Drugs for Management of Hypertension

Diuretics

Types:

Thiazides – Inhibits ion transporter, thus causing water retention in urine. Works at different location (distal convoluted tubule) from loop.

Loop Diuretics – generally location of action is at the loop of Henle by inhibiting reabsorption of sodium. Hence, water which usually follows sodium into ECF now follows sodium into urine.

Potassium-sparing – these kinds of diuretics are more oriented towards function than location. Hence, potassium sparing means potassium is spared from being secreted into urine.

Adverse effects are uncommon, unless high doses are used. These include increased serum cholesterol, glucose and uric acid; decreased potassium, sodium and magnesium levels and erectile dysfunction.

Beta-blockers

Work by slowing heart rate down, hence decreasing blood pressure.

They are particularly useful in hypertensive patients with effort angina, tachyarrhythmias or previous myocardial infarction where they have been shown to reduce cardiovascular morbidity and mortality.

Adverse effects reported include masking of hypoglycaemia (since you inhibit sympathetic system activity which shows symptoms), increased incidence of new onset diabetes mellitus, erectile dysfunction, nightmares and cold extremities.

Contraindications of beta-blockers are related to their cardiac mechanisms and include bradycardia, reduced exercise capacity, heart failure, hypotension, and atrioventicular (AV) nodal conduction block. Beta-blockers are therefore contraindicated in patients with sinus bradycardia and partial AV block. The side effects listed above result from excessive blockade of normal sympathetic influences on the heart.

Bronchoconstriction can occur, especially when non-selective beta-blockers are administered to asthmatic patients. Therefore, non-selective beta-blockers are contraindicated in patients with asthma or chronic obstructive pulmonary disease. Bronchoconstriction occurs because sympathetic nerves innervating the bronchioles normally activate β₂-receptors that promote bronchodilation. Blockade of these receptors can lead to bronchoconstriction.

Calcium Channel Blockers

Dihydropyridine calcium channel blockers are often used to reduce systemic vascular resistance and arterial pressure. However, the vasodilation and hypotension can lead to reflex tachycardia.

Phenylalkylamine calcium channel blockers are relatively selective for myocardium, reduce myocardial oxygen demand and reverse coronary vasospasm, and are often used to treat angina. They have minimal vasodilatory effects compared with dihydropyridines and therefore cause less reflex tachycardia, making it appealing for treatment of angina.

Benzothiazepine calcium channel blockers (Diltiazem) are an intermediate class between phenylalkylamine and dihydropyridines in their selectivity for vascular calcium channels. By having both cardiac depressant and vasodilator actions, benzothiazepines are able to reduce arterial pressure without producing the same degree of reflex cardiac stimulation caused by dihydropyridines.

Adverse effects include initial tachycardia, headache, flushing, constipation and ankle oedema. Unlike other CCBs, Verapamil may reduce heart rate and care should be exercised when used with beta- blockers.

ACE Inhibitors

They lower arteriolar resistance and increase venous capacity; increase cardiac output, stroke volume, lower renovascular resistance, and lead to increased excretion of sodium in the urine.

Normally, angiotensin II will have the following effects:

▪ vasoconstriction (narrowing of blood vessels), which may lead to increased blood pressure

▪ stimulation of the adrenal cortex to release aldosterone, a hormone that acts on kidney tubules to retain sodium and chloride ions and excrete potassium. Sodium is a "water-holding" molecule, so water is also retained, which leads to increased blood volume, hence an increase in blood pressure.

ACE Inhibitors inhibits the production of angiotensin II from angiotensin I, thus, assisting in increasing blood pressure.

In pregnant women, ACE inhibitors taken during the first trimester have been reported to cause major congenital malformations, stillbirths, and neonatal deaths. Commonly reported fetal abnormalities include hypotension, renal dysplasia, anuria/oliguria, patent ductus arteriosus and incomplete ossification of the skull.

Adverse effects include cough (bradykinin increase but disputed) and renal failure.

Angiotensin Receptor Blockers

Angiotensin II receptor antagonists are primarily used for the treatment of HT where the patient is intolerant of ACE Inhibitor therapy. They do not inhibit the breakdown of bradykinin or other kinins, thus rarely associated with the persistent dry cough. However, may present dizziness or headache.