Captopril use as ACE inhibitor

 Captopril

Captopril is an angiotensin-converting enzyme (ACE) inhibitor used to treat high blood pressure, heart failure, and certain kidney conditions.

· Captopril is a sulfhydryl-containing analogue of proline with antihypertensive activity & antineoplastic activity.

·   Captopril is a specific competitive inhibitor of angiotensin I-converting enzyme (ACE) that enzyme responsible for the conversion of angiotensin I to angiotensin II. Captopril is a white to off-white crystalline powder that may have a slight sulphurous odour; it is soluble in water, methanol, & ethanol and sparingly soluble in chloroform and ethyl acetate. 

Discovery of Captopril

·   One of the first drugs marketed for lowering blood pressure was found by studying the venom from Bothrops jararaca, a poisonous snake. Captopril, an analog of the snake venom's ACE-inhibiting peptide, was first synthesized in 1975 by three researchers at the U.S. drug company E.R. Squibb & Sons Pharmaceuticals. The development of captopril was among the earliest successes of the revolutionary concept of ligand- based drug design.

Active site of Captopril

·   The thiol (SH) group of captopril makes direct interaction with Zn2+.

·   The carbonyl group forms strong hydrogen bonding with two histidine.

·   The carboxylate group interacts with a cationic group on the enzyme.

·   The proline and the methyl are involved in a stereospecific hydrophobic and van der Waals interactions.

 

Mechanism of action

·   it is an Angiotensin converting enzyme (ACE) inhibitor

·   By blocking this enzyme it inhibit formation of angiotensin from angiotensinogen.

·   Angiotensin increases blood pressure (BP) by increasing aldosterone secretion from adrenal gland.

·   After giving Captopril (Prime ACE inhibitor):No Angiotensin

·   No Angiotensin = No High BP!

·   Net result: Decrease Blood Pressure.

 Pharmacokinetics

·   Bioavailability                       -       70%

·   Metabolism                          -       Liver

·   Excretion                             -       Kidney

·   Half life                               -       2 Hours

·   Route of administration      -       Per oral

·   Pregnancy category            -          D

USSES

·   Hypertension (First line treatment)

·   Congestive Heart Failure (CHF)

·   Myocardial Infarction (MI)

·   Diabetic Proteinuria in hypertensive patient

·   Unilateral renal artery stenosis (Drug of choice)

·   Anti-depressant activity noted in animal study

·   Anti-cancer property (Recent study)

Side Effects

·   Postural hypotension

·   Cough, itching, angioedema (because it increases level of bradykinin)

·   Hyperkalaemia (because it indirectly inhibit action of aldosterone)

·   Teratogenicity

·   Leukopenia (Rare)

·   Taste alteration

·   Agranulocytosis (Rare)

Contraindications

• Hypotensive shock (of course!)
•   Patient with dizziness problem

• Pregnant lady