Typical (Conventional) Antipsycotics

Introduction
Illustrated mechanism of action
Examples of Medication Brand Names (with Images)
Indication
Side Effects
Precautions & Contraindications
Monographs
Reference

Introduction

History of Typical Antipsychotics

Discovery and Early Use:

Typical antipsychotics emerged in the 1950s after chlorpromazine, a phenothiazine derivative initially developed as an anesthetic, was found to calm agitated psychiatric patients. French surgeon Henri Laborit noted its calming effects in 1951, and psychiatrists Jean Delay and Pierre Deniker later confirmed its antipsychotic properties, marking the start of the "psychopharmacological revolution".

Mechanism and Classification:

These drugs function as dopamine D2 receptor antagonists, with their efficacy linked to blocking mesolimbic pathway activity. The dopamine hypothesis of schizophrenia emerged from this mechanism, as amphetamine-induced psychosis (linked to dopamine excess) was mitigated by these drugs. Key classes include phenothiazines (e.g., chlorpromazine) and butyrophenones (e.g., haloperidol).

Clinical Impact:

Chlorpromazine replaced invasive treatments like lobotomy and insulin coma therapy, enabling deinstitutionalization of psychiatric patients in the 1950s–60s. By the 1970s, over 40 typical antipsychotics were available globally, though their use declined due to extrapyramidal symptoms (EPS) like Parkinsonism and tardive dyskinesia.

Legacy and Evolution:

Despite their side effects, typical antipsychotics remain critical for acute agitation. The 1990s introduced atypical antipsychotics (e.g., clozapine) with reduced EPS risk, though debates persist about distinctions between drug generations.

Mechanism of action

Typical antipsychotics (also known as first-generation antipsychotics, FGAs) primarily work by blocking dopamine D2 receptors in the brain. Here's a breakdown of their mechanism of action:

Primary Mechanism:

D2 Receptor Antagonism:

These drugs block dopamine D2 receptors, especially in the mesolimbic pathway, which helps reduce positive symptoms of schizophrenia (like hallucinations and delusions).

Effects on Dopaminergic Pathways:

1. Mesolimbic pathway – Blocked D2 receptors → reduces positive symptoms.

2. Mesocortical pathway – May worsen negative symptoms (e.g., apathy, social withdrawal) due to dopamine blockade

3. Nigrostriatal pathway – D2 blockade here can lead to extrapyramidal side effects (EPS), such as Parkinsonism, dystonia, akathisia, and tardive dyskinesia.

4. Tuberoinfundibular pathway – D2 blockade increases prolactin → hyperprolactinemia (leading to galactorrhea, amenorrhea, gynecomastia).

Additional Receptor Effects (Variable by Drug):

Some typical antipsychotics also have:

Anticholinergic effects (e.g., dry mouth, constipation)

Antihistaminic effects (e.g., sedation)

Alpha-1 adrenergic blockade (e.g., orthostatic hypotension)

Examples of Medication Brand Names

Neurazine (Chlorpromazine )

MOTIVAL (Fluphenazine)

Haloperidol Retard (haloperidol)

Trilafon 4mg (perphenazine)

Thiozin 100mg ( thioridazine Hcl)

Indication

Typical antipsychotics are prescribed for conditions like:

1.Schizophrenia (especially positive symptoms like hallucinations and delusions)

2.Acute psychosis

3.Mania in bipolar disorder

4.Severe agitation or aggression (e.g., in dementia)

5.Nausea and vomiting (e.g., prochlorperazine)

4.Tourette's syndrome (e.g., haloperidol)

Side Effects:

1. Extrapyramidal Symptoms (EPS):

Acute dystonia (muscle spasms, especially of the neck/face)

Parkinsonism (tremors, stiffness, bradykinesia)

Akathisia (restlessness, urge to move)

Tardive dyskinesia (involuntary movements, especially of the face and tongue; can be irreversible)

