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Chapter: Modern Medical Toxicology: Miscellaneous Drugs and Poisons: Gastrointestinal and Endocrinal Drugs

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Biguanides - Oral Hypoglycaemics

Metformin and phenformin are derivatives of guanidine, and are active components of the French lilac (Galega officinalis).

Biguanides

Metformin and phenformin are derivatives of guanidine, and are active components of the French lilac (Galega officinalis). While both drugs are used widely in India, phenformin has been withdrawn from several countries in the West because of the serious risk of lactic acidosis (64 cases/100,000 patient years). Metformin has a risk of only 3 cases/100,000 patient years.

Uses

·              Biguanides are used orally in the management of mild to moderate NIDDM, especially if the patient is elderly and obese.

·              Metformin is said to be relatively safe in pregnancy

Toxicokinetics

These drugs are absorbed from the small intestine, do not bind to plasma proteins, and are excreted unchanged in the urine. Oral bioavailability is 50 to 60%. The half-life of metformin varies from 1.3 to 4.5 hours.

Mode of Action

·              Biguanides induce increase in peripheral glucose utilisation, decrease in hepatic gluconeogenesis, and decrease in intestinal absorption of glucose, vitamin B and bile acids. They usually do not lower the blood sugar in normal individuals (unless other hypoglycaemic agents or ethanol has been concomitantly ingested).

Adverse Effects

·              Diarrhoea, abdominal discomfort, metallic taste.

·              Lactic acidosis: While phenformin is associated with a greater risk of lactic acidosis, the other biguanides can also cause it in the presence of renal or hepatic impairment, cardiac failure, or chronic hypoxic lung disease.

o     Manifestations: Acute onset of diarrhoea, vomiting, hyperventilation, and alteration of consciousness.

o     Diagnosis: Anion gap metabolic acidosis, low serum pH and bicarbonate, elevated serum potassium, normal or depressed serum chloride, increased blood lactate and lactate/pyruvate.

o     Treatment: Sodium bicarbonate IV (1 to 2 mEq/kg). Upto 50 mEq every 15 minutes may be required. Total dose should not exceed 400 mEq.

Clinical (Toxic) Features

■■   GIT: Nausea, vomiting, diarrhoea, abdominal cramps, haematemesis.

■■   CNS: Agitation, confusion, convulsions, coma.

■■ RS: Rapid, deep breathing, pulmonary hypertension.

■■   CVS: Tachycardia, hypotension.

■■   Others: Lactic acidosis.

Diagnosis

■■Elevation of lactate/pyruvate ratio.*

■■Elevation of 3-b-hydroxybutyrate concentration.

■■Blood glucose may be depressed, normal, or elevated.

■■Leucocytosis, thrombocytopenia.

■■Elevated serum creatinine, albuminuria.

■■Lactic acidosis is characterised by a number of abnormal laboratory values (vide supra).

Treatment

■■Stabilisation—Establish airway, undertake endotracheal

■■intubation, and perform assisted ventilation (if necessary). Stomach wash, activated chacoal.

■■Treatment of hypoglycaemia with 50 ml of 50% glucose IV (0.5 gm/kg/dose in children).

■■Treatment of acidosis with IV sodium bicarbonate (1 to 2 mEq/kg). Upto 200 to 400 mEq may be required.

■■Treatment of hypotension with Trendelenberg position and IV fluids. Pressor amines such as dopamine must be used with caution, since they can aggravate lactic acidosis.

■■Haemodialysis.


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