Captopril Uses, Side Effects, and More

 Captopril

Brand name:- Angiopril 25mg tab, Aceten, Captopril 12.5, 25mg tab.

Captopril is an angiotensin converting enzyme (ACE) inhibitor. It works by reducing stress on the heart and relaxing blood vessel so that blood flows more smoothly and the heart can pump blood more efficiently.

Pharmacodynamic:- 

Captopril, an ACE inhibitor, antagonizes the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain its effects by causing increased vasodilation and decreased blood pressure.

Pharmacokinetics:- 

About 70% of orally administered captopril is absorbed. Presence of food in stomach reduce its bioavailability. Penetration in brain is poor . It is partly metabolized and partly excreted unchanged in urine. The plasma t½ is ~ 2 hours, but actions last for 6-12 hours.

Mechanism of action:- 

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 much greater affinity for and 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.

used:-

Captopril is used in the treatment of Hypertension (high blood pressure), prevention of heart attack and stroke and Heart failure. It lowers the risk of heart attack and stroke.

 side effects:- 

Nausea, Taste change, Epigastric pain, Nonproductive cough, Sleep disorder.

Doses:-

25mg BD , increased gradually upto 50mg TDS according to response. In patients on diuretic and in CHF patients it is wise to start with 6.25 mg BD to avoid marked fall in BP initially. Tablet should be taken 1 hr before or 2 hr after a meal & as directed by your doctor.