Lec 81 Antipsychotics Flashcards
What is mech of conventional antipsychotics?
block D2/D3/D4 DA receptors [primarily D2]
relationship between clinical efficacy and affinity for D2
treatment over 2-3 wks = causes silencing DA neurons in substantia nigra and ventral tegmental area [VTA]
What are the 3 DA pathways and their function?
nigrostrial = extrapyramidal motor function
mesocorticolimbic = regulates emotional behavior and cognition
arcuate-pituitary = inhibits prolactin secretion from pituitary
What are the different ways to classify typical antipsychotics?
- by chem structure: butyrophenones and tricyclic antipsychotics
- by potency at D2 receptors
- – low = more H1/M1/a2 blockade, less D2, more extrapyramidal effects
- – mid
- – high = highest potency D2 blockade, fewer extrapyramidal effects, least H1/M1/a2 blockade
What are the 3 classes of antipsychotics?
- typical = conventional = 1st gen = DA antagonists
- atypical = novel = 2nd gen = 5HT2A/DA antagonists
- glutamate antagonists
What type of receptors are DA receptors?
- all G protein coupled
D1, D5 = coupled to Gs
D2, D3, D4 = coupled to Gi
What therapeutic uses of typical antipsychotics?
- schizophrenia [pos symptoms]
- psychosis
- acute mania
- tourettes
- mood disorders: bipolar/MDD with psychotic feat
What is mnemonic for high potency antipsychotics? side effects
high potency = try to fly high
- trifluoperazine
- fluphenazine
- haloperidol
neurologic side effects
What is mnemonic for low potency antipsychotics? side effects
Low = cheating thieves are low
- chlorpromazine
- thioridazine
- low
What should you think if drug ends in -azine?
typical antipsychotic
What is the old DA hypothesis of schizophrenia?
- overactivity DA in mesolimbic causes pos symptoms of psychosis
- underactivity DA in mesocortical mediate negative/cognitive/affective symptoms
What are side effects of typical antipsychotics?
- neuro side effects [most often by high potency agents]
- – extrapyramidal symptoms: parkinsonism, acute dystonia, akathisia, antidotes to DA related side effects
- – tardive dyskinesia
- – neuroleptic malignant syndrome
- hyperprolactinemia
- blockade muscarinic/cholinergic receptors
- blockade H1 receptors
- blockade a1 receptors
- cardiac
How do you treat parkinsonian/ dystonia/ akathisia side effects of high potency antipsychotics?
- anticholinergics anti-parkinson meds: benzotropine, trihexyphenidyl
- antihistaminic diphenhydramine
What is tardive dyskinesia?
- continuous writhing tongue/mouth/fingers/hands
- caused by chronic use of antipsychotics
What is time course of extrapyramidal [EPS] side effects associated with typical antipsychotics?
- 4 hr: acute dystonia = muscle spasm, stiffness
- 4 day: akathisia = restlessness
- 4 wk: bradykinesia = parkinsonism
- 4 mo: tardive dyskinesia
What is neuroleptic malignant syndrome [NMS]? treat?
think FEVER: fever, encephalopathy, vitals unstable, enzymes increase, rigidity of muscles
rigidity, myoglobinuria, autonomic instability
findings: increase WBC, creatinine phosphokinase, liver enzymes
mortality 20-30%
treat: dantrolene, D2 agonists [bromocriptine]
