Antihypertensive agents

By Cardiologist on June 8th, 2010

A 50-year-old man presents for follow-up of his hypertension. He is maintaining a low-sodium diet, exercising regularly, and taking metoprolol at maximum dosage. He is on no other medications. His blood pressure remains elevated at 150/100 mm Hg. His examination is otherwise unremarkable. You decide to add a thiazide diuretic to his regimen.

What is the mechanism of action of metoprolol?

What is the mechanism of action of thiazide diuretics?

What electrolyte abnormalities commonly occur with thiazide diuretics?

Answers to case: Antihypertensive agents

Summary: A 50-year-old man with inadequately controlled hypertension is prescribed a thiazide diuretic.

Mechanism of action of metoprolol: β₁-Selective adrenoreceptor antagonist.

Mechanism of action of thiazide diuretics: Inhibit active reabsorption of NaCl in the distal convoluted tubule by interfering with a specific Na⁺/Cl^- cotransporter.

Electrolyte abnormalities seen with thiazide diuretics: Hypokalemia, hyponatremia, hypochloremia.

Clinical correlation

Thiazide diuretics are the recommended first-line agents for most people with hypertension. They are frequently used in combination with other classes of antihypertensives. Thiazides inhibit the active reabsorption of Na⁺. This causes an increase in the excretion of Na⁺, Cl^-, and K⁺. They also reduce the excretion of Ca²⁺ by increasing its absorption. The excretion of sodium and water reduces intravascular volume and contributes to their antihypertensive effect. Thiazides are used as single agents primarily in mild to moderate hypertension. They are often added as second agents when other drugs alone cannot control a patient’s hypertension. The electrolyte abnormalities caused by thiazides can be clinically important. Hypokalemia occurs frequently, especially when higher doses of thiazides are used. Patients need to be instructed to follow a high potassium diet and frequently require potassium supplementation. Thiazides can also elevate serum uric acid levels, which can precipitate gout in susceptible individuals.

Approach to pharmacology of antihypertensive agents

Objectives

1. Know the classes of antihypertensive medications and their mechanisms of action.

2. Know the common side effects of the antihypertensive agents.

Definitions

Hypertension: Blood pressure continuously elevated to levels greater than 120/80 mm Hg. Pressures of 130/90 mm Hg are considered prehypertensive.

Essential hypertension: Hypertension of unknown etiology makes up approximately 90 percent of hypertensive patients.

Pharmacology pearls

The ALLHAT clinical trial (Antihypertensive and lipid-lowering treatment to prevent heart attack) compared amlodipine, a dihydropyridine Ca²⁺-channel blocker, lisinopril, an ACE inhibitor, doxazosin, an α₁-adrenergic antagonist with chlorthalidone, a thiazide diuretic.

Thiazide diuretics are the preferred initial therapy for hypertension in most cases.

Beta-blocking agents can cause depression, insomnia, male impotency, bronchoconstriction, and decreased production of insulin.

Questions

[1] The inclusion of spironolactone with a thiazide diuretic in a regimen to treat hypertension is done to achieve which of the following?

A. Reduce hyperuricemia

B. Reduce Mg⁺ loss

C. Decrease the loss of Na⁺

D. Reduce K⁺ loss

[2] Which of the following drugs would be the best to treat moderate hypertension in a diabetic patient with mild proteinuria?

A. Enalapril

B. Propranolol

C. Hydrochlorothiazide D Nifedipine

[3] A 33-year-old man is diagnosed with essential hypertension. He is started on a blood pressure medication, and after 6 weeks, he notes fatigue, rash over his face, joint aches, and effusions. A serum antinu-clear antibody (ANA) test is positive. Which of the following is the most likely agent?

A. Hydralazine

B. Propranolol

C. Thiazide diuretic

D. Nifedipine

E. Enalapril

Answers

[1] D. Spironolactone is a “potassium-sparing” diuretic that reduces K⁺excretion in the collecting duct. It diminishes the K⁺-wasting effects of thiazide diuretics.

[2] A. ACE inhibitors, such as enalapril, have been shown to reduce the progressive loss of renal function that is often seen in diabetic patients. The nonselective beta blocker, propranolol, would worsen the diabetes.

[3] A. Hydralazine is associated with a lupus-like presentation, with pho-tosensitivity, malar rash, joint pain, and sometimes pericardial effusion or pleura! effusion.

Continuation: Antihypertensive agents. Class

This post has been viewed 9182 times.

Posts Related to Antihypertensive agents

Diuretics
Overview Diuretics have been available since the mid 1950s and are predominantly marketed in generic forms. The generic manufacturer Mylan has the largest market share for these agents. Despite their age, diuretics, particularly thiazide diuretics, remain an important treatment option for hypertension. The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, ...
Diuretic Combination Therapies
Overview Treatment with a combination of a potassium-sparing diuretic and a thiazide diuretic is used to temper metabolic effects, including thiazide-induced hypokalemia. Fixed-dose, single-pill, potassium-sparing/thiazide diuretic combinations have been available for more than two decades. Examples include triamterene/hydrochlorothiazide (GlaxoSmithKline's Dyazide, generics) and amiloride/hydrochlorothiazide (Merck's Moduretic, generics). These combinations are not very different in terms of ...
Antihypertensive agents. Class
There are 12 major classes of drugs that are used as oral antihypertensive drugs, and these include drugs that act centrally and those that work in the periphery. Antihypertensive drugs may cause vascular smooth-muscle relaxation, vascular volume reduction, or a decrease in cardiac output. This is accomplished by decreasing Ca2+ in vascular smooth muscle cells ...
Grug Therapy: Diuretics
Diuretics lower blood pressure in hypervolemic patients by reducing blood volume. They may also work in patients with normal blood volume by increasing venous capacitance. Advantages include low cost and the convenience of once-a-day dosing. A variety of thiazide-type diuretics are commercially available, including hydrochlorothiazide, chlorthalidone, metolazone, and indapamide. All have similar hypotensive effects, although ...
Diuretics
Overview Diuretics are commonly used to treat pulmonary arterial hypertension patients with right-ventricular failure (e.g., those suffering from peripheral edema and/or ascites). The ACCP guidelines emphasize that the long-term management of pulmonary arterial hypertension patients requires the maintenance of near-normal intravascular volume via the use of diuretics in addition to reduced dietary salt intake. However, ...

Categorized under: Antihypertensive Drugs.
Tagged with: ACE Inhibitors, Calcium channel blockers, Diuretics, Vasodilators, α-Blockers, β-Blockers.

Comments are closed.

High Blood Pressure / Hypertension

Hypertension Management