EXAM 4 antipsychotics

Question 1

etiology schizophrenia

Answer 1

Neurodevelopment/anatomical: increased ventricle size and changes in gray and white matter
Genetics- neuronal growth, migration of neurons
Environmental: birth complications + infections
Gene-environment interations: COMT-marijuana
Neurodevelopmental-environmental interactions

Question 2

positive symptoms schizophrenia

Answer 2

responds well to drug therapy: older agents
hallucinations, delusions, bizarre behavior, thought disorders

Question 3

negative symptoms schizophrenia

Answer 3

little response drug therapy
newer agents are better
blunted emotion

Question 4

cognitive symptoms

Answer 4

decrease cognitive function
involves D1 receptors and glutamate receptors

Question 5

dopamine hypothesis

Answer 5

dopaminergic agents exacerbate symptoms of schizophrenia
increased D2 receptor density in patients with schizophrenia

Question 6

serotonin hypothesis

Answer 6

LSD, mesacline are 5HT agonists
5HT2a receptor is a mediator of hallucinations
5HT2a receptor modulate DA release in cortex, limbic, striatum

Question 7

glutamate hypothesis

Answer 7

major excitatory neuron
phencyclidine and ketamine are noncompetitive inhibitors of NMDA receptors that exacerbate psychosis and cognition deficit

Question 8

binding affinity

Answer 8

intermolecular force between ligand and receptor
lower the number is better
Kd/Ki: estimated concentrations at which 1/2 receptors are occupied

Question 9

what receptors antagonized by antipsyschotics

Answer 9

major: DA
newer: 5HT
minor NE, ACh, Histamine

Question 10

what is binding affinity vs clinical dose

Answer 10

binding to D2 receptors is directly correlated to clinical dose

Question 11

what are anatgonist actions at the synapse

Answer 11

presynaptic terminal acts like safety switch of an autoreceptor
D2 receptors modulate synthesis of DA
DA transporters reduce DA at the synapse

Question 12

what are dopamine’s effect on parts of the brain?

Answer 12

basal ganglia is responsible for EPS motor effects
mesolimbic is where primary therapeutic effects take place
mesocortical is responsible for hypofunction in schizophrenia

Question 13

what is receptor occupancy for DA

Answer 13

for DA, about 60% for efficacy
for DA, at 90% occupancy, there is 50% H1 occupancy

Question 14

what is EPS

Answer 14

extrapyramidal symptoms
occurs early and is reversible
symptoms: dystonia, pseudoparkinsonism, tremor, akathisia

Question 14

what are the three drug induced movement disorders?

Answer 14

1. EPS
2. tardive dyskinesia
3. neuroleptic malignant syndrome

Question 15

what is drug therapy for EPS?

Answer 15

anticholinergics due to excess cholinergic side effects
benztropine, trihyphenidyl, akineton
diphenhydramine
amatadine
propranolol

Question 16

what is tardive dyskinisea

Answer 16

occurs late and is irreversible
unknown MOA
symptoms: involuntary mouth movements, choreiform (irregular purposelessness), athetoid (worm-like movements), axial hyperkinesias (to-fro movements)
monitor AIMS every 6 months

Question 17

treatment for tardive dyskinesias?

Answer 17

prevention is best
but reduce dose, change to different drug, eliminate anticholinergics, VMAT inhibitors
tetrabenazine, valbenazine, deuterabenazine

Question 18

what is neuroleptic malignant syndrome NMS?

Answer 18

rapid block of DA receptor
symptoms: EPS with fever, impaired cognition, muscle rigidity

Question 19

treatment of NMS

Answer 19

discontinue drug
DA agonist, diazepam, dantrolene

Question 20

what are the therapeutic uses of antipsychotics?

Answer 20

treatment of psychosis: 2-3 weeks for effectiveness, 6 weeks to 6 months for maximal efficacy
mood disorders
tourettes

Question 21

what are adverse effects on autonomic system for antipsychotics?

Answer 21

muscarinic blockade: constipation, dry mouth, trouble urinating
alpha blockade: orthostatic hypotension, impotence

Question 22

what are antipsychotic adverse effects on CNS

Answer 22

DA block: parkinsons, akathisia, dystonia
supersensitivity to DA receptors: tardive dyskinesias
muscarinic block: toxic confused state
H1: sedation

Question 23

what are adverse effects of antipsychotics related to the endocrine system?

Answer 23

DA block so hyperprolactemia: amenorhea galactorrhea, infertility

Question 24

what are first generation antipsychotics?

Answer 24

phenothiazines
thioxanthines
butrophenones (haloperidol)
molindone
pimozide

Question 25

which ones are phenothiazines?

Answer 25

aliphatic phenothiazines:
chlorpromazine
promethazine
Piperidine:
thioridazine
piperazine:
fluphenazine, prochlorperazine, perphenazine

Question 26

which ones are other antipsychotics:

Answer 26

thioxanthines
haloperidol

Question 27

what are atypical antipyschotics

Answer 27

reduced EPS
more metabolic problems
like olanzapine and clozapine

Question 28

what is smoking in relation to antipsychotics

Answer 28

1A2 inducer due to the hydrocarbons

Question 29

how do you treat EPS acute dystonia

Answer 29

IM anticholinergics now
benztropine 2mg
diphenhydramine 50mg

Question 30

how do you treat EPS drug induced parkinsons

Answer 30

oral anticholinergics
benztropine
trihexyhendyl
diphenhydramine

Question 31

how do you treat akathisia

Answer 31

BB - propranolol first line
BZD - normally lorazepam

Question 32

how do you treat tardive dyskinesias?

Answer 32

VMAT2 inhbitors

Question 33

what is neuroleptic malignant syndrome

Answer 33

life threatening medical emergency
hyperpyrexia(high fever), tachycardia, labile BP
muscle rigidity, elevated CK

Question 34

how to treat NMS?

Answer 34

discontinue antipsychotic
consider dopamine agonists
future antipsychotic use is not CI