The anti-hypertensives are an important & broad group of medications.
Hypertension is a very common condition that represents a significant source of morbidity and mortality. It is a major risk factor for MI, stroke and chronic kidney disease. Hypertension is managed in a step-wise fashion according to the NICE guidelines (see our Hypertension notes for more).
Several groups of drugs, by varying mechanisms, are used to reduce blood pressure.
Blood pressure is maintained by a number of physiological reflexes that respond to acute and chronic changes.
Blood pressure = cardiac output x peripheral vascular resistance
Numerous interconnected systems contribute to the regulation of blood pressure. There are both immediate and long-term mechanisms, these include:
Angiotensin-converting enzyme (ACE) inhibitors are a commonly used class of antihypertensives. They are also frequently utilised in heart failure and chronic kidney disease.
ACE inhibitors cause a reduction in circulating angiotensin II & aldosterone.
Examples: Ramipril, Lisinopril.
ACE inhibitors act by blocking the effect of ACE, causing a reduction in circulating angiotensin II. Reduction of angiotensin II has numerous effects:
A dry cough is a common side effect of ACE inhibitors. This is due to an increase in bradykinin within the lungs (ACE breaks down bradykinin).
Caution is also advised during intercurrent illnesses when using an ACE inhibitor. Their mechanism disrupts the kidneys autoregulation mechanisms and may prevent maintenance of adequate renal perfusion - resulting in an acute kidney injury (AKI). It is often advisable to stop ACE inhibitors during severe illness.
Other adverse effects include:
Calcium channel blockers (CCBs) are also a commonly used class of antihypertensives.
There are two main types of CCBs:
Dihydropyridine CCBs block the action of L-type calcium channels, which are found in vascular and cardiac tissue.
Examples: Amlodipine, Nifedipine.
CCBs block the action of voltage-gated L-type calcium channels, which are found in vascular and cardiac tissue. Within vascular smooth muscle, L-type channels permit the entry of calcium ions leading to contraction and subsequent vasoconstriction. Dihydropyridine CCBs inhibit this influx of calcium ions and induce vasodilatation, which reduces the peripheral vascular resistance.
The antihypertensive effects of thiazide diuretics are due to vasodilation, not diuretic action.
Examples: Bendroflumethiazide, Indapamide.
Thiazide diuretics act on the distal convoluted tubule (DCT) of the nephron where it inhibits the Na+/Cl- co-transporter. This prevents sodium and chloride entering the tubule cells and, therefore, water cannot follow.
This mechanism has an initial hypotensive effect, however, this is mostly abolished by the renin-angiotensin system (RAS). Instead, thiazide diuretics long-term antihypertensive effects are due to vasodilation of peripheral vasculature through a mechanism that is poorly understood.
Alpha-1 blockers act to blockade alpha-1 adrenoreceptors
Alpha-1 adrenoreceptors are found in most sympathetic tissues including vascular smooth muscle and have excitatory effects. Stimulation results in vasoconstriction.
Consequently, blockade of alpha-adrenoreceptors causes:
Beta-blockers act to reduce sympathetic activity
Examples: Propanolol, Atenolol.
Different agents may have variably selective action on beta-1 receptors (predominantly found in the heart) and beta-2 receptors (predominantly found in the lungs).
These drugs antagonise catecholamines at beta-adrenoceptors. The antihypertensive effect is mediated primarily by blockade of beta-1 adrenoreceptors. As such, they reduce the effect of the sympathetic nervous system on the heart. They, therefore, have both negative inotropic and negative chronotropic effects. That is they reduce the heart rate and the strength of contractions.
Beta-blockers cause a reduction in blood pressure through a number of mechanisms:
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