Week 7
CHAPTER 30: ANTIPSYCHOTIC AGENTS AND THEIR
USE IN SCHIZOPHRENIA
CHAPTER 30 OBJECTIVES
At the conclusion of this chapter, the student will be able to:
1. Describe the principal indications for antipsychotic drugs.
2. Discuss antipsychotic agents in regard to groups of drugs and reasons for relief of symptoms.
3. Describe the anticipated responses and reasons for the responses in the use of traditional antipsychotic agents.
4. Differentiate between benefits and side effects of antipsychotic agents.
5. Determine the usual treatments for side effects of antipsychotic agents.
6. Differentiate between high- and low-potency agents.
7. Identify which agents require laboratory tests for evaluation of effects.
8. Discuss indications for nondrug therapy for management of schizophrenia.
CHAPTER 30 OUTLINE
I. Introduction—Antipsychotic agents for schizophrenia, delusional disorders, acute mania, depressive psychoses, drug-induced psychoses, suppression of emesis, treatment of Tourette’s syndrome and Huntington’s chorea
II. Schizophrenia—Clinical Features and Etiology
A. Clinical Features—A chronic psychotic illness with disordered thinking and reduced ability to comprehend reality
1. Positive symptoms (hallucinations, delusions, agitation, tensions and paranoia) and negative symptoms (lack of motivation, poverty of speech, blunted affect, poor self-care, and social withdrawal)
2. Acute episodes—Delusions and hallucinations, loose associations and disordered thinking
3. Residual symptoms—Less vivid symptoms remain
4. Long-term course—Episodic acute exacerbations separated by intervals of partial remission
B. Etiology—Evidence of biologic basis, etiology unknown
III. Conventional Antipsychotic Agents I—Group’s properties (All block dopamine
receptors in CN and all can cause extrapyramidal reactions); known as neuroleptics
A. Classification
1. Classification by potency—Low, medium, or high; differ in potency but equal in ability to relieve symptoms of psychoses; major difference is in side effects
2. Chemical classification—Five categories
B. Mechanism of Action—Vary in ability to block receptors for dopamine, acetylcholine (muscarinic), histamine, and norepinephrine (alpha1); therapeutic effects may be by blocking dopamine2
C. Therapeutic Uses—Schizophrenia primary reason for antipsychotic drugs to suppress symptoms (not cure) and help prevent relapse, with positive symptoms responding better than negative symptoms; also for treatment of bipolar disorder, Tourette’s syndrome, prevention of emesis, Huntington’s chorea, dementia and other organic mental syndromes
D. Adverse Effects—Antipsychotic drugs block several kinds of receptors leading to an array of side effects (see Table 30-5 in the text); on the whole, very safe; worst is TD
1. Extrapyramidal symptoms (EPS) or movement disorder (questionable D2 blockade)
a. Acute dystonia—Early development (hours to days) with spasm of muscles of tongue, face, neck and back including oculogyric crisis and opisthotonus-intense dystonia requires rapid treatment with anticholinergic
b. Parkinsonism—See bradykinesia, mask-like faces, drooling, tremor, rigidity, shuffling gait, cogwheeling and stooped posture inn the first month by blocking dopamine receptors in striatum requiring treatment with anticholinergics and amantadine but NOT Levodopa
c. Akathisia—Pacing ad squirming due to uncontrolled need to be in motion usually from high-potency drugs and should change dosage or drug but may need to give beta blockers, benzodiazepines or anticholinergics
d. Tardive dyskinesia—Most troubling in 15%–20% patients with involuntary choreoathetoid movements of tongue and face and may be irreversible but need to switch to atypical antipsychotic agent; must evaluate patients on long-term therapy first at 12 months then every 3 months to prevent TD
2. Other adverse effects
a. Neuroleptic malignant syndrome (4% mortality rate) with treatment by withdrawing antipsychotic drug, supportive measures (treat hyperthermia, hydrate patient), drugs (dantrolene and bromocriptine) and wait 2 weeks before restarting antipsychotic treatment, lowest dosage, avoid high-potency drugs)
b. Anticholinergic effects from blocking muscarinic cholinergic blockade, which are seen more often with low-potency agents
c. Orthostatic hypotension by blocking alpha1 adrenergic receptors
d. Sedation during early days that subsides
e. Neuroendocrine effects by increasing circulating prolactin, which promotes gynecomastia, galactorrhea and menstrual irregularities; agents must be avoided in prolactin-dependent carcinoma
f. Seizures due to decrease in seizure threshold from agents
g. Sexual dysfunction in males and females leading to noncompliance
h. Dermatologic effects from phenothiazines making skin sensitive to ultraviolet light; can be problem for health care provider if drug is touched
i. Agranulocytosis is rare but more common with chlorpromazine and certain phenothiazines
E. Physical and Psychologic Dependence—Rare but sudden withdrawal may precipitate in mild abstinence syndrome
F. Drug Interactions
1. Anticholinergic drugs intensify anticholinergic responses
2. CNS depressants (ETOH, antihistamines, benzodiazepines, barbiturates)
3. Levodopa counteracts antipsychotic effects of neuroleptics
G. Toxicity—Death by overdosage extremely rare because of large therapeutic index and lethal dose being many times greater; overdosage does occur and emetics cannot be used because of blocking of antiemetic action by neuroleptic
