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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
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
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.
how do many antipsychotic drugs work with regard to dopamine? many of htem block post synaptic D2 receptors (including partial agonists)
drugs that increase dopamine signaling do what? aggravate schizophrenia and produce psychosis de novo
what affect do antipsychotics have on dopamine activity? blocks it
what is the mechanism of action of the typical antipsychotic drugs? competitive blockade of dopamine receptors and/or serotonin receptors
blockade of D2 receptors with antipsychotics produces what kinds of side effects? extrapyramidal side effects
do atypical antipsychotics cause extrapyramidal side effects? no
tyipcal antipsychotics require how much occupancy of striatal D2 receptors? At what percent receptor occupancy does EPS occur? sixty percent, eighty percent
atypical antipsychotics require what percent receptor occupancy of D2 receptors? thirty percent (due to more concurrent high occupancy of 5HT2A receptors)
list the typical antipsychotics haloperidol, chlorpromazine, thioridazine, fluphenazine
list the Atypical antipsychotics risperidone, clozapine, quetiapine, olanzapine, ziprazadone, aripiprazole
describe the absorption and distribution of antipsychotics most are readily absorbed, undergo significant first pass metabolism, distribution: most are lipid soluble, have large Vd
describe the enzyme metabolism of antipsychotics most undergo xidation or demethylation reactions (CYP2D6, CYP1A2, CYP3A4)
describe the excretion of antipsychotics can be proonged
how long can it take chlorpromazine to be excreted? weeks
how long can it take a long acting injectable antipsychotic to be excreted? three to six months (haloperidol)
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
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
describe the CV effects of thioridazine (reversed upon D/C): prolonged QT interval, abnormal ST segment and T waves
describe the CV effects of Haloperidol increased risk of torsades de pointes, incresed QT prolongation
which atypical antipsychotic causes increased QT interval? quetiapine
which atypical antipsychotic causes elevated levels of prolactin? risperidone (atypical)
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)
list some psychiatric indications for antipsychotics schizophrenia, drug induced psychosis, psychosis involved with manic phase of bipolar disorder, schizoaffective disorders, tourettes syndrome, alzheimers disease
drug of choice depends on what factors? efficacy, symptoms, drug formulation, adverse effects, cost
which types of anit-psychotics work best for positive symptoms for schizophrenia? typicsl and atypicals work equally well
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
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
what is the best guide to which antipsychotic to choose/ patient's past response
for typical antipsychotics, what is preferred more, higher potency or low potency drugs? high potency
which drug is indicated to reduce the risk of suicide in schizophrenia or as a last resort medication? clozapine
antipsychotics are given with what to treat concomitant depression TCCA, SSRI
antipsychotics are given with what to treat concomitant mania? lithium, valproic acid
list some Extrapyramidal side effects of antipsychotics tremor, slurred speech, akathisia, dystonia, anxiety, distress, paranoia, bradyphrenia
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)
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
patients on risperidone who have tarditive dyskinesia should be switched to what drug? quetiapine or clozapine
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
which drugs cause adverse neurological side effects of seizures, pseudodepression, toxic-confused states/ chlorpromazine (rare), clozapine
which drugs causes ANS adverse effects that are antimuscarinic such as urinary retention, constipation, dry mouth, orthostatic hypotension or impaired ejaculation chlorpromazine
which drugs cause ocular adverse effects by depositing into the cornea and lens? chlorpromazine
which drugs cause ocular adverse effects by depositing in the retina thioridazine. it resembles retinitis pigmentosa, associated with browning of vision
which drugs cause adverse effects of weight gain and require monitoring of carbs (hyperglycemia), hyperlipidemia, and management? cloazpine or olanzapine.
describe some reproductive adverse effects in women amneorrhea, galactorrhea, false positive pregnancy tests, increased libido
describe some reproductive adverse effects in men decreased libido, gynecomastia
which drug causes toxic or allergic agranulocytosis? clozapine
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.
how do you treat NMS? antiparkinson drugs, muscle relaxants (diazepam) or dantrolene, switch to atypical
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
this drug is associated with myocarditis, clozapine
overdoses are rarely fatal except with these drugs: mesoridazine and thioridazine (ventricular tachyarrhythmias)
antipsychotics and pregnancy? little risk to fetus, but controversial
Created by: aferdo01