Pharmacology of Anti-Psychotics

Question 1

What are Anti-Psychotics also known as?

Answer 1

Neuroleptics

Question 2

Outline the two main theories or Schizophrenia pathophysiology

Answer 2

DA Theory
• Amphetamine -> Schizophrenia Sx
• D2-receptor agonists -> Similar Symptoms
• Strength of Neuroleptics and D2 antagonist action
• Increased Dopamine content in amygdala (temporal lobe)

Glutamate Theory
• NMDA receptor antagonists (phencyclidine/ketamine)  psychotic Sx
• Reduced glutamate receptor density and expression -> Schizophrenic brain slices
• TG mice with NMDA receptor expression -> Schizophrenic behaviours
-> Restored with antipsychotics/neuroleptics

Question 3

What class of drug is Haloperidol?

Answer 3

FG Antipsychotics

Question 4

What class of drug is Chlorpromazine?

Answer 4

FG Antipsychotics

Question 5

What class of drug is Flupentixol?

Answer 5

FG Antipsychotics

Question 6

What is the MOA of FGAs?

Answer 6

Bind to D1, D2, a1, H1, mACh and 5-HT2A receptors

Question 7

What class of drug is Amisulpride?

Answer 7

SGA

Question 8

What class of drug is Onlazapine?

Answer 8

SGA

Question 9

What class of drug is Risperidone?

Answer 9

SGA

Question 10

What class of drug is Quetiapine?

Answer 10

SGA

Question 11

What is the MOA of Clozapine?

Answer 11

Binds all Anti-Pyschotic receptors but strongest at 5HT2A, a1 and H1

Question 12

What is the MOA of Quetiapine?

Answer 12

a1 and H1 blocker

Question 13

What is the MOA of Aripiprazole?

Answer 13

high D2 affinity

Question 14

In which groups of patients is Venlafaxine contraindicated?

Answer 14

MI

Question 15

What is a potential complication of antipsychotic drugs causing elevated blood pressure, sweating, urinary incontinence, elevated CPK level and muscle rigidity?

Answer 15

Neuroleptic Malignant Syndrome

Question 16

What is the MOA of Lithium?

Answer 16

Decrease NE/increase 5-HT synthesis and increase GABA (modulates dopamine and glutamate)

Question 17

State the ASEs of Lithium.

Answer 17

• Leukocytosis
• Increased Weight/Dryness
• Taste/Thirst (Nephrogenic Diabetes Insipidus)
• Hypothyroidism/Hyperparathyroidism/Hypercalcemia
• Increased Urine Output (Polyuria)
• Movement/Memory change

Question 18

State the potential SEs of Anti-psychotics

Answer 18

1. Behavioural Effects
   • Apathy and reduced initiative
   • Drowsy (easily stirred)
   • Aggressive tendencies inhibited
2. Motor Disturbances (Extrapyramidal/Tardive dyskinesia)
   • Parkinsonian-like Sx: Acute, reversible
   -> Block Nigro-Striatal DA
   • Tardive dyskinesia (stiff, jerky movements appearing months/years after Rx which occurs insidiously and irreversible due to proliferation of DA receptors in corpus striatum)
   -> Chose SGAs
3. Endocrine
   • Tuberohypophyseal pathway -> Increase PL secretion = gynecomastia and galactorrhoea
4. Anti-Muscarinic
   • SLUDGE DUMBELS: Salivation/Lacrimation/Urination/Diarrhoea/GI upset/Emesis ; Diaphoresis/ Urination/Miosis/Bradycardia/Brocnhospasm/Emesis/Lacrimation/Salivation
5. A-Adrenoceptor Blocking Actions
   • OH
6. H1-Blockking actions
   • Sedative and anti-emetic actions

Question 19

What pathway would an antipsychotic increasing PL secretion affect?

Answer 19

Tuberophyseal pathway

Question 20

What effect on haemodynamics may an antipsychotic have?

Answer 20

OH due to a-adrenoceptor blocking

Question 21

What are the potential SEs of Antipsychotics?

Answer 21

Sedation/Skin
Hypotension
Anticholinergic (SLUDGE DUMBELS)/Agranulocytosis
Dermatological SEs (Cutaneous)
Endocrine (Diabetes/Weight gain)/ Extrapyramidal