Term
| what is the butyrophenone antipsychotic? |
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Definition
| **haloperidol (high potency) |
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Term
| what is the phenylbutyl-piperidine antipsychotic? |
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Definition
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Term
| what are the phenothiazine antipsychotics? |
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Definition
| aliphatics (low potency): **chlorpromazine, promazine, triflupromazine. piperazines (high potency): pimozidefluphenazine, *prochlorperazine, trifluoperazine. piperidines (low potency): mesoridazine, piperacetazine, thioridazine. |
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Term
| what is the thioxanthine antipsychotic? |
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Definition
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Term
| what are the atypical antipsychotics? |
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Definition
| aripiprazole, risperidone, paliperidone, ziprasidone, zonisamide, and the dibenzepines: *clozapine, loxapine, *olanzapine, quetiapine |
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Term
| what is the MOA for the typical antipsychotic agents? |
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Definition
| 1) alpha adrenergic blockade [antisympathetic - ADRs: vasodilation, postural hypotension, etc]. 2) anticholinergic blockade at M1 (CNS), M2 (CV), and M3 (smooth muscle) sites [antiparasympathetic - ADRs: mydriasis, dry mouth, constipation, urinary retention, tachycardia - more common w/low potency [LP] agents - require higher dose]. 3) antihistaminic: H-1 blockade. 4) hypothermic [will reduce normal body temperature]. 5) D2 dopamine blockade [schizophrenia is thought to be due to hyperactivity of central dopaminergic systems (converted to homovanillic acid in CSF which can then reach plasma), esp the mesolimbic]. |
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Term
| what are the typical antipsychotic agents indicated for? |
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Definition
| psychosis, acute mania, organic mental syndromes (delirium, dementia), severe anxiety unresponsive to other drugs, ballismus, alcoholic hallucinosis, antiemetic (phenothiazines and butyrophenones), gilles de la tourettes syndrome, huntington's, intractable hiccough (promethazine, methdilazine, trimeprazine), and extensive pruritus |
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Term
| what characterizes the effect of the typical antipsychotics on psychosis? |
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Definition
| *improvement in: anorexia, combativeness, delusions, hallucinations, hostility, hyperactivity, insomnia, negativism. *lack of improvement in: insight, judgment, memory. acutely: efficacy may occur in 1-2 days. chronically: several weeks of drug administration my be required w/progressive dosing. |
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Term
| what ANS ADRs are associated w/the typical antipsychotics? (*know these*) |
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Definition
| blurred vision, mydriasis, dry mouth, constipation, urinary retention, tachycardia (anticholinergic actions more likely w/LP agents). |
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Term
| what endocrine ADRs are associated w/the typical antipsychotics? |
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Definition
| amenorrhea, galactorrhea (increased milk production due to increased prolactin - normally inhibited by DA, avoid in breast CA pts), gynecomastia (DA blockade), inhibition of ejaculation (w/o erection interference), wt gain (common w/atypical drugs). |
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Term
| what CV ADRs are associated w/the typical antipsychotics? |
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Definition
| hypotension (orthostatic), reflex tachycardia, EKG abnormalities (more likely w/LP agents). *hypersensitivity: skin rash, gray/blue skin discoloration, jaundice, photosensitivity . |
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Term
| what CNS ADRs are associated w/the typical antipsychotics? |
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Definition
| sedation, confusion, drowsiness, EPRs (avoid these drugs in geriatric pts). |
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Term
| what early onset EPR (extrapyramidal reaction) ADRs are associated w/the typical antipsychotics? |
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Definition
| early onset EPRs: akathisia (uncontrollable motor restlessness in the lower extremities), dystonia/torticollis (muscle spasms of face, tongue, neck + trismus [lock jaw]), parkinson-like syndrome (akinesia, bradykinesia, suffling gait, resting tremor). these are most frequent w/high potency (HP) derivatives piperazines (trifluoperazine) and butyrophenones (haloperidol) in children and geriatric pts. tx options: reduce dose, change to LP agent, and pharmacotherapy (anticholinergic, DA agonist [amantadine]). as more D2 receptors are blocked - EPRs increase. |
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Term
| what late onset EPR (extrapyramidal reaction) ADRs are associated w/the typical antipsychotics? |
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Definition