IV. Conventional Antipsychotic Agents II: Properties of Individual Drugs (block dopamine receptors differently, thus low incidence of extrapyramidal reactions)
A. Low-Potency Agents
1. Chlorpromazine (Thorazine) is a phenothiazine; uses (schizophrenia, psychotic disorders, suppression of emesis and relief of intractable hiccoughs); pharmacokinetics (well absorbed orally but bioavailability is 30% due to first pass effect, usually IM, excreted renally); adverse effects (common effects are sedation, orthostatic hypotension and anticholinergic effects with occasional effects of neuroendocrine, photosensitivity, and low risk of extrapyramidal reactions); drug interactions (intensifies CNS depressants and anticholinergic drugs); preparations (comes as tablets, sustained-release capsules, syrup, liquid concentrate, rectal suppositories and injection; use less with elderly)
2. Thioridazine (Mellaril) for schizophrenia and other psychotic disorders
B. Medium-Potency Agents—Loxapine, Molindone, and Perphenazine used for schizophrenia and other psychotic disorders
C. High-Potency Agents—Cause more extrapyramidal reactions but less sedation, orthostatic hypotension and anticholinergic effects
1. Haloperidol (Haldol)—A member of the butyrophenone family; uses (for schizophrenia, acute psychoses and especially for Tourette’s syndrome); pharmacokinetics (orally or IM, hepatic metabolism, excreted in urine); adverse effects (early extrapyramidal reactions occur frequently with uncommon effects of sedation, hypotension, anticholinergic effects and tardive dyskinesia; preparations (tablets, liquid concentrate and parenteral)
2. Other high-potency agents—Fluphenazine (Prolixin, Permitil) is piperazine subclass of phenothiazines; Trifluoperazine (Stelazine) is piperazine subclass of phenothiazines; Thiothixene (Navane); Pimozide (Orap) is approved only for suppressing Tourette’s syndrome
D. Depot Preparations—Long-acting, injectable for long-term maintenance therapy for schizophrenia with no evidence of increased risks with most common drugs; haloperidol decanoate and fluphenazine decanoate are most used
V. Atypical Antipsychotic Agents—Differences from traditional: few or no extrapyramidal symptoms and can relieve positive and negative symptoms of schizophrenia
A. Clozapine (Clozaril) for schizophrenia when other agents do not work or when too many extrapyramidal effects; mechanism of action: blocks mostly dopamine1 receptors and then serotonin, norepinephrine, histamine and acetylcholine; uses: schizophrenia (only if no response to other agents, then 40%–60% success with negative symptoms) and levodopa—induced psychosis; pharmacokinetics: rapidly absorbed orally with half-life 12 hours; adverse effects: common effects include sedation, orthostatic hypotension, weight gain, drug mouth, blurred vision, urinary retention, constipation and tachycardia; low risk of EPS and TD may even improve; neuroendocrine effects, and minimal sexual dysfunction with agranulocytosis being 1%–2%, requiring weekly hematologic studies; seizures occur in 3%; drug interactions: do not give with drugs suppressing bone marrow function due to agranulocytosis
B. Other Atypical Antipsychotics
1. Risperidone (Risperdal)—Rapid-acting (not affected by food) for positive and negative symptoms; not related to clozapine; uses: improvement seen in one week and can be used long-term; adverse effects: infrequent but more with high doses
2. Olanzepine (Zyprexa)—Similar to clozapine but does not cause agranulocytosis: therapeutic effects:effective with few EPSE and does relieve psychosis induced by drugs for Parkinson’s without reversing beneficial effects, unknown for long-term; adverse effects: well tolerated, somnolence in 26%, constipation, and anticholinergic effects and weight gain with long-term use
3. Quetiapine (Seroquel)—For positive and negative symptoms but negative respond less; like other atypical agents
VI. Management of Schizophrenia
A. Drug Therapy—Suppression of acute episodes, prevention of acute exacerbations, and maintenance of highest possible level of functioning
1. Drug selection—With conventional antipsychotic agent initially with choice based on side effects (patients with prostatic hypertrophy or glaucoma should not receive low-potency neuroleptics; patients with extrapyramidal reactions should not receive high-potency drugs and low-potency should be avoided more than high-potency agents); alternative is with atypical agents
2. Dosing—Must be individualized with elderly receiving small doses (30%–50% of younger adult); may need to increase dosages but avoid high doses; note that dosage size and timing may change over time with bedtime dosages helping to promote sleep
3. Routes—Oral is preferred with liquid formulations requiring special handling, IM for severe problems
4. Initial therapy—Symptoms begin to resolve in 1–2 days but 1–2 weeks for significant improvement
5. Maintenance therapy—Chronic therapy but increased adverse risks; after acute, continue for 12 months with gradual withdrawal; depot suited for long-term therapy
6. Adjunctive drugs—Benzodiazepines to decrease anxiety and promote sleep and antidepressants (tricyclic antidepressant)
7. Promoting compliance—Be sure drug swallowed; family to oversee; written instructions of schedule and side effects; relationship with patient and family; use depot for long-term therapy
1. Care counseling—Therapeutic relationship for compliance and evaluation
2. Support CHAPTER 31: ANTIDEPRESSANTS
CHAPTER 31 OBJECTIVES
At the conclusion of this chapter, the student will be able to:
