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]
What is tardive dyskinesia?
stereotypic oral facial movements as a result of long term antipsychotic use
potentially irreversible
What are cardiac effects of typical antipsychotics?
- can prolong QT interval
- ventricular arrhythmias
- sudden death
What is mech of atypical antipsychotics?
not completely understood
most 5HT2A and D2 receptor antagonists
What is action of 5HT and DA in atypical antipsychotics?
5HT2A receptors act as DA brake
by blocking 5HT2A –> increase DA –> DA can compete with atypical antipsychotic for D2 receptor == less DA inhibition = less likely to cause extrapyramidal symptoms or tardive dyskinesia
What are theoretical benefits of atypicals over typical antipsychotics?
- reduced risk of EPS
- reduced risk of hyperprolactinemia
- cognitive enhancement
- better efficacy for negative symptoms
- better long term outcomes
What are side effects of atypical antipsychotics?
metabolic syndrome: clo > ola > quet > risp > zip > arip
cardiac
sedation
Why do atypical antipsychotics cause metabolic syndrome?
H1 receptor blockade –> weight gain
esp clozapine + olanzapine
Which atypical antipsychotic causes agranulocytosis?
clozapine
What are common side effects of clozapine?
- weight gain
- sedation
- agranulocytosis
- seizures
- hyperlipidemia
- hyperglycemia
What are common side effects of olanzapine?
- weight gain
- sedation
- hyperlipidemia
- hyperglycemia
What are common side effects of quetiapine?
sedation
What are common side effects of ziprasidone?
QTc interval prolongation
What are side effects of risperidone?
- extrapyramidal symptoms with some lowish frequency
- hyperprolactinemia
What is haloperidol most effective at treating?
- reduce agitation in medically sick or intoxicated rather than schizophrenia
What are first antipsychotics used?
- use atypicals first then typicals because side effects are easier tolerated
