Perindopril Arginine/Indapamide

Perindopril Arginine/Indapamide Uses, Dosage, Side Effects, Food Interaction and all others data.

Perindopril is an ACE inhibitor. It works by blocking the action of angiotensin converting enzyme (ACE). ACE produces angiotensin II, as part of the body's natural control of blood pressure. Angiotensin II causes blood vessels to constrict and narrow, which increases the pressure within the blood vessels. Perindopril blocks the action of ACE, it reduces the production of angiotensin II, thus allows the blood vessels to relax and widen. The overall effect of this is a drop in blood pressure.

Perindopril is a nonsulfhydryl prodrug that is metabolized via first pass effect (62%) and systemic hydrolysis (38%) to perindoprilat, its active metabolite, following oral administration. Perindoprilat lowers blood pressure by antagonizing 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 the effects of perindoprilat by causing increased vasodilation and decreased blood pressure.

Perindopril Arginine/Indapamide
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Perindopril Arginine/Indapamide
Generic	Perindopril + Diuretika
Type
Therapeutic Class
Manufacturer	Dr Fisher Farma
Available Country	Netherlands
Last Updated:	September 19, 2023 at 7:00 am

Uses

Perindopril is a long-acting ACE (Angiotensin Converting Enzyme) inhibitor and is used for Essential hypertension, Stable coronary artery disease, Congestive heart failure.

Perindopril Arginine/Indapamide is also used to associated treatment for these conditions: Cardiovascular Events, Diabetic Nephropathy, High Blood Pressure (Hypertension), Hypertension,Essential, Myocardial Infarction, NYHA Class I Congestive heart failure, Stroke, Chronic heart failure with reduced ejection fraction (NYHA Class II), Chronic heart failure with reduced ejection fraction (NYHA Class III)

How Perindopril Arginine/Indapamide 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. Perindoprilat, the active metabolite of perindopril, 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. Perindopril 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.

Dosage

Perindopril Arginine/Indapamide dosage

Hypertension: One Perindopril 4 tablet once daily preferably in the morning. If necessary, the dose may be increased to 8 mg after 1 month of treatment. Perindopril should be taken before food.

Stable coronary artery disease: Perindopril 4 once daily for two weeks, then increased to 8 mg once daily, depending on renal function and provided that the 4 mg dose is well tolerated. Elderly patients should receive Perindopril 2 mg once daily for one week, then Perindopril 4 once daily the next week, before increasing the dose up to 8 mg once daily, depending on renal, function. The dose should be increased only if the previous lower dose is well tolerated.

Congestive heart failure: Perindopril should be started under close medical supervision at a starting dose of 2 mg in the morning. If necessary dose may be increased to 4 mg.

Elderly patients: Start treatment at Perindopril 2 mg daily.

Side Effects

Rare and mild: usually at the start of treatment cough, fatigue, asthenia, headache, disturbances of mood and/or sleep have been reported.

Less often: Taste impairment, epigastric discomfort, nausea, abdominal pain and rash. Reversible increase in blood urea and creatinine may be observed. Proteinuria has occurred in some patients.

Rarely: Angioneurotic edema and decrease in hemoglobin, red cells and platelets have been reported.

Toxicity

The most likely symptom of overdose is severe hypotension. The most common adverse effects observed in controlled clinical trials include cough, digestive symptoms, fatigue, headache, and dizziness.

Precaution

In the following cases, Perindopril should be used with caution:

Renovascular hypertension
Surgery/Anesthesia
Renal failure: The dose should be cautiously adjusted in accordance with the creatinine clearance
Symptomatic hypotension is rarely seen, but is more likely in volume-depleted patients, those receiving diuretics, or with the first two doses
In diuretic-treated patients: stop the diuretic 3 days before starting Perindopril. A diuretic may later be given in combination if necessary; potassium-sparing diuretics are not recommended
Combination with neuroleptics or imipramine-type drugs may increase the hypotensive effect. Serum lithium concentrations may rise during lithium therapy

Interaction

May enhance hypotensive effect with diuretics. Additive hyperkalaemic effect with K supplements, K-sparing diuretics, and other drugs (e.g. ciclosporin, heparin, indometacin). May increase serum levels and toxicity of lithium. Antihypertensive effect may be reduced by aspirin or other NSAIDs. Coadministration with NSAIDs may also increase the risk of renal impairment. Increased risk of hypoglycaemia with antidiabetic agents. Rarely, nitritoid reactions occur with concomitant use of gold (Na aurothiomalate).

Elimination Route

Rapidly absorbed with peak plasma concentrations occurring approximately 1 hour after oral administration. Bioavailability is 65-75%. Following absorption, perindopril is hydrolyzed to perindoprilat, which has an average bioavailability of 20%. The rate and extent of absorption is unaffected by food. However, food decreases the extent of biotransformation to peridoprilat and reduces its bioavailability by 35%.

Half Life

Perindopril, 1.2 hours; Peridoprilat, 30-120 hours. The long half life of peridoprilat is due to its slow dissociation from ACE binding sites.

Clearance

219