Antipsychotic Drugs

Question 1

positive symptoms

Answer 1

delusions
hallucinations
disorganized speech/thought

Question 2

negative symptoms

Answer 2

anhedonia
flattened affect
apathy

Question 3

primary mechanisms of antipsychotics

Answer 3

Blockade of dopamine (D2) receptors

• -typical agents
• -help with positive symptoms

Blockade of serotonin (5HT2) receptors

• -atypical/2nd generation
• -help with negative symptoms

Question 4

how are negative symptoms relieved?

Answer 4

blockade of serotonin (5HT2) receptors

–atypical, 2nd gen

Question 5

how are positive symptoms relieved?

Answer 5

blockade of dopamine (D2) receptors

–typical, 1st gen

Question 6

negative symptoms due to

Answer 6

insufficient DA activity in mesocortical tract

Question 7

positive symptoms due to

Answer 7

overactivity of DA activity in mesolimbic system

Question 8

dopamine hypothesis

Answer 8

Assumes over activity of DA in mesolimbic pathway correlates with positive symptoms
-block dopamine type 2 receptors, then alleviate positive symptoms

Question 9

serotonin hypothesis

Answer 9

Insufficient DA release at ends of neurons in mesocortical pathways correlates with negative symptoms
-less DA to interact with prefrontal cortex

• serotonin suppresses release of DA from mesocortical pathway
• block serotonin (5HT2) receptor, then take away inhibition and allow DA to be released
• alleviates negative symptoms

Question 10

chlorpromazine

Answer 10

low potency older/typical agent

name recognition

Question 11

haloperidol

Answer 11

high potency older/typical agent

name recognition

Question 12

clozapine

Answer 12

most common newer/atypical agent

Question 13

newer/atypical agents have a _______ potency, so they have a ________ dose

Answer 13

newer/atypical agents have a HIGHER potency, so they have a LOWER dose

Question 14

consequences of blockage of dopamine in mesolimbic pathway

Answer 14

antipsychotic

-decreases positive symptoms

Question 15

consequences of blockage of dopamine in mesocortical pathway

Answer 15

antipsychotic

-decreases negative symptoms

Question 16

consequences of blockage of dopamine in nigrostriatal pathway

Answer 16

causes extrapyramidal movements

-Parkinson’s like symptoms

Question 17

consequences of blockage of dopamine in tuberoinfundiblar pathway

Answer 17

causes prolactin release

• amenorrhea, galactorrhea (women)
• gynecomastia, reduced libido (men)
• fertility problems

Question 18

common adverse reactions to antipsychotics

Answer 18

Hyperprolactinemia
-galactorrhea, amenorrhea, gynecomastia, reduced libido

Postural hypertension
-due to NE stimulating alpha-1 receptors, increasing BP

QT prolongation
-cardiotoxicity

Extrapyramidal Syndromes (EPS)
-dystonias, parkinsonism

Question 19

why do psychostimulants cause cardiotoxicity?

Answer 19

• block K+ channels
• longer ventricular repolarization
• ventricular dysrhythmia
• prolonged QT interval

Question 20

how to treat extrapyramidal side effects

Answer 20

Lower dose of antipsychotics.
Change drug.

Drug therapy:

• benzotropine (cogentin)
• trihexyphenidyl
• ANTIMUSCARINICS

Question 21

why do extrapyramidal sx occur with antipsychotics?

Answer 21

DA and ACh are in balance.

• if DA is blocked, then balance is tipped to favor ACh
• increased ACh = increased output to basal ganglia = EPS

Question 22

Acute dystonic reaction

what is it?
Tx?

Answer 22

EPS related adverse effect

• oculogyric crisis
• torticollis

Tx: antimuscarinics (antihistamines) (benztropine)

Question 23

tardive dyskinesia (TD)

what is it?
Tx?

Answer 23

• persistent EPS
• could persist rest of life
• elderly at greater risk
• use minimal doses for minimal duration
• change to atypical agent

Tx: valbenzazine (Ingrezza)

Question 24

neuroleptic malignant syndrome

what is it?
Tx?

Answer 24

• hyperpyrexia (fever)
• rigidity
• autonomic instability
• delerium
• more likely with high doses
• rare

Tx:

• stop drug
• dantrolene, bromocriptine

Question 25

what should you consider if the patient is pregnant (with antipsychotic use)?

Answer 25

- infant may have abnormal motor movements | - withdrawal effects

Question 26

poikilothermia

Answer 26

- inability to control body temp - common in low potency, older agents - due to changes in hypothalamus

Question 27

most common atypical antipsychotics

Answer 27

``` Clozapine Risperidone Olanzapine Quetiapine Aripiprazole ``` - newer - more expensive (even the generic)

Question 28

adverse effects of atypical antipsychotics

Answer 28

- increases in weight, blood glucose, and lipids - orthostasis (alpha-receptor blockade) - others: somnolence, dizziness, inc LFTs, CYP450 interactions) - EPS is LESS likely to occur - --decreased prolactin disturbances

Question 29

clozapine role? adverse effects?

Answer 29

- atypical, newer - most effective antipsychotic - seldom used - least likely to develop EPS Adverse Effects - sedation - weight gain - sialorrhea (xs saliva) - seizures (rare) - agranulocytosis (v rare, but super serious)

Question 30

time to effect for antipsychotics

Answer 30

- most sx improve slowly | - higher potency = higher response

Question 31

duration of treatment for antipsychotics

Answer 31

- most require prolonged maintenance - rebound effect if abruptly stopped maintenance is the best efficacy, but due to illness are likely not to be continued

Question 32

receptor blockade of typical vs atypical antipsychotics

Answer 32

TYPICAL: D2 > 5HT2A ATYPICAL: 5HT2A > D2

Question 33

effectiveness of typical vs atypical antipsychotics

Answer 33

TYPICAL: mainly for positive symptoms ATYPICAL: both positive and negative symptoms

Question 34

movement disorders of typical vs atypical antipsychotics

Answer 34

TYPICAL: more ATYPICAL: less

Question 35

metabolic effects of typical vs atypical antipsychotics

Answer 35

TYPICAL: less ATYPICAL: more

Question 36

consequences of blocking alpha-1 receptor

Answer 36

orthostasis

Question 37

consequences of blocking dopamine-2 receptor

Answer 37

extrapyramidal movements

Question 38

consequences of blocking histamine-1 receptor

Answer 38

sedation | weight gain

Question 39

consequences of blocking muscarinic receptor

Answer 39

dry mouth, blurred vision, urinary retention, constipation

Question 40

class wide safety concern for antipsychotics

Answer 40

eldery patients with dementia-related psychosis is treated with antipsychotic drugs are at an increased risk of death compared to a placebo - more pleasant with antipsychotic, easier to treat - may shorten life

Question 41

drug-induced psychoses can be commonly caused by which drugs?

Answer 41

``` anticholinergic drugs benzodiazepines antipsychotic agents dopaminergic agents corticosteroids withdrawal from sedatives/alcohol ```