Introduction
Cardopril Tablet 50 mg 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). Cardopril Tablet 50 mg may be used in the treatment of hypertension.
Uses
Cardopril Tablet 50 mg is an ACE inhibitor used for the management of essential or renovascular hypertension, congestive heart failure, left ventricular dysfunction following myocardial infarction, and nephropathy.
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.
Associated Conditions
Pharmacodynamics
Cardopril Tablet 50 mg, 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.
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. Cardopril Tablet 50 mg, 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. Cardopril Tablet 50 mg 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. Cardopril Tablet 50 mg’s affinity for ACE is approximately 30,000 times greater than that of ATI.
Absorption
60-75% in fasting individuals; food decreases absorption by 25-40% (some evidence indicates that this is not clinically significant)
Protein Binding
25-30% bound to plasma proteins, primarily albumin
Half Life
2 hours
Toxicity
Symptoms of overdose include emesis and decreased blood pressure. Side effects include dose-dependent rash (usually maculopapular), taste alterations, hypotension, gastric irritation, cough, and angioedema.
Food Interactions
- Avoid hypertensive herbs (e.g. bayberry, blue cohosh, cayenne, ephedra, and licorice).
- Avoid potassium-containing products. Potassium products increase the risk of hyperkalemia.
- Limit salt intake. Salt may attenuate the antihypertensive effect.
- Take separate from meals. The presence of food decreases absorption. Take one hour prior to meals.
Dosage
Mild-to-moderate hypertension: The initial dose is 12.5 mg twice daily. The usual maintenance dose is 25mg twice daily which can be increased incrementally, at two to four week intervals, until a satisfactory response is achieved, to a maximum of 50 mg twice daily.
Severe hypertension: In severe hypertension the starting dose is 12.5 mg b.d. The dosage may be increased incrementally to a maximum of 50 mg t.d.s.
Heart failure: A starting dose of 6.25mg or 12.5mg may minimise a transient hypotensive effect. The usual maintenance dose is 25mg three times a day. The usual maximum dose is 150 mg daily.
Cardopril Tablet 50 mg must be taken 1 hour before meals to ensure maximum absorption.
Use in Child: Safety and effectiveness in pediatric patients have not been established.
