antipsychotics
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| describe the sequence of events that lead to schizophrenia | hypofunction of the NMDA receptors located on GABA interneurons cause diminished inhibitory influences on glutamate neuron funciton, hyper stimulation of cortical neurons through non-NMDA receptors, leads to schizophrenia
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| which atypical antipsychotics are the inverse agonists of the 5HT2A receptor? how do inverse agonists work? | clozapine and quetiapine. they bind to the inactive form of the receptor abd block them from becoming active
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| what do the 5HTA receptors do? | they mediate the release of dopamine in the cortex, limbic region and striatum. their receptor subtypes may mediate synergistic effects or protect against extrapyramidal side effects.
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| how do many antipsychotic drugs work with regard to dopamine? | many of htem block post synaptic D2 receptors (including partial agonists)
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| drugs that increase dopamine signaling do what? | aggravate schizophrenia and produce psychosis de novo
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| what affect do antipsychotics have on dopamine activity? | blocks it
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| what is the mechanism of action of the typical antipsychotic drugs? | competitive blockade of dopamine receptors and/or serotonin receptors
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| blockade of D2 receptors with antipsychotics produces what kinds of side effects? | extrapyramidal side effects
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| do atypical antipsychotics cause extrapyramidal side effects? | no
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| tyipcal antipsychotics require how much occupancy of striatal D2 receptors? At what percent receptor occupancy does EPS occur? | sixty percent, eighty percent
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| atypical antipsychotics require what percent receptor occupancy of D2 receptors? | thirty percent (due to more concurrent high occupancy of 5HT2A receptors)
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| list the typical antipsychotics | haloperidol, chlorpromazine, thioridazine, fluphenazine
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| list the Atypical antipsychotics | risperidone, clozapine, quetiapine, olanzapine, ziprazadone, aripiprazole
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| describe the absorption and distribution of antipsychotics | most are readily absorbed, undergo significant first pass metabolism, distribution: most are lipid soluble, have large Vd
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| describe the enzyme metabolism of antipsychotics | most undergo xidation or demethylation reactions (CYP2D6, CYP1A2, CYP3A4)
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| describe the excretion of antipsychotics | can be proonged
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| how long can it take chlorpromazine to be excreted? | weeks
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| how long can it take a long acting injectable antipsychotic to be excreted? | three to six months (haloperidol)
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| describe the EEG effects with antispychotics | it shifts the pattern of EEG frequencies, slowing them, increasing their synchrony. hypersynchrony is focal or unilateral. some can lower seizure threshold
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| describe the typical CV effects of phenothiazines (chlorampromazine, thioridazine, fluphenazine) | orthostatic hypotension and tachycardia, decreased mean arterial pressure, peripheral resistance and stroke volume. increased HR
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| describe the CV effects of thioridazine | (reversed upon D/C): prolonged QT interval, abnormal ST segment and T waves
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| describe the CV effects of Haloperidol | increased risk of torsades de pointes, incresed QT prolongation
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| which atypical antipsychotic causes increased QT interval? | quetiapine
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| which atypical antipsychotic causes elevated levels of prolactin? | risperidone (atypical)
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| give some non-psychiatric indications for antipsychotics | anti-emetics (prochlorperazine, benzquinamide) due to dopamine receptor blockade. H1 receptor blocking activity (pruritis, pre-operative sedatives (promethazine), neuroleptanesthesia (droperidol+fentanyl)
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| list some psychiatric indications for antipsychotics | schizophrenia, drug induced psychosis, psychosis involved with manic phase of bipolar disorder, schizoaffective disorders, tourettes syndrome, alzheimers disease
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| drug of choice depends on what factors? | efficacy, symptoms, drug formulation, adverse effects, cost
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| which types of anit-psychotics work best for positive symptoms for schizophrenia? | typicsl and atypicals work equally well
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| which type of antipsychotis work better for negative symptoms of schizophrenia? | atypical drugs. They also have fewer adverse drug reactions such as tarditive dyskinesia, other EPS, and minimal increases in prolactin
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| describe drug formulations and cost of anti psychotics | typical drugs can be IM formulations for both acute and chronic treatment. older antipsychotics are available in parenteral forms. typical drugs are cheaper
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| what is the best guide to which antipsychotic to choose/ | patient's past response
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| for typical antipsychotics, what is preferred more, higher potency or low potency drugs? | high potency
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| which drug is indicated to reduce the risk of suicide in schizophrenia or as a last resort medication? | clozapine
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| antipsychotics are given with what to treat concomitant depression | TCCA, SSRI
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| antipsychotics are given with what to treat concomitant mania? | lithium, valproic acid
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| list some Extrapyramidal side effects of antipsychotics | tremor, slurred speech, akathisia, dystonia, anxiety, distress, paranoia, bradyphrenia
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| describe some more adverse effects | typical parkinsons syndrome (treated with antimuscarinic antparkinsonism drugs), akathisia (treated with sedative antihystamine with anticholinergic properties), acute dystonic rxns (treated with sedative antihistamine with anticholinergic properties)
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| this is an adverse effect and is a late occurring syndrome of abnormal choreathetoid movements. early recognition is important, and cannot be reversed in late stages. caused by: typicals and possibly risperidone. | tarditive dyskinesia
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| patients on risperidone who have tarditive dyskinesia should be switched to what drug? | quetiapine or clozapine
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| what is the tratment for tarditive dyskinesia? | discontinue or reduce concurrent treatment (typical) and switch to newer anytpsychotic (atypical). remove all drugs with anticholinergic properties (antiparkinson drugs and TCAs) treat iwth diazepam to enhance GABA activity
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| which drugs cause adverse neurological side effects of seizures, pseudodepression, toxic-confused states/ | chlorpromazine (rare), clozapine
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| which drugs causes ANS adverse effects that are antimuscarinic such as urinary retention, constipation, dry mouth, orthostatic hypotension or impaired ejaculation | chlorpromazine
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| which drugs cause ocular adverse effects by depositing into the cornea and lens? | chlorpromazine
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| which drugs cause ocular adverse effects by depositing in the retina | thioridazine. it resembles retinitis pigmentosa, associated with browning of vision
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| which drugs cause adverse effects of weight gain and require monitoring of carbs (hyperglycemia), hyperlipidemia, and management? | cloazpine or olanzapine.
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| describe some reproductive adverse effects in women | amneorrhea, galactorrhea, false positive pregnancy tests, increased libido
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| describe some reproductive adverse effects in men | decreased libido, gynecomastia
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| which drug causes toxic or allergic agranulocytosis? | clozapine
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| describe some neuroleptic malignant syndrome | resuls from rapid blockade of post synaptic dopamine receptorss can be life threatening, pt will be extremely sensitive to extrapyramidal effects, initial symptom: muscle rigidity, fever, autonomic instability with altered BP and pusle.
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| how do you treat NMS? | antiparkinson drugs, muscle relaxants (diazepam) or dantrolene, switch to atypical
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| whichdrug causes minor abnormalities in T waves, and overdoses are associatd with torsades de pointes, cardiac conduction block and sudden death. (should be combined with TCAs with great care) | thioridazine
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| this drug is associated with myocarditis, | clozapine
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| overdoses are rarely fatal except with these drugs: | mesoridazine and thioridazine (ventricular tachyarrhythmias)
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| antipsychotics and pregnancy? | little risk to fetus, but controversial
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