1. Discuss the clinical features of depression.
2. Describe antidepressant therapy.
3. Differentiate among the drugs used for depression.
4. Identify other therapies used for treating depression.
CHAPTER 31 OUTLINE
I. Major Depression—Most common psychiatric illness, 30% of population; with 25% of suicides related to depression; only 30% seek treatment; 85%–90% could be helped; 70% helped with drugs and another 20% with electroconvulsive therapy (ECT)
A. Clinical Features (see Table 31-1 in the text)—Depressed mood and loss of pleasure or interest in all or nearly all of one’s activities and pastimes; also following symptoms: insomnia, hypersomnia, anorexia, weight loss or gain, mental slowing, loss of concentration, feelings of guilt, worthlessness and helplessness, thoughts of death and suicide
B. Pathogenesis—Monoamine hypothesis of depression as a conceptual framework but more complex than this
C. Treatment Modalities—Drugs, electroconvulsive therapy and psychotherapy; for those who do not respond to antidepressants, may add lithium, thyroid hormone, and pindolol or antianxiety agents such as diazepam (not routine, however); CNS stimulants not beneficial
II. Tricyclic Antidepressants (TCAs)—First-choice drugs
A. Chemistry—Similar to 3-ring nucleus of
phenothiazines
B. Mechanism of Action—Block monoamine reuptake,
TCAs additional effects
C. Pharmacokinetics—Long and variable half-lives;
given in single daily dose
D. Therapeutic Uses
1. Depression—Takes 1–3 weeks for initial
responses and up to 2 months
2. Bipolar disorder, chronic insomnia,
attention-deficit/hyperactivity disorder
3. Other uses—Chronic insomnia, ADHD, and panic
disorder
E. Adverse Effects—Orthostatic hypotension is
most common; anticholinergic effects; diaphoresis; sedation; cardiac toxicity
is most serious; seizures; hypomania; and yawngasm if taking clomipramine
F. Drug Interactions—Monoamine oxidase
inhibitors combined leads to severe hypertension; direct-acting sympathomimetic
drugs potentiate responses; indirect-acting sympathomimetic drugs decrease
responses; anticholinergic agents intensify effects; CNS depressants
G. Toxicity—Overdosage
can be life-threatening with anticholinergic and cardiotoxic actions
(dysrhythmias); treatment with gastric lavage, then activated charcoal,
physostigmine, and antidysrhythmics (not procainamide or quinidine)
H. Dosage and Routes of Administration—Low
initial dosages and once per day, usually orally, after effective dosage
established and continued for 6–12 months after remission; select based on side
effects
III. Selective Serotonin Reuptake Inhibitors (SSRIs)—Effective as TCA without hypotension, sedation, or anticholinergic effects; overdose doesn’t cause cardiotoxicity
A. Fluoxetine (Prozac)—The most widely prescribed antidepressant in U.S. since it is as effective as TCAs, has fewer side effects and less dangerous but should avoid MAOIs
1. Mechanism of action—Selective inhibition of serotonin reuptake to intensify transmission at serotonergic synapses, produces CNS excitation rather than sedation
2. Therapeutic uses—For major depression, obsessive compulsive disorder, and is not approved but used for panic disorder and premenstrual syndrome with investigations into bulimia, ETOH abuse, obesity, etc.
3. Pharmacokinetics—Well absorbed regardless of food, 94% protein bound, fluoxetine (half-life 2 days) hepatic conversion to norfluoxetine (half-life 7 days) then excreted in urine and takes 4 weeks for steady state
4. Adverse effects—Sexual dysfunction (70%); nausea (21%); headache (20%); CNS stimulation including nervousness (15%), insomnia (14%), and anxiety (10%); also weight gain up to 20 lb; serotonin syndrome; withdrawal syndrome characterized by dizziness, headache, anxiety, etc.; EPS side effects and other (rash, diarrhea [12%], sweating)
5. Drug interactions—Do not combine with MAOI (can get serotonin syndrome); can replace other protein-bound drugs like warfarin; may elevate TCAs and lithium levels
B. Other SSRIs—Others available: sertraline
(Zoloft), fluvoxamine (Luvox), paroxetine (Paxil), Citalopram (Celexa); none
should be combined with MAOIs
IV. Monoamine Oxidase Inhibitors (MAOIs)—Second- and third-choice drugs especially since major problem is hypertensive crisis with tyramine foods
A. Mechanism of Action—MAO is enzyme in liver, intestinal wall and terminals of monoamine-containing neurons, which convert monoamine transmitters into inactive products—Two forms of MAO (MAO-A and MAO-B); by inhibiting MAO-A there is increased amount of norepinephrine and serotonin available; currently 2 drugs: phenelzine (irreversible inhibition lasting 2 weeks) and tranylcypromine (reversible inhibition)
B. Therapeutic Uses
1. Depression, but only if patient did not respond to other drugs or for atypical depression; takes weeks to reach peak benefits
2. Other uses—Bulimia nervosa, obsessive-compulsive disorders, and panic attacks
C. Adverse Effects—CNS stimulation, orthostatic hypotension, hypertensive crisis with dietary tyramine
D. Drug Interactions—With many drugs with disastrous results and all must be approved by physician: indirect-acting sympathomimetics, drugs inhibiting hepatic MAO, antidepressants (TCAs and SSRIs), antihypertensive drugs, and merperidine
V. Atypical Antidepressants
