Antipsychotics

Question 1

Term/Concept

Answer 1

Definition/Explanation

Question 2

Psychotropic Drugs

Answer 2

Medications acting on the central nervous system, modifying brain biochemical/physiological processes, often by affecting neurotransmitters like dopamine, serotonin, and noradrenaline.

Question 3

Psycholeptics

Answer 3

A class of psychotropic drugs that are psychic sedatives. Includes neuroleptics (antipsychotics), tranquilizers, and hypnotics.

Question 4

Neuroleptics (Antipsychotics)

Answer 4

Major tranquilizers, major sedatives with symptomatic antipsychotic action. Defined by Delay & Deniker (1957) based on 5 criteria (psychomotor indifference, reduced aggression/agitation, antipsychotic action, neurological/neurovegetative side effects, subcortical action).

Question 5

Psychosis

Answer 5

Severe mental disorders characterized by a global impairment of personality and a loss of contact with reality (e.g., schizophrenia, acute delirium, manic episodes).

Question 6

Positive Symptoms (Psychosis)

Answer 6

Productive symptoms like delusions and hallucinations.

Question 7

Negative Symptoms (Psychosis)

Answer 7

Deficit symptoms like autism, apathy, aboulia (lack of will/initiative).

Question 8

1st Generation Antipsychotics (Typical)

Answer 8

Older antipsychotics primarily acting via D2 receptor antagonism. Chemical classes include Phenothiazines (e.g., Chlorpromazine), Thioxanthenes (e.g., Flupentixol), Butyrophenones (e.g., Haloperidol), Benzamides (e.g., Sulpiride).

Question 9

Phenothiazines

Answer 9

Sub-classified by side chain: Aliphatic (Chlorpromazine), Piperidine (Thioridazine - withdrawn due to QT risk), Piperazine (Fluphenazine).

Question 10

Butyrophenones

Answer 10

Examples include Haloperidol (Haldol), Droperidol, Pimozide.

Question 11

Benzamides

Answer 11

Examples include Sulpiride (Dogmatil), Amisulpride (Solian), Tiapride.

Question 12

2nd Generation Antipsychotics (Atypical)

Answer 12

Newer antipsychotics, often with broader receptor activity (D2 and 5HT2A antagonism). Chemical classes include Dibenzodiazepines (Clozapine, Olanzapine), Benzisoxazoles (Risperidone), Quinolinones (Aripiprazole).

Question 13

Long-Acting Injectable (LAI) Antipsychotics

Answer 13

Formulations allowing spaced administration (weeks/months). Either polymer-based (Risperdal Consta) or prodrugs (esterified, e.g., Haloperidol Decanoate).

Question 14

Clinical Classification: Sedative

Answer 14

Primarily act on anxiety and agitation. Cause mainly neurovegetative side effects. Examples: Chlorpromazine (Largactil), Levomepromazine (Nozinan).

Question 15

Clinical Classification: Incisive

Answer 15

Primarily act on delusions and hallucinations in schizophrenia. Examples: Haloperidol (Haldol), Fluphenazine (Moditen).

Question 16

Clinical Classification: Disinhibitory

Answer 16

Primarily act to improve communication and reduce negative symptoms. Examples: Sulpiride (Dogmatil), Amisulpride (Solian).

Question 17

Dopamine Hypothesis of Schizophrenia

Answer 17

Suggests an excess of dopamine in the mesolimbic pathway (causing positive symptoms) and a deficit of dopamine in the mesocortical pathway (causing negative symptoms).

Question 18

Mechanism of Action (General)

Answer 18

All antipsychotics antagonize D2 receptors. Atypicals also significantly antagonize 5HT2A receptors.

Question 19

D2 Antagonism Effects

Answer 19

Mesolimbic: Therapeutic effect on positive symptoms. Nigrostriatal: Extrapyramidal side effects (EPS). Tuberoinfundibular: Hyperprolactinemia. Mesocortical: May worsen negative symptoms (less with atypicals).

Question 20

5HT2A Antagonism (Atypicals)

Answer 20

Modulates D2 effects: May reduce EPS, potentially improve negative symptoms, and mitigate hyperprolactinemia compared to typicals. Also linked to weight gain.

Question 21

Other Receptor Blockade

Answer 21

H1: Sedation, weight gain. Alpha-1 Adrenergic: Orthostatic hypotension. M1 Cholinergic (Muscarinic): Anticholinergic effects (dry mouth, constipation, blurred vision, tachycardia, cognitive issues).

Question 22

Pharmacokinetics: Absorption

Answer 22

Oral: Generally well absorbed but significant first-pass metabolism (FPH). IM: Complete absorption, higher bioavailability (>90%).

Question 23

Pharmacokinetics: Distribution

Answer 23

Large volume of distribution (Vd: 5-20 L/kg), lipophilic, crosses placenta and enters breast milk.

Question 24

Pharmacokinetics: Metabolism

Answer 24

Extensive hepatic metabolism, primarily via Cytochrome P450 enzymes. Some have active metabolites (e.g., Phenothiazines).

Question 25

Pharmacokinetics: Elimination

Answer 25

Generally long half-lives (e.g., ~24h), though atypicals may be shorter. Primarily renal elimination after metabolism.

Question 26

Acute Phenothiazine Intoxication

Answer 26

*Aliphatic/Piperidine:* Deep coma, hypotonia, hypothermia, hypotension. *Piperazine:* Coma with extrapyramidal hypertonia. *Thioridazine:* Cardiotoxicity (QT prolongation). Treatment: Supportive care, decontamination.

Question 27

Acute Butyrophenone Intoxication

Answer 27

Primarily diffuse or localized extrapyramidal symptoms (EPS), oculogyric crises (especially in children).

Question 28

Acute Benzamide Intoxication

Answer 28

*Sulpiride (1-2g):* Agitation, confusion. EPS can occur even at therapeutic doses.

Question 29

Acute Dibenzodiazepine Intoxication (Olanzapine)

Answer 29

Tachycardia, agitation/aggression, EPS, sedation, potentially coma.

Question 30

Extrapyramidal Symptoms (EPS)

Answer 30

Neurological side effects due to D2 blockade in the nigrostriatal pathway. Includes Parkinsonism, akathisia (restlessness), dystonia (muscle spasms, e.g., torticollis). Treatment: Anticholinergics (e.g., Trihexyphenidyl/Artane), Benzodiazepines.

Question 31

Neuroleptic Malignant Syndrome (NMS / Syndrome Malin)

Answer 31

Rare but life-threatening reaction. Characterized by high fever (40-42°C), severe muscle rigidity ("lead pipe"), autonomic instability, altered mental status, rhabdomyolysis (elevated CPK), elevated transaminases. Treatment: Stop antipsychotic, Dantrolene, supportive care (hydration, cooling), possibly renal replacement therapy.

Question 32

Toxicological Analysis: Colorimetric

Answer 32

Rapid, semi-quantitative methods for phenothiazines using electron-donating properties. *FPN Reagent:* Reacts with phenothiazines in urine/gastric lavage to give various colors (pink, violet, blue, red, orange). *Libermann Reagent:* Detects Haloperidol after extraction (brown color).

Question 33

Toxicological Analysis: Chromatographic

Answer 33

More specific methods. Thin Layer Chromatography (TLC), High-Performance Liquid Chromatography (HPLC) with UV detection, Gas Chromatography (GC) often requiring derivatization (e.g., silylation).

Question 34

Immunochemical Methods

Answer 34

Generally *not* available for routine neuroleptic screening/quantification.