is in some way involved. Symptoms can be reduced by lowering levodopa dosage, but this will reduce beneficial effects too. Treatment of levodopa-induced psychosis with first-generation antipsychotics is problematic. Yes, these agents can decrease psychologic symptoms. However, they will also intensify symptoms of PD because they block receptors for dopamine in the striatum. In fact, when first-generation antipsychotic agents are used for schizophrenia, the biggest problem is Parkinsonian side effects, referred to as extrapyramidal symptoms (EPS). Two second-generation antipsychotics—clozapine and quetiapine—have been used successfully to manage levodopa-induced psychosis. Unlike the first-generation antipsychotic drugs, clozapine and quetiapine cause little or no blockade of dopamine receptors in the striatum, and hence do not cause EPS. In patients taking levodopa, these drugs can reduce psychotic symptoms without intensifying symptoms of PD. Interestingly, the dosage of clozapine is only 6.25 to 50 mg/day, which is much lower than the dosage used for schizophrenia. Clozapine and quetiapine are discussed in Chapter 31. Central Nervous System Effects. Levodopa may cause a number of central nervous system (CNS) effects. These range from anxiety and agitation to memory and cognitive impairment. Insomnia and nightmares are common. Some patients experience problems with impulse control, resulting in behavioral changes associated with promiscuity, gambling, binge eating, or alcohol abuse. Other Adverse Effects. Levodopa may darken sweat and urine; patients should be informed about this harmless effect. Some studies suggest that levodopa can activate malignant melanoma; however, others have failed to support this finding. Until more is known, it is important to perform a careful skin assessment of patients who are prescribed levodopa. (Burchum 179-181)

Major Nursing Implications - Patient Education

Advise patients to administer lithium with meals or milk to decrease gastric upset. Instruct patients to swallow slow-release tablets intact, without crushing or chewing. To promote adherence, educate patients and families about the nature of BPD and the importance of taking lithium as prescribed. Encourage family members to oversee lithium use, and advise them to urge the patient to visit the prescriber or a psychiatric clinic if a pattern of nonadherence develops. Teach patients the signs of toxicity, and instruct them to withhold medication and notify the prescriber if they develop. Instruct patients to maintain normal sodium intake. Inform patients that diarrhea can cause significant sodium loss. Instruct patients to drink 8 to 12 glasses of fluid daily to maintain hydration. Counsel women of child-bearing age about the importance of avoiding pregnancy. Rule out pregnancy before initiating therapy. Lithium enters breast milk. Advise patients to avoid breast-feeding.

Therapeutic Uses of Cholinesterase Inhibitors

All cholinesterase inhibitors are approved for patients with mild to moderate symptoms, and one agent—donepezil—is also approved for those with severe symptoms. Unfortunately, treatment only benefits 1 in 12 patients. Among those who do benefit, improvements are seen in quality of life and cognitive functions (eg, memory, thought, reasoning). However, these improvements are modest and short lasting. There is no convincing evidence of marked improvement or significant delay of disease progression. Nonetheless, although improvements are neither universal, dramatic, nor long lasting, and although side effects are common, the benefits may still be worth the risks for some patients. (Burchum 193) **MOA - Prevent the breakdown of acetylcholine by acetylcholinesterase (AChE), and thereby increase the availability of ACh at cholinergic synapses. The result is enhanced transmission by central cholinergic neurons that have not yet been destroyed...for neurons that haven't been destroyed.

Management of Anxiety Disorders

Anxiety is an uncomfortable state that has both psychologic and physical components. The psychologic component can be characterized with terms such as fear, apprehension, dread, and uneasiness. The physical component manifests as tachycardia, palpitations, trembling, dry mouth, sweating, weakness, fatigue, and shortness of breath. *Fortunately, anxiety disorders often respond well to treatment—either psychotherapy, drug therapy, or both. For most patients, a combination of psychotherapy and drug therapy is more effective than either modality alone. As indicated in Table 35-1, two classes of drugs are used most: benzodiazepines and selective serotonin reuptake inhibitors (SSRIs). Benzodiazepines are used primarily for one condition: generalized anxiety disorder (GAD). In contrast, the SSRIs are now used for all anxiety disorders. It should be noted that, although SSRIs were developed as antidepressants, they can be very effective against anxiety—whether or not depression is present.

