Capozide 25/15
Capozide 25/15 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.
Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.
Hydrochlorothiazide prevents the reabsorption of sodium and water from the distal convoluted tubule, allowing for the increased elimination of water in the urine. Hydrochlorothiazide has a wide therapeutic window as dosing is individualized and can range from 25-100mg. Hydrochlorothiazide should be used with caution in patients with reduced kidney or liver function.
| Trade Name | Capozide 25/15 |
| Generic | Captopril + Hydrochlorothiazide |
| Weight | 25mg + 15mg, 25mg + 25mg, 50mg + 15mg, 50mg + 25mg |
| Type | Oral, Oral Tablet |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
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.
Hydrochlorothiazide is used for-
- Edema associated with congestive heart failure, hepatic cirrohosis, various forms of renal dysfunction and corticosteroid and estrogen therapy
- Management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe form of hypertension
- Management of diabetes insipidus
- Management of proximal renal tubular acidosis
- Idiopathic hypercalciuria and calcium nephrolithiasis, osteoporosis and exercise induced hyperkalemia
Capozide 25/15 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 dysfunctionAcidosis, Renal Tubular, Calcium Nephrolithiasis, Cirrhosis of the Liver, Congestive Heart Failure (CHF), Diabetes Insipidus, Edema, High Blood Pressure (Hypertension), Hypertension,Essential, Hypokalemia caused by diuretics, Nephrotic Syndrome, Premenstrual tension with edema, Sodium retention, Stroke, Prophylaxis of preeclampsia
How Capozide 25/15 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.
Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4).
Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water.
Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.
Dosage
Capozide 25/15 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.
Adults-
For Edema: The usual adult dosage is 25 to 100 mg daily as a single or divided dose.
For Control of Hypertension: The usual initial dose in adults is 25 mg daily given as a single dose. The dose may be increased to 50 mg daily, given as a single or two divided doses. Doses above 50 mg are often associated with marked reductions in serum potassium. In some patients (especially the elderly) an initial dose of 12.5 mg daily may be sufficient.
Infants and children-
For diuresis and for control of hypertension: The usual pediatric dosage is 1 to 2 mg/kg/day in single or two divided doses, not to exceed 37.5 mg per day in infants up to 2 years of age or 100 mg per day in children 2 to 12 years of age. In infants less than 6 months of age, doses up to 3 mg/kg/day in two divided doses may be required.
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.
Generally, Hydrochlorothiazide is well tolerated. However, a few side effects may occur like weakness, restlessness, dizziness, headache, fever, diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia, and hypotension. In rare case hyperglycemia, glycosuria, hyperuricemia and muscle spasm may occur.
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.
The oral LD50 of hydrochlorothiazide is >10g/kg in mice and rats.
Patients experiencing an overdose may present with hypokalemia, hypochloremia, and hyponatremia. Treat patients with symptomatic and supportive treatment including fluids and electrolytes. Vasopressors may be administered to treat hypotension and oxygen may be given for respiratory impairment.
Precaution
Patients with bilateral renal artery stenosis, collagen vascular disease, aortic or mitral valve stenosis, volume and/or Na depletion. Renal impairment. Lactation.
Thiazides should be used with caution in patients with severe renal disease, impaired hepatic function or progressive liver disease and gout.
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).
Alcohol, Barbiturates, or Narcotics: Potentiation of orthostatic hypotension may occur.
Antidiabetic Drugs (oral agents and insulin): Thiazides can impair control of diabetes mellitus by diet and antidiabetic Drugs. Antihypertensive Drugs: Additive effect or potentiation.
Volume of Distribution
The volume of distribution varies widely from one study to another with values of 0.83-4.19L/kg.
Elimination Route
60-75% in fasting individuals; food decreases absorption by 25-40% (some evidence indicates that this is not clinically significant)
An oral dose of hydrochlorothiazide is 65-75% bioavailable, with a Tmax of 1-5 hours, and a Cmax of 70-490ng/mL following doses of 12.5-100mg. When taken with a meal, bioavailability is 10% lower, Cmax is 20% lower, and Tmax increases from 1.6 to 2.9 hours.
Half Life
2 hours
The plasma half life of hydrochlorothiazide is 5.6-14.8h.
Clearance
The renal clearance of hydrochlorothiazide in patients with normal renal function is 285mL/min. Patients with a creatinine clearance of 31-80mL/min have an average hydroxychlorothiazide renal clearance of 75mL/min, and patients with a creatinine clearance of ≤30mL/min have an average hydroxychlorothiazide renal clearance of 17mL/min.
Elimination Route
Hydrochlorothiazide is eliminated in the urine as unchanged hydrochlorothiazide.
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
Pregnancy: Evidence of fetal risk in hydrochlorothiazide therapy is found, but it is indicated if benefits outweigh risks. Thiazides are indicated in pregnancy when edema is due to pathologic causes.\
Lactation: Neonatal side effects have been seen incase of hydrochlorothiazide therapy and therefore it is not recommended.
Contraindication
Angioedema related to previous ACE inhibitor treatment, hereditary or idiopathic angioneurotic oedema. Concomitant use with aliskiren in diabetic patients. Pregnancy.
Hydrochlorothiazide is contraindicated to the patients of anuria and those who are sensitive to hydrochlorothiazide or to other sulfonamide-derived drugs. Therapy is not to be initiated in diabetes mellitus.
Special Warning
Elderly: in some patients specially the elderly an initial dose of 12.5 mg daily may be sufficient.
Children: An initial dose for children has been 1 to 2 mg per kg body-weight in 2 divided doses. Infants under 6 months may need doses upto 3 mg per kg daily.
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.
The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. Rarely, autoimmune hemolytic anemia and other hypersensitivity reactions may complicate the picture.
In the event of over dosage, symptomatic and supportive measures should be employed. Emesis should be induced or gastric lavage performed. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. Hemodialysis can be used successfully to treat severe intoxication.
Storage Condition
Store below 30° C
Store between 15-30°C. Protect from light, moisture and freezing.
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