Angiotensin converting enzyme inhibitors reduce the plasma levels of angiotensin II (AII) by inhibiting the enzymatic conversion of angiotensin I to angiotensin II by angiotensin converting enzyme. Reduced AII levels have many direct and indirect effects on the cardiovascular system:
- decreased blood pressure due to vasodilation of peripheral vessels (arterial and venous) and sodium loss by decreased aldosterone levels (by reducing stimulation of the RAAS)
- reduced sympathetic tone
- decreased hypertrophy (cardiac remodelling) of the heart directly and indirectly via an increase in growth inhibiting factors after increased bradykinin levels
ACE inhibitors are first-line therapy for heart failure, as they have been shown to reduce the progression in all stages of the disease. In addition, they have been shown to decrease the rate of progression to heart failure in post-myocardial infarction patients.
Adverse effects of ACE inhibitors are mild. Renal dysfunction and hyperkalaemia can occur, but are reversible when the drug is stopped. A cough appears in 5% of the patients treated with ACE inhibitors due to accumulation of bradykinin. Potassium-sparing diuretics are better not used in combination with ACE inhibitors because of the risk of hyperkalaemia. NSAIDs inhibit the action of ACE inhibitors. Since both drugs can cause renal insufficiency, the combination should be avoided or closely monitored.
The choice of ACE inhibitor depends on drug characteristics such as potency, pharmacokinetics, and action (as prodrug or directly). ACE inhibitors such as captopril, enalapril, and lisinopril are first choices for heart failure.
Elevated levels of the hormones ADH and angiotensin II will produce
Mr D is a 60-year old black man with a BP ranging from 135-140/95-100 mmHg despite strict adherence to his diet and exercise regimen. He is taking enalapril 10 mg twice a day. How will you manage Mr D's hypertension?
Extra info: Black people do not respond well to ACE inhibitor therapy. So, the only option is to stop enalapril therapy and start with a diuretic.
Mr. E is a CHF-patient who has experienced severe allergic reactions to ACE inhibitors and ATII-antagonists. Another way to efficiently decrease preload and afterload includes
Extra info: Nitrates are powerful reducers of preload and hydralazine is efficient in arterial dilation and thus reducing afterload.
ACE inhibitors should NOT be used in hypertensive patients with co-existing
Extra info: Therapy with ACE inhibitors can be effective for patients with diabetes (as they decrease microalbuminuria), patients with hyperlipidemia (they do not have negative effects), and patients with cardiac failure. However, because ACE inhibitors can cause problems in patients with renal artery stenosis, any patient with a decrease in renal function should be monitored carefully for the first few weeks after initiating ACE inhibitor therapy.
One important adverse effect to monitor with ACE inhibitors is
Extra info: ACE Inhibitors do not cause tachycardia, liver dysfunction and hyperglycemia.