Anti-psychotics Flashcards
Dopamine hypothesis of psychosis
In patients of psychosis:
🔼 dopamine in limbic system ➡️ 🔼 D2 (Gi) ➡️ 🅱️ action potential ➡️ 🅱️ thought, affect
Typical anti-psychotics
mechanism and uses
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
Classification of typical antipsychotics
Low potency: 1. Molindone 2. Phenothiazines: Thioridazine & chlorpromazine High potency: 1. Phenothiazines 2. Butyrophenone 3. Thioxanthene
Examples of high potency antipsychotics
1. Phenothiazines: Fluphenazine, perphenazine, trifluoperazine 2. Butyrophenone: Haloperidol 3. Thioxanthene
List of side effects of typical antipsychotics
- D2 receptor: hyperprolactinemia, EPS
- Other receptor S/E: M, H1, 5HT, α1-R
- Metabolic S/E: insulin resistance, dyslipidemia
Other side effects of typical antipsychotics
- 🔼 cerebrovascular events: 🔼 risk in patients with dementia
- Thioridazine: brown vision, retinal deposits
- Chlorpromazine: lens pigmentation, retinopathy
Other receptor side effects of typical antipsychotics
M constipation, dry mouth
H1 sedation
5HT obesity
α1 postural hypotension
EPS of typical antipsychotics
- Akathesia: M/C
- Acute dystonia: earliest
- Parkinsonism
- Tardive dyskinesia: after many years
- Neuroleptic malignant syndrome
Akathesia as EPS of typical antipsychotics
Characterised by restlessness
M/C EPS
DoC: β blocker
Cause: unknown
Relation between EPS and other side effects of typical antipsychotics
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
Acute dystonia as EPS of antipsychotics
Involuntary muscle contractions (face, neck, eye muscles)
Cause: D2 R (like Parkinsonism)
Seen in young patients
Treatment of acute dystonia and Parkinsonism caused by typical antipsychotics
To 🔼 Dopamine levels indirectly DoC: anticholinergics: • Benzhexol • Trihexphenidyl • Biperiden Otherwise H1 🅱️ with max anticholinergic effect like: • promethazine • diphenhydramine • dimenhydrinate
Tardive dyskinesia
Occurs after many years due to upregulation of D2 receptors
🔼 D2 action
Rx:
DoC VMAT2 blockers like deutetrabenazine, valbenazine and change to atypical antipsychotics
Neuroleptic malignant syndrome caused by typical antipsychotics
Cause D2 🅱️ Severe form of EPS 1. Muscle rigidity 2. Hyperthermia 🤒 3. 🔼 CPK 4. Hypotension Rx: DoC: Dantrolene 🅱️ ryanodine R (Most specific drug bromicriptine)
Serotonin hypothesis
In LSD abusers, hallucinations and 5HT 🔼 in urine, both are observed
So serotonin may be responsible for psychosis
Atypical antipsychotics
mechanism
Block 5HT2 (more) Block D2 (less) so less EPS
Uses of atypical antipsychotics
- 1st line drug for schizophrenia (effective for both +ve & -ve symptoms)
- Mania
- Tics associated with Tourette’s syndrome
- Huntington’s chorea
For 2. - 4. uses, preferred over typical - Depression
- Levodopa induced psychosis
- Autism induced irritability
- Insomnia: quetiapine
Atypical antipsychotics used for depression
- Olanzapine
- Risperidone
- Aripiprazole
- Quetiapine
All are used as add on drug except Quetiapine which is used as monotherapy
Atypical antipsychotics used for levodopa induced psychosis
- Clozapine
- Olanzapine
- Risperidone
- Quetiapine
Atypical antipsychotics used for autism associated irritability
Risperidone
Aripiprazole
Clozapine
properties and uses
Most toxic and effective antipsychotic
Use:
1. DoC for resistant schizophrenia
2. DoC for suicidal tendency (ToC is ECT⚡️). Other drugs are lithium,…
Side effects of clozapine
Atypical antipsychotic
- Agranulocytosis
- De novo seizure
- Myocarditis
- Sialorrhea: wet pillow syndrome
- Sedation 🥱: M/C
Clozapine and agranulocytosis
🔼 risk with HLA-DQBI gene polymorphism
CI with carbamazepine
TDM useless as agranulocytosis is dose-independent
Quetiapine
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
Risperidone
Atypical antipsychotic
Most potent D2 🅱️
Max S/E ➡️ hyperprolactinemia, EPS
Aripiprazole and Brexipiprazole
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
Atypical antipsychotics
side effects
Other receptor S/E: M: constipation, dry mouth H1: sedation 5HT: obesity α1: postural hypotension Metabolic S/E: 1. Insulin resistance 2. Dyslipidemia
Atypical antipsychotics
side effects and drugs
Maximum: Clozapine > olanzapine Minimum: 1. Aripiprazole 2. Brexipiprazole 3. Ziprasidone 4. Cariprazine
