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ACE Inhibitors

ACE inhibitors (angiotensin converting enzyme inhibitors) e.g.

ramipril, lisinopril, captopril

These competitively inhibit the ACE, and thus reduce the generation of
angiotensin-II, and also consequently aldosterone. This reduces
sodium and water retention.

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.

Unwanted effects

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
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 info
They are generally used as first line treatment, but should not be
used in patients with severe renal artery stenosis as it will
cause deterioration of renal function

Other uses of ACE inhibitors:
Treatment of heart failure
Secondary prevention after MI
Diabetic nephropathy in IDDM
Standard dose is 2-10mg daily

Combining an ACE inhibitor with a potassium sparing diuretic such
as spironolactone can result in massively raised potassium