Drugs to Facilitate Withdrawal Alcohol

Benzodiazepines - Of the drugs used to facilitate alcohol withdrawal, benzodiazepines are the most effective. Beta-Adrenergic blockers - atenolol propranolol Central Alpha2-Adrenergic Agonist - Clonidine Antiepileptic Drug - Carbamazepine

Therapeutic Use of Buspirone (BuSpar) - Page 389

Buspirone [BuSpar] is an anxiolytic drug that differs significantly from the benzodiazepines. Most notably, buspirone is not a central nervous system (CNS) depressant. For treatment of anxiety, buspirone is as effective as the benzodiazepines and has two distinct advantages: It has no abuse potential and does not intensify the effects of CNS depressants (benzodiazepines, alcohol, barbiturates, and related drugs). Its major disadvantage is that anxiolytic effects develop slowly: Initial responses take a week to appear, and several more weeks must pass before responses peak. Because therapeutic effects are delayed, buspirone is not suitable for PRN use or for patients who need immediate relief. Since buspirone has no abuse potential, it may be especially appropriate for patients known to abuse alcohol and other drugs. Because it lacks depressant properties, buspirone is an attractive alternative to benzodiazepines in patients who require long-term therapy but cannot tolerate benzodiazepine-induced sedation and psychomotor slowing. Buspirone is labeled only for short-term treatment of anxiety. However, the drug has been taken for as long as a year with no reduction in benefit. Buspirone does not display cross-dependence with benzodiazepines. Hence, when patients are switched from a benzodiazepine to buspirone, the benzodiazepine must be tapered slowly. Furthermore, since the effects of buspirone are delayed, buspirone should be initiated 2 to 4 weeks before beginning benzodiazepine withdrawal. In contrast to benzodiazepines, buspirone lacks sedative, muscle relaxant, and anticonvulsant actions—and hence cannot be used for insomnia, muscle spasm, or epilepsy. The mechanism by which buspirone relieves anxiety has not been established. The drug binds with high affinity to receptors for serotonin and with lower affinity to receptors for dopamine. Buspirone does not bind to receptors for GABA or benzodiazepines.

Sedative-Hypnotic Drugs

Dependent on dose (same drug is anti anxiety or anxiolytics) - low level = relieve anxiety high level = induce sleep drugs that depress central nervous system (CNS) function. With some of these drugs, CNS depression is more generalized than with others. The sedative-hypnotics are used primarily for two common disorders: anxiety and insomnia. Agents given to relieve anxiety are known as antianxiety agents or anxiolytics; an older term is tranquilizers. Agents given to promote sleep are known as hypnotics. The distinction between antianxiety effects and hypnotic effects is often a matter of dosage: typically, sedative-hypnotics relieve anxiety in low doses and induce sleep in higher doses. Hence, a single drug may be considered both an antianxiety agent and a hypnotic agent, depending upon the reason for its use and the dosage employed.

Drugs for Parkinson's Disease

From powerpoint Two major categories 1. Dopaminergic agents By far the most commonly used drugs for PD Promote activation of dopamine receptors Levodopa 2. Anticholinergic agents - *Prevent activation of cholinergic receptors Benztropine (Cogentin) Parkinson's Disease is second only to Alzheimer's Disease as the most common degenerative disease of nerves. Symptoms include tremor, rigidity, postural instability, and slowed movement, which are caused by loss of dopaminergic neurons in the substantia nigra. As the disease progresses, levodopa eventually becomes ineffective. The principle drugs are levodopa, levodopa/carbidopa, dopamine agonists, catechol-O-methyltransferase (COMT) inhibitors, levodopa/carbidopa/enacapone, selegiline, amantadine, and centrally acting anticholinergic drugs. Meds manipulate dopamine and acetylcholine. Dopamine is affected the most. No cure for motor symptoms Drug therapy can maintain functional mobility for years (prolongs/improves quality of life). Book (1) dopaminergic agents (ie, drugs that directly or indirectly activate dopamine receptors); and (2) anticholinergic agents (ie, drugs that block receptors for acetylcholine). Of the two groups, dopaminergic agents are by far the more widely employed. (Burchum 177)

