The kidney regulates blood pressure through the renin-angiotensin-aldosterone system (RAAS). Low blood pressure or sodium levels cause the kidney to release renin, which converts angiotensinogen to angiotensin I and II. Angiotensin II constricts blood vessels and stimulates aldosterone secretion, both of which increase blood pressure. ACE inhibitors block the conversion of angiotensin I to angiotensin II, reducing vasoconstriction and aldosterone secretion. They are used to treat hypertension, heart failure, myocardial infarction, and diabetic nephropathy by decreasing blood pressure and improving cardiac function. Common side effects include dry cough, rash,

1. Renin–angiotensin–aldosterone system
The kidney provides long-term control of blood pressure by altering the blood volume.
Baroreceptors in the kidney respond to reduced arterial pressure (and to sympathetic
stimulation of β1-adrenoceptors) by releasing the enzyme renin.
• Low sodium intake and greater sodium loss also increase renin release.
• Renin converts angiotensinogen to angiotensin I, which is converted in turn to
angiotensin II, in the presence of angiotensin-converting enzyme (ACE).
• Angiotensin II is a potent circulating vasoconstrictor, constricting both arterioles and
veins, resulting in an increase in blood pressure.
• Furthermore, angiotensin II stimulates aldosterone secretion, leading to increased
renal sodium reabsorption and increased blood volume, which contribute to a further
increase in blood pressure.

6. ANGIOTENSIN-CONVERTING ENZYME (ACE)
INHIBITORS
These drugs block the enzyme that cleaves angiotensin I to form the potent
vasoconstrictor angiotensin II. ACE inhibitors also decrease the secretion of
aldosterone..
Captopril
Enalapril
Fosinopril
Lisinopril
Quinapril
Ramipril

7. Pharmacokinetics
• After Oral administration ACE inhibitors are adequately absorbed
• Food may decrease the absorption of Captopril. so it should be taken on
an empty stomach.
• Except for captopril, ACE inhibitors are prodrugs that require activation
by hydrolysis via hepatic enzymes.
• Renal elimination of the active moiety is important for most ACE
inhibitors.
• Plasma half-lives of active compounds vary from 2 to 12 hours, although
the inhibition of ACE may be much longer.

8. Pharmacological effects
• Actions on the heart: ACE inhibitors decrease vascular resistance
(afterload) and venous tone (preload), resulting in increased cardiac
output. ACE inhibitors also blunt the usual angiotensin II–mediated
increase in epinephrine and aldosterone seen in HF.
• ACE inhibitors improve clinical signs and symptoms of HF and
have been shown to significantly improve patient survival in HF.

9. Indications:
• ACE inhibitors may be considered for patients with asymptomatic and
symptomatic HFrEF. Importantly.
• Patients with the lowest ejection fraction show the greatest benefit from use
of ACE inhibitors.
Depending on the severity of HF, ACE inhibitors may be used in combination
with diuretics, β-blockers, digoxin, aldosterone antagonists, and
hydralazine/isosorbide dinitrate fixed-dose combination. Patients who have had
a recent MI also benefit from long-term ACE inhibitor therapy. ACE inhibitors
are also used for the treatment of hypertension.

10. Therapeutic uses
• ACE inhibitors slow the progression of diabetic nephropathy and decrease albuminuria and,
thus, have a compelling indication for use in patients with diabetic nephropathy.
• ACE inhibitors are a standard in the care of a patient following a myocardial infarction and
first-line agents in the treatment of patients with systolic dysfunction.
• Chronic treatment with ACE inhibitors achieves sustained blood pressure reduction,
regression of left ventricular hypertrophy, and prevention of ventricular remodeling after a
myocardial infarction.
• ACE inhibitors are first-line drugs for treating heart failure, hypertensive patients with
chronic kidney disease, and patients at increased risk of coronary artery disease.
• All of the ACE inhibitors are equally effective in the treatment of hypertension at equivalent
doses

11. Adverse effects
• Common side effects include dry cough (mostly in women due to bradykinin),
rash, fever, altered taste, hypotension (in hypovolemic states), and
hyperkalemia.
• Angioedema is a rare but potentially life-threatening reaction that may also be
due to increased levels of bradykinin.
• Potassium levels must be monitored while on ACE inhibitors, and potassium
supplements and potassium-sparing Diuretics should be used with caution due
to the risk of hyperkalemia.
• Serum creatinine levels should also be monitored, particularly in patients with
underlying renal disease.
• ACE inhibitors can induce fetal malformations and should not be used by
pregnant women