2. Neuroleptic Malignant Syndrome (NMS):

Rare but life-threatening: high fever, rigidity, confusion, autonomic instability

3. Sedation:

Especially with low-potency FGAs like chlorpromazine

4. Anticholinergic Effects:

Dry mouth, blurred vision, constipation, urinary retention

5. Orthostatic Hypotension

Especially with chlorpromazine

6. Hyperprolactinemia:

Can lead to galactorrhea, gynecomastia, menstrual irregularities

7. Weight gain and metabolic effects:

Less prominent than atypical antipsychotics but still possible

8. QT prolongation:

Risk of arrhythmias (e.g., thioridazine)

Precautions & Contraindications

Contraindications of Typical Antipsychotics

• Severe allergies to antipsychotics.

• Concurrent CNS depressants (barbiturates, benzodiazepines, opioids) due to additive sedation/respiratory depression.

• Anticholinergic medications (e.g., scopolamine) or phencyclidine use.

• Severe cardiac abnormalities (e.g., prolonged QTc, arrhythmias).

• History of seizures (lowers seizure threshold).

• Narrow-angle glaucoma (anticholinergic effects increase intraocular pressure).

• Prostatic hypertrophy (worsens urinary retention).

• Tardive dyskinesia (risk of exacerbation).

No relevant photos are available in the provided sources. For visual summaries, consult medical databases or prescribing guidelines.

Key Risks

• Neuroleptic malignant syndrome (life-threatening rigidity/fever).

• QTc prolongation (cardiac arrest risk).

• Hyperprolactinemia and sedation.

• High EPS risk (dystonia, akathisia, parkinsonism).

Use cautiously in elderly patients or those with dementia due to mortality/stroke risks.

Typical (conventional) antipsychotics require several precautions due to their side effect profile and patient-specific risks:

• Dose adjustment: Start with lower doses in patients with liver impairment and use the lowest effective dose to minimize side effects.

• Pregnancy and breastfeeding: Avoid or use the lowest dose possible in pregnant women; breastfeeding is generally discouraged during treatment.

• Elderly patients: Increased risk of death in dementia-related psychosis; monitor closely for cardiovascular or infection-related events.

• Cardiac monitoring: Obtain ECG before and during treatment to monitor for QT interval prolongation and other cardiac effects, especially in patients with heart disease or arrhythmia history.

• Side effects to watch for:

• Extrapyramidal symptoms (tremor, rigidity, akathisia)

• Tardive dyskinesia (more common with older drugs like haloperidol)

• Neuroleptic malignant syndrome (rare but life-threatening)

• Sedation, orthostatic hypotension, dry mouth, weight gain, sexual dysfunction

• Increased risk of falls due to sedation and motor instability.

• Drug interactions: Monitor for neurotoxicity when combined with lithium.

• General advice: Only prescribe when benefits outweigh risks, discontinue if no clear benefit, and regularly monitor for adverse effects.

Monographs

pharma activity final (1).docx

Thioridazine

haneen Essawy.docx

Haloperidol

Salma eldsokey .docx

Perphenazine

Sara Fouad pharma activity.docx

Fluphenazine

Drug monograph-2-1_250423_215514.docx

Chlorpromazine

Reference

Page updated

Report abuse

Typical (Conventional) Antipsycotics

Introduction

History of Typical Antipsychotics

Mechanism of action

Examples of Medication Brand Names

Neurazine (Chlorpromazine )

MOTIVAL (Fluphenazine)

Haloperidol Retard (haloperidol)

Trilafon 4mg (perphenazine)

Indication

Side Effects:

Precautions & Contraindications

Contraindications of Typical Antipsychotics

Typical (conventional) antipsychotics require several precautions due to their side effect profile and patient-specific risks:

Monographs

Thioridazine

Haloperidol

Perphenazine

Fluphenazine

Chlorpromazine

Reference

Introduction

mechanism of action

Indication and Side Effects

Precautions & Contraindications