Beta blockers

Pharmacodynamics

1.       Selectively block beta-receptor effects of noradrenaline and adrenaline.

2.    They may be pure antagonists or may have some agonist activity in addition (partial agonist).

3.       Partial agonists cause less fall in resting heart rate than do the pure antagonists and may be less effective in angina pectoris.

4.       Abrupt withdrawal may be less likely to lead to a rebound effect if there is some partial agonist action.

Antihypertensive effects

1.       Blocks cardiac beta1-receptors to slow the heart rate and reduce the force of contraction, thus lowering the cardiac output.

2.       Suppresses the renal secretion of renin causing inhibition of the renin-angiotensin-aldosterone system.

3.       Reduces central sympathomimetic discharge to decrease peripheral vascular resistance.

Clinical response

1.       Depends on on-going physiological or pathological state of the individual.

2.       Beta-receptor blockade has little effect on the normal heart at rest, but may have profound effect when the sympathetic control of the heart is highest as in exercise.

3.       Similarly its action on respiratory smooth muscle of asthmatics could be hazardous.

4.       Physiological stresses such as exercise, upright posture are not accompanied by hypotension as the alpha-receptors are not blocked.

Pharmacokinetics

1.       Bioavailability after an oral dose is limited to varying degree and except for pindolol is usually less than 50%.

2.       Rapidly distributed and have large volumes of distribution.

3.       Elimination is rapid with half-lives in the range of 2 – 5h.

4.       Propranolol and metoprolol are extensively metabolized in the liver, pindolol and atenolol less completely so.

5.    Thus liver disease diminished hepatic blood flow and hepatic enzyme inhibition will affect the elimination of propranolol and metoprolol.

Therapeutic indications

1.       Angina pectoris: beta-blockade reduces cardiac work and oxygen consumption.

2.       Hypertension.

3.       Cardiac arrhythmias: beta-blockade reduces drive to cardiac pacemakers.

4.       Myocardial infarction: early use within 6h of onset reduces size of infarct; late use for secondary prevention of another myocardial infarction.

5.       Aortic dissection and after subarachnoid haemorrhage: by reducing the force and speed of systolic ejection and blood pressure.

6.       Hepatic portal hypertension and esophageal variceal bleeding: reduction in portal pressure.

7.       Cardiac failure: use in some cases of dilated cardiomyopathy and hypertrophic obstructive cardiomyopathy.

8.       Endocrine uses:

a.       Hyperthyroidism: beta-blockade reduces unpleasant symptoms of sympathetic overactivity.

b.       Phaeochromocytoma.

9.       Other uses:

a.       Anxiety with somatic symptoms.

b.       Migraine prophylaxis.

c.       Alcohol and opioid acute withdrawal symptoms.

d.       Glaucoma: timolol.

Adverse drug effects

1.    CVS: bradycardia, hypotension, syncope, shock or angina pectoris.

2.       CNS: ataxia, dizziness, hearing loss, insomnia, mental depression, visual disturbances, fatigue.

3.    GI: nausea & vomiting, diarrhea, epigastric distress, abdominal cramping, constipation and flatulence.

4.       Hypoglycaemia: beta2-receptors mediate the release of insulin from pancreatic islet cells.

5.       Bronchoconstriction, especially in asthmatics.

6.       Contraindications:

a.       Pregnancy.

b.       Diabetes.

c.       Heart failure.

d.       Asthma and chronic obstructive lung disease.

e.       Abrupt withdrawal of therapy can be dangerous in angina pectoris and after myocardial infarction and withdrawal should be gradual.

7.  Drug interactions:

a.       NSAIDs: attenuate antihypertensive effect due to inhibition of formation of renal vasodilator prostaglandins.

b.    Anti-diabetic agents: potentiate hypoglycaemia of insulin and sulphonylurea.

c.       Calcium channel blockers: bradycardia, heart block and cardiac failure.

d.       Rifampicin: increase metabolism.

e.       Warfarin: propranolol inhibits metabolism of warfarin.

f.       Reduce hepatic blood flow and the metabolism of other beta-blockers, lignocaine and chlorpromazine.

g.       Clonidine: withdrawal hypertension.

8.       Overdose:

a.       Causes bradycardia, heart block, hypotension and low output cardiac failure that can proceed to cardiogenic shock.

b.       Atropine: eliminate unopposed vagal activity.

c.       Glucagon: has cardiac inotropic and chronotropic actions independent of beta-receptor.

d.    i.v. injection of a beta-receptor agonist, e.g. isoprenaline.