Classify antihypertensive agents by their mechanism of action, with a brief outline of each
mechanism, and an example of a drug in each class.

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College Answer

There are many valid lists that can be used as a template to answer this question. One such list
might broadly classify antihypertensive agents into sympatholytic agents, vasodilators, calcium
channel antagonists, renin-angiotensin inhibitors and diuretics. Within each of these categories
are a variable number of sub classes, for example diuretics might include thiazides, loop
diuretics and potassium sparing diuretics.
A good answer would include such a listing with a brief description of the mechanism of action
with respect to the antihypertensive effect and the name of a typical drug that acts in the manner
described. Most candidates were able to generate such a list and populate it as required by the
question, thus being rewarded with good marks. Poorer answers lacked any logical
classification system and were merely a random list of antihypertensive drugs and their actions.
Candidates are reminded that organisation within an answer helps in answering the question and
achieving marks.
Syllabus: C2b,2e
References: Berne & Levy, Physiology, Ch 2-3

Discussion

Classification of Antihypertensive Agents
Class Mechanism Examples

RAAS antagonists

Renin antagonists Inhibits the activity of renin, which reduces the activation of angiotensin , thus prevents RAAS activation Aliskiren

ACE-inhibitors

Interrupts the conversion of Ang-I into Ang-II, thereby interrupting the effects of RAAS activation Perindopril

Angitensin receptor blockers

Interferes with the binding of Ang-II and its AT1 receptor. Irbesartan

Sympatholytic drugs

Beta blockers

Selective (β1)

By binding to Gs-protein coupled β1 and β2 receptors, blocks cAMP synthesis

Metoprolol
Non-selective Propanolol
Alpha-1 blockers Reversible By inding to the Gq-protein-coupled alpha-1 receptor, this drug decreases the activation of phospholipase C, resulting in a decreased concentration of the secondary messengers IP3 and DAG. The result is decreased intracellular calcium availability, which in turn leads to decreased smooth muscle contraction tone. Prazocin
Irreversible Phenoxybenzamine
Alpha-2 agonists Central alpha-2 agonist effect decreases sympathetic outflow by presynaptic downregulation of noradrenaline release. Clonidine
α-methyldopa
Ganglionic blockers Blocks ganglionic autonomic neurotransmission by inhibiting the nicotinic Ach receptors, therefore decreasing both sympathetic tone and vagal neurotransmission. Hexamethonium
Monoamine transport inhibitors Blocks VMAT-2 in the adrenergic neurotransmission pathway, causing the depletion of catecholamine and serotonin stores in central and peripheral nerve terminals Reserpine
Catecholamine synthesis inhibitors By inhibiting the conversion of tyrosine into dopa, blocks the synthesis of catecholamines α-methyltyrosine

Vasodilators

Calcium channel blockers Dihydropyridine Modulates the opening of voltage-gated calcium channels, which prevents  intracellular calcium influx during depolarisation. This decreases the availability of intracellular calcium for vascular smooth muscle cells, decreasing their resting tone. In cardiac myocytes, this decreases contractility as well as the automaticity of pacemaker cells. Amlodipine
Nimodipine
Non-dihidropyridine Verapamil
Diltiazem
Nitrate vasodilators
(nitric oxide donors)
Acts as donor of nitric oxide (NO) which activates guanylate cyclase, resulting in an increase of cyclic GMP in vascular smooth muscle. This hyperpolarises the membrane by increasing potassium channel conductivity and decreases the availability of inracellular calcium, thereby decreasing the resting tone and contractility of vascular smooth muscle GTN
Nitroprusside
Potassium channel activators Activates ATP-sensitive potassium channels which inhibits the opening of voltage-dependent calcium channels indirectly, by hyperpolarising the membrane. Hydralazine
Phosphodiesterase inhibitors Increases cyclic AMP by inhibiting phosphodiesterase (with maximum selectivity for PDE10), which is responsible for cAMP catabolism. Selective for vascular smooth muscle. Papaverine