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30 Cards in this Set
- Front
- Back
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History and general characteristics of antipsychotic drugs?
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Neuroleptic; affecting the nervous system
Introduced in early 1950s – chlorpromazine is the prototype Not specific for schizophrenia, but rather used to treat psychosis of any etiology Share central anti-dopaminergic properties |
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What are the typical antipsychotic drugs?
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Chlorpromazine
Haloperidol |
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Chlorpromazine potency and mechanism?
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Low potency
D2 antagonist |
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Haloperidol potency and mechanism?
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High potency
D2 antagonist |
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What are the atypical antipsychotic drugs?
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Clozapine
Risperidone Olanzepine Quetiapine Aripiprazole Ziprasidone |
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Clozapine MOA?
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D2/5-HT2 antagonist
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Risperidone MOA?
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D2/5-HT2 antagonist
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Olanzapine MOA?
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D2/5-HT2 antagonist
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Aripiprazole MOA?
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D2 partial agonist/5-HT2 antagonist
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What is the criteria for the atypical neuroleptic?
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Clinical
1. antipsychotic efficacy 2. low likelihood of extrapyramidal side effects 3. no tardive dyskinesias (long-term) 4. no to small increase in plasma prolactin 5. efficacy on negative symptoms Pre-Clinical 1. greater potency at blocking 5-HT2 serotonin than D2 dopamine receptors Works on both positive and negative symptoms |
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Positive symptoms of schizophrenia?
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Hallucinations
Delusions Conceptual disorganization in speech and behavior Agitation |
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Negative symptoms of schizophrenia?
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Social and emotional withdrawal
Blunted affect Poverty of speech Anhedonia (lack of pleasure) Avolition (lack of initiating goal-directed behavior) |
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Autonomic side effects of typical antipsychotics?
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1. antiadrenergic (mostly α1 and α2)
-- sedation -- orthostatic hypotension 2. anticholinergic -- dry mouth, blurred vision -- urinary retention, sinus tachycardia -- constipation 3. antihistamine -- sedation -- weight gain 4. general toxicity -- skin reactions (photosensitivity) -- jaundice -- ventricular arrhythmias -- agranulocytosis |
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Neuroendocrine side effects of typical antipsychotics?
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Dopamine antagonism in hypothalamic/pituitary tract
Increased prolactin can lead to -- gynecomastia -- galactorrhea -- amenorrhea -- weight gain |
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Neurologic/extrapyramidal side effects (EPS)?
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Treatment involves use of anticholinergic drugs such as benztropine
1. acute dystonia -- muscle spasms 2. pseudoparkinsonism -- rigidity -- tremor -- shuffling gait 3. akasthesia -- motor restlessness 4. tardive dyskinesias -- oral facial dyskinesias -- late onset -- not always reversible |
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What is the rationale for selection of typical antipsychotics?
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Low potency drugs
-- more anticholinergic -- more sedative -- more likely to produce orthostatic hypotension -- CHLORPROMAZINE High potency drugs -- more likely to produce EPS -- much less likely to produce autonomic side effects -- HALOPERIDOL |
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What is the side-effect profile of atypical antipsychotics?
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Relatively similar antiandrenergic, anticholinergic and antihistamine profile as the typical antipsychotics except
1. Risperidone and Quetiapine are not anticholinergic 2. Olanzapine is very antihistaminic NEUROLOGIC/EXTRAPYRAMIDAL(EPS) NEUROENDOCRINE S/Es due to increased prolactin 1. not seen w/ clozapine, olanzapine, quetiapine 2. possible w/ risperidone Greater weight gain with many of the atypicals than the typical antipsychotics Development of Type II DM and hyperlipidemia Neuroleptic malignant syndrome |
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What are the extrapyramidal S/E's of atypical antipsychotics?
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1. in general, much less incidence
2. no reports of dystonia, some of akathesia 3. Risperidone: inicidence of EPS is dose-related; at 4-6mg/day, EPS is low 4. no incidence of tardive dyskinesia -- CLOZAPINE can actually decrease tardive dyskinesias in pts who develop TD w/ typical neuroleptic use |
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Describe the neuroleptic malignant syndrome?