| late onset EPRs: *tardive dyskinesia (TD), repetitive involuntary movements of the jaw, lips, tongue (may involve neck/trunk) which cease while the pt sleeps. any type of neuroleptic agent can induce TD, which is possibly related to compensatory increases in DA activity w/in the CNS due to blockade. this may remain after drug termination, therefore antipsychotics should be used conservatively and discontinued if TD appears. *neuroleptic malignant syndrome (NMS), more common w/HP antipyschotics, characterized by catatonia/tremor/ANS instability (hyperthermia). fatal in 10% of pts - but w/monitoring, rapid d/c of offending drug and rapid initiation of tx (bromocriptine, dantrolene: antepyretic), fatality risk is low. *seizures. *pseudodepression. |
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Term
| what hematologic ADRs are associated w/the typical antipsychotics? |
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Definition
| leukocytosis, leukopenia, agranulocytosis (lower risk w/chlorpromazine, higher risk w/clozapine - patients should be monitored weekly) |
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Term
| what genital ADRs are associated w/the typical antipsychotics? |
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Definition
| priapism: painful, prolonged (congestion/swelling) penile erection which does not result from sexual desire - rather failure of detumescence (dysregulation of ANS). this is considered a urologic emergency b/c if not treated w/in 4-6 hrs = fibrosis/permanent impotence. not dose related or related to duration of tx, may be related to alpha-1 adrenergic blocking activity (agonists are tx) and higher rates are seen w/thioridazine/chlorpromazine (LP agents). tx: ice pack, alpha 1 adrenergic agonists, and decompressive sx. |
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Term
| what ocular ADRs are associated w/the typical antipsychotics? |
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Definition
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Term
| what is the MOA for the atypical antipsychotic agents? |
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Definition
| increased blockade of the 5HT-2A (serotonin) receptor vs the D2 receptor |
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Term
| is there a risk in treating elderly pts w/dementia-related psychosis w/any antipsychotics? |
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Definition
| yes - there is an increased mortality rate, due apparently to CV or infectious etiology |
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Term
| what are the common atypical antipsychotics? |
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Definition
| clozapine, risperidone, paliperidone, pimozide |
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Term
| what characterizes clozapine? MOA? |
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Definition
| first atypical antipsychotic, developed to reduce the incidence of EPR, but major problem is increased agranulocytosis. like typical antipsychotics it blocks D2 receptors (but weakly) as well as blocking M1/2/3 receptors and alpha 1/2 adrenergic receptors. however, it is **also a D1 antagonist and 5HT-2A antagonist - *but does not produce parkinsonism. |
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Term
| what characterizes management of clozapine in terms of agranulocytosis? |
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Definition
| clozapine requires a weekly CBC. if mild leukopenia (3000-3500 WBC/mm3), the CBC needs to be performed 2x/week. if leukopenia (<3000 WBC/mm3 or <1500 granulocytes/mm3), immediate d/c. if agranulocystosis (<1000 WBC/mm^3 or <500 granulocytes/mm^3), the pt can never receive clozapine again. |
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Term
| what CNS ADRs are associated w/clozapine? |
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Definition
| confusion, sedation, seizures (higher rate than w/other antipyschotics, mostly grand-mal [tonic-clonic], carbamazepine is effective). prolonged psychotic relapse is also a potential risk following abrupt withdrawal. |
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Term
| what characterizes risperidone? |
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Definition
| high affinity: blockade of alpha 1/2 adrenergic, H-1, and 5HT-2A > D2 receptors. moderate-low affinity: D-1, 5HT-1A, 5HT-1C, 5HT-1D. does not interact w/cholinergic or beta receptors. claims less EPRs than clozapine (poss. due to 5HT-2 block > D-2 block). biotransformed by CYP to active metabolite (9-OH-risperidone; **paliperidone) in t1/2 hrs, which then has a t1/2 of 21 hrs = potential drug interactions, and necessity for decreased dose in geriatri/hepatic/renally impaired pts. ADRs: orthostatic hypotension, cardiac arrhythmias, neuroleptic malignant syndrome, and tardive dyskinesia. |
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Term
| what characterizes paliperidone? |
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Definition
| this active metabolite of risperidone is used in schizophrenia tx (PO/IM), but not dementia-related psychosis. ADRs: EPRs, tachycardia, orthostatic hypotension, sleepiness. |
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Term
| how do clozapine and olanzapine compare in terms of t1/2, D2 %, 5HT-2A %, pos/neg symp, depol block, and ADRs? |
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Definition