A. Bupropion (Wellbutrin)—Actions and uses (unique, similar to amphetamine with stimulant properties, suppresses appetite; begins 1–3 weeks; doesn’t cause sexual dysfunction; helps stop smoking); adverse effects (well tolerated but can cause seizures if dose greater than 450 mg); interactions (MAOIs increase risk of toxicity; wait 2 weeks)
B. Other Atypical Antidepressants
1. Trazodone (Desyrel)—Second-line agent for depression; very sedative effects; may cause priapism
2. Nefazodone (Serzone)—Only use for depression; well tolerated; can increase other drugs due to inhibiting hepatic metabolism
3. Venlafaxine (Effexor)—For major depression and generalized anxiety; common effect is nausea; dose-dependent weight loss; can increase BP
4. Mirtazepine (Remeron)—New class increases release of serotonin and NE; causes somnolence; increases appetite
5. Amoxapine (Ascedin) antidepressant with neuroleptic properties; anticholinergic effects; can block dopamine receptors causing EPS
6. Reboxetine (Vestra)—Selective NE reuptake inhibitors; similar effects to TCAs and fluoxetine; new drug
VI. Electroconvulsive Therapy (ECT)—Candidates are severely depressed and suicidal patients, older adults at risk of starving because of depression, and patients who failed to respond to antidepressant drugs; prior to delivery of ECT, patients are given thiopental and succinylcholine
VII. Key Points
VIII. Summary of Major Nursing Implications
A. Implications That Apply to All Antidepressants
B. Tricyclic Antidepressants
C. Selective Serotonin Reuptake Inhibitors
D. Monoamine Oxidase Inhibitors
IX. Special Interest Topics
A. St. John’s Wort: Mother Nature’s Prozac—Herbal preparation used widely for depression; moderately effective; true name is Hypericum perforatum; studies indicate about equal to antidepressants for mild to moderate depression but research designs had flaws and short duration of treatment; don’t know long-term effects
CHAPTER 32: DRUGS FOR BIPOLAR DISORDER
CHAPTER 32 OBJECTIVES
At the conclusion of this chapter, the student will be able to:
1. Identify the principal drugs for bipolar disorder.
2. Describe the best way to determine therapeutic lithium levels.
3. Describe the physiologic problem that significantly affects lithium levels.
CHAPTER 32 OUTLINE
I. Bipolar Disorder (Manic-Depressive Illness)
A. Clinical Manifestations—A cyclic disorder of recurrent fluctuations of mood (mania and depression with periods of normal mood); periods of mania or depression generally last 4–13 months
B. Treatment Strategy—Combination of drugs and psychotherapy
1. Nondrug therapy—Supportive therapy and education
2. Drug therapy
a. Overview of treatment—Mainstay is lithium for manic and depressive episodes and prophylactic; for initial control of acute mania, may combine lithium with benzodiazepine or antipsychotic, then discontinue gradually in about 2 weeks; for depressive phase, may combine with antidepressant; additional drugs for treatment of bipolar disorder include two antiseizure drugs (carbamazepine and valproic acid)
b. Promoting compliance—Patients fail to see anything wrong so stop drugs, need patient and family education
II. Lithium—Symptomatic control
A. Chemistry—Inorganic ion with positive charge, occurs in animal tissues but unknown physiologic function
B. Pharmacokinetics—Well absorbed; short half-life due to rapid renal excretion so need divided daily doses; since similar to other natural elements (potassium and sodium), sodium depletion affects renal excretion (low sodium leads to decreased excretion); plasma lithium levels must be less than 1.5 mEq/L (maintenance levels 0.4 to 1.0 mEq/L), and sodium must be normal—draw levels 12 hours after evening dose
C. Therapeutic Uses—Bipolar disorder takes 2–3 weeks for full effect; has also been used with other psychiatric disorders with varying success
D. Mechanism of Action—Do not know how it really works for bipolar disorders
E. Adverse Effects—Monitor plasma levels every 2–3 days initially, then 1–3 months
1. Effects from excessive drug levels—Death at >2.5 mEq/L
2. Effects occurring at therapeutic levels—Fine hand tremor; polyuria (in 50%–70%) but can be decreased with thiazide diuretic; renal toxicity (with chronic use), goiter; teratogenesis; use in lactation—enters breast milk and can be potentially harmful to infant
F. Drug Interactions—Diuretics and anticholinergics
G. Preparation and Dosage—Available in two salts (lithium carbonate and lithium citrate) and can cause GI upset (administer with milk or meals); base dosage on plasma levels and dosage is 3–4 times per day
III. Anticonvulsants—Carbamazepine (Tegretol, etc.) and valproic acid (Depakene, Depakote) are given in combination with lithium initially
A. Carbamazepine—May be superior choice for severe mania with rapid cycles, target plasma levels of 6–12 μg/ml; side effects include sedation, GI disturbance, tremor, leukopenia and hepatotoxicity
B. Valproic Acid—For those who cannot tolerate other drugs, therapeutic levels in 1–2 weeks, side effects include sedation, nausea, tremor, hepatotoxicity and hair loss; plasma levels of 50–125 μg/ml; valproic acid alters GABA
IV. Key Points
V. Summary of Major Nursing Implications
A. Lithium
VI. Special Interest Topics
A. Omega-3 Fatty Acids for Bipolar Disorder—Research study from Harvard found that 9.6 gm of fish oil daily improved patients with bipolar disorder
CHAPTER 33: BENZODIAZEPINES AND OTHER DRUGS
FOR ANXIETY AND INSOMNIA
CHAPTER 33 OBJECTIVES
At the conclusion of this chapter, the student will be able to:
