Angiotensin converting enzyme inhibitors (ACE Inhibitors):

1. inhibit the generation of angiotensin II which is a potent vasoconstrictor.

2. inhibit the degradation of bradykinin which is a potent vasodilator

3. stimulate the synthesis of vasodilating PGs through bradykinin and

4. reduce sympathetic nervous system activity.

They also reduce aldosterone production hence sodium and water retention. All these actions contribute to their anti hypertensive effect.

ACE inhibitors dilate both arteries as well as veins, hence they reduce afterload and preload.

ACE inhibitors are preferred antihypertensive agents in younger age group. They are used in all forms of hypertension, especially in patients with diabetes, CHF and renovascular hypertension. ACE inhibitors are preferred in patients with diabetes because they delay or prevent the progression of renal complications.

Pharmacokinetics: ACE inhibitors are usually given orally. In emergency, enalaprilat can be given intravenously. Food reduces the absorption of captopril and ramipril hence they should be given 1 hour before meals. They poorly cross the BBB; metabolized in the liver and excreted in urine.

Adverse effects*

Cough (Dry cough) is due to increased bradykinin levels. Appearance of cough is the indication to stop the drug.

Angioedema

Proteinuria

Taste alteration, Teratogenic effect (growth retardation and neonatal death) – hence contraindicated in pregnancy.

Severe hypOtension may occur 1-2 hours after taking the first dose. Hence ACE inhibitors should be started with a small dose and then gradually increased.

NeutroPenia

Rash

Itching

Loss of appetite, nausea, vomiting and diarrhoea.

* Mnemonic for adverse effects of ACE inhibitors: ‘ CAPTOPRIL’

Hyperkalemia may be seen in patients with renal insufficiency and when combined with K⁺ sparing diuretics.

Drug Interactions

Tetracyclines X ACE inhibitors: Absorption of tetracycline is reduced.

ACE inhibitors X Potassium sparing diuretics: Simultaneous administration of these drugs can cause dangerous hyperkalemia.

ACE inhibitors X Lithium: ACE inhibitors retard the renal elimination of lithium and potentiate its toxicity.

ACE inhibitors X NSAIDs: NSAIDs by inhibiting PG synthesis promote Na⁺ and water retention on chronic use. Thus, they decrease the antihypertensive effect of ACE inhibitors.

Therapeutic uses of ace inhibitors:

1. Hypertension: Use of ACE inhibitors reduce the incidence of heart disease in hypertensive patients. ACE inhibitors are useful in all grades of hypertension. They prevent or retard myocardial hypertrophy and remodeling.

2. Congestive cardiac failure: ACE inhibitors should be prescribed to all patients with impaired left ventricular function. For explanation see Ch: (Pg ).

3. Myocardial Infarction (MI): ACE inhibitors should be started within 24 hours in patients with MI. They have shown both short-term and long-term improvement in survival.

4. Diabetic Nephropathy: ACE inhibitors and Angiotensin II receptor blockers (ARBs) are the preferred drugs in diabetic nephropathy as they control both systemic hypertension and intraglomerular pressure. They reduce the rate of progress from microalbuminuria to macroalbuminuria and delay the development of end stage renal disease. Therefore, ACE-inhibitors are the preferred antihypertensives in diabetics.

5. Scleroderma renal crisis: ACE inhibitors produce dramatic improvement in patients with renal crisis and accelerated hypertension.

Table: Pharmacokinetic features of ACE inhibitors

Category: Pharmacology Notes