ACE inhibitors (angiotensin converting enzyme inhibitors) e.g. ramipril, lisinopril, captopril
- Reduced tissue concentration of angiotensin-II also leads to arterial and venous dilation
- There is no reflex tachycardia – probably due to stimulation of the vagus nerve and a reduction in sympathetic activation caused by reduced angiotensin-II
- These drugs also inhibit bradykinin breakdown by ACE – bradykinin is a vasodilator.
- Angiotensin-II is associated with arterial, and left ventricular hypertrophy in hypertension. However, the role of ACE inhibitors in this system is not fully understood – there may be some extra benefit on top of the hypotensive benefits of the drug
- Usually given as pro-drugs, as the active forms are water soluble, and thus poorly absorbed from the gut. They are converted in the liver to the active agent, e.g. ramipril becomes ramiprilat.
- For most forms, the active drug is excreted, unchanged, by the kidney
- Half-lives are generally short, but the half-life of enanapril is long.
- Persistent dry cough – this is non-dose related, and may be caused by accumulation of kinins. It is more common in women, and occurs in approximately 20-30% of those who take the drug
- Postural hypotension – this is rare unless there is salt and water depletion, e.g. in people who are also taking diuretics. In people where it does occur there can be very profound hypotension, particularly after the first dose. This is rarely a problem when treating hypertension, but can occur when treating heart failure. Risks such as this can be minimised by taking a once-a-day preparation, when lying down, just before going to sleep at night
- Renal impairment – particularly in those with severe bilateral renal artery stenosis, who are relying on angiotensin mediated efferent glomerular arterial vasoconstriction to maintain a good filtration pressure
- Disturbance of taste, nausea, vomiting, dyspepsia, bowel disturbance
- Angioedema – this is the rapid swelling of the dermis and subcutaneous tissues. It if very similar to urticaria (hives), except that hives occurs in the upper layers of the dermis and angioedema occurs in lower layers.
Other uses of ACE inhibitors:
- Treatment of heart failure
- Secondary prevention after MI
- Diabetic nephropathy in IDDM
- Standard dose is 2-10mg daily