Pharmacology of Antihypertensive Drugs


In this section we take a quick look at the pharmacology of antihypertensive drugs – looking at the various classes, their mechanism of action, pharmacokinetics, and unwanted effects. Before we begin, however, let’s look at how pervasive hypertension is in modern society.

Antihypertensive Drugs Mindmap

Approximately one in three adults in the United States have hypertension, but only half of patients diagnosed with hypertension have the condition under control. Statistics show that age, ethnicity, and pre-existing illness all determine the likelihood of developing hypertension. For example, men (age 20-34) are 11 percent likely to develop hypertension, in contrast to older men (age 45-54), where this risk rises to 35 percent. African-Americans are 10-12 percent points more likely to develop hypertension than white Americans. In 2013 alone, there were over 350,000 deaths involving hypertension as the direct/indirect cause.

These statistics bring home the prevalence of hypertension in the United States, but statistics like these can be mapped worldwide. It is with these statistics in mind that we study the pharmacology of antihypertensive drugs – medicines aimed at attenuating these figures.

Pharmacology of Antihypertensive Drugs

There are quite a few classes of antihypertensive drugs; some work as alpha blockers and beta blockers, whereas others work as ACE inhibitors, diuretics, and potassium channel openers. In this summary piece, we will study the following 11 classes of antihypertensive drugs:

These can be divided into drugs acting on the sympathetic nervous system, centrally-acting antihypertensive drugs, drugs affecting the renin-angiotensin system, and vasodilators. We will use this latter classification in our study below, as it conveniently assesses these drugs in terms of their mechanism of action.

Drugs acting on Sympathetic Nervous System

This includes:

  • Beta blockers
  • Alpha blockers

Check out this page for more detailed information on the pharmacology of beta blockers.

Examples of beta blockers include atenolol, metoprolol, and bisoprolol. They reduce blood pressure by antagonising beta-1 receptors – receptors which are located on the heart (this contrasts with beta-2 receptors nestled in the lung). Beta blockers reduce heart rate and myocardial contractility and indirectly reduce renin secretion, among other effects.

Generations of Beta Blockers

Alpha blockers are divided into two groups: selective α1 antagonists, and non-selective antagonists.

Selective antagonists include doxazosin and prazosin, whereas non-selective antagonists include phenoxybenzamine (irreversible) and phentolamine (reversible). Alpha blockers reduce blood pressure by blocking postsynaptic α1-adrenoceptors – lowering peripheral resistance and increasing venous dilation.

Alpha blockers increase HDL (or 'good') cholesterol levels, while also reducing triglyceride levels. Unwanted effects with alpha blockers include postural hypotension, lethargy, headache, nausea, rhinitis, urinary incontinence, and palpitations. Selective antagonists are well absorbed from the gut and undergo extensive first-pass metabolism (half-lives: prazosin (3h), doxazosin (10h).

Centrally Acting Antihypertensive Drugs

Examples of centrally-acting agents include clonidine and methyldopa.

These drugs are agonists at α2-adrenoceptors, agonism at presynaptic autoreceptors in the central nervous system. Peripheral arterial and venous tone is reduced by two means: agonism reduces sympathetic nervous system outflow and, second, it increases vagal outflow from the medulla.

Methyldopa is a prodrug – metabolised into its active component α-methylnoradrenaline, a metabolite with potent α2-adrenoceptor agonism activity. Clonidine has also been shown to display agonism at α1-adrenoceptors, resulting in peripheral vasoconstriction. However, this vasoconstriction does not overwhelm the α2 receptor agonism.

Methyldopa is moderately absorbed from the gut and undergoes dose-dependent hepatic metabolism. It has a half-life of 1-2 hours. Clonidine is, in contrast, completely absorbed from the gut and is eliminated by a) hepatic and b) renal means. It has a half-life of around 24 hours. Unwanted effects include sympathetic blockade, diarrhoea, dry mouth, sedation, drowsiness, peripheral oedema. Sudden withdrawal of clonidine can cause severe rebound hypertension.

Drugs affecting Renin-Angiotensin System

Many commonly prescribed antihypertensive drugs derive from their effects on the renin-angiotensin system. Among their classes include:

  • ACE inhibitors (enalapril, Ramipril, Lisinopril etc.)
  • Angiotensin receptor antagonists (candesartan, losartan, valsartan etc.)
  • Direct renin inhibitors (aliskiren)

Check out this page for more detailed information on the pharmacology of ACE inhibitors.

Ace Inhibitors

ACE inhibitors reduce blood pressure by several means, including: reducing circulating angiotensin II and subsequent release of aldosterone, inhibition of tissue ACE from the vascular wall, and reduction of angiotensin II-mediated potentiation of the sympathetic nervous system. Unwanted effects include a persistent dry cough, postural hypotension, taste disturbance, rash, and angioedema.

Patients experiencing a persistent dry cough with an ACE inhibitor are commonly switched to an angiotensin receptor antagonist – drugs which are selective for the AT1 receptor subtype (located in the heart, kidney, vasculature, lung, brain, and adrenal cortex). Angiotensin II is inhibited as it causes vasoconstriction, aldosterone release, sympathetic stimulation, and water retention.

Losartan is well absorbed from the gut, though its oral bioavailability is quite low. It has a half-life of approximately 2 hours (the active metabolite has a half-life of 6 hours). Losartan is a competitive antagonist of the AT1 receptor, whereas its metabolite is a non-competitive antagonist. Unwanted effects with angiotensin receptor antagonists include headache, dizziness, bone pain, muscle pain, and fatigue.

Aliskiren – a direct renin inhibitor – binds to the renin enzyme and prevents binding of angiotensin I. As a result, angiotensin II synthesis is reduced – leading to vasodilation. It is poorly absorbed from the gut and is excreted unchanged in the bile. It has a very long half-life of around 38 hours. Unwanted effects include diarrhoea and cough.


The next class in our summary of the pharmacology of antihypertensive drugs is vasodilators, among them being:

  • Diuretics
  • Calcium channel blockers
  • Potassium channel openers

Diuretics are themselves divided into thiazide (and ‘thiazide-like’) diuretics, loop diuretics, and potassium-sparing diuretics. Check out this page for more detailed information on the pharmacology of diuretics.

Classes of Diuretic

Calcium channel blockers include amlodipine, diltiazem, nifedipine, and verapamil. They lower blood pressure by arterial vasodilation. Potassium channel openers – such as minoxidil – work by acting on ATP-sensitive Kir subunit in order to open KATP channels – resulting in the efflux of potassium from the cell. This hyperpolarisation causes calcium channels to close, leading to relaxation of the vasculature.

Calcium Channel Blockers

Minoxidil is well absorbed from the gut and has a short half-life of around 2-4 hours. Unwanted effects include flushing, headache, tachycardia and palpitations (reflex responses), and hirsutism. Sodium nitroprusside is the most common nitrovasodilator used for its antihypertensive effects. It works in a similar way to organic nitrates. It is administered by IV infusion. Unwanted effects include headache, dizziness, retching, and abdominal pain.

That’s about it for the pharmacology of antihypertensive drugs. Go to this page to find out more about how you can test your knowledge of this drug class – ten questions covering just about everything you need to know

By | 2016-12-03T16:12:08+00:00 March 31st, 2016|Pharmacology Guides|0 Comments

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