This document discusses anti-psychotic medications. It describes how anti-psychotics work by inhibiting dopamine to treat psychosis symptoms. The document categorizes anti-psychotics as first-generation or typical, and second-generation or atypical. Typical anti-psychotics are further divided into basal and incisive, while atypical anti-psychotics have multi-receptor targets and include multi-acting receptor targeted antagonists, dopamine-serotonin antagonists, dopamine D2-D3 antagonists, and a dopamine partial agonist. The document notes the pharmacokinetics, side effects, and therapeutic strategies for using anti-psychotics.

1. Anti-Psychotics
Mgr. Malek Azar
CHARLES UNIVERSITY IN PRAGUE
FACULTY OF PHARMACY

2. Psychosis
• A mental disorder characterized by loss of contact with reality caused by
excess of dopamine in the limbic system in the brain.
• Types of psychosis: Schizophrenia, Bipolar disorder, others.
Psychosis Symptoms
Positive Negative
Hallucination Cognitive, Emotional Impairment
Delusions Isolation
Agitation Apathy

3. Anti-Psychotics
• They are medications used in psychosis by inhibiting dopamine (D).
• They are divided into two main parts:
1st Generation
2nd Generation
• They may be used in: Aggressive patients, vomiting, bipolar disorder,
refractory pain, depression and anxiety.

4. Pharmacokinetics
• Mainly orally
• Good absorption
• High lipophilicity
• Extensively metabolized in the liver by CYP450
• Once daily (long half life)

5. Side Effects
Mainly they inhibit dopamine receptors so they cause Extra-pyramidal side
effects:
• Dystonia: sustained muscle contraction
• Akathisia: restlessness, constant movement
• Parkinsonism
• Dyskinesia: involuntary muscle movement

6. Other Side Effects
Many of them inhibit many receptors
• Alpha: hypotension, sexual dysfunction
• Muscarinic: dry mouth, blurred vision, constipation, urinary retention,…
• Histaminic: sedation, weight gain
• QT prolongation.

7. 1st GENERATION ANTI-PSYCHOTICS
• These are divided into two parts:
Basal
Incisive

8. Incisive Anti-Psychotics
• High affinity to D2 receptors
• Low affinity to other types of receptors.
• They affect positive symptoms of schizophrenia mainly.
• They bring extrapyramidal symptoms (EPS).

9. Incisive Anti-Psychotics
Pheno-thiazines / Thio-xanthenes Butyro-phenones
Perphenazine Haloperidol
Fluphenazine Melperone
Flupenthixol

10. Basal Anti-Psychotics
• Lower affinity to D2 receptors
• Higher affinity to other receptor types.
• They affect positive and negative symptoms of schizophrenia.
• They have sedative, anticholinergic, antihistaminic and cardiovascular side
effect, but extrapyramidal symptoms are less frequent.

11. Basal Anti-Psychotics
Pheno-thiazines Thio-xanthenes
Chlor-promazine Chlor-prothixene
Levome-promazine Zuclo-penthixol

12. 2nd GENERATION ANTI-PSYCHOTICS
(ATYPICAL ANTI-PSYCHOTICS)
• In general, they are serotonin-dopamine antagonists (antagonists of D2 and
serotonin receptors 5HT-2A)
• They affect in general many other types of receptors.
• They are much more efficient in treatment of negative symptoms of
schizophrenia in comparison with conventional antipsychotics.
• Have lower side effects (lower EPS)

13. 2nd GENERATION ANTI-PSYCHOTICS
• They are metabolized by CYP450 in liver.
• They potentiate the sedation effects of analgesics, alcohol and
antihistamines.

14. Atypical anti-psychotics
Multi Acting
Receptor Targeted
Antagonists
Dopamine-
Serotonin
Antagonists
D2-D3 Antagonists
Dopamine Partial
Agonist

15. Multi Acting Receptor Targeted Antagonists
(MARTA)
• They block many types of receptors: D2, M, A, H1, 5HT2
• They have low risk of causing Extrapyramidal SE and hyperprolactenemia
• They have other side effects (due to their multi antagonism): sedation, weight
gain and hypotension.
• Risk of induction of Diabetes Mellitus 2.
• Clozapine – Olanzapine – Quetiapine – Zotepine.

16. Dopamine-Serotonin Antagonists
• They block D2-D3 and 5HT2 receptors and some others (H-A).
• They cause less sedation and hypotension but more risk of
hyperprolactinemia and extrapyramidal SE.
• Similar effects to MARTA compounds.
• Risperidone – Paliperidone – Sertindole – Ziprasidone

17. Dopamine D2-D3 Antagonists
• They block selectively D2-D3 receptors
• In low dose, they block the presynaptic receptors affect negative symp.
• In high dose, they block the postsynaptic ones affect positive symp.
• High risk of Extrapyramidal and hyperprolactinemia SE.
• Sulpiride – Amisulpiride

18. Dopamine Partial Agonist
• It has D2 , 5HT1A partial agonism and 5HT2A antagonism.
• It has a very low incidence of side effects.
• Aripiprazole

19. Therapeutic Strategy
• Atypical anti-psychotics are the drugs of choice.
• Onset of beneficial effects may take 2-3 weeks and till the optimal effects, it
requires 4-6 weeks of therapy.
• Discontinuation may lead to relapse.