Anti-psychotics

Question 1

Dopamine hypothesis of psychosis

Answer 1

In patients of psychosis:

🔼 dopamine in limbic system ➡️ 🔼 D2 (Gi) ➡️ 🅱️ action potential ➡️ 🅱️ thought, affect

Question 2

Typical anti-psychotics

mechanism and uses

Answer 2

Blocks D2 receptor
Uses:
1. Schizophrenia:
 2nd line and effective for only +ve symptoms 
2. Tics associated with Tourette’s syndrome 
3. Huntington’s chorea 
4. Migraine attack
5. Antiemetic except thioridazine 
6. Antipruritic: H2 🅱️
7. Mania

Question 3

Classification of typical antipsychotics

Answer 3

Low potency:
1. Molindone
2. Phenothiazines:
 Thioridazine & chlorpromazine
High potency:
1. Phenothiazines 
2. Butyrophenone
3. Thioxanthene

Question 4

Examples of high potency antipsychotics

Answer 4

1. Phenothiazines:
 Fluphenazine, perphenazine, trifluoperazine
2. Butyrophenone:
 Haloperidol
3. Thioxanthene

Question 5

List of side effects of typical antipsychotics

Answer 5

1. D2 receptor: hyperprolactinemia, EPS
2. Other receptor S/E: M, H1, 5HT, α1-R
3. Metabolic S/E: insulin resistance, dyslipidemia

Question 6

Other side effects of typical antipsychotics

Answer 6

1. 🔼 cerebrovascular events: 🔼 risk in patients with dementia
2. Thioridazine: brown vision, retinal deposits
3. Chlorpromazine: lens pigmentation, retinopathy

Question 7

Other receptor side effects of typical antipsychotics

Answer 7

M constipation, dry mouth
H1 sedation
5HT obesity
α1 postural hypotension

Question 8

EPS of typical antipsychotics

Answer 8

1. Akathesia: M/C
2. Acute dystonia: earliest
3. Parkinsonism
4. Tardive dyskinesia: after many years
5. Neuroleptic malignant syndrome

Question 9

Akathesia as EPS of typical antipsychotics

Answer 9

Characterised by restlessness
M/C EPS
DoC: β blocker
Cause: unknown

Question 10

Relation between EPS and other side effects of typical antipsychotics

Answer 10

EPS is max with haloperidol and min with thioridazine whereas it is opposite for other receptor side effects
This is due to their affinity to receptors

Question 11

Acute dystonia as EPS of antipsychotics

Answer 11

Involuntary muscle contractions (face, neck, eye muscles)
Cause: D2 R (like Parkinsonism)
Seen in young patients

Question 12

Treatment of acute dystonia and Parkinsonism caused by typical antipsychotics

Answer 12

To 🔼 Dopamine levels indirectly
DoC: anticholinergics:
• Benzhexol
• Trihexphenidyl
• Biperiden
Otherwise H1 🅱️ with max anticholinergic effect like:
• promethazine 
• diphenhydramine 
• dimenhydrinate

Question 13

Tardive dyskinesia

Answer 13

Occurs after many years due to upregulation of D2 receptors
🔼 D2 action
Rx:
DoC VMAT2 blockers like deutetrabenazine, valbenazine and change to atypical antipsychotics

Question 14

Neuroleptic malignant syndrome caused by typical antipsychotics

Answer 14

Cause D2 🅱️
Severe form of EPS
1. Muscle rigidity
2. Hyperthermia 🤒 
3. 🔼 CPK
4. Hypotension
Rx:
 DoC: Dantrolene 🅱️ ryanodine R
 (Most specific drug bromicriptine)

Question 15

Serotonin hypothesis

Answer 15

In LSD abusers, hallucinations and 5HT 🔼 in urine, both are observed
So serotonin may be responsible for psychosis

Question 16

Atypical antipsychotics

mechanism

Answer 16

Block 5HT2 (more)
Block D2 (less) so less EPS

Question 17

Uses of atypical antipsychotics

Answer 17

1. 1st line drug for schizophrenia (effective for both +ve & -ve symptoms)
2. Mania
3. Tics associated with Tourette’s syndrome
4. Huntington’s chorea
   For 2. - 4. uses, preferred over typical
5. Depression
6. Levodopa induced psychosis
7. Autism induced irritability
8. Insomnia: quetiapine

Question 18

Atypical antipsychotics used for depression

Answer 18

1. Olanzapine
2. Risperidone
3. Aripiprazole
4. Quetiapine
   All are used as add on drug except Quetiapine which is used as monotherapy

Question 19

Atypical antipsychotics used for levodopa induced psychosis

Answer 19

1. Clozapine
2. Olanzapine
3. Risperidone
4. Quetiapine

Question 20

Atypical antipsychotics used for autism associated irritability

Answer 20

Risperidone

Aripiprazole

Question 21

Clozapine

properties and uses

Answer 21

Most toxic and effective antipsychotic
Use:
1. DoC for resistant schizophrenia
2. DoC for suicidal tendency (ToC is ECT⚡️). Other drugs are lithium,…

Question 22

Side effects of clozapine

Answer 22

Atypical antipsychotic

1. Agranulocytosis
2. De novo seizure
3. Myocarditis
4. Sialorrhea: wet pillow syndrome
5. Sedation 🥱: M/C

Question 23

Clozapine and agranulocytosis

Answer 23

🔼 risk with HLA-DQBI gene polymorphism
CI with carbamazepine
TDM useless as agranulocytosis is dose-independent

Question 24

Quetiapine

Answer 24

Atypical antipsychotic
Use: 
1. Monotherapy in depression
2. Insomnia
S/E:
1. Cataract
2. QT prolongation:
 Seen with ziprasidone, sertindole (max)
Overall QT prolongation: Typical > atypical

Question 25

Risperidone

Answer 25

Atypical antipsychotic
Most potent D2 🅱️
Max S/E ➡️ hyperprolactinemia, EPS

Question 26

Aripiprazole and Brexipiprazole

Answer 26

Atypical antipsychotics 
Mechanism: 
• 5HT2 🅱️
• partial agonist of 5HT1A & D2 ➡️ least EPS
DoC:
1. Schizophrenia
2. Mania in 🤰 
3. Acute mania
S/E:
 Least weight gain and metabolic S/E

Question 27

Atypical antipsychotics

side effects

Answer 27

Other receptor S/E:
 M: constipation, dry mouth
 H1: sedation
 5HT: obesity
 α1: postural hypotension
Metabolic S/E:
1. Insulin resistance
2. Dyslipidemia

Question 28

Atypical antipsychotics

side effects and drugs

Answer 28

Maximum:
 Clozapine > olanzapine
Minimum:
1. Aripiprazole 
2. Brexipiprazole
3. Ziprasidone
4. Cariprazine