EXAM 4 antipsychotics Flashcards
etiology schizophrenia
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
positive symptoms schizophrenia
responds well to drug therapy: older agents
hallucinations, delusions, bizarre behavior, thought disorders
negative symptoms schizophrenia
little response drug therapy
newer agents are better
blunted emotion
cognitive symptoms
decrease cognitive function
involves D1 receptors and glutamate receptors
dopamine hypothesis
dopaminergic agents exacerbate symptoms of schizophrenia
increased D2 receptor density in patients with schizophrenia
serotonin hypothesis
LSD, mesacline are 5HT agonists
5HT2a receptor is a mediator of hallucinations
5HT2a receptor modulate DA release in cortex, limbic, striatum
glutamate hypothesis
major excitatory neuron
phencyclidine and ketamine are noncompetitive inhibitors of NMDA receptors that exacerbate psychosis and cognition deficit
binding affinity
intermolecular force between ligand and receptor
lower the number is better
Kd/Ki: estimated concentrations at which 1/2 receptors are occupied
what receptors antagonized by antipsyschotics
major: DA
newer: 5HT
minor NE, ACh, Histamine
what is binding affinity vs clinical dose
binding to D2 receptors is directly correlated to clinical dose
what are anatgonist actions at the synapse
presynaptic terminal acts like safety switch of an autoreceptor
D2 receptors modulate synthesis of DA
DA transporters reduce DA at the synapse
what are dopamine’s effect on parts of the brain?
basal ganglia is responsible for EPS motor effects
mesolimbic is where primary therapeutic effects take place
mesocortical is responsible for hypofunction in schizophrenia
what is receptor occupancy for DA
for DA, about 60% for efficacy
for DA, at 90% occupancy, there is 50% H1 occupancy
what is EPS
extrapyramidal symptoms
occurs early and is reversible
symptoms: dystonia, pseudoparkinsonism, tremor, akathisia
what are the three drug induced movement disorders?
- EPS
- tardive dyskinesia
- neuroleptic malignant syndrome
what is drug therapy for EPS?
anticholinergics due to excess cholinergic side effects
benztropine, trihyphenidyl, akineton
diphenhydramine
amatadine
propranolol
what is tardive dyskinisea
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
treatment for tardive dyskinesias?
prevention is best
but reduce dose, change to different drug, eliminate anticholinergics, VMAT inhibitors
tetrabenazine, valbenazine, deuterabenazine
what is neuroleptic malignant syndrome NMS?
rapid block of DA receptor
symptoms: EPS with fever, impaired cognition, muscle rigidity
treatment of NMS
discontinue drug
DA agonist, diazepam, dantrolene
what are the therapeutic uses of antipsychotics?
treatment of psychosis: 2-3 weeks for effectiveness, 6 weeks to 6 months for maximal efficacy
mood disorders
tourettes
what are adverse effects on autonomic system for antipsychotics?
muscarinic blockade: constipation, dry mouth, trouble urinating
alpha blockade: orthostatic hypotension, impotence
what are antipsychotic adverse effects on CNS
DA block: parkinsons, akathisia, dystonia
supersensitivity to DA receptors: tardive dyskinesias
muscarinic block: toxic confused state
H1: sedation
what are adverse effects of antipsychotics related to the endocrine system?
DA block so hyperprolactemia: amenorhea galactorrhea, infertility
what are first generation antipsychotics?
phenothiazines
thioxanthines
butrophenones (haloperidol)
molindone
pimozide
which ones are phenothiazines?
aliphatic phenothiazines:
chlorpromazine
promethazine
Piperidine:
thioridazine
piperazine:
fluphenazine, prochlorperazine, perphenazine
which ones are other antipsychotics:
thioxanthines
haloperidol
what are atypical antipyschotics
reduced EPS
more metabolic problems
like olanzapine and clozapine
what is smoking in relation to antipsychotics
1A2 inducer due to the hydrocarbons
how do you treat EPS acute dystonia
IM anticholinergics now
benztropine 2mg
diphenhydramine 50mg
how do you treat EPS drug induced parkinsons
oral anticholinergics
benztropine
trihexyhendyl
diphenhydramine
how do you treat akathisia
BB - propranolol first line
BZD - normally lorazepam
how do you treat tardive dyskinesias?
VMAT2 inhbitors
what is neuroleptic malignant syndrome
life threatening medical emergency
hyperpyrexia(high fever), tachycardia, labile BP
muscle rigidity, elevated CK
how to treat NMS?
discontinue antipsychotic
consider dopamine agonists
future antipsychotic use is not CI