Drug to Drug Interaction of MAO-B Inhibitors - Selegiline

Levodopa. When used with levodopa, selegiline can intensify adverse responses to levodopa-derived dopamine. These reactions—orthostatic hypotension, dyskinesias, and psychologic disturbances (hallucinations, confusion)—can be reduced by decreasing the dosage of levodopa. Meperidine. Like the nonselective MAO inhibitors, selegiline can cause a dangerous interaction with meperidine [Demerol]. Symptoms include stupor, rigidity, agitation, and hyperthermia. The combination should be avoided. Selective Serotonin Reuptake Inhibitors (SSRIs). Selegiline should not be combined with SSRIs such as fluoxetine [Prozac]. The combination of an MAO-B inhibitor plus an SSRI can cause fatal serotonin syndrome. Accordingly, SSRIs should be withdrawn at least 5 weeks before giving selegiline. (Burchum 186)

Drug Interactions - SSRIs - fluoxetine

MAOIs and Other Drugs That Increase the Risk of Serotonin Syndrome. MAOIs increase 5-HT availability, and hence greatly increase the risk of serotonin syndrome. Accordingly, use of MAOIs with SSRIs is contraindicated. Because MAOIs cause irreversible inhibition of monoamine oxidase (MAO; see below), their effects persist long after dosing stops. Therefore, MAOIs should be withdrawn at least 14 days before starting an SSRI. Because fluoxetine and its active metabolite have long half-lives, at least 5 weeks should elapse between stopping fluoxetine and starting an MAOI. For other SSRIs, at least 2 weeks should elapse between treatment cessation and starting an MAOI.

Safety Alert - Management of Epilepsy During Pregnancy

Management of Epilepsy During Pregnancy The risk to a fetus from uncontrolled seizures is greater than the risk from AEDs. Therefore, patients with major seizure disorders should continue to take AEDs throughout pregnancy. To minimize fetal risk, the lowest effective dosage should be determined and maintained, and just one drug should be used whenever possible. To reduce the risk of neural tube defects that can occur with AEDs, pregnant patients should take supplemental folic acid before conception and throughout pregnancy. A dose of 2 mg/day has been recommended. Maternal and fetal/infant bleeding risks are also a concern. Phenobarbital, phenytoin, carbamazepine, and primidone reduce levels of vitamin K-dependent clotting factors by inducing hepatic enzymes, increasing the risk of bleeding. To reduce the risk, pregnant patients should be given 10 mg of vitamin K daily during the last few weeks of pregnancy, and the fetus should be given a 1-mg IM injection of vitamin K at birth. (Burchum 234)

Adverse Effects of Lithium (from slides)

Monitor levels every 2 to 3 days at initiation of therapy and then every 3 to 6 months. Renal function (for example, serum creatinine level, creatinine clearance, urinalysis) should be evaluated before the administration of lithium; patients with reduced renal function are at risk for lithium toxicity. Adverse Effects at Excessive Levels Page 367 - Table 33-2 - Signs of Toxicity ****Below 1.5 mEq/L (know these!)-Nausea, vomiting, diarrhea, thirst, polyuria, lethargy, slurred speech, muscle weakness, fine hand tremor ****1.5 - 2 mEq/L (know these!) - Persistent GI upset, coarse hand tremor, confusion, hyperirritability of muscles, ECG changes, sedation, incoordination 2 - 2.5 mEq/L - worsening, ataxia, giddiness, seizures, stupor Above 2.5 mEq/L - convulsions, oliguria, death ***Goiter and Hypothyroidism - Lithium can reduce incorporation of iodine into thyroid hormone, and can inhibit thyroid hormone secretion. With long-term use, the drug can cause goiter. ***Treatment with thyroid hormone (Levothyroxine) or withdrawal of Lithium will reverse goiter and hypothyroidism. Sodium levels: Lithium excretion reduced when sodium level low Plasma levels*** 0.8 to 1.4 mEq/L

