Anti-hypertensive drugs

Question 1

What are the mechanisms for blood pressure regulation?

Answer 1

Short term regulation: Sympathetic nervous system

Long term regulation: Kidney

Question 2

What are the classes of drug to treat hypertension?

Answer 2

1. Diuretics: Thiazides, Loop Diuretics
2. Beta blockers: Propanolol (non-selective), Atenolol (B1-selective)
3. Angiotensin Converting Enzyme Inhibitors: Captopril, Enalapril, Lisinopril

Question 3

What is the MOA, uses and AEs of thiazides?

Answer 3

MOA: Inhibits NaCl reabsorption at the DCT by blocking Na+Cl- cotransporter, hence reducing Na+ reabsorption. It also increases Ca2+ reabsorption at the DCT. This leads to decreased Na+ in blood and thus decreased blood volume = decreased BP.

Uses: 1st line treatment for HTN and CHF

AEs:

1. Hyponatremia
2. Hypokalemia
3. Hypercalcemia
4. Hyperlipidemia (should not be used in diabetics)
5. Hyperuricemia (should not be used in patients with gout)
6. Hyperglycemia

Question 4

What is the MOA, uses and AEs of loop diuretics?

Answer 4

MOA: Loop diuretics inhibit the reabsorption of Na+/H2O, leading to a decrease in blood volume and thus decreased BP. It also increases K+/H+ excretion.

Uses: HTN, CHF, oedema (loop diuretics are more potent than thiazides in reducing blood volume, hence, they are usually used in cases with renal/cardiac failure)

AEs:

1. Hyponatremia
2. Hypokalemia
3. Metabolic alkalosis
4. Dehydration (loss of water = acute hypovolemia = hypotension)
5. Hyperuricemia

Question 5

What is the MOA, uses and AEs of beta-blockers?

Answer 5

MOA: Inhibit beta adrenoreceptors (B1 receptors in the heart) by reducing heart rate and contractility, thus reducing BP

Uses:

1. HTN
2. Angina
3. Following MI: To decrease contractility, to decrease workload and prevent recurrence of MI

AEs:

1. Bronchospasm (B2 adrenoreceptors also blocked, especially if non-selective Propanolol is used; Should not be used in asthmatics!)
2. Bradycardia
3. Sedation/vivid dreams

Question 6

What is the MOA, uses and AEs of ACE inhibitors?

Answer 6

MOA:

1. Inhibits ACE, thus reducing production of angiotensin 2 (ang 2 is responsible for producing aldosterone which increases BP; ang 2 also constricts blood vessels to increase BP), thus reduces blood pressure
2. Inhibits degradation of bradykinin, which is responsible for decreasing blood pressure

Uses:

1. HTN
2. Following MI
3. Cardiac failure

AEs:

1. Bradycardia
2. Severe hypotension
3. Hyperkalemia
4. Angioedema
5. Acute renal failure (due to loss of blood volume from a lack of Na+/H2O reabsorption) ; Should not be used in 2nd and 3rd trimester due to risk of fetal renal failure