Captopril is a sulfhydryl-containing analog of proline with antihypertensive activity and potential antineoplastic activity. Captopril competitively inhibits angiotensin-converting enzyme (ACE), thereby decreasing levels of angiotensin II, increasing plasma renin activity, and decreasing aldosterone secretion. This agent may also inhibit tumor angiogenesis by inhibiting endothelial cell matrix metalloproteinases (MMPs) and endothelial cell migration. Captopril may also exhibit antineoplastic activity independent of effects on tumor angiogenesis.
Captopril is an angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. It is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE), the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Captopril may be used in the treatment of hypertension.
Mechanism of Action of Captopril
There are two isoforms of ACE the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have a much greater affinity for an inhibitory activity against the C-domain. Captopril, one of the few ACE inhibitors that is not a prodrug, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Captopril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors. Captopril’s affinity for ACE is approximately 30,000 times greater than that of ATI.
Angiotensin converting enzyme inhibitors effectively inhibit the conversion of angiotensin I to the active vasoconstrictor angiotensin II, a hormone that also promotes, via aldosterone stimulation, increased sodium and water retention. The angiotensin converting enzyme inhibitors, therefore, are capable of lowering blood pressure primarily by promoting vasodilatation and reducing intravascular fluid volume.
Indications of Captopril
- High blood pressure
- Heart failure
- Diabetic kidney disease
- Hypertensive emergency
- Left ventricular dysfunction
- Migraine prevention
- Anatomic renal artery stenosis
- Congestive heart failure
- Diabetic nephropathies
- Heart failure, unspecified
- High blood pressure (Hypertension)
- Hypertensive crisis
- Non ST segment elevation Acute coronary syndrome
- Raynaud’s Phenomenon
- Ejection fraction of 40% or less left ventricular dysfunction
For the treatment of essential or renovascular hypertension (usually administered with other drugs, particularly thiazide diuretics). May be used to treat congestive heart failure in combination with other drugs (e.g. cardiac glycosides, diuretics, β-adrenergic blockers). May improve survival in patients with left ventricular dysfunction following myocardial infarction. May be used to treat nephropathy, including diabetic nephropathy.
Therapeutic Indication of Captopril
- Captopril is used in the management of mild to severe hypertension. The drug has been used as monotherapy or in combination with other classes of antihypertensive agents.
- Captopril is used in conjunction with cardiac glycosides and diuretics in the management of congestive heart failure resistant to or inadequately controlled by cardiac glycosides and diuretics.
Angiotensin converting enzyme (ACE) inhibitor
- For the initiation of therapy for heart failure and hypertension … Lowers systemic vascular resistance and mean, diastolic, and systolic blood pressures in various hypertensive states
- ACE inhibitors are indicated alone or in combination with a thiazide diuretic, in the treatment of hypertension.
- Captopril is also used for the treatment of neonatal hypertension.
- ACE inhibitors are also used for (treatment of malignant, refractory, or accelerated hypertension /NOT included in US product labeling/) and for treatment of renovascular hypertension (except in patients with bilateral renal artery stenoses or renal artery stenosis in a solitary kidney. /Included in US product labeling/
- Captopril, is indicated, in combination with diuretics and digitalis therapy, for the treatment of congestive heart failure not responding to other measures.
- Captopril is used for the treatment of congestive heart failure secondary to ventricular left-to-right shunt not responding to standard therapy in infants and neonates.
- Captopril is indicated following myocardial infarction in clinically stabile patients with left ventricular dysfunction (ejection fraction < or = 40%) to improve survival and decrease the incidence of overt heart failure and subsequent hospitalization for congestive heart failure.
- Captopril may be used in the treatment of nephropathy in patients with Type I insulin dependent diabetes mellitus (IDDM). Captopril has been shown to slow the progression of diabetic nephropathy in normotensive and hypertensive IDDM patients with documented diabetic retinopathy, a serum creatinine concentration of < or = 2.5 mg per decilder, and urinary protein excretion of > or = 500 mg in 24 hours. The greatest effect has been seen in those patients with poorer renal function at baseline (mean serum creatinine concentration > or = 1.5 mg/dl.
- Captopril is used for the treatment of hypertension and in the management of heart failure.
Contra-Indications of Captopril
- Low amount of sodium in the blood
- High amount of potassium in the blood
- Inherited disorder of continuing episodes of Swelling
- Reduction in the body’s resistance to infection
- Decreased function of bone marrow
- Decreased neutrophils a type of white blood cell
- Narrowing of the aortic heart valve
- Renal artery stenosis
- Abnormally low blood pressure
- Kidney disease with a reduction in kidney function
- Giant hives
- Recipient of Organ Transplant
- Brain Blood Flow Problem
- Hemodialysis with High-Flux Membrane
Dosage of Captopril
Strengths: 12.5 mg; 25 mg; 50 mg; 100 mg
- Initial dose: 25 mg orally 2 to 3 times a day one hour before meals
- Maintenance dose: May increase every 1 to 2 weeks up to 50 mg orally three times a day.
Congestive Heart Failure
- Initial dose: 25 mg orally three times a day (6.25 to 12.5 mg orally three times a day if hypotensive, hyponatremic, or hypovolemic)
- Target maintenance dose: 50 mg orally three times a day for at least two weeks to ensure a satisfactory response
- Maximum dose: 450 mg/day
Left Ventricular Dysfunction
- Initial dose: 6.25 mg orally once as early as three days post-myocardial infarction, followed by 12.5 mg orally three times a day; increase to 25 mg orally three times a day over the next several days, and then increase to target dose over the next several weeks as tolerated.
- Target maintenance dose: 50 mg orally three times a day
- 25 mg orally three times a day
Side Effects of Captopril
The most common
- Nausea and vomiting
- Severe stomach ache
- epigastric pain
- fainting, fast or pounding heartbeats;
- confusion, hallucinations; or
- problems with vision (difficulty focusing, double vision).
- Nausea and vomiting
- Severe stomach ache
- Severe diarrhea
- Chest pain
- cloudy urine
- fast, pounding, or irregular heartbeat or pulse
- Vaginal thrush
- Skin rash
- Ringing or buzzing in the ears
- Decreased appetite
- Body aches or pain
- dryness or soreness of the throat
- runny nose
- tender or swollen glands in the neck
- trouble swallowing
- voice changes
- Arm, back, or jaw pain
- bloody urine
- chest discomfort
- chest tightness or heaviness
- decreased blood pressure
- decreased or increased frequency or amount of urine
- dilated neck veins
Drug Interactions of Captopril
Captopril may interact with following drugs , supplyments & may change the efficacy of drugs
- other diuretics such as furosemide , hydrochlorothiazide,
- angiotensin receptor blockers such as candesartan , losartan, and telmisartan
- aspirin and other NSAIDs (non-steroidal anti-inflammatory drugs) such as:celecoxib , diclofenac ,etodolac
- iron dextran complex
- ketorolac intranasal
- mefenamic acid
Pregnancy & Lactation of Captopril
FDA Pregnancy Catagory D
Captopril has been shown that the use of captopril in pregnant women caused some babies to be born with problems. More specifically, it has been shown that use of drugs like captopril during the second and third trimesters of pregnancy harms the unborn baby’s kidneys and even increases the risk of death to the unborn baby. However, in some serious situations, the benefit of using this medication may be greater than the risk of harm to the baby.
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