MAO-B Inhibitor - Selegiline (Eldepryl, Zelapar)

Monotherapy or used with levodopa Causes selective, irreversible inhibition of type B monoamine oxidase (MAO-B) Reduce "wearing off" effects (off phenom)

Drugs for Bipolar Disorder

Mood stabilizers: Lithium divalproex sodium carbamazepine Formerly known as manic-depressive illness Afflicts an estimated 3.7% of the adult population Mainstays of therapy are lithium & valproic acid Many patients also receive an antipsychotic Chronic condition that requires lifelong treatment Cause may be disruption of neuronal growth and survival

Selective Serotonin Reuptake Inhibitors

Most commonly prescribed antidepressants As effective as tricyclic antidepressants (TCAs) but do not cause hypotension, sedation, or anticholinergic effects Overdose does not cause cardiac toxicity Death by overdose is extremely rare

Adverse Effects of SSRIs - fluoxetine (Prozac)

Most widely prescribed SSRI in the world **Serotonin syndrome (know this specifically)** Begins 2 to 72 hours after treatment Altered mental status (agitation, confusion, disorientation, anxiety, hallucinations, & poor concentration) Incoordination, myoclonus, hyperreflexia, excessive sweating, tremor, and fever Deaths have occurred Resolves spontaneously after discontinuing the drug **Risk increased by concurrent use of MAOIs STOP MAOIs at least 2 weeks prior to starting SSRIs (know this specifically)** Withdrawal syndrome Neonatal effects when used during pregnancy Teratogenesis Extrapyramidal side effects Bruxism Bleeding disorders Sexual dysfunction Weight gain

Safety Alert for Muscle Relaxants

Older Adults anticholinergic effects (eg, blurred vision, constipation, urinary retention, elevated heart rate) older adults are more sensitive to benzodiazepines than younger patients. These drugs may cause sedation and cognitive impairment, thus creating a fall risk. Drug accumulation Carisoprodol, chlorzoxazone, cyclobenzaprine, metaxalone, methocarbamol, orphenadrine, and tizanidine have anticholinergic effects (eg, blurred vision, constipation, urinary retention, elevated heart rate) that may create problems for older-adult patients. At the dosage required to have adequate effect, sedation creates an increased fall risk. In addition, older adults are more sensitive to benzodiazepines than younger patients. These drugs may cause sedation and cognitive impairment, thus creating a fall risk. Long-acting benzodiazepines such as diazepam are particularly troublesome because older-adult patients tend to have a slower metabolism. Elimination may be delayed, and active drug may accumulate. (Burchum 240)

Drug Interactions of New AED - Oxcarbazepine - Page 229

Oral contraceptives made less effective. Phenytoin levels raised - maybe toxic level. Oxcarbazepine affects reduced with phenytoin, phenobarbital, carbamazepine. Don't use with diuretics can lower Na+ too much Oxcarbazepine induces some drug-metabolizing enzymes and inhibits others. It does not induce enzymes that metabolize other AEDs. However, it does induce enzymes that metabolize oral contraceptives, and can thereby render them less effective. Accordingly, women should employ an alternative birth control method. Oxcarbazepine inhibits the enzymes that metabolize phenytoin, and can thereby raise phenytoin levels. Toxicity can result. Phenytoin levels should be monitored and dosage adjusted accordingly. Drugs that induce drug-metabolizing enzymes (eg, phenytoin, phenobarbital, carbamazepine) can reduce levels of MHD, the active form of oxcarbazepine. Accordingly, dosage of oxcarbazepine may need to be increased. Alcohol can intensify CNS depression caused by oxcarbazepine, so it should be avoided. As noted, oxcarbazepine should be used with caution in patients taking diuretics and other drugs that can lower sodium levels.

