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Flashcards in Lec 81 Antipsychotics Deck (30)
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1

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]

2

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

3

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

4

What are the 3 classes of antipsychotics?

- typical = conventional = 1st gen = DA antagonists

- atypical = novel = 2nd gen = 5HT2A/DA antagonists

- glutamate antagonists

5

What type of receptors are DA receptors?

- all G protein coupled
D1, D5 = coupled to Gs
D2, D3, D4 = coupled to Gi

6

What therapeutic uses of typical antipsychotics?

- schizophrenia [pos symptoms]
- psychosis
- acute mania
- tourettes
- mood disorders: bipolar/MDD with psychotic feat

7

What is mnemonic for high potency antipsychotics? side effects

high potency = try to fly high
- trifluoperazine
- fluphenazine
- haloperidol

neurologic side effects

8

What is mnemonic for low potency antipsychotics? side effects

Low = cheating thieves are low
- chlorpromazine
- thioridazine
- low

9

What should you think if drug ends in -azine?

typical antipsychotic

10

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

11

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

12

How do you treat parkinsonian/ dystonia/ akathisia side effects of high potency antipsychotics?

- anticholinergics anti-parkinson meds: benzotropine, trihexyphenidyl
- antihistaminic diphenhydramine

13

What is tardive dyskinesia?

- continuous writhing tongue/mouth/fingers/hands
- caused by chronic use of antipsychotics

14

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

15

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]

16

What is tardive dyskinesia?

stereotypic oral facial movements as a result of long term antipsychotic use

potentially irreversible

17

What are cardiac effects of typical antipsychotics?

- can prolong QT interval
- ventricular arrhythmias
- sudden death

18

What is mech of atypical antipsychotics?

not completely understood
most 5HT2A and D2 receptor antagonists

19

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

20

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

21

What are side effects of atypical antipsychotics?

metabolic syndrome: clo > ola > quet > risp > zip > arip

cardiac

sedation

22

Why do atypical antipsychotics cause metabolic syndrome?

H1 receptor blockade --> weight gain

esp clozapine + olanzapine

23

Which atypical antipsychotic causes agranulocytosis?

clozapine

24

What are common side effects of clozapine?

- weight gain
- sedation
- agranulocytosis
- seizures
- hyperlipidemia
- hyperglycemia

25

What are common side effects of olanzapine?

- weight gain
- sedation
- hyperlipidemia
- hyperglycemia

26

What are common side effects of quetiapine?

sedation

27

What are common side effects of ziprasidone?

QTc interval prolongation

28

What are side effects of risperidone?

- extrapyramidal symptoms with some lowish frequency
- hyperprolactinemia

29

What is haloperidol most effective at treating?

- reduce agitation in medically sick or intoxicated rather than schizophrenia

30

What are first antipsychotics used?

- use atypicals first then typicals because side effects are easier tolerated