Antipsychotics Flashcards
psychosis definition
denotes a variety of mental disorders with multiple causes and manifestations
-systemic, psychiatric or chemical (toxic)
what is a characteristic of severe psychiatric disorders?
disturbances in behavior or thought processing
- delusions (false beliefs)
- various types of hallucinations (auditory, visual, tactile, olfactory)
Schizophrenia
- what is it?
- when does it develop?
- severe type of psychosis
- develops during childhood and adolescence == genetic disorder with high heritability
typical antipsychotics - list drugs?
Chlorpromazine
thioridazine
fluphenazine
haloperidol
2 Types of symptoms in schizophrenia:
- positive
- negative
Positive schizophrenia symptoms:
-Manifestation of abnormal beh: delusions hallucinations (auditory) agitation paranoia aberrant thinking intrusion of thoughts
Negative schizophrenia symptoms:
-Absence of normal beh:
emotional apathy (flat affect)
socially withdrawn
inattentiveness
Schizophrenia- pathophysiology:
dopamine hypothesis among many others:
hyperactivity of the mesolimbic/mesocortical DA system = excessive limbic DA activity = psychosis
Atypical antipsychotics - list the drugs we need to know:
clozapine olanzapine risperidone aripiprazole quetiapine ziprasidone
What are neuroleptic drugs?
subtype of antipsychotic drugs that produce high incidence of extrapyramidal side effects (EPS)
Why are atypical antipsychotics more widely used?
These are the NEWER drugs (typical are old ones)
These have fewer EPS effects at equivalent therapeutic doses
Uses for antipsychotic agents:
1) schizophrenia
2) psychotic beh
a) psychotic bipolar disorder
b) psychotic depression
c) Tx-resistant depression
3) severe mania - manic phase of bipolar disorder
4) antiemetic (prochlorperazine, phenergan)
Phenothiazines -Aliphatic (R1)
What is the potency of…
= chlorpromazine
LEAST POTENT
Phenothiazines -Piperidine (R1)
What is the potency of…
=thioridazine
MEDIUM POTENT
Phenothiazines -Piperazine (R1)
What is the potency of…
=prochlorperazine
=fluphenazine
HIGHEST POTENCY
Butyrophenol drug name and potency?
haloperidol
HIGHEST HIGHEST POTENCY (even higher than pipierazines)
Name the dibenzapines?
- clozapine
- olanzapine
Name the benzisoxazoles:
-risperidone
Name the other atypical antipsychotics?
aripiprazole
quetiapine
ziprasidone
antipsychotics - general pharmacokinetics:
- low bioavailability - Lipophilic drugs
- large Vd
- metabolized by liver
*Antipsychotics - what is special about typical and atypical agent metabolism?
- typical- the metabolites ARE NOT active after going through liver
- -atypical-the metabolites are significantly activated when going through CYP450
Typical antipsychotic drugs -MOA?
dopamine receptor antagonist - D2 recepotrs!!
Atypical antipsychotic drugs- MOA?
antagonist at 5-HT_2A receptors and D2 receptors
Primary action of antipsychotic drugs?
-Meso-limbic-mesocortical
- VTA (ventral tegmental area)–>limbic system & neocortex
- related to behavior and psychosis
Other actions of antipsychotic drugs?
1) Nigrostriatal-
a) Substantia nigra–>dorsal striatum
b) coordination of voluntary movement
c) blcokage of D2 receptor responsible for EPS
2) Tuberoinfundibular - inh of prolactin secretion from ant pituitary
3) Medullary periventricular area
a) chemoreceptor trigger zone (CTZ)
b) eating behavior
Antidopaminergic effects of Antipsychotics:
1) cognitive function (antipsychotic) - more effective with positive symptoms than neg
2) Motor behavior (EPS)
a) parkinson like syndrome: rigidity, tremor, bradykinesia
b) Akathesia -motor restlessness and anxiety
c) Dystonia
- torticollis-spasm of neck
- episthotonus-spasm of back
- oculogyric reaction-eyes roll back
- facial grimacing
d) Tardive dyskinesia
- involuntary movements of tongue, mouth, face and head
- generally irreversible
3) Nausea & vomiting (antiemetic)
a) effective in drug induced conditions (cancer chemo)
b) not effective in motion sickness
c) thioridazine is a poor antiemetic
* 4) endocrine - hyperprolactinemia
a) decreased testosterone production (male)
b) gynecomastia (male)
c) changes in libido, impotence and infertility (male)
d) galactorrhea and infertility (female)
e) menstrual irregularities
5) Weight gain
a) DA, or H1 mechanism, maybe also 5-HT
b) Clozapine and olanzapine
Which class and which drugs typically have WG as side effect?
Atypicals usually
Clozapine and olazapine
Pharmacological effects/which receptors - antipsychotics?
1) anticholinergic (M-receptors)
- urinary retention
- dry mouth
- blurred vission
- constipation
- mental confusion
2) Antihistaminic (H1)
- sedation
- WG
3) Anti-adrenergic (most alpha1)
- postural hypotension
- reflex tachycardia
- erectile dysfunction and impaired ejaculation
Adverse effects of antipsychotics?
1) DA-mediated
a) EPS effects
- parkinsonian-like
- akathesia
- dystonia
- tardive dyskinesia
b) hypoprolactinemia
c) neuroleptic malignant syndrome
- hypertension & hyperthermia
- rare though significant mortality
- treatment=supportive, dantrolene, diazepam, bromocriptine
2) Anticholinergic
3) Antiadrenergic
4) Antihistaminic
5) WG - inc risk for Type2Diabetes; metabolic syndrome
WHcih class has lower EPS symptoms?
the atypicals
Which atypical is most strongly associated with EPS?
risperidone
Which atypicals least strongly associated with EPS?
clozapine
quetiapine
EPS risk is influenced by?
- rapid dose escalation
- target dose (concentration/receptor occupancy)
- patient vulnerability
Tardive dyskinesia affects what age population most?
the elderly