Patient and Family Education for PCA (Patient-controlled analgesia) - Opioid Agonists

Patient education is important for successful PCA. Surgical patients should be educated preoperatively. Education should include an explanation of what PCA is, along with instruction on how to activate the PCA device. Patients should be told not to fear overdose; the PCA device will not permit self-administration of excessive doses. Families should be informed that activating the device for the patient while he or she is sleeping can lead to drug overdose. Patients should be informed that there is a time lag (about 10 minutes) between activation of the device and production of maximal analgesia. To reduce discomfort associated with physical therapy, changing of dressings, ambulation, and other potentially painful activities, patients should be taught to activate the pump prophylactically (eg, 10 minutes before the anticipated activity). Patients should be informed that, at night, the PCA device will be adjusted to deliver larger doses than during waking hours. This will prolong the interval between doses and thereby facilitate sleep. (Burchum 276-277)

Safety Alert - Varenicline - Page 429

Postmarketing reports indicate that varenicline can cause serious neuropsychiatric effects, including mood changes, erratic behavior, and suicidality. As of February 2011, there were 2925 cases of self-injurious behavior or depression in patients taking varenicline—out of more than 5 million people using the drug. At this time, we don't know if varenicline was the cause of suicidality, or if these patients had an underlying psychiatric illness. All patients should be advised to contact their prescriber if they experience a significant change in behavior or mental status. Varenicline should be used with caution in patients with a history of psychiatric disease.

Patient Education for MAOIs - Dietary

Risk of triggering hypertensive crisis if patient eats foods rich in tyramine: *Severe headache *Tachycardia *Hypertension *Nausea and vomiting *Confusion *Profuse sweating *Stroke *Death strong or aged cheeses like cheddar, blue cheese, or gorgonzola. cured or smoked meats or fish, such as sausage or salami. beers on tap or home-brewed. some overripe fruits. soy products like miso soup, bean curd, or tofu. certain beans, such as fava or broad beans. Note: Drug of choice for atypical depression Isocarboxazid [Marplan] Phenelzine [Nardil] Tranylcypromine [Parnate]

Safety Alert - IV Administration of Phenytoin

Safety Alert IV Administration of Phenytoin The chemical and pharmacodynamic properties of phenytoin present unique challenges for IV administration that can be managed through safe administration. 1. To prevent development of significant hypotension and bradycardia during IV administration of phenytoin, administration should not exceed 50 mg/min in adults. 2. If phenytoin is piggybacked into an existing IV line, only normal saline should be used as the primary IV fluid. The injection hub or IV line should be flushed with normal saline before and after administration. 3. Phenytoin can cause severe tissue damage if the solution infiltrates the area surrounding the IV site. This risk can be decreased by initiating infusion in a larger, easily accessible vein. Close monitoring for extravasation is essential. Normal saline should be injected through the catheter to flush out any residual solution once the infusion is completed. (Burchum 223)

COMT Inhibitors ( catechol-O-methyl transferase) - Entacapone

Selective, reversible inhibitor of COMT Only for use with levodopa Inhibits metabolism of levodopa in the intestines and peripheral tissues Prolongs time that levodopa is available to the brain Increases levodopa availability by inhibiting COMT, which decreases production of levodopa metabolites that compete with levodopa for transport Adverse effects: from increasing levodopa levels

