James Whyte Black (1924-2010)was one of the three pharmacologists awarded the 1988 Nobel Prize for discovering important principles of drug treatment. American investigators Gertrude B. Elion and George H. Hitchings were recognized for their innovative research methods which led to the production of drugs to treat a range of major diseases. Black was honoured for work that paved the way for the invention of the beta-blocker propranolol, and cimetidine, used in the treatment of stomach ulcers. Propranolol is a non-selective beta adrenergic antagonist used to treat hypertension, angina, atrial fibrillation, myocardial infarction, migraine, essential tremor, hypertrophic subaortic stenosis, and pheochromocytoma.Propranolol is a racemic mixture of 2 enantiomers where the S(-)-enantiomer has approximately 100 times the binding affinity for beta adrenergic receptors.Propranolol is used to treat a number of conditions but most commonly is used for hypertension.Propranolol was granted FDA approval on 13 November 1967.
4. Therapeutic Indications:
• The control of hypertension
• The management of angina pectoris
• Long term management against re-infarction after recovery from acute myocardial infarction;
• The control of most forms of cardiac dysrhythmias
• The prophylaxis of migraine
• The management of essential tremor
• Relief of situational anxiety and generalised anxiety symptoms, particularly those of somatic type
• Prophylaxis of upper gastrointestinal bleeding in patients with portal hypertension and oesophageal varices
• The adjunctive management of thyrotoxicosis and thyrotoxic crisis
• Management of hypertrophic obstructive cardiomyopathy
• Management of phaeochromocytomaperi-operatively (with an alpha- blocker)
Mechanism of action:
Propranolol is a competitive antagonist at both beta1- and beta2-adrenoceptors. It has no agonist activity at the beta adrenoceptor, but has membrane stabilising activity at concentrations exceeding 1- 3mg/litre, though such concentrations are rarely achieved during oral therapy. Competitive betablockade has been demonstrated in man by a parallel shift to the right in the dose-heart rate response curve to beta-agonists such as isoprenaline. Propranolol as with other beta-blockers, has negative inotropic effects, and is therefore contraindicated in uncontrolled heart failure. Propranolol is a racemic mixture and the active form is the S (-) isomer of propranolol. With the exception of inhibition of the conversion of thyroxine to triiodothyronine, it is unlikely that any additional ancillary properties possessed by R (+) propranolol, in comparison with the racemic mixture, will give rise to different therapeutic effects. Propranolol is effective and well tolerated in most ethnic populations, although the response may be less in black patients.
Mechanism of action:
Propranolol is a competitive antagonist at both beta1- and beta2-adrenoceptors. It has no agonist activity at the beta adrenoceptor, but has membrane stabilising activity at concentrations exceeding 1- 3mg/litre, though such concentrations are rarely achieved during oral therapy. Competitive betablockade has been demonstrated in man by a parallel shift to the right in the dose-heart rate response curve to beta-agonists such as isoprenaline. Propranolol as with other beta-blockers, has negative inotropic effects, and is therefore contraindicated in uncontrolled heart failure. Propranolol is a racemic mixture and the active form is the S (-) isomer of propranolol. With the exception of inhibition of the conversion of thyroxine to triiodothyronine, it is unlikely that any additional ancillary properties possessed by R (+) propranolol, in comparison with the racemic mixture, will give rise to different therapeutic effects. Propranolol is effective and well tolerated in most ethnic populations, although the response may be less in black patients.
7. Clinical features:
Cardiac:
Bradycardia, hypotension, pulmonary oedema, syncope and cardiogenic shock may develop. QRS complex prolongation, ventricular tachycardia, first to third degree AV block, ventricular fibrillation or asystole may also occur. Development of cardiovascular complications is more likely if other cardioactive drugs, especially calcium channel blockers, digoxin cyclic antidepressants or neuroleptics have also been ingested. Older patients and those with underlying ischaemic heart disease are at risk of developing severe cardiovascular compromise.
CNS:
Drowsiness, confusion, seizures, hallucinations, dilated pupils and in severe cases coma may occur. Neurological signs such as coma or absence of pupil reactivity are unreliable prognostic indicators during resuscitation.
Other features:
Bronchospasm, hyperkalaemia and occasionally CNS-mediated respiratory depression may occur.