| *clozapine: t1/2: 10 hrs, D2%: 15-60, 5HT%: 80-90, 2+pos, 1+ neg, depol block: meso-limbic, ADRs: agranulocystosis, wt gain. *olanzapine: t1/2: 31 hrs, D2%: 60, 5HT%: 0, 1+pos, 1+ neg, depol block: meso-limbic, ADRs: wt gain. (pos symp: hallucinations, delusions, reality distortions, neg symp: anhedonia, social withdrawal) |
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Term
| what is the risk w/5HT-2A > > D-2? |
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Definition
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Term
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Definition
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Term
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Definition
| agonist at H-1 ≈ sedation |
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Term
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Definition
| blocks reuptake of NE and DA – useful in assoc. depression |
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Term
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Definition
| reserved for treatment of motor and phonic tics in patients with tourette's syndrome - indicated when other tx has failed or tics are severe. ADRs are the same as other neuroleptics |
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Term
| what characterizes the antimanic drugs? |
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Definition
| lithium is the mainstay. it does not have any specific CNS depressant effect, just a "mood stabilizing effect". t1/2: 20-24 hrs, onset of therapeutic effect: 6-10 days. it is the DOC for bipolar disorder but may also be used for acute mania, prevention of mania/depression, alcoholism if 2/2 to primary mood disorder, and aggressive behavior. |
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Term
| what is the safe therapeutic plasma range for lithium? (know this) |
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Definition
| 0.75 - 1.25 mEq/L - usually achieved by 900 mg/daily (blood sample drawn right before AM dose: usually 12 hrs after PM dose [plasma levels most stable before dosing] -> 2x/wk @ initiation, 1x/2 mos for stable pts). depletion of Na+ (diuretics, diarrhea) can cause greater retention of Li+ and lead to ADRs. however, in heavy sweating, Li+ may be secreted > Na+. toxic reactions can occur at levels below 1.0 mEq/L. |
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Term
| what ADRs are associated w/Li+ at mild intoxication (> 1.5 mEq/L)? |
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Definition
| ataxia, abdominal pain, diarrhea, n/v, small tremors, sedation, tinnitus |
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Term
| what ADRs are associated w/Li+ at mod intoxication (1.5 -> 2.5 mEq/L) to severe intoxication (> 2.5 mEq/L)? |
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Definition
| CNS: confusion---> coma---> death, respiratory depression, major tremors/EPS, seizures. CV: arrhythmias, hypotension. other: decreased thyroid function, wt gain, edema, polyuria, polydipsia, possible kidney damage (monitoring of serum creatinine if > 1.6 mg/dL), and metallic taste. |
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Term
| what drug interactions are associated w/Li+? |
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Definition
| increased Li+ concentrations by: **thiazide diuretics > loop diuretics (e.g., furosemide), ACE Inhibitors, NSAIDs (e.g., indomethacin) but apparently not by ASA or acetaminophen. |
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Term
| what anticonvulsants have been used off label for mania tx? |
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Definition
| carbamezepine, clonazepam, valproic acid, gabapentin, lamotrigine, and topiramate. |
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Term
| what characterizes the use of carbamezepine (anticonvulsant) as an antipsychotic? |
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Definition
| efficacy similar to lithium in both treatment of acute mania and prophylaxis of bipolar disorder. superior in more severe mania, rapid cyclers, pts w/o fam hx of mania. it induces its own biotranformation - may need to increase dosage after a week. |
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Term
| what characterizes the use of clonazepam (anticonvulsant) as an antipsychotic? |
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Definition
| this is shown to have efficacy in the first week (early) tx of acute mania and is less effective in prophylaxis of bipolar. |
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Term
| what characterizes the use of valproic acid (anticonvulsant) as an antipsychotic? |
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Definition
significant antimanic action occurs within 1 to 4 days following
establishment of therapeutic serum levels (same as for epilepsy:
8-12 ug/mL). |
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Term
| what characterizes the use of topiramate/lamotrigine/gabapentin (anticonvulsants) as an antipsychotics? |
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Definition
| clinical evidence for efficacy of these anticonvulsants is more impressive for *acute mania than for long-term maintenance of bipolar disorder. some investigations indicate particular effectiveness of lamotrigine in bipolar depression. currently, other than for valproic acid, there is no FDA approval of anticonvulsant administration in bipolar disorder; this can limit insurance coverage for these meds. |
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