Pharmacological Targets for Controlling Hypertension

We finally get the lecture on the stuff we were quizzed on last week! I love it when that happens... not...

Ca²⁺-channel blocking drugs

I've explained quite a bit about the role of calcium in the cardiovascular system (see here for cardiac muscle and here, here and here for smooth muscle). In a couple of those posts, I also mentioned that there are drugs available that block this system. Here's a brief list:

• Cardioselective (i.e. selective on the heart): Verapamil
• Vascular selective (i.e. selective on the blood vessels): Dihydropyridines such as nifedipine, felodipine and amlodipine (all end with -dipine)
• Non-selective (i.e. act on heart and blood vessels): Diltiazem

RAAS blockers

An explanation on the RAAS system is given here.

• ACE (angiotensin-converting enzyme) inhibitors: Ramipril, perindopril, many other drugs ending in -pril
• AT₁ blockers/ARBs (angiotensin-receptor blockers): Candesartan, irbesartan, many other drugs ending in -sartan

α₁ and β₁ adrenoceptor blockers

Activation of β₁ receptors, present on the heart, increase heart rate and contractility in order to increase cardiac output and therefore blood pressure . Hence, drugs that inhibit these receptors decrease heart rate and contractility. Drugs that inhibit these receptors include metoprolol, atenolol and many other drugs ending in -olol.

Activation of α₁ receptors, present in many blood vessels, cause vasoconstriction. This increases total peripheral resistance and, by extension, blood pressure. Prazosin, which inhibits these receptors, decreases peripheral resistance and blood pressure.

Diuretics

Diuretics work by reducing your blood volume, generally by making you pee more. A certain class of diuretics, known as thiazides, work by blocking reabsorption of Na⁺ in the distal tubule. If this makes no sense to you, I've written quite a bit on reabsorption in the kidneys here and here.

Choice of Drugs

Given all of this, which drugs do we use? Here's the approach that seems to give the most benefit for the least risk:

• Start off with a thiazide, ACE inhibitor, ARB OR Ca²⁺ channel blocker
• If control is still inadequate, add a second or third drug
• If control is still inadequate, try an α- or β-blocker