1. Discuss the drugs used to treat anxiety.
2. Differentiate between barbiturates and benzodiazepines.
3. Identify treatment of benzodiazepine overdosage.
4. Describe the important considerations when using benzodiazepines for insomnia.
CHAPTER 33 OUTLINE
I. Introduction—Anxiety and insomnia common complaints; can use same drugs with different dosages
A. Drugs used for anxiety called “antianxiety agents” or “anxiolytics” (old term was “tranquilizers”)
B. Drugs used for sleep known as “hypnotics”
C. Historical Perspective—Barbiturates and CNS depressants were used before benzodiazepines
II. Benzodiazepines—First choice for treating anxiety and insomnia; most produce identical effects
A. Overview of Pharmacologic Effects—Actions on CNS
1. CNS—Depressant action on CNS (benefit and adverse effect) by depressing neuronal function at multiple sites (antianxiety at limbic system, sleep at cortical area, muscle relaxation at supraspinal motor area, side effects of confusion and anterograde amnesia by effects on hippocampus and cerebral cortex)
2. Cardiovascular system—Negligible effects when taken orally, IV dosages can produce hypotension and cardiac arrest
3. Respiratory system—Weak depressants but caution in patients with COPD and obstructive sleep apnea (OSA)
B. Molecular Mechanism of Action—Potentiates the actions of gamma-aminobutyric acid (GABA) which is an inhibitory neurotransmitter
C. Pharmacokinetics
1. Absorption and distribution—Lipid-soluble
2. Metabolism—Metabolites very active
3. Time course of action—Selection based on time course
4. Therapeutic uses—Three major uses: anxiety, insomnia, and seizure disorders; also for muscle spasm, ETOH withdrawal, panic disorder, and anesthesia induction
5. Adverse effects—CNS depression, anterograde amnesia, paradoxical effects, respiratory depression, and low incidence of abuse (Schedule IV); not for pregnancy and lactation (most are class D, 4 are class X)
6. Drug interactions—Additive effect to other CNS depressants (including ETOH) and can lead to respiratory depression, coma, and death
7. Tolerance and physical dependence—Little or no tolerance with anxiolytic and hypnotic effects but significant tolerance to antiseizure effects; dependence low, but most common one is alprazolam (Xanax); discontinue gradually
8. Acute toxicity—Oral dosage rarely causes problems but can be removed with lavage and activated charcoal; IV can cause severe life-threatening reactions; sedative effects can be reversed with flumazenil (Romazicon)
III. Barbiturates—Nonselective depression of CNS; can be used for daytime sedation, induction of sleep suppression of seizures, and general anesthesia (powerful respiratory depressants that can be fatal with overdosage)
A. Classification—Ultrashort-acting, short-to-intermediate acting, and long-acting
B. Mechanism of Action—Bind to GABA and can mimic action or enhance inhibitory action of GABA; also depress the reticular activating system
C. Pharmacologic Effects—CNS depression, cardiovascular effects, induction of hepatic drug-metabolizing enzymes
D. Tolerance and Physical Dependence—Cross-tolerance occurs, and prolonged use results in physical dependence
E. Pharmacokinetics—Lipid-soluble so rapid redistribution occurs in highly lipid-soluble; low-lipid solubility has prolonged duration with long half-lives
F. Therapeutic Uses—Insomnia, seizure disorders, induction of anesthesia
G. Adverse Effects—Respiratory depression, abuse (overdosage resulting in death), exacerbation of intermittent porphyria, paradoxical excitement, hyperalgesia, hangovers; should not be used in pregnancy; potential for abuse
H. Drug Interactions and Toxicity—Interacts with other CNS depressants, since it stimulates hepatic drug-metabolizing enzymes, some medications need increased dosages (warfarin, oral contraceptives, phenytoin)
I. Acute Toxicity—Medical emergency with classic symptoms (respiratory depression, coma, and pinpoint pupils); treatment includes removing drug from body and providing oxygen to brain
J. Preparations, Dosage, and Administration—Routes
A. Buspirone (BuSpar)—Does not cause sedation; no abuse potential; does not enhance depression caused by CNS depressants; devoid of hypnotic, muscle relaxant and anticonvulsant actions with disadvantage of delayed anxiolytic effects
1. Therapeutic use—Short-term use for anxiety; takes 1–2 weeks to develop antianxiety effects
2. Adverse effects—Dizziness, nausea, headache, nervousness, lightheadedness, and excitement with little risk of suicide
3. Drug and food interactions—Increased by erythromycin, ketoconazole, and grapefruit juice
4. Tolerance, dependence, and abuse—Used for up to 1 year without evidence of tolerance, physical or psychologic dependence
B. Zolpidem (Ambien)—For short-term management of insomnia; binds to GABA; plasma level peaks in 2 hours after oral dose with side effects of daytime drowsiness and dizziness
C. Zaleplon (Sonata)—New class of hypnotics; rapid onset, short duration; helps for falling asleep not for staying asleep
D. Miscellaneous General CNS Depressants—Similar to barbiturates; all are potentially dangerous and include chloral hydrate, glutethimide, meprobamate, paraldehyde, and ethchlorvynol
V. Management of Anxiety—DSM-IV divides anxiety disorders into six classes: generalized anxiety disorder (GAD), panic disorder, phobic disorders, obsessive-compulsive disorder, post-traumatic stress disorder, and acute stress disorder
A. Contrasts Between Situational Anxiety and Generalized Anxiety Disorder
1. Situational is a normal response to stressful situations; short-term
2. GAD is unrealistic or excessive anxiety that lasts 6 months
