Comprehensive Study Notes on Deliriant Poisons: Dhatura, Atropa Belladonna, and Hyoscyamus Niger

Classification and Introduction

Dhatura is a member of the Solanaceae family and belongs to the genus Datura, which consists of nine species, including Datura ferox, Datura alba, and Datura fastuosa. It is known by several common names, such as Thorn apple (due to its spherical fruits with sharp spines), Jimson weed, Hell's bell, and devil's trumpet (inspired by its large trumpet-shaped flowers). The name "Jimson weed" is a shortened version of "Jamestown weed," titled after the first recorded accidental ingestion of the plant in Jamestown, Virginia, US, in 1676.

Dhatura falls under the broader category of plants containing tropane alkaloids. This group includes Datura stramonium, Atropa belladonna (deadly nightshade), Hyoscyamus niger (henbane), and Mandragora officinarum (mandrake). Within the classification of alkaloid amines, there are three major subgroups: hallucinogenic alkaloid amines, stimulant alkaloid amines, and anticholinergic tropane alkaloids, also known as belladonna alkaloids or bicyclic alkaloids.

Every part of the dhatura plant is poisonous, including the fruit, flowers, and seeds. However, the highest concentrations of toxic alkaloids are found in the roots and the seeds. Poisoning typically occurs only if the seeds are masticated (chewed) and swallowed. The usual routes of intake involve ingesting seeds or other plant parts in the form of tea, or smoking the dried leaves.

Active Principles and Pharmacological Action

The plant contains belladonna alkaloids that exhibit primary anticholinergic actions. The most important active principles are Hyoscine (also known as scopolamine), Hyoscyamine, and Atropine. These alkaloids function by blocking the acetylcholine receptor, producing sympathomimetic or parasympatholytic actions.

In the early phase of toxicity, the compounds act as a CNS stimulant, but this is followed by CNS depression, particularly affecting the respiratory center. Additionally, the alkaloids exhibit a vagolytic action, which results in the stimulation of the heart. These substances are absorbed through the mucous membranes of the gastrointestinal tract (GIT) and the respiratory tract, as well as through the skin and conjunctiva. Metabolism occurs in the liver via the enzyme atropinase, and a portion of the alkaloids is excreted through the urine.

Differentiation Between Dhatura and Capsicum Seeds

Dhatura seeds are frequently confused with capsicum (chilli) seeds, but they can be distinguished by several physical and sensory features:

1. Size and Shape: Dhatura seeds are large, thick, and kidney-shaped, whereas capsicum seeds are small, thin, and rounded.
2. Color: Dhatura seeds are dark brown; capsicum seeds are pale yellow.
3. Border: Dhatura seeds have a convex border with a double edge, while capsicum seeds have a single edge.
4. Smell and Taste: Dhatura seeds are odorless and bitter. Capsicum seeds have a pungent smell and a pungent taste.
5. Surface: Dhatura seeds have a surface with small depressions, while capsicum seeds are smooth.
6. Internal Structure: In a longitudinal section (LS) of a Dhatura seed, the embryo is curved outwards. In a capsicum seed, the embryo is curved inwards, resembling the figure $6$.

Signs and Symptoms: The Anticholinergic Toxidrome

Anticholinergic syndrome follows the ingestion of tropane alkaloids from plants or medications (including illicit drugs like heroin ‘cut’ with scopolamine). Symptoms typically manifest within $30-60$ minutes and can persist for $24-48$ hours because tropane alkaloids delay gastric emptying and absorption. The toxidrome is often remembered by the mnemonic: "red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, and full as a flask."

The clinical presentation is summarized by the "11 Ds":

1. Dryness of the mouth: Characterized as "dry as a bone," accompanied by a bitter taste, burning pain in the stomach, and vomiting.
2. Dysphagia: Difficulty in swallowing.
3. Dysarthria: Difficulty in talking due to inhibited salivation; speech is mumbling and often incomprehensible.
4. Dilatation of cutaneous blood vessels: Described as "red as a beet," featuring a flushed face and congested conjunctiva.
5. Diplopia: Double vision caused by dilated pupils (mydriasis) and loss of accommodation for near vision. This can progress to temporary blindness ("blind as a bat") and photophobia. The light reflex becomes sluggish and eventually absent.
6. Dry hot skin: Known as "hot as a hare." Fever occurs due to the inhibition of sweat and stimulation of the heat-regulating center. Mucous membranes and axillae are dry, and body temperature may rise by $1-2\,^\circ\text{C}$.
7. Distention of urinary bladder: Characterized as "full as a flask" due to urinary retention.
8. Drunken gait: Giddiness, confusion, restlessness, agitation, and an unsteady, staggering gait.
9. Delirium: Often described as "mad as a wet hen." This involves an altered mental status where the patient mutters indistinct words and exhibits carphologia (aimless picking at imaginary objects, clothes, or bed linens) and pill-rolling movements (the index finger and thumb performing a circular movement together). Visual and auditory hallucinations are common, and the patient may fail to recognize relatives or exhibit undressing behavior.
10. Diminished bowel sounds: The patient may present with paralytic ileus (pseudo-obstruction).
11. Drowsiness: Delirium eventually passes into drowsiness, which may progress to stupor, coma, or death from respiratory paralysis.

Additional clinical signs include a rapid pulse of $120-140$ beats per minute (initially full and bounding, later weak and irregular), increased respiration, scarlatiniform rash, and amnesia regarding events following ingestion.

Fatal Dose and Diagnosis

For Dhatura seeds, the fatal dose is approximately $75-125$ seeds, while a stupefying dose is $40-50$ seeds. For pure Hyoscine, the fatal dose is $15-30\,mg$. The fatal period is generally $24$ hours. Differential diagnoses include drunkenness and heat stroke.

Atropine can be detected using radioimmunoassay, GC-MS (Gas Chromatography-Mass Spectrometry), thin-layer chromatography, and liquid chromatography. Scopolamine can be analyzed in plasma and urine through radio-receptor assay and GC-MS.

Treatment and Management

Treatment should occur in a low-stimulus environment. Agitation is controlled with intravenous benzodiazepines. General measures include:

1. Emetics and Gastric Lavage: Lavage is performed with tannic acid, $KMnO_4$, or activated charcoal. The first dose of charcoal may be given with a cathartic like sorbitol. Additional doses may be administered at $1-2$ hour intervals.
2. Physiological Antidote: Physostigmine salicylate, a reversible acetylcholinesterase inhibitor, can antagonize CNS manifestations. The dose is $0.5-1\,mg$ via slow IV over $5$ minutes with continuous ECG monitoring ($0.02\,mg/kg/dose$). It should be used cautiously as it can induce cholinergic crises (seizures, asystole) and is contraindicated in patients using tricyclic antidepressants, quinidine, or cocaine.
3. Supportive Care: Purgatives, colonic lavage, and catheterization (for urinary retention). Tepid sponge baths are used for fever, and intravenous diazepam for seizures. Morphine must be avoided.
4. Respiratory Support: Oxygen inhalation and artificial respiration as needed. Hemodialysis and hemoperfusion are generally ineffective because tropane alkaloids are lipophilic and cross the blood-brain barrier.

Progress is monitored by the moistening of the tongue and changes in pupil size, which indicate normalization.

Postmortem Findings and Medico-legal Aspects

External postmortem findings usually show signs of asphyxia. Internally, seeds may be detected in the stomach and small intestines; these seeds resist putrefaction and can be found even in decomposed bodies. The stomach mucosa may show inflammation, the lungs are often edematous and congested, and the heart may show petechial hemorrhages in the endocardium.

In India, dhatura is frequently used as a "rail-road poison," where robbers disguised as saints offer travelers "prasad" mixed with seeds to stupefy them for robbery, kidnapping, or rape. Other medico-legal contexts include:

• Voluntary abuse by teenagers for hallucinogenic effects.
• Suicidal use or use in criminal abortion.
• Use by Yaqui women in Mexico to lessen childbirth pain.
• Accidental poisoning in children or mistaking seeds for chilli seeds.
• Therapeutic overdose from herbal medicines for asthma or bronchitis.
• Use of scopolamine as a "truth serum" alternative to sodium amytal in narco-analysis.
• Adulteration of country liquor to enhance its effects or use as an aphrodisiac.

Related Plants: Atropa Belladonna and Hyoscyamus Niger

Atropa belladonna belongs to the Solanaceae family and grows in the Himalayan ranges of India. Its active principles include atropine, hyoscine, and belladonine. It acts by inhibiting the muscarinic effects of acetylcholine. The fatal dose of atropine is $100-130\,mg$, with a fatal period of $24$ hours. Symptoms, treatment, and postmortem findings are identical to Dhatura. Accidental poisoning often occurs from swallowing eye drops or children eating the plant.

Hyoscyamus niger yields hyoscyamine, hyoscine, and atropine. It produces signs and symptoms similar to Dhatura. The fatal dose for hyoscyamine is $200\,mg$, and the fatal period is within $24$ hours. Treatment protocols are consistent with those for Dhatura poisoning.