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Clinical features
1. hyperthermia 2. severe EPS 3. autonomic dyxfxn 4. characteristic signs -- clouded consciousness: delirium, mutism, stupor, coma -- leukocytosis: WBC > 15,000 -- elevated CPK: >300 (myoglobinuria, eventually renal failure) Mortality: estimated as high as 30% -- respiratory arrest -- myoglobinuria w/ acute renal failure -- cardiovascular collapse Treatment -- DANTROLENE (↓ hypertherm) + Bromocriptine (stim D2 in brain) -- hydration |
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How does dantrolene decrease hyperthermia?
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↓Ca2+ release from SR to decrease contraction
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What is the most important side effect of clozapine?
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Induced granulocytopenia and/or agranulocytosis
NOT dose related 1. Overall incidence has been claimed to be 1-3% (10-30times higher than with typical drugs) but may actually be about 0.6% 2. Approximately 80% of cases occur w/in the first 18wks 3. Fall in WBC may be abrupt or gradual 4. If total WBC <2000, discontinue |
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What is a treatment for bipolar disorder?
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LITHIUM (usually a later choice)
1. remains standard treatment for bipolar illness -- effective as antimanic agent; may take days to begin to work -- effective for “prophylaxis” of bipolar disorder -- reduces the severity and frequency of mood swings from mania or hypomania to depression -- many patients do not respond (35-50%) 2. typically given as lithium carbonate -- doses range of 300mg to 3000mg as needed to achieve appropriate plasma level about 1mM -- therapeutic range often cited as 0.5-1.4mM |
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Lithium excretion?
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Excreted by kidneys w/ a half life of about 24 hours
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Lithium renal, endocrine and pregnancy side effects?
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RENAL
-- polyuria, due to impaired concentrating ability (interferes w/ action of ADH) and polydipsia. Very common ENDOCRINE -- direct antithyroid effects -- can cause hypothyroidism and goiter PREGNANCY AND NURSING -- increased incidence of CV abnormalities in fetus—avoid use in first trimester of pregnancy; secreted in breast milk |
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Lithium cardiovascular, weight, and CNS effects?
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CARDIOVASCULAR
-- non-specific T wave changes, dysrhythmias, SA block, tachycardia WEIGHT GAIN -- leads to patient non-compliance CNS EFFECTS -- tremor, fatigue, drowsiness, ataxia, and cognitive deficits (slowing, confusion) -- hallucinations, encephalopathy -- worsens myasthenia gravis, delirium, coma |
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What should you warn patients about regarding lithium and sodium intake?
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Inverse relationship between either restricting sodium intake or excessive sodium loss and serum lithium concentrations
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Anticonvulsants?
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Carbamazepine
Oxcarbazepine Valproate |
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Effectiveness of anticonvulsants on mania?
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Comparable effectiveness in mania to Li, w/ similar time course of action
Less information is available about effectiveness of these drugs in prophylaxis of bipolar disorder in comparison w that of Li, but existing info indicated compatibility |
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Carbamazepine interactions?
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Potential for drug-drug interactions as it induces liver enzymes
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MOA of mood stabilizing agents?
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Common effect of Li: to inhibit or dampen processes that are overactive but can cause different behavioral effects
-- overactive excitatory pathways -- overactive inhibitory pathways Inhibits coupling of G-protein coupled receptors to G-proteins. -- seen w/ carbamazepine treatment also -- Li competes w/ Mg ions for low affinity in Mg sites on G-proteins essential for guanine nucleotide exchange Inhibits some enzymes through competition for a Mg++ binding site -- several inositol phosphates so as to decrease agonist-stimulated phosphatidylinositol turnover -- uncompetitive inhibition produces effects that depend on the concentration of enzyme substrate -- thus the greater the receptor stmulation to produce more IP, the greater will be the inhibitory effect of Li+. May account for SELECTIVE effects of Li+ on overactive pathways -- glycogen synthasse kinase-3 (GSK-3) Inhibits agonist-mediated activation of adenyl cyclase to cause less stimulation of cyclic AMP |