Drug Interactions with Traditional AEDs

Slides: Decreases the effects of oral contraceptives, warfarin, glucocorticoids Increases levels of diazepam, isoniazid, cimetidine, alcohol, and valproic acid Dosing: Highly individualized Administration: With food Book: Drug Interactions Phenytoin interacts with a large number of drugs. The more important interactions are discussed below. Interactions Resulting from Induction of Hepatic Drug-Metabolizing Enzymes. Phenytoin stimulates synthesis of hepatic drug-metabolizing enzymes. As a result, phenytoin can decrease the effects of other drugs, including oral contraceptives, warfarin (an anticoagulant), and glucocorticoids (antiinflammatory/immunosuppressive drugs). Because avoiding pregnancy is desirable while taking antiseizure medications, and because phenytoin can decrease the effectiveness of oral contraceptives, women should increase the contraceptive dosage, or switch to an alternative form of contraception. Drugs That Increase Plasma Levels of Phenytoin. Since the therapeutic range of phenytoin is narrow, slight increases in phenytoin levels can cause toxicity. Consequently, caution must be exercised when phenytoin is used with drugs that can increase its level. Drugs known to elevate phenytoin levels include diazepam (an antianxiety agent and AED), isoniazid (a drug for tuberculosis), cimetidine (a drug for gastric ulcers), and alcohol (when taken acutely). These agents increase phenytoin levels by reducing the rate at which phenytoin is metabolized. Valproic acid (an AED) elevates levels of free phenytoin by displacing phenytoin from binding sites on plasma proteins. Drugs That Decrease Plasma Levels of Phenytoin. Carbamazepine, phenobarbital, and alcohol (when used chronically) can accelerate the metabolism of phenytoin, thereby decreasing its level. Breakthrough seizures can result. CNS Depressants. The depressant effects of alcohol, barbiturates, and other CNS depressants will add with those of phenytoin. Advise patients to avoid alcohol and all other drugs with CNS-depressant actions. (Burchum 223)

Priority Adverse Effect of Epidural and Spinal Anesthesia

The most significant adverse effect of spinal anesthesia is hypotension. Blood pressure is reduced by venous dilation secondary to blockade of sympathetic nerves. (Loss of venous tone decreases the return of blood to the heart, causing a reduction in cardiac output and a corresponding fall in blood pressure.) Loss of venous tone can be compensated for by placing the patient in a 10- to 15-degree head-down position, which promotes venous return to the heart. If blood pressure cannot be restored through head-down positioning, drugs may be indicated; ephedrine and phenylephrine have been employed to promote vasoconstriction and enhance cardiac performance. (Burchum 249)

Tolerance and Physical Dependence - Pure Opioid Agonists

Tolerance: *Increased doses needed to obtain the same response *Develops with analgesia, euphoria, sedation, and respiratory depression *Cross-tolerance to other opioid agonists *No tolerance to miosis or constipation develops Physical dependence: *Abstinence syndrome with abrupt discontinuation *About 10 hours after last dose, the initial reaction occurs and includes yawning, rhinorrhea, and sweating *Progresses to violent sneezing, weakness, nausea, vomiting, diarrhea, abdominal cramps, bone and muscle pain, muscle spasms, and kicking movements *Lasts 7 to 10 days if untreated *Withdrawal is unpleasant but not lethal, as it may be with CNS depressants

Drugs for Muscle Spasm and Spasticity

Two groups of drugs that cause skeletal muscle relaxation *One group for localized muscle spasm *One group for spasticity Most drugs (except dantrolene) produce their effects through actions in the central nervous system (CNS) Groups are not interchangeable Muscle spasm: Involuntary contraction of muscle or muscle group *Causes *Epilepsy *Hypocalcemia *Pain syndromes: Adult and chronic *Trauma: Localized skeletal muscle injury

Treatment with flumazenil (Romazicon) - Page 377

benzodiazepine antagonist...can reverse the sedative effects of benzodiazepines but may not reverse respiratory depression is a competitive benzodiazepine receptor antagonist. The drug can reverse the sedative effects of benzodiazepines but may not reverse respiratory depression. Flumazenil is approved for benzodiazepine overdose and for reversing the effects of benzodiazepines following general anesthesia. The principal adverse effect is precipitation of seizures. This is most likely in patients taking benzodiazepines to treat epilepsy and in patients who are physically dependent on benzodiazepines. Flumazenil is administered IV. Doses are injected over 15 seconds and may be repeated every minute as needed up to a dose of 3 mg. The first dose is 0.2 mg, the second is 0.3 mg, and all subsequent doses are 0.5 mg. Effects of flumazenil fade in about 1 hour, hence repeated doses may be required.