Antipsychotics Flashcards
What are antipsychotics?
- Drugs that reduce psychomotor excitement
* Controls symptoms of psychosis
Therapeutic uses of antipsychotics
- Hallucination
- Delusions
- Agitation
- Psychomotor excitement
- Mania
- Schizophrenia
- Psychosis 2ndary to medical condition - Prophylaxis – prevent relapse of psychotic illness/episodes
MOA of antipsychotics
• Blockade of DA pathways - reduces irrational behavior, agitation and aggressiveness along with psychotic symptomology
• In schizophrenia, DA overactivity is not the only abnormality
- Monoaminergic (5-HT) and aminoacid (glutamate) neurotransmitter systems may also be affected
• Only positive symptoms (hallucinations, aggression etc.) are linked with DA overactivity
• Negative symptoms (apathy, cognitive deficit etc.) are not necessarily linked with DA, however reduction of dopaminergic neurotransmission is the major mechanism of antipsychotic action.
Effect of DA antagonism on CVS
Hypotension (primarily postural) - d/t central and peripheral action on sympathetic tone
QT prolongation
Suppression of T wave (ECG)
Arrythmia (overdose)
Effect of DA antagonism on endocrine system
Increased prolactin release - d/t blockage of DA which has an inhibitory action on pituitary lactotrophs - gynaecomastia and galactorrhea, amenorrhea, hyperprolactinemia
Deacreased ADH - increased urine volume
Impair glucose tolerance - aggravate diabets, weight gain
Name the two classes of anti-psychotics
Typical
Atypical
What are typical antipsychotics? Give examples
• Work primarily through inhibition of D2 receptor – extrapyramidal side effects • Reduced tendency to induce neurologic movement disorder • Examples: a) Chlorpromazine b) Thioridazine c) Fluphenazine d) Haloperidol e) Zuclopentixol
What are atypical antipsychotics?
• Second generation anti-psychotics with weak dopamine blocking potential but strong 5-HT2 antagonistic activity. • Minimal extrapyramidal SE and tardive dyskinesia • Examples a) Risperidone b) Clozapine c) Olanzapine d) Aripiprazole e) Quetiapine f) Amisulpride
Which class is used as the first line treatment?
Atypical antipsychotics
Chlorpromazine (receptors involved and SEs)
- Receptor involved: alpha1, H1, muscarinic cholinergic
- SE: sedation (blockade of alpha1 and histamine), hypotension (a1), anticholinergic (dry mouth, constipation, urinary incontinence), EPSE
Haloperidol (receptors involved and SEs)
- Receptor involved: dopamine receptor
* SE: high risk of EPSE
Risperidone (receptors involved and SEs)
- Receptors involved: 5-HT2, D2 and alpha1
* SE: mild sedation, hypotension
Olanzapine (receptors involved and SEs)
- Receptors involved: D2 (weak), anticholinergic, H1 (strong)
- SE: sedation (H1), dry mouth, constipation, weight gain, metabolic syndrome (worsens diabetes)
Quetiapine (receptors involved and SEs)
• Receptors: 5-HT, D2, A1 and 2, H1, D2 (low)
• SE: sedation, postural hypotension, urinary retention/incontinence
- Extremely minimal EPSE and hyperprolactinaemic SE as D2 blocking activity is low
Aripiprazole (receptors involved and SEs)
- Receptors: partial dopamine agonist at D2 receptor, but antagonist at 5-HT2 receptor
- SE: nausea, dyspepsia, constipation, light-headedness
Clozapine
(used when unresponsive to other medication)
• Receptors: D2 (weak), 5-HT2 (strong), H1, alpha and muscarinic
• SE: sedation, potent anticholinergic, hypersalivation, agranulocytosis, bloody dyscrasia, precipitation of diabetes, myocarditis
What monitoring is to be done when patient is on clozapine?
• Regular blood tests are mandatory for a patient on clozapine to monitor the white cell count - First 6 months – weekly - Next 6 months – fortnightly - Thereafter – every 4 weeks - For one month after cessation • ECG
List the extrapyramidal SE seen with conventional antipsychotics
- Acute dystonia – painful contractions of muscles in neck, jaw or eyes (more common in men)
- Parkinsonism – reduced facial movements, shuffling gait, stiffness, tremor
- Akathisia – involuntary restlessness (typically in the legs)
- Tardive dyskinesia – involuntary grimacing movements of the face, tongue or upper body
List the general side effects seen with the use of atypical antipsychotics
- Weight gain - worst with clozapine and olanzapine
- Hyperglycaemia and type 2 diabetes - can induce this along with insulin resistance
- Metabolic syndrome the above two + dyslipidemia and HTN
- Stroke - caution with elderly patients and in dementia
Treating acute dystonia
Stop antipsychotic AND/OR give anticholinergic
Treatment of parkinsonism
Change antipsychotic - to something less D2 related
Treating Akathisia
Reduce/ change antipsychotic
Treating tardive dyskinesia
Sometimes reducing antipsychotics make it worse - not treatable
Therefore, prevent it rather than let it develop.
Choosing antipsychotic
No real difference in efficacy
Consider previous use of antipsychotic - use what has helped before
Consider preexisting comobrbidties - diabetes, overwieght, parkinsons
Consider patient concerns for SE.
