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positive schizophrenia symptoms
- hallucinations
- delusions
- disordered thinking
- disorganized speech
- combativeness
- agitation
- paranoia
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negative schizophrenia symptoms
- social withdrawal
- emotional withdrawal
- lack of motivation
- poverty of speech
- blunted affect
- poor insight, judgement, and self care
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phenothiazine - aliphatic
chlorpromazine - thorazine
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phenothiazine -piperazine
- fluphenazine - prolixin
- prochlorperazine - compazine
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phenothiazine - piperidine
thioridazine - mellaril
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butyrophenones
- haloperidol - haldol
- droperidol
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7 atypicals
- clozapine - clozaril
- risperidone - risperdal
- olanzapine - zyprexa
- quetiapine - seroquel
- ziprasidone - geodon
- ariprazole - abilify
- palliperidone - invega
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5 SE of tricyclic structures
- anticholinergic actions
- tachycardia; cardiac toxicity
- weight gain
- orthostatic hypotension
- seizures
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MOA of typicals
DA receptor block→ blocks postsynaptic DA receptors but also ↑ DA turnover (compensatory mechanism); after about 12 weeks of therapy, get inactivation (depolarization blockade) of DA neurons; correlates with antipsychotic effects
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4 areas affecting the vomiting center
- vestibular apparatus
- sensor input (sight,smell,pain)
- higher centers (anticipation,fear,memory)
- CTZ
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2 areas affecting the CTZ
- stomach and small intestine
- blood borne emetics
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5 antiemetic MOA
- serotonin antagonist
- DA antagonist
- cannabinoids
- anticholinergic
- antihistamine
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4 extrapyramidal symptoms of phenothiazines
- iatrogenic parkinsonism
- akathisia
- dystonias
- tardive dyskinesia
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DA blockade in Mesolimbic pathway causes
antipsychotic effect
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DA blockade in nigrostriatal pathway causes
extrapyramidal effects
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Tx of dystonic reactions
- anticholinergics (diphenhydramine, benztropine)
- benzodiazepines
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Tx of parkinsonism
- reduction of neuroleptic agent
- anticholinergics
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Tx of akathisia
- reduction of neuroleptic dose
- anticholinergics
- benzodiazepines
- propranolol
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Tx of tardive dyskinesia
- stop offending agent
- add or increase neuroleptic dose
- switch to another drug, atypical (clozapine)
- prevent with drug holidays
- anticholinergic agents (botulinum toxin) tetrabenazine - nitoman
- reserpine
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MOA tardive dyskinesia
- increase DA stores presynaptic
- increase DA receptors postsynaptic
- increase DA hypersensitivity
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NMS
neuroleptic malignant syndrome - life threatening disorder that occurs in patients with extreme sensitivity to EPS of antipsychotics, more common in high potentcy agents
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Tx of NMS
- dscontinue causative agent
- supportive care
- bromocriptine - DA agonist
- dantrolene - direct acting skeletal muscle relaxant
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5 AE of phenothiazines on endocrine system
- menstrual irregularities
- gynecomastia
- decrease sex drive
- weight gain
- hyperglycemia & glycosuria
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3 rare AE of phenothiazine hypersensitivity reactions
- hematologic - blood dyscrasias
- hepatic - cholestatic jaundice
- dermatologic - contact dermatitis, photosensitivity
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MOA of atypicals
5-HT2A & D2 antagonists
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most effective
AE - agranulocytosis
seizures
clozapine - clozaril
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more effective against decreasing (-) symptoms
high dose = EPS and decrease BP
risperidone - risperdal
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less side effect
slow potential for drug interactions
decreased weight gain
olanzapine - zyprexa
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bipolar disorder
seldom causes weight gain
prolongation of QT interval
ziprasidone - geodeon
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blocks multiple receptor types
DA stabilizer
little or no effect on weight
ariprazole - abilify
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active metabolite of risperidone
extended release
paliperidone - invega
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3 depot neuroleptics
- haloperidol
- fluphenazine
- risperidone
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3 major objectives of schizophrenia therapy
- supression of acute episodes
- prevention of acute exacerbations
- maintenance of the highest possible level of functioning
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D2 block of the mesolimbic pathway
inhibit the release of DA and thereby alleviate the positive symptoms of schizophrenia in the nucleus accumbens
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5HT block of the mesocortical pathway
5HT receptor blockers increase the release of DA and thereby alleviate the negative symptoms of schizophrenia in the prefrontal cortex
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