B. Treatment of GAD—With nondrug therapy (supportive therapy, cognitive therapy, biofeedback, and relaxation training) and anxiolytics, such as benzodiazepines (diazepam and alprazolam) and buspirone; also antidepressants (imipramine, amitriptyline, and trazodone) and beta blockers
VI. Management of Insomnia—An inability to sleep
A. Sleep Physiology—Rapid eye movement (REM) and nonrapid eye movement (NREM)
B. Causes of Insomnia—The inability to sleep; about 10% of U.S. population have a problem
C. Management Strategy
1. Nondrug management—Avoid naps, decrease caffeine beverages, restful activity before bedtime, sleep fitness rules
2. Cause and specific drug therapy—Treat underlying medical disorder
3. Therapy with hypnotic drugs—Used when other means do not work
D. Transient Insomnia—Basic guidelines for drug therapy: short-term therapy, hypnotics, but when using these, prevent drug-dependency insomnia
E. Transient Insomnia—Specific drugs used for treatment: benzodiazepines, barbiturates, other CNS depressants, and over-the-counter drugs
VII. Key Points
VIII. Summary of Major Nursing Implications
A. Benzodiazepines
B. Barbiturates
CHAPTER 34 OBJECTIVES
At the conclusion of this chapter, the student will be able to:
1. Discuss the effects of amphetamines on the CNS.
2. Describe the most common adverse effects of
amphetamines.
3. Describe the treatment for
attention-deficit/hyperactivity disorders.
4. Discuss the action of caffeine and other
methylxanthines.
CHAPTER 34 OUTLINE
I. Introduction to Central Nervous System (CNS) Stimulants—Most act by enhancing neuronal excitation; at sufficient dosage all can cause convulsions; currently two principal indications (ADHD and narcolepsy)
II. Amphetamines—Family consists of amphetamine,
dextroamphetamine, and methamphetamine; in addition to CNS stimulation, can
cause cardiac stimulation and vasoconstriction; have high potential for abuse
A. Chemistry—Can have mirror images (optical isomers or enantiomers)—dextroamphetamine and levamphetamine): similar effects but dextroamphetamine more selective for CNS and less peripheral side effects; amphetamine (50:50 mixture of dextroamphetamine and levamphetamine); mechanism of action (promote release of biogenic amines of norepinephrine, dopamine, and serotonin from neurons)
B. Pharmacologic
Effects—CNS (affect mood and arousal, increase wakefulness and alertness,
reduce fatigue, elevate mood, and augment self-confidence, initiative,
stimulate respirations, suppress appetite and pain, and likely result in
euphoria, talkativeness, and increased motor activity); cardiovascular system
(secondary to release of norepinephrine from sympathetic nerves to increase AV
conduction, heart rate, and force of contraction, which can produce
dysrhythmias and vasoconstriction, leading to hypertension)
C. Tolerance—Develops to elevation of mood,
suppression of appetite, and stimulation of heart and blood vessels requiring
up to 1000 mg (IV) every few hours
D. Physical Dependence—Abstinence syndrome occurs
with abrupt withdrawal in long-term users with symptoms of exhaustion,
depression, prolonged sleep, excessive eating, and craving of drug)
E. Abuse—Caused by euphoria, so get psychologic
dependence, as with cocaine
F. Adverse Effects
1. CNS stimulation—Insomnia, restlessness, extreme loquaciousness
2. Weight loss—For obese patients, desirable;
for lean patients, an adverse effect
3. Cardiovascular effects—Dysrhythmias, anginal
pain, and hypertension
4. Psychosis—Paranoid psychosis characterized
by hallucinations and paranoid delusions that look like schizophrenia; thought
to be a result from release of dopamine
5. Acute Toxicity—Symptoms (overdosage produces dizziness, confusion, hallucinations,
paranoid delusions, palpitations, dysrhythmias and hypertension with fatal OD
rare but associated with convulsions, coma and cerebral hemorrhage); treatment (hallucinations with
chlorpromazine, hypertension with alpha-adrenergic blocker like phentolamine,
seizures with diazepam, and acidification of urine accelerates excretion)
1. Attention-deficit/hyperactivity disorder (ADHD)
2. Narcolepsy—Daytime somnolence and
uncontrollable attacks of sleep are alleviated by amphetamines due to arousal
effects
3. Obesity—Have been used but high potential for
abuse, so not good choice
H. Dosage and Administration—Four oral preparations; IV is illegal
III. Methylphenidate (Ritalin)—Similar to amphetamines with same mechanism of action, adverse effects and abuse liability and used for ADHD and narcolepsy
IV. Methylxanthines—Xanthine family
1. Dietary sources—In chocolate, and beverages (cola nut), tea and coffee
2. Mechanism of action—Proposed is reversible blockade of adenosine receptors, enhancement of calcium permeability in sarcoplasmic reticulum and inhibition of cyclic nucleotide phosphodiesterase, so get an increase of cyclic adenosine monophosphate (cyclic AMP)
3. Pharmacologic effects—CNS (decreases drowsiness and fatigue and increases capacity for prolonged intellectual exertion, but increasing dosages lead to nervousness, insomnia and tremors and convulsions); heart (dysrhythmias); blood vessels (periphery has vasodilation, in CNS get vasoconstriction); bronchi (relaxes bronchial smooth muscle, especially theophylline); kidney (diuretic); reproduction (concern about ingestion of caffeine causing fetal harm, no real association)
4. Pharmacokinetics—Readily absorbed from GI tract and peaks 1 hour, half-life is 3–7 hours and eliminated by hepatic metabolism
5. Therapeutic uses
a. Neonatal apnea—Promotes more regular breathing
b. Promoting wakefulness—Many OTC drugs or drink coffee, etc.
c. Other applications—IV caffeine may relieve headaches from spinal punctures; PO to enhance analgesia by opioids and NSAIDs
6. Acute toxicity—In poisoning, see CNS excitement, restlessness, and insomnia; with large doses, see convulsions, tachycardia, respiratory stimulation and rarely death (5–10 grams)
7. Preparation, dosage, and administration—PO capsules and tablets, IV and IM injections
B. Theophylline—Like caffeine, good for asthma because of bronchodilation (Chapter 69)
C. Theobromine—Occurs in seeds of Theobroma cacao used to make cocoa and chocolate; low caffeine; this is not a CNS stimulant
V. Miscellaneous CNS Stimulants
A. Pemoline—Like amphetamines with less cardiac and vasoconstriction-hepatic problems
B. Modafinil (Provigil)—New drug only for narcolepsy
C. Strychnine—Rat poison; powerful convulsant and remains poison potential
D. Doxapram—Stimulates respiration but dangerous drug
E. Cocaine—Powerful CNS stimulant with high abuse potential
VI. Attention-Deficit/Hyperactivity Disorder (ADHD)
A. ADHD in Children—Most common psychiatric disorder of childhood; boys 4–8 times greater incidence; symptoms between ages 3–7, persist into teens
1. Signs and symptoms—Inattention, hyperactivity, impulsiveness, fidgety behaviors, inability to concentrate on schoolwork, inability to wait turn, calling out excessively in class, and not completing tasks; symptoms appear before age 7 and last at least 6 months
2. Etiology—Underlying pathophysiology not completely established but thought to be dysregulation in neuronal pathways that employ monoamine transmitters
3. Management overview—Drugs, family therapy, parent training and cognitive therapy for child
4. Treatment with stimulant drugs—Most effective are methylphenidate (Ritalin), dextroamphetamine (Dexedrine), and pemoline (Cylert)
a. Methylphenidate (Ritalin)—70% receive this; it increases attention span and goal-oriented behavior while decreasing impulsiveness, distractibility, hyperactivity and restlessness; dosages come in tablets given 2–3 times per day or sustained release given 1 time per day; symptoms and blood levels followed; may affect growth; therefore weekends off and periodic time off (summers off) to assess need and minimize growth suppression
b. Dextroamphetamine (Dexedrine)—For some who fail to respond to methylphenidate
c. Amphetamine mixture (Adderall)—Has prolonged action
d. Pemoline (Cylert)—Less effective; has prolonged life; may be hepatotoxic; lower abuse
5. Treatment with nonstimulant drugs
a. Tricyclic antidepressants—Decrease hyperactivity with little effect on impulsivity and inattention; slow response takes 2–3 weeks and peaks in 6 weeks; must continue therapy
b. Clonidine (Catapres)—Reduces hyperactivity and impulsiveness with hypotension and sedation major side effects
B. ADHD in Adults—Can persist into adulthood with symptoms of poor concentration, stress intolerance, antisocial behavior, outbursts of anger, and inability to maintain a routine; 33% of adults fail to respond to stimulants or can’t tolerate side effects; try nonstimulants
VII. Key Points
VIII. Summary of Major Nursing Implications
A. Amphetamines and Methylphenidate
B. Caffeine
CHAPTER 35 OBJECTIVES
At the conclusion of this chapter, the student will be able to:
