Part 8: Anticholinergics and Antihistamines

Clinical Reference for Healthcare Professionals.

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1. Promethazine Hydrochloride

Field	Detail
INN / Salt	Promethazine Hydrochloride
Drug Class	Phenothiazine (First-Generation Antihistamine / Antiemetic)
Schedule	Schedule H
Indian Brands	Phenergan, Avomine, Promethazine (generic)
Legitimate Uses	Allergic rhinitis, nausea/vomiting, motion sickness, pre-operative sedation

Mechanism of Action

Promethazine blocks H1 histamine receptors (producing sedation and antipruritic effects), muscarinic acetylcholine receptors (anticholinergic effects), and dopamine receptors. It readily crosses the blood-brain barrier, producing pronounced CNS depression.

Why It Is Abused

Promethazine is the critical “second ingredient” in the infamous codeine cough syrup abuse culture (“Lean”). The combination of Codeine (opioid euphoria) + Promethazine (extreme sedation + antiemetic preventing the nausea from Codeine) produces a powerful, sustained sedated high. Promethazine itself, at high doses, can produce a dissociative, dreamlike state.

Side Effects & Dangers of Abuse

• Severe Respiratory Depression: Especially when combined with opioids or alcohol. This is the leading cause of “Lean”-related deaths.
• Seizures: At high doses, particularly in children and young adults.
• Neuroleptic Malignant Syndrome (NMS): A rare, life-threatening reaction (high fever, muscle rigidity, autonomic instability).
• Anticholinergic Toxicity: Dry mouth, urinary retention, blurred vision, tachycardia, delirium.

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2. Diphenhydramine Hydrochloride

Field	Detail
INN / Salt	Diphenhydramine Hydrochloride
Drug Class	Ethanolamine (First-Generation Antihistamine)
Schedule	OTC (Over-the-Counter)
Indian Brands	Benadryl (diphenhydramine formulations), Caladryl
Legitimate Uses	Allergic reactions, insomnia (OTC sleep aid), motion sickness

Mechanism of Action

Diphenhydramine is a potent H1 receptor antagonist that also has significant muscarinic acetylcholine receptor blocking activity (anticholinergic). It easily crosses the blood-brain barrier, producing strong sedation.

Why It Is Abused

At extremely high doses (500mg+), Diphenhydramine produces a full-blown anticholinergic delirium — vivid, often terrifying hallucinations (seeing shadow people, conversations with entities that aren’t there), extreme confusion, and amnesia. Unlike typical hallucinogens (LSD, psilocybin), these hallucinations are indistinguishable from reality to the user, making them uniquely dangerous.

Side Effects & Dangers of Abuse

• Anticholinergic Toxicity Syndrome (“Hot as a hare, blind as a bat, dry as a bone, red as a beet, mad as a hatter”): Hyperthermia, dilated pupils, dry skin, flushing, delirium.
• Cardiac Arrhythmias: QT prolongation and Torsades de Pointes at massive overdoses.
• Rhabdomyolysis: Muscle breakdown from prolonged agitation and seizures.
• Death: Diphenhydramine overdose can be fatal, and there have been documented fatalities.

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3. Trihexyphenidyl Hydrochloride

Field	Detail
INN / Salt	Trihexyphenidyl Hydrochloride (Benzhexol)
Drug Class	Anticholinergic / Antimuscarinic
Schedule	Schedule H
Indian Brands	Pacitane, Parkin, Broflex
Legitimate Uses	Drug-induced extrapyramidal symptoms (from antipsychotics), Parkinson’s disease (adjunct)

Mechanism of Action

Trihexyphenidyl is a centrally-acting anticholinergic that blocks muscarinic acetylcholine receptors in the basal ganglia. It is prescribed to counteract the muscle stiffness, tremors, and dystonia caused by antipsychotic drugs.

Why It Is Abused

In psychiatric populations, Trihexyphenidyl is widely known and abused. At supratherapeutic doses, it produces a mild euphoria, a feeling of “lightness,” and altered perceptions. It is particularly abused in institutional settings (psychiatric hospitals, prisons). Its abuse has been extensively documented in Indian psychiatric literature.

Side Effects & Dangers of Abuse

• Anticholinergic Psychosis: Hallucinations, severe confusion, paranoia.
• Memory Impairment: Profound short-term memory loss.
• Urinary Retention: Can require catheterization.
• Worsening of Tardive Dyskinesia: Paradoxically makes the very movement disorder it treats worse in the long term.

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Next: Part 9: Muscle Relaxants and Barbiturates