Antipsychotics Flashcards
What are the different types of antipsychotics?
- First generation (typical) antipsychotics
- Second generation (atypical) antipsychotics
Which receptor is involved in the mechanism of action of antipsychotics?
D2 receptors
Name 2 first generation antipsychotics
- Haloperidol
- Chlorpromazine
What is the mechanisms of action of FGAs?
D2-antagonism in the CNS
List 2 indications for Haloperidol
- Acute emergency rapid tranquillisation and sedation in:
- Acute delirium
- Agression/psychosis in Alzheimers
- Schizophrenia and psychosis
- Mania and hypomania
- Severe tic disorders
- NaV in palliative care
- Restlessness/confusion in palliative care
- Consider for post-op NaV
Name 2 side effects of Haloperidol
- EPSP
- Neuroleptic Malignant Syndrome
How is choice of antipsychotic decided?
Side effect profile (patient preference)
What is Neuroleptic Malignant Syndrome?
Life-threatening reaction in response to neuroleptic medication - due to dopamine blackage.
- Fever
- Autonomic instability
- Tachycardia
- Hypertension
- Delirium/mental state changes
- Muscular rigitiy
Outline the extrapyramidal symptoms which may be seen with antipsychotic use
Oculogyric crisis can be seen with arirpiprazole
How does efficacy vary between antipsychotics?
All antipsychotics have similar efficacy (60-70%). Therefore, choice is decided on side effect profile.
Name 4 second generation antipsychotics
- Aripiprazole
- Clozapine
- Olanzapine
- Quetiapine
- Risperidone
Name 3 side effects of SGAs
- Anti-histaminic: Weight gain, sedation
- Anti-adrenergic: Tachycardia, sexual dysfunction, postural hypotension
- Anti-cholinergic: dry mouth, blurred vision, urinary retention, constipation, cutaneous flushing
- HTN
- Hyperprolactinaemia
- Impaired glucose tolerence: hyperglycaemia/diabetes
- EPSE
- Prolonged QTc
- Neuroleptic malignant syndrome
Name two common side effects of Olanzapine and Clozapine?
- Weight gain
- Sedation
What 2 SGAs have the greatest risk of weight gain and sedation?
- Olanzapine
- Clozapine
What is the benefit of SGAs over FGAs?
SGAs have a lower risk of EPSEs. However, they still have potentially significant side effects that shouldn’t be ignored.
Outline the NICE guidance on first line choice of antipsychotic medication
SGAs and FGAs can be prescribed as first line medication, and this should be determined by side effect profile and patient preference.
Which side effects are Risperidone associated with?
Increased prolactin secretion Erectile dysfunction Feminisation (rare cause of SIADH)
Which side effect does not appear whilst on Quetiapine?
Quetiapine does not increase prolactin secretion
How does Aripiprazole differ from other SGAs? What is the effect of this?
Aripiprazole is a partial D2 agonist rather than a D2 antagonist. It has less metabolic side effects, but is also less effective.
Besides D2 receptors, SGAs interact with which receptors?
Alpha 1 and 2 receptors Histamine receptors
What syndrome is associated with SGAs?
Metabolic syndrome:
- Waist circumference
- HTN
- Diabetes
- Hyperlipidaemia
How does Risperidone cause hyper-prolactinaemia?
Dopamine blockade removes the inhibition on prolactin secretion
What is the effect of hyper-prolactinaemia?
*Think pregnancy state* Amenorrhoea Galactorrhea Gynaecomastia Sexual dysfunction - vaginal dryness or erectile dysfunction Feminisation - loss of body hair and muscle mass (osteoporosis)
Outline the anti-muscarinic/cholinergic side effects
Blurred vision Urinary retention Dry mouth Constipation (Can’t see, can’t pee, can’t spit, can’t shit)
Describe general antipsychotic monitoring needs
Metabolic: Weight, BMI, waist, BP, glucose, lipids at baseline, 3 months, and every 12 months ECG: assess QTc - beware that dual antipsychotics exponentially lengths QTc rather than additively. before starting antipsychotics
What monitoring is required when taking clozapine?
FBC weekly (18wk), fortnightly (until 1yr) then monthly (indefinite). Clozapine levels if concerns over compliance.
What is the indication for Clozapine?
Treatment-resistant schizophrenia: reduces overall mortality Not responding to at least two different antipsychotics, one of which is a non-clozapine SGA.
What is the mechanism of action of Clozapine?
Blocks D1 and D4 receptors Low affinity to D2 - lack of EPSEs and hyperPRL
Name 2 potentially fatal side effects of Clozapine
Agranulocytosis - acute severe dangerous leukopenia Myocarditis Cardiomyopathy
What is the dosing regime of Clozapine?
Start at 12.5mg Second day: 25-50mg Gradually increase by 25-50mg up to 300mg May be increased by 50-100mg weekly *Seizure frequency increases above 600mg/d
What is the traffic light reporting symptoms for Clozapine?
A written report system for blood results that advises the use of Clozapine and the risk of agranulocytosis. Green - Clozapine may be administered Amber - Caution, further blood samples advised Red - STOP Clozapine immediately
Outline important DDIs of Clozapine
Clozapine undergoes extensive first pass metabolism via CYP enzymes. CYP1A2 inducers: Carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin. CYP1A2 inhibitors: Cimetidine, clarithryomycin, erythromycin, ciprofloxacin. CYP2D6 inhibitors: Amiodarone, cimetidine, clomipramine, haloperidol, fluoxetine, paroxetine, sertraline
Name 3 highly protein-bound drugs, and state the effect this has on serum Clozapine
Digoxin Heparin Phenytoin Warfarin May increase serum concentration as it displaces protein-bound Clozapine.
Name 3 CYP enzyme inducers
Carbamazepine Phenytoin Rifampicin Phenobarbital Rifabutin
Name 3 CYP enzyme inhibitors
Clarithryomycin and erythromycin Ciprofloxacin Amiodarone Clomipramine Haloperidol Fluoxetine, paroxetine, sertraline
What is the effect of smoking cigarettes whilst taking Clozapine?
Clozapine dosage becomes less effective as smoking increases its clearance, and may substantially reduce serum levels.
What is an effect of Clozapine that is highly desirable for Schizophrenia?
Reduces mortality by lowering risk of suicide.
Despite its potency, why is Clozapine not first line treatment for Schizophrenia?
Risk of fatal Agranulocytosis (1:4250) Risk of fatal myocarditis or cardiomyopathy (up to 1:1300)
Why does Clozapine have such a strict dosing regime?
It is cardiotoxic to Clozapine naive patients Narrow therapeutic window
Besides oral medication, what is the other route for antipsychotics?
Depot injections
What is the benefit of depot injections over oral antipsychotics?
Depot injections are long-acting and provide a sustained release over 1-4 weeks. This increases compliance as the patient does not need to take as many tablets on a daily basis.
What are the indications for depot injections?
Poor compliance with oral treatment Failure to respond to oral medication Memory problems Community Treatment Order
Where are depot antipsychotics injected?
Large muscles - most commonly gluteus maximus
Name 2 complications of depot injections
Pain/swelling at injection site Abscess Nerve Palsy
What antipsychotic medications can be given as a depot?
Olanzapine Haloperidole Risperidone Aripiprazole
Which specific side effects may occur when antipsychotics are used in elderly patients?
Increased risk of stroke Increased risk of VTE
