Pertacilon

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.

Pertacilon 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 Pertacilon 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. Pertacilon, 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. Pertacilon 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. Pertacilon’s affinity for ACE is approximately 30,000 times greater than that of ATI.

Dosage

Pertacilon 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).

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 meals. The presence of food decreases absorption. Take one hour prior to meals.

[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.

Pertacilon Drug Interaction

Moderate: aspirin, aspirin, aspirin, aspirin, furosemide, furosemideUnknown: atorvastatin, atorvastatin, acetaminophen, acetaminophen, clopidogrel, clopidogrel, levothyroxine, levothyroxine, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol

Pertacilon Disease Interaction

Major: angioedema, bone marrow suppression, CHF, hemodialysis, hyperkalemia, hypotensionModerate: liver disease, renal dysfunction

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

Innovators Monograph

You find simplified version here Pertacilon