This document discusses angiotensin converting enzyme (ACE) inhibitors and their use in treating hypertension. It begins by explaining how ACE converts angiotensin I to the vasoconstrictor angiotensin II. ACE inhibitors work by inhibiting this enzyme, lowering blood pressure. Common ACE inhibitors are then classified and their individual mechanisms of action and uses described. In conclusion, ACE inhibitors are now first-line treatments for hypertension by preventing the formation of angiotensin II.

1. ACE INHIBITORS IN HYPERTENSION
: Submitted by :
Name : MAITREYEE MUKHERJEE
Sem : 6th Year : 3rd Sec : II
Registration No. : 162080210032 of 2016-2017
Roll No. : 20801916079

2. INTRODUCTION
Angiotensin Converting Enzyme has important role in hypertension.
It is located mainly in the capillaries of the lungs but can also be found in epithelial cells
of kidney. It converts Angiotensin I (Ang I) to Angiotensin II (Ang II).
Angiotensin II is potent vasoconstrictor which binds to the type 1 angiotensin II receptor
which is caused of vasoconstriction and increased blood pressure.
 Angiotensin Converting Enzyme Inhibitors inhibit the angiotensin-converting enzyme,
an important component of the renin–angiotensin system.
 This group of drugs causes relaxation of blood vessels as well as a decrease in blood
volume, which as leads to lower blood pressure and decreased oxygen demand from
the heart. ACE Inhibitors are used antihypertensive agents.
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Structure of ACE

3. MECHANISM OF ACTION OF ACE INHIBITORS :
Angiotensinogen (14 amino acids)
Renin
Angiotensin I (Decapeptide, biologically inactive)
ACE ACE Inhibitors
Angiotensin II (Octapeptide)
Angiotensin II Antagonist
Vasoconstriction
Sodium and water retention
Hypertension
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4. : CLASSIFICATION OF ACE INHIBITORS :
i. Sulfhydryl Group Containing Drugs : Example – Captopril
ii. Dicarboxylate group Containing Drugs : Example - Enalapril, Lisinopril
iii. Phosphonate Group Containing Drugs : Example - Fosinopril
Captopril Enalapril Lisinopril Fosinopril
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5. CAPTOPRIL
MECHANISM OF ACTION :
Captopril is a sulfhydryl containing dipeptide substitute of proline which abolishes
the pressor action of Ang I but not that of Ang II.
 Captopril competitively inhibits angiotensin converting enzyme (ACE), thereby
decreased the levels of angiotensin II in plasma.
Increased plasma renin activity.
Decreased aldosterone secretion.
Small increase in serum potassium with sodium and fluid loss.
PHARMACOKINETICS :
• About 70% of orally administered captopril is absorbed.
• Duration of action:- 6-12 hr.
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6. ADVERSE EFFECT:
Captopril is well tolerated by most of the patients, especially if daily dose is kept
below 150 mg.
oHypotension : An initial sharp fall in Blood Pressure occurs especially in diuretic
treated and Congestive Heart Failure (CHF) patients.
oHyperkalaemia : The patients with impaired renal function and in those taking K+
sparing diuretics, NSAIDs or beta blockers.
oCough : It is not dose related and appears to be caused by inhibition of bradykinin
in lungs.
oAngioedema : Resulting in swelling of lips, mouth, nose, larynx may develop
within hours or few days.
oOthers : Proteinuria, taste alteration, headache, dizziness, nausea.
CONTRAINDICATION: Hypersensitivity, renal impairment, pregnancy
CLINICAL USES: Hypertension, Congestive Heart Failure, Myocardial Infarction
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7. ENALAPRIL
Enalapril is the second ACE inhibitor to be introduced. It is a prodrug, de esterified in
the liver to enalaprilat (a tripeptide analogue).
MECHANISM OF ACTION:
Enalaprilat competes with Ang I for binding at ACE, blocking the conversion of Ang I
to Ang II.
As Ang II is a vasoconstrictor and a negative feedback mediator for renin activity,
lower concentrations result in a decrease in blood pressure.
Enalaprilat may also act on kininase II, that degrades the vasodilator bradykinin.
PHARMACOKINETICS:
• Effective dose- 5-20 mg OD or BD.
• Enalapril is not use as such orally because of poor absorption.
• Duration of Action:- 24 hr.
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8. ADVERSE EFFECT:
Hypotension, Cough, Dizziness etc.
CONTRAINDICATION:
Hypersensitivity, pregnancy, children etc.
CLINICAL USES:
oHypertension : The ACE inhibitors are first line drugs in all grades
of hypertension. Enalapril is a long acting antihypertensive drug.
oCHF : ACE inhibitors cause both arteriolar and vasodilatation in
Congestive Heart Failure (CHF) patients, reduce afterload as well as
preload.
oOthers : Post myocardial infarction, high coronary disease risk etc.
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9. FOSINOPRIL
• This ACE inhibitor is unique in being a phosphonate compound that is
glucuronide conjugated and eliminated by liver and kidney.
• It is a prodrug suitable for once daily administration.
MECHANISM OF ACTION:
Fosinopril is hydrolyzed by esterase to the pharmacologically active form,
fosinoprilat, a specific competitive inhibitor of ACE.
Fosinoprilat prevents conversion of Ang I to Ang II.
Decreased plasma Ang II, which leads to decrease vasopressor activity and to
decreased aldosterone secretion.
Small increase in serum potassium.
PHARMACOKINETICS:
Duration of action:- 24 hr.
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10. ADVERSE EFFECT:
Hypotension, Cough, Dizziness, Nausea, Vomiting etc.
CONTRAINDICATION:
Hypersensitive, Pregnancy etc.
CLINICAL USES:
oFosinopril is used to treat hypertension. Lowering high blood pressure helps to
prevent strokes, heart attack and also kidney problems.
oIt is used in treatment of Congestive Heart Failure.
Fig: ACE in complex with inhibitor lisinopril, zinc cation
shown in grey ,chloride anions in yellow.
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11. CONCLUSION:
Angiotensin Converting Enzyme (ACE) converts Ang I to Ang II. Angiotensin
converting enzyme inhibitors inhibit the angiotensin-converting enzyme, an
important component of the renin–angiotensin system.
Captopril, Enalapril, Fosinopril, Lisinopril etc. are used as ACE inhibitors. Now a
days, the ACE inhibitors are first line drugs in all grades of hypertension. These are
also applied in the treatment of Congestive Heart Failure, Myocardial Infarction etc.
REFERENCES:
Tripathi KD, Essentials of Medical Pharmacology (7th Edition)
D. Sriram, P. Yogeeswari, Medicinal Chemistry (2nd Edition)
https://www.drugbank.ca/
https://pubchem.ncbi.nlm.nih.gov/
Wikipedia
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12. THANK
YOU
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