Captopril/Hydrochloorthiazide Sandoz

Captopril/Hydrochloorthiazide Sandoz Uses, Dosage, Side Effects, Food Interaction and all others data.

Captopril competitively inhibits the conversion of angiotensin I (ATI) to angiotensin II (ATII), thus resulting in reduced ATII levels and aldosterone secretion. It also increases plasma renin activity and bradykinin levels. Reduction of ATII leads to decreased Na and water retention. This promotes vasodilation and BP reduction.

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.

Trade Name Captopril/Hydrochloorthiazide Sandoz
Generic Captopril + Diuretika
Type
Therapeutic Class
Manufacturer Sandoz
Available Country Netherlands
Last Updated: September 19, 2023 at 7:00 am
Captopril/Hydrochloorthiazide Sandoz
Captopril/Hydrochloorthiazide Sandoz

Uses

Hypertension: Mild to moderate hypertension as an adjunct to thiazide therapy in patients who have not responded effectively to thiazide treatment alone.

Severe hypertension: Where standard therapy has failed. Cardopril is effective alone or in combination with other antihypertensive agents especially thiazide type of diuretics. The blood pressure lowering effect of Cardopril and thiazides are approximately additive.

Congestive heart failure: It is also used as an adjunct to the treatment of severe congestive heart failure.

Captopril/Hydrochloorthiazide Sandoz is also used to associated treatment for these conditions: Aldosteronism, Anatomic renal artery stenosis, Congestive Heart Failure (CHF), Diabetic Nephropathy, Heart Failure, 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

How Captopril/Hydrochloorthiazide Sandoz works

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.

Dosage

Captopril/Hydrochloorthiazide Sandoz dosage

Diabetic nephropathy:

  • Adult: Type 1 diabetics: 75-100 mg/day in divided doses.

Post-myocardial infarction:

  • Adult: May be started 3-16 days after MI. Initially, 6.25 mg/day followed by 12.5 mg tid for 2 days, then 25 mg tid. Maintenance: 75-150 mg/day in 2 or 3 divided doses.

Hypertension:

  • Adult: Initially, 12.5 mg bid, 1st dose preferably at bedtime to avoid precipitous fall in BP, gradually increased at 2-4-wk intervals according to response. Maintenance: 25-50 mg bid. Max: 50 mg tid. Patients on diuretics: 6.25 mg bid.
  • Child: Neonates and infants: 0.15 mg/kg. Max: 6 mg/kg in 2 or 3 divided doses according to response. Childn and adolescents: 0.3 mg/kg. Max: 6 mg/kg in 2 or 3 divided doses according to response.
  • Elderly: Initially, 6.25 mg bid.

Heart failure:

  • Adult: Initially, 6.25-12.5 mg bid or tid. Maintenance: 25 mg bid or tid. Max: 50 mg tid.
  • Child: Initially, 0.25 mg/kg/day, increased up to 2.5 or 3.5 mg/kg/day in 3 divided doses.

Side Effects

Neutropenia, anaemia and thrombocytopenia; proteinuria, elevated blood urea and creatinine, elevated serum potassium and acidosis; hypotension, tachycardia; rashes usually pruritic, may occur; Reversible and usually self limiting taste impairment has been reported. Stomatitis resembling aphthous ulcers has also been reported.

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.

Precaution

Patients with bilateral renal artery stenosis, collagen vascular disease, aortic or mitral valve stenosis, volume and/or Na depletion. Renal impairment. Lactation.

Interaction

Concurrent treatment with NSAIDs reduces hypotensive action and increases the risk of nephrotoxicity. Additive hyperkalaemic effect with K supplements, K-sparing diuretics, and other drugs (e.g. heparin). May increase risk of leucopenia with procainamide, allopurinol, cytostatic or immunosuppressants. May increase risk of lithium toxicity. Increased risk of nitritoid reactions with gold (Na aurothiomalate).

Elimination Route

60-75% in fasting individuals; food decreases absorption by 25-40% (some evidence indicates that this is not clinically significant)

Half Life

2 hours

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk

Contraindication

Angioedema related to previous ACE inhibitor treatment, hereditary or idiopathic angioneurotic oedema. Concomitant use with aliskiren in diabetic patients. Pregnancy.

Acute Overdose

Symptoms: Severe hypotension, shock, stupor, bradycardia, electrolyte disturbances and renal failure.

Management: Perform gastric lavage, administer adsorbent and sodium sulfate with in 30 min of ingestion; NaCl 0.9% IV infusion. Treatment with angiotensin-II may also be considered. Administer atropine in case of extensive vagal reactions or bradycardia. Pacemaker is also an option. Elimination may be enhanced by haemodialysis.

Storage Condition

Store below 30° C

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