Final: Antipsychotic Drugs

Question 1

extreme form of slowness/absence of motor movements and affective indifference

Answer 1

neurolepsis

Question 2

drugs that produce neurolepsis

Answer 2

neuroleptics (aka antipsychotics)

Question 3

examples of classical neuroleptics

Answer 3

phenothiazines (chlorpromazine)

butyrophenones (haloperidol)

Question 4

second generation (atypical antipsychotic) examples

Answer 4

clozapine
risperidone
aripiprazole

Question 5

do classical or atypical antipsychotics produce less side effects

Answer 5

atypical antipsychotics

Question 6

law of thirds

Answer 6

1/3: patients respond well
1/3: show significant improvements but may relapse
1/3: fail to respond

Question 7

why are antipsychotic drugs considered “dirty”

Answer 7

they have binding affinity for MANY different neurotransmitter systems
-can be good bc indirectly treating many issues BUT can have wide range of side effects

Question 8

antipsychotic actions are attributed to what neurotransmitter system

Answer 8

dopamine D2 receptor antagonists

Question 9

where are the D2 receptors located

Answer 9

basal ganglia, Nacc, amygdala, hippocampus, cerebral cortex

Question 10

ROA antipsychotics

Answer 10

oral - most common

IV or IM injections - more common when sedation is the goal

Question 11

depot injection

Answer 11

high concentration of lipid soluble drug dissolved in oil and injected into muscle

• slow diffusion from oil into body fluids over long period of time
• single injection can last up to 4 weeks

Question 12

absorption of antipsychotics

Answer 12

most readily absorbed in GI tract
many do first pass metabolism
bioavailabilty 25-65%

Question 13

distribution of antipsychotics

Answer 13

placenta and BBB
high depot binding: blood protein and in body fat
- released slowly
injections can take weeks to reach steady state
ex: risperidone - 28 days

Question 14

metabolism of antipsychotics

Answer 14

LIVER cytochrome p450s

• most have inactive metabolites
• considerabe individual varieties
• interact with antidepressants, anxiolytics due to competition

Question 15

excretion of antipsychotics

Answer 15

• due to high depot binding - long half life - metabolites found in urine for months
• atypical excreted quicker - less depot binding since less lipophillic

Question 16

neuroleptic induced deficit syndrome

Answer 16

D2 receptor antagonists
blocking mesolimbic D2 receptors causes apathy, anhedonia, loss of motivation
-worsening negative symptoms
dec Da - neg symptoms

Question 17

mesocortical DA system in Scz

Answer 17

dec activity - cognitive deficits and flat affect

can worsen cognitive ability by exaerbatig DA signaling defiicts in cortex

Question 18

nigrostriatal Da in Scz

Answer 18

substantia nigra - striatum
- movement
extrapyramidal symptoms (EPS): involuntary changes in motor ability resulting from classical antipsychotic drug treatments (akathisia, dystonia, PD, tardive dyskinesia, blockage of nigrostriatal D2

Question 19

akathisia

Answer 19

restlessness

Question 20

dystonia

Answer 20

sustained muscle contractions

Question 21

tardive dyskinesia

Answer 21

cannot stop moving - only chronic treatment

Question 22

acute D2 receptor antagonism

Answer 22

blocking D2 receptors in nigrostriatal pathway can cause a drug-induced parkinsonism

Question 23

chronic D2 receptor antagonism

Answer 23

chronic D2R blockade causes compensatory changes in dopamine system
tardive dyskinesia inc with duration of treatment

Question 24

tuberoinfundibular dopamine system in Scz

Answer 24

within hypothalamus
regulates pituitary hormone secretion/neuroendocrine effects
blocking D2 receptors impairs function
- excessive prolactin secretion, inhibition of growth hormone
-dec sex drive, no menstruation, breast tissue growth
-neuroleptic malignant syndrome

Question 25

neuroleptic malignant syndrome

Answer 25

life threatening

fever, rigidity, altered consciousness, ANS instability

Question 26

side effects if antipsychotics

Answer 26

depend on what receptor the drug binds to

• blocking cholinergic - dry mouth, blurred vision, difficulty urinating, GI problems
• anti-adrenergic: dizziness, faintness, blacking out
• sedation

Question 27

DA D2R antagonism is paired with what other antagonism

Answer 27

5-HT2A

together they help treat psychosis

Question 28

5-HT2AR antagonism stimulates DA release to reduce side effects

Answer 28

• reduces EPS from nigrostriatal pathway
• reduces neg symptoms and improves mood by inc DA in PFC
• reduces prolactin release from hypothalamus

Question 29

atypical antipsychotica

Answer 29

reduce positive symptoms without causing EPS or side effects

• selective D2 receptor antagonists
• DA partial receptor agonists
• broad spectrum antipsychotics block other receptor types in addition to D2 receptors

Question 30

selective D2 receptor antagonists

Answer 30

• high affinity for D2 receptors, slight for D3
• effects on ANS and cardiac mild
• BUT: hormonal side effects and risk of fatal blood disorders reduces their use

Question 31

dopamine system stabilizers - atypical antipsychotics

Answer 31

partial DA agonists compete with DA for receptors and reduce DA effect
- inc DA in PFC while also reducing DA in mesolimbic pathway

ex: aripiprazole (ABlilify) - partial agonist with low side effects

Question 32

clozapine

Answer 32

broad spectrum antipsychotics
-weak affinity for D1 and D2, strong affinity for adrenergcm seretonergic, muscarinic, histaminergic, and D4

effective for people not responding to typical neuroleptics
reduces some neg and cognitive symptoms but many side effects due to action on multiple receptors

Question 33

other conditions treated by antipsychotics

Answer 33

• disorders with excess DA (Tourette’s, Huntington’s)
• powerful antiemetics: useful for motion sickness
• chronic pain
• hiccups, stuttering, delirium tremens, drug-induced psychosis

Question 34

what other diseases are atypicals used for we already learned about

Answer 34

MDD, bipolar disorder, mania, irritability in autistic children