1. Discuss the treatment and outcomes for panic disorders.
2. Discuss the obsessive-compulsive disorder treatments.
3. Discuss Alzheimer’s disease.
4. Describe the therapeutic modalities for Alzheimer’s disease.
5. List the major adverse effects of treatment modalities for Alzheimer’s disease.
CHAPTER 35 OUTLINE
I. Panic disorder
A. Characteristics—Recurrent, intensely uncomfortable episodes of panic attacks with sudden onset, peak intensity within ten minutes, and dissipation within 30 minutes; many experience agoraphobia; must have four or more of the following symptoms:
1. Palpitations, pounding heart, racing heartbeat
2. Chest pain or discomfort
3. Feeling of choking
4. Dizziness, lightheadedness
5. Nausea or abdominal discomfort
6. Derealization or depersonalization
7. Fear of losing control or going crazy
8. Fear of dying
9. Tingling or numbness in the hands
10. Flushes or chills
B. Treatment—70%–90% respond well to treatment; use drug and cognitive-behavioral therapies; drug therapy suppresses panic attacks while cognitive-behavior therapy helps patients become more comfortable; avoid caffeine and sympathomimetics, sleep deprivation and do regular exercise; primary drugs are antidepressants and benzodiazepines; continue drug therapy for 6–9 months; relapse may occur if stop therapy early
1. Antidepressants—Initial drugs of choice; decrease frequency and intensity of attack, anticipatory anxiety and avoidance behaviors; all three classes (SSRIs, tricyclic antidepressants, and MAOIs) are all equally effective; start dosages low and increase slowly; MAOIs cause significant adverse effects and have to adhere to tyramine-free diet
2. Benzodiazepines—Alprazolam (Xanax) provides rapid and effective protection against panic attacks; reduces anticipatory anxiety and phobic avoidance in first few doses; tolerance develops to sedation in about 7–10 days; withdraw drugs slowly
II. Obsessive-Compulsive Disorder (OCD)
A. Characteristics—Potentially disabling with persistent obsessions and compulsions causing marked distress, consume at least one hour/day and interfere with daily living; obsession is recurrent, persistent thought, impulse or mental image that is unwanted and distressing; compulsion is ritualized mental act or behavior that patient is driven to perform in response to obsession
B. Treatment—Drug and behavioral therapy; five drugs approved for use and all are antidepressants (one TCA which is clomipramine and 4 SSRIs which are fluoxetine, fluvoxamine, sertraline, and paroxetine) and treatment should be continued for 10 weeks
1. Clomipramine (Anafranil) is only tricyclic antidepressant (TCA) effective in OCD; 70% get significant improvement; start low and increase gradually; take with meals and divided doses to decrease side effects; does cause multiple adverse effects (sedation, dizziness, tremor in 50%); other effects are weight gain, constipation, etc.
2. Selective serotonin reuptake inhibitors—Fluoxetine (Prozac), fluvoxamine (Luvox), sertraline (Zoloft), and paroxetine (Paxil) are approved for OCD; enhanced serotonergic transmission; may get insomnia, anorexia, dyspepsia, and sexual dysfunction but safer than the TCA
III. Alzheimer’s Disease (AD)—Characterized by progressive memory loss, impaired thinking, personality changes and inability to perform routine tasks of daily living; cost is high; no clearly effective therapy
A. Pathophysiology—Unknown cause
1. Degeneration of neurons—Occurs in hippocampus (memory) then degeneration of neurons in cerebral cortex (speech, perception, reasoning, etc.)
2. Degeneration of neurotransmitters—Degeneration occurs in hippocampus early in AD, followed by degeneration in cerebral cortex
3. Reduced cholinergic transmission—In advanced AD levels of ACh decrease by 90%; ACh important transmitter in hippocampus and cerebral cortex; ACh also critical to forming memories but cannot explain cognitive deficits early in disease
4. Neuritic plaques and beta-amyloid—Neuritic plaques outside neurons are hallmark of AD; beta-amyloid present in high levels
5. Neurofibrillary tangles and tau—Neurofibrillary tangles are prominent feature of AD; underlying is the abnormal tau (normal protein that forms cross bridges)
6. Apolipoprotein E4 (apoE)—Known for cholesterol transport now linked to AD
7. Endoplasmic reticulum-associated binding protein—Compound with neurotoxic effects
B. Risk Factors, Symptoms, and Diagnosis
1. Risk factors—Major factor is advancing age (>65); being female may also be risk factor
2. Symptoms—Symptoms intensify in evening (“sundowning”)
3. Diagnosis—No specific test; diagnosis at autopsy; diagnosis by exclusion
C. Drug Therapy—Only two drugs (tacrine and donepezil) are approved by FDA; tacrine and donepezil enhance cholinergic transmission and have modest effects
1. Tacrine—A cholinesterase inhibitor (Cognex)
a. Mechanism of action—Reversible inhibitor of AChE so increased availability of ACh; helps those with transmission in tact
b. Therapeutic effect—For mild-to-moderate AD; some respond with modest improvement that is short-lived
c. Adverse effects—Hepatotoxicity common and troubling; check ALT every 2 weeks for first 4 months, then gradually go to every 3 months
2. Other cholinesterase inhibitors
a. Donepezil (Aricept)—Recently approved; inhibits AChE to enhance transmission; does not injure liver
b. Metrifonate and Rivastigmine—Investigational drugs
3. Other preparations for Alzheimer’s disease
a. NSAIDs (ibuprofen) can decrease risk of AD (10 times reduced with NSAIDs); estrogens appear to decrease risk by 30%–40%; vitamin E and selegilline, researchers say, can slow disease progression in moderately severe cases, but study was flawed; acetyl-L-carnitine is similar to ACh and has improved cognition in AD; gingko biloba is herbal therapy with benefits like tacrine
4. Drugs for delusions, agitation, anxiety, and depression—Haloperidol, clozapine, or risperidone help with delusions; propranolol, trazodone, thioridazine, and haloperidol for agitation; lorazepam and buspirone help with anxiety; fluoxetine helps with depression; tricyclic antidepressants may make AD worse
IV. Key Points