Apo-Fosinopril
Apo-Fosinopril Uses, Dosage, Side Effects, Food Interaction and all others data.
Apo-Fosinopril is a phosphinic acid-containing ester prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly hydrolyzed to fosinoprilat, its principle active metabolite. Apo-Fosinoprilat inhibits 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). Apo-Fosinopril may be used to treat mild to moderate hypertension, as an adjunct in the treatment of congestive heart failure, and to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.
Following oral administration, fosinopril is rapidly and completely hydrolyzed to its principle active metabolite, fosinoprilat. Hydrolysis is thought to occur in the gastrointestinal mucosa and liver. Apo-Fosinoprilat is a competitive inhibitor of ACE, a peptidyl dipeptidase that is part 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 further sustain the effects of fosinoprilat by causing increased vasodilation and decreased blood pressure.
| Trade Name | Apo-Fosinopril |
| Availability | Prescription only |
| Generic | Fosinopril |
| Fosinopril Other Names | Fosenopril, Fosinopril |
| Related Drugs | amlodipine, lisinopril, metoprolol, losartan, furosemide, carvedilol, hydrochlorothiazide, spironolactone, valsartan, ramipril |
| Type | |
| Formula | C30H46NO7P |
| Weight | Average: 563.672 Monoisotopic: 563.301189823 |
| Protein binding | Fosinoprilat is ≥95% protein bound |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | Canada, United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Apo-Fosinopril is an ACE inhibitor used to treat mild to moderate hypertension, congestive heart failure, and to slow the progression of renal disease in hypertensive diabetics.
For treating mild to moderate hypertension, use as an adjunct in treating congestive heart failure, and may be used to slow the rate of progression of renal disease in hypertensive individuals with diabetes mellitus and microalbuminuria or overt nephropathy.
Apo-Fosinopril is also used to associated treatment for these conditions: Diabetic Nephropathy, Heart Failure, High Blood Pressure (Hypertension)
How Apo-Fosinopril 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. Apo-Fosinoprilat, the active metabolite of fosinopril, 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. Apo-Fosinoprilat 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.
Toxicity
Human overdoses of fosinopril have not been reported, but the most common manifestation of human fosinopril overdosage is likely to be hypotension. Oral doses of fosinopril at 2600 mg/kg in rats were associated with significant lethality. The most common adverse effects include dizzines, cough, fatigue, and headache.
Food Interaction
- 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 antacids. Take at least 2 hours before or after antacids. Taking this medication with antacids can reduce absorption.Taking this medication with antacids can reduce absorption.
- Take with or without food. The absorption is unaffected by food.
[Moderate] GENERALLY AVOID: Moderate-to-high dietary intake of potassium can cause hyperkalemia in some patients who are using angiotensin converting enzyme (ACE) inhibitors.
In some cases, affected patients were using a potassium-rich salt substitute.
ACE inhibitors can promote hyperkalemia through inhibition of the renin-aldosterone-angiotensin (RAA) system.
MANAGEMENT: It is recommended that patients who are taking ACE inhibitors be advised to avoid moderately high or high potassium dietary intake.
Particular attention should be paid to the potassium content of salt substitutes.
Apo-Fosinopril Drug Interaction
Moderate: aspirin, aspirin, furosemide, furosemideUnknown: rosuvastatin, rosuvastatin, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, atorvastatin, atorvastatin, metoprolol, metoprolol, clopidogrel, clopidogrel, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol
Apo-Fosinopril Disease Interaction
Major: angioedema, bone marrow suppression, CHF, hemodialysis, hyperkalemia, hypotensionModerate: liver disease, renal dysfunction, liver impairment
Elimination Route
Average absolute absorption is 36%. The primary site of absorption is the proximal small intestine (duodenum/jejunum). Food slows the rate of absorption with no effect on the extent of absorption.
Half Life
12 hours
Clearance
- 26 - 39 mL/min [healthy]
Elimination Route
After oral administration of radiolabeled fosinopril, approximately half of the absorbed dose is excreted in the urine and the remainder is excreted in the feces.
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