Introduction
• Ergot is produced by the dried sclerotia of the fungus Clavices purpurea.
• It is a parasitic fungus attacking the grains of several plants such as rye, maize, barley, wheat, oats, bajra etc. in wet seasons.
• The fungus at grains germinates into hyphae and these hyphae penetrate deep into the grains and hardened into a purplish structure called sclerotium, which elaborates number of ergot alkaloids.
• It is dark-purple or black in colour.
• It has disagreeable taste.
• Natural ergot is also the source of the potent hallucinogen lysergic acid diethylamide or LSD.
Alkaloids of Ergot
• Ergotoxin
• Dihydroergocornine
• Dihydroergocristine
• Dihydroergosine
• Dihydroergotamine
• Dihydroergotaxime
• Ergobasine
• Ergocornine
• Ergocristine
• Ergocryptine
• Ergosine
• Ergometrine
• Ergonovine
• Ergotamine
• Ergotaxime
• Methylergonovine
• Bromocriptine
• Lergotrile
• Lisuride
• Lysergol
• Metergoline
• Methylergonovine
• Methysergide.
Uses
• It is used in some medicinal preparation.
• As its action on the uterus is more effective, it is largely used an abortifacient.
• It is used in treatment of migraine and cluster headaches.
• It is also used in the treatment of Parkinsonism, suppression of lactation, hypogonadism, galactorrhoea, and mastalgia.
• Ergot derivatives are used for the treatment of prolactin-secreting pituitary tumours and hyperprolactinaemic infertility.
Route of Administration
• Orally
• Intramuscular
• Intravenous
Fatal Dose
• The fatal dose of ergot is 5 to 10gm.
Fatal Period
• The fatal period of ergot is within 1 day.
Mode of Action
• The ergot alkaloids act as partial agonists or antagonists at adrenergic, dopaminergic, and tryptaminergic (serotonin) receptors.
• Each alkaloid at these receptor sites varies with its degree of activity and determines pharmacological activity of the different agents.
• These pharmacological effects results in smooth muscle stimulation, resulting in vasoconstriction, hypertension, increased uterine muscle activity, peripheral adrenergic blockade, and central sympatholytic activity, resulting in hypotension.
• Generally, its freckles use in the hands of quacks leads to death.
Sign and Symptoms
Acute Poisoning
• Nausea
• Vomiting
• Diarrhoea
• Giddiness
• Breathlessness
• Muscular weakness
• Tingling and numbness in hand and feet.
• Paraesthesia
• Cramps in muscle.
• Bleeding from nose and other mucosal surface.
Chronic Poisoning (Ergotism)
Prolonged use of ergot leads to a condition called ergotism characterized by-
• Burning of extremities.
• Hemorrhagic vesication.
• Pruritis
• Formication
• Nausea
• Vomiting
• Bradycardia
• Peripheral ischemia leading to gangrene of fingers and toes.
• Headache
• Meiosis
• Delirium
• Hallucinations
• Convulsions
• Ischemia of cerebral, mesenteric, coronary and renal vessels.
Absorption, Metabolism and Excretion
• In general, Oral administration of ergot alkaloids is associated with poor absorption and extensive first-pass hepatic metabolism.
• Ergotamine is absorbed through GI tract following with therapeutic oral doses. Rectal doses seem to be absorbed more predictably.
• Ergometrine is rapidly absorbed after oral and intramuscular injection; onset of uterine contractions occurs in about 5 to 15 minutes after an oral dose, and 2 or 3 minutes after an intramuscular dose.
• Intramuscular absorption is unpredictable but is approximately 10 times more when compared to oral administration.
• Suppositories may increase bioavailability by as much as 20 times.
• Ergotamine is metabolised by the liver by largely undefined pathways.
• 90% of the metabolites are excreted in the bile. Less than 10% is excreted in the urine.
Drug Interaction
• Life-threatening peripheral ischaemia has been associated with the coadministration of ergotamine with potent CYP 3A4 inhibitors. The latter include protease inhibitors (ritonavir, nelfinavir, indinavir) and macrolide antibiotics (erythromycin, clarithromycin, and troleandomycin).
• Based on an increased risk for ergotism and other serious vasospastic adverse events, ergotamine use is contraindicated with these agents.
Treatment
Acute Poisoning
• Gastric lavage is common.
• Activated charcoal is very effective.
• Hypertension or cerebral/mesentric/cardiac ischemia – IV nitroglycerine or nitroprusside has been suggested for the treatment for hypertension.
• Phentolamine has beneficial for treatment of severe hypertension or cerebral, myocardial or mesenteric ischaemia.
• In case of peripheral ischemia oral prazocin, captopril or nifedipine titrated to adequate perfusion.
• Administration of sodium nitroprusside in doses of 1 to 5 mcg/kg/min intravenously has been shown to dramatically reduce systemic vascular resistance with accompanying improvement of ischaemia.
• Plethysmography may support the diagnosis of peripheral vascular ischaemia and be useful in assessing the efficacy of treatment.
• Angiography is often used when the history and clinical features are inadequate to confirm diagnosis of vascular insufficiency.
• In case of convulsions and hallucinations diazepam or lorazepam has been administered.
• In case of hypercoagulable state heparin or dextran is titrated until coagulated.
• Anticoagulant (heparin in combination with sodium nitroprusside or nitroglycerin) therapy should be introduced in all patients with evidence of vascular insufficiency.
• In case of Bradycardia atropine is given.
• Hyperbaric oxygen treatment has been successful in reversing ergotamine-induced peripheral ischaemia when other measures (including nitroprusside) had failed.
Chronic Poisoning
• Withdraw drug.
• Surgery (if gangrene is advanced).
• Sympathetic block, epidural block, or sympathectomy which were all advocated in the past are no more recommended today.
• These methods may relieve vasoconstriction mediated via the CNS, but do not antagonise the direct action of ergot on arteriolar smooth muscle.
Medico Legal Aspects
• Accidental poisoning occurs with consumption of contaminated grains.
• Ergots preparations are used to induce abortion.
• Foetal mortality and hypoxic-type anomalies along with other multiple deformities have been observed in humans and experimental animals. Foetal distress, stillbirths and abortion have also occurred.
• Ergotamine is secreted into human milk and can exert its pharmacological effects to an infant by this route.
Detection
• Van erk reagent and p-dimethylaminobenzaldehyde in acid solution which reacts with the molecules of ergot alkaloids to give blue colour.
• Liquid chromatography with tandem mass spectrometry (LC-MS/MS) is widely applied to the analysis of cereals and processed cereal products such as rye bread.
• Liquid chromatography with fluorescence detection (LC-FLD).
• High performance liquid chromatography.
References
• Dr. K.S. Narayan Reddy. The essential of forensic medicine and toxicology.34th edition.
• VV Pillay. Modern medical toxicology.4th edition.
• R.K.Sharma. Concise textbook of forensic medicine and toxicology. 3rd edition.
