Description
ANTIHYPERTENSIVE DRUG CLASSES
Antihypertensive drugs are organized around a clinical indication − the need to treat a disease − rather than a receptor type. The drugs covered in this unit have a variety of mechanisms of action including diuresis, sympathoplegia, vasodilation, and antagonism of angiotensin, and many agents are available in most categories.
Antihypertensive drug classes are as follows:
• ACE inhibitors
• Angiotensin II receptor antagonists
• Diuretics
• Calcium channel blockers
• β-blockers
• α-blockers
• α2-blockers
• Renin inhibitors
• Vasodilators
For each drug class, we offer examples, their mechanism of actions (MOA), side effects and drug interaction profiles and any other relevant clinical features.
ACE Inhibitors (Angiotensin Converting Enzyme Inhibitors (ACEIs))
Example: Ramipril, Lisinopril, Perindopril.
MOA: Angiotensin converting enzyme inhibitors (ACEIs) are those drugs which are frequently used for the treatment of cardiovascular disorders including hypertension and heart failure. This group of drugs diminishes blood pressure and oxygen demand by dilating blood vessels. These drugs principally inhibit an angiotensin converting enzyme which is an integral part of RAA (Renin-angiotensin-aldosterone system). The detailed mode of action is described in the following diagram.
Side effects:
• Hypotension-first dose hypotension is prevalent with ACE inhibitors.
• Persistent dry cough-due to pulmonary kinin accumulation.
• Hyperkalemia-ACE inhibitors promote potassium retension.
• Other effects- fatigue, nausea, dizziness, headache.
3.3.2 Angiotensin II Receptor Antagonists
Angiotensin II receptor antagonist are also known as ARBs or angiotensin receptor
blockers. They are sometime used in place of ACE inhibitors particularly where the persistent
dry cough has become unbearable for the patient.
Examples: Candesartan, lrbesartan, Losartan, Telmisartan.
MoA:
Bradykinin
Cough
Natriuresis
Angiodema
Vasodilaton
Extracellular matrix
degradation
ACE
ACE
Inhibitor
Inactive
Metabolite
Hypertension
Vasoconstriction
Vascular growth
AIIRA
AT 1 AT 2
ACE
Renin
Angiotensinogen
Non-ACE
pathways
Angiotensin II
Angiotensin I
Kidney
Vasodilation
Natriuresis
Aldosterone Decerased water and sodium secretion
Increse potassium secretion
Spironolactone
: The Renin-Angiotensin System (RAS)
Side effects: Hypotension, Hyperkalemia
Renal failure (as with ACE inhibitors):
• Cough-though less likely than with an ACE inhibitors.
• Due to risk of hyperkalemia, other potassium-elevating drugs should not be
prescribed.
• This includes potassium supplements, potassium-sparing diuretics.
• As with ACE inhibitors, taking ARBs with NSAIDs increase risk of renal failure.
3.3.3 Diuretics
Diuretics are drugs that promote dieresis or water loss. There are many different diuretic classes, too many to review in detail here. However, we have examined many of the major diuretic classes elsewhere. Diuretic drug classes:
• Loop diuretics-furosemide, bumetanide.
• Thiazide and thiazide – like diuretics – bendroflumethiazide, hydrochlorothiazide,
indapamide, metolazone.
• Potassium-sparing diuretics- amiloride, spironolactone.
• The purpose of diuretics is to eliminate excess sodium and water from the body. Some diuretic classes also eliminate potassium, increasing the risk of hypokalemia.
• Other drugs though, such as a amiloride and spironolactone, retain potassium ions-
increasing the risk of hyperkalemia. However, diuretic combinations are invariably used to balance and offset these risks. Diuretics act at different points along the nephron:
For example:
• Loop diuretics act at the thick ascending limb.
• Thiazide diuretics act at the distal convoluted tubule.
• Potassium-sparing diuretics act at the cortical collecting duct.
• Osmotic diuretics, such as mannitol, act at the proximal tubule.
• Carbonic anhydrase inhibitors, such as acetazolamide, also act at the proximal tubule.
Side effects: In general terms, the broad side effects associated with diuretics include:
• Loop diuretics: Hypovolemia, hypokalemia, metabolic alkalosis, hyperuricemia.
• Thiazides: Associated with the side effects listed for loop diuretics, plus hypercalcemia and hyponatremia.
• Hyperkalemia: Amiloride, triamterene, spironolactone.
Calcium Channel Blockers (CCB)
• Not all calcium channel blockers are used for their antihypertensive effects.
Examples:
• Amlodipine, Nifedipine, Diltiazem, Verapamil.
• Amlodipine and nifedipine may be used for hypertension whereas diltiazem and verapamil are predominantly used to control heart rate/ arrhythmias.
MoA: Calcium channel blockers reduce calcium entry into vascular and cardiac cells. This reduces intracellular calcium concentration which, in turn causes relaxation on vasodilation in atrial smooth muscle. Calcium channel blockers also reduce myocardial contractility in the heart.
Side effects: Because diltiazem and verapamil (the non-dihydropyridine CCBs) are used
as class III anti-arrhythmic drugs, the side effects profile below focuses on amlodipine and nifedipine.
Flushing, Headache, Ankle swelling, palpitations, Light headedness. β-blockers
β-blockers are not just used in the treatment of hypertension (though not generally given as initial therapy), they also used in the treatment of ischemic heart disease, chronic heart failure, atrial fibrillation and supraventricular tachycardia.
Examples: Metoprolol, Bisoprolol, Labetalol, Nebivolol.
MoA: β-blockers act through a variety of means for hypertension they act to reduce renin secretion from the kidney-an effect ordinarily mediated by β-1 receptors. Recall that β-1 receptors are located mainly in the heart, whereas β-2 receptors are mainly located in
the smooth muscle of blood vessels and in the airways.
