Antipsychotics

Question 1

What is the MoA of 2nd gen antipsychotics vs 1st gen

Answer 1

2nd gen
o Dopamine specific antagonists (D2 receptors) – less than 1st generation
o 5-HT2A (serotonin) receptor antagonists

1st gen
D2 dopamine receptor binding and blockade

Question 2

indications for 2nd gen vs 1st gen antipsychotics

Answer 2

2nd gen indications
Schizophrenia (good for positive and negative sx)
o Bipolar disorder
o Acute psychosis
o Post-partum psychosis
o Major depressive disorder with psychotic disorders
o OCD (concomitant therapy)
o Tourette syndrome
o Huntington disease

1st gen indications are same except added
- delirium
- acute agitated states (aggressive)
and NOT for huntington s

Question 3

What are the adverse effects of second vs 1srt gen antipsychotics as well as clozapine specifically
Give examples of which mainly with

Answer 3

2nd gen effects
o Metabolic effects – weight gain, hyperglycaemia, dyslipidaemia :
(Mainly with Clozapine, Olanzapine and Quetiapine. Olanzapine also affects LFTs.

o Sedation – tolerance usually develops within a few days of treatment

Constipation

o Prolonged QT interval

o Hyperprolactinemia =gynaecomastia, sexual dysfunction, amenorrhoea, risk for osteo– mainly with risperidone

o Anti-ACh (muscarinic) effects – dry mouth, blurred vision, mydriasis, constipation, urinary retention, tachy
- Mainly with Clozapine, olanzapine and quetiapine

o Repetitive non-purposeful movement of mouth, head, limbs, trunk (lip smacking, excessive blinking)

Neuroleptic malignant syndrome = fever, muscle rigidity/tremor, Autonomic NS instability (tachy, labile BP, sweating, dysrhythmias), mental status changes (confusion, delirium, stupor),

• rhabdomyolysis and elevated CK. Within 2 weeks of first dose.

o Orthostatic hypotension – common during initial treatment, especially with Olanzapine

1st gen effects = these +
Extrapyramidal Side effects
o Dystonia = sustained involuntary muscle contractions: (Wry neck, Oculogyric crisis)
o Akathisia = restlessness, esp in legs
o Pseudoparkinsonism = slowness, rigidity, gait disorder
o Tardive dyskinesia = Repetitive non-purposeful movement of mouth, head, limbs, trunk (lip smacking, excessive blinking)

o Clozapine – agranulocytosis (usually in first 4/12), myocarditis, cardiomyopathy, toxic megacolon

Question 4

What is the onset and treatment of Extrapyramidal SE

Answer 4

• Dystonia
• Rare in the elderly(problem of young people
• Easily treated if new(Benztropine, Procyclidine)
• Pseudoparkinsonism
• Weeks after starting(more likely in older patients, bilateral, hypomimia)
• Stop medication or lower dose
• Parkinson’s medications don’t work well and may cause worsening of psychosis
• Akathisia
• (Rule out Restless Leg Syndrome, Anxiety)
• Treatment (Beta-blockers, Benzodiazepines)
• Tardive dyskinesia
• Onset is usually after many years on antipsychotics
• No effective treatment–Stopping antipsychotic may worsen TD
  
  • Change agents (Clozapine)

Question 5

What are the IMI versions of antipyschotics and their dosing frequency and the risks of using depot

Answer 5

Zuclopenthixol (accuphase for short periods),
Fluphenazine,
Risperidone (every 2/52),
Haloperidol,
Olanzapine (post injection syndrome),
Paliperidone (every 4/52),
Flupenthixol (Depixol)

Can use typical antipsychotics in depot form for those at high rise of poor adherence -
higher risk of EPSEs, sedation and
hyperprolactinemia.

Question 6

What is the general monitoring required for antipsychotics and time in between

Answer 6

Prior to prescribing:
* FBC
* U&E
* LFT
* Lipids
* Weight
* BP (hypertension)
* Fasting blood glucose/ HbA1c
* Prolactin

Physical Cardio exam
* - ECG - if abnormalities/ risk factors, personal hx

3months
- Lipid profile, weight then yearly

6months
- fasting blood glucose
CVS risk every year
- Prolactin then yearly

Yearly
– FBC, U&E, LFT
- fasting blood glucose

Question 7

how to manage weight gain in antipscyhotics

Answer 7

• can switch to weight-sparing
  antipsychotic e.g. aripiprazole, provide
  lifestyle advice and assistance, add weight loss medication

Question 8

What are the pretreatment screening for clozapine

Answer 8

• WBC and absolute neutrophil count (weekly for 18 weeks then every 4 weeks)
• monitor for constipation - bowel habit (weekly for first 4 months)
• Signs and symptoms of myocarditis or cardiomyopathy - HF symptoms (6-8 weeks of treatment)
• GEneral monitoring for antipsychotics
• LFTS if liver disease
  Blood pressure- sitting and standing during dose titrations