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

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Catecholamines

– Adrenaline (Epinephrine) – Noradrenaline (Norepinephrine, Levarterenol)

CATECHOLAMINES

The term catecholamine refers to a biologically active amine derived from the amino acid tyrosine. Classic examples include adrenaline (epinephrine), and noradrenaline (norepinephrine). Other examples include dopamine and isoproterenol, both of which have been discussed elsewhere.

Adrenaline (Epinephrine)

Uses

·      Rapid relief of respiratory distress due to bronchospasm.

·      Rapid relief of hypersensitivity reactions.

·      Prolongation of action of local anaesthetics.

·      Restoration of cardiac rhythm in patients with cardiac arrest.

·      Topical haemostatic agent in surgical procedures of the nose, throat and larynx.

Toxicokinetics

Adrenaline is not effective orally since it is rapidly conjugated and oxidised in the GI mucosa and liver. The usual route of administration is subcutaneous injection (slow, steady absorp-tion), but it can also be given intramuscularly, intravenously (rapid infusion can be dangerous), or by inhalation (nebulised), or topical application.

Adrenaline is quickly inactivated by the liver after absorp-tion by COMT and MAO. 

Mode of Action

Adrenaline is a potent stimlant of both alpha- and beta-adrenergic receptors, and therefore has myriad effects on the body. A comparative analysis of the effects of adrenaline and noradrenaline are mentioned in Table 32.5.




Adverse Effect

·              Fear, anxiety, restlessness, headache, weakness, vertigo.

·              Tremor, palpitations.

·              Respiratory difficulty.

·              Cardiac arrhythmias, subarachnoid or cerebral haemorrhage (due to rapid IV injection, or infusion of excessive dose).

Drug Interactions

·              Accidental intra-arterial injection of adrenaline can lead to hypotension, loss of consciousness, ventricular tachycardia, and marked pallor of the limb. Treatment involves imme- diate arterial injection of phentolamine (1.5 mg).

·              Rapidly acting vasodilators (sodium nitroprusside or nitrites), and a-adrenergic blockers counteract the pressor effects of adrenaline.

·     Use of adrenaline during anaesthesia with halogenated hydrocarbon anaesthetics can precipitate ventricular fibril-lation.

·     Possibility of severe hypertension and cerebral haemor-rhage is greatly increased when adrenaline is combined with beta-adrenergic blockers.

Clinical (Toxic) Features

·      Immediate—pallor, cyanosis, throbbing headache, sweating,tachycardia, hypertension, chest pain, palpitations, paraes-thesias of hands and feet, abdominal pain, and ECG changes : premature ventricular contractions, bigeminal rhythmic changes.

·      Delayed—hypotension, metabolic acidosis, pulmonaryoedema.

·              Accidental intra-arterial injection of adrenaline can lead to hypotension, loss of consciousness, ventricular tachycardia, and marked pallor of the limb. Treatment involves imme-diate arterial injection of phentolamine (1.5 mg).

Noradrenaline (Norepinephrine, Levarterenol)

Noradrenaline is commonly used in the treatment of shock and hypotension (especially resulting during spinal anaesthesia, or due to overdose with antihypertensives). Adverse effects are similar to those of adrenaline, but are less frequent and less pronounced. Common effects include anxiety, respiratory diffi-culty, headache, and a slow, forceful heartbeat. Overdose causes severe hypertension with agonising headache, photophobia, stabbing chest pain, pallor, profuse sweating, and vomiting. Treatment is on general lines as mentioned for adrenaline.

 

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