CHAPTER 11: ANTIPSYCHOTIC DRUGS Flashcards
psychotic disorders are? two main symptoms?
severe mental disorders that cause ABNORMAL thinking and perception, lose touch with reality
TWO MAIN SYMPTOMS= delusions (false beliefs) and hallucinations (false perceptions)
schizophrenia
- type of chronic psychosis
- strong genetic component (combo fo genes play a role in the psychosis)
-biochem abnormality, dysfunc of mesocortical or limbic dopaminergic neuronal pathways
pos vs neg symptoms
hyperreaction=pos
underreaction of pathways=neg symptoms
dopamine (DA) hypothesis
changes in dopamine causes unusual behavior and experiences associate with psychosis
4 TYPES OF DOPAMINERGIC PATHWAYS IN THE BRAIN
Nigrostriatal, mesocortical, mesolimbic, tuberoinfundibular
Nigrostriatal Pathway
- control motor func
- deficiency DA leads to parkinson like symptoms
- excess DA lead to hyperkinetic movement
Mesocortical Pathway
underactive, mediate negative symptoms
Mesolimbic Pathway
Hyperactive in schizophrenia
- mediate positive symptoms
Tuberoinfundibular Pathway
control prolactin secretion
FIRST GEN AGENTS
- 2 types depend on what?
first gen–> split into low potency or high potency depending on affinity for DOPAMINE D2 RECEPTOR
First Gen Antipsychotics- CONVENTIONAL
- competitive inhibitors (d1-d5 receptors)
- competitive D2 blockade cause antipsychotic effects
- EPS: extrapyramidal symptoms depend on binding affinity
EPS- extrapyramidal symptoms
- symptoms due to dysfunction of movement
- dystonia, tardive dyskinesia
EX) Haloperidol binds tightly, chlorpromazine binds less tightly
Second Gen Antipsychotics- ATYPICAL
first-line therapy
- LOWER incidence of EPS
- HIGHER risk metabolic adv effects (diabetes, hypercholesterolemia, weight gain)
- BLOCKADE 5HT (serotonin) and DA receptors
ALL FIRST GEN/ SOME SECOND- MOA
- BLOCK D2 dopamine rec in brain and periphery
on POST synaptic membrane
MOST SECOND GEN- MOA
- additional action through inhibition of serotonin 5-HT receptors
- 5-HT2a receptors
- acting on serotonin receptors shows therapeutic effects
DRUG ACTIONS- other receptors blocked?
- cholinergic, adrenergic, histaminergic
- unknown if these alleviate psychosis symptoms
- may cause undesirable effects
ANTIPSYCHOTIC EFFECTS
- pos and neg symptoms
POSITIVE:
- reduce hallucinations/delusions–> block mesolimbic D2
NEGATIVE
- blunted affect, apathy, attention, cognitive impairment–> not as responsive, especially 1st gen
2nd gen may alleviate neg symptoms
EXTRAPYRAMIDAL EFFECTS
- dystonias (twitching muscles)
- Parkinson like symp (bradykinesia, tremor, rigidity)
- akathisia (motor restlessness)
- tardive dyskinesia (involun movements)–> ex) tongue/fly catching movement
2nd gen lower EPS incidence
ANTIEMETIC EFFECTS
- mediated by blocking D2 of chemoreceptor trigger zone of medulla
(once stimulated causes nausea/vomiting)
ANTICHOLINERGIC EFFECTS
- thioridazine, chlorpromazine, clozapine, olanzapine
- blurred vision, dry mouth, confusion, inhibition GI/urinary tract smooth muscle
OTHER EFFECTS
- inhibition alpha adrenergic–> orthostat hypo, syncope/dizzy
- block D2 in pituitary–> inc prolactin (blocking tuberoinfun)
- block H1 histamine rec–> sedation
( chlorpromazine, olanzapine, quetiapine, clozapine) - sexual dysnfunc/weight gain
THERAPEUTIC USES
-schizophrenia (1st gen best)
- manic symptoms/bipolar (lurasidone, quetiapine)
- drug induced nausea/vomit (prochlorperazine)
- tic disorder (pimozide, risperidone, haloperidol)
- refractory depression (no adequate response to treatment)–> (aripiprazole, brexpiprazole, quetiapine)
- intractable hiccups (chlorpromazine)
ADVERSE EFFECTS- Extrapyramidal
- dystonias (few hrs of treatment)
- akathisias (days to weeks)
- PD like symptoms (weeks to months)
- Tardive dyskinesia (months to years)–> can be irreversible
how do we minimize extrapyramidal effects
block cholinergic activity, restores normal balance
- ex) benztropine
ADVERSE EFFECTS- Neuroleptic malignant syndrome
- what is it
- treatment
- fatal reaction to antipsychotics
- muscle rigidity, fever, altered mental status, unstable BP, myoglobinemia
treatment: discontinue drug, supportive therapy
- administer DANTROLENE or BROMOCRIPTINE
ADVERSE EFFECTS- other
- drowsiness, confusion
- antimuscarinic activity
- alpha adrenergic–> lower BP, orthostat hypo
- depression of hypothalamus–> amenorrhea, galactorrhea, gynecomastia, infertility, erectile dys
- weight gain
MAINTENANCE THERAPY
- for what kinds of PTs?
- how does it work
- PT w 2 or more psychotic episodes secondary to schizo receive maintenance therapy for AT LEAST 5 years
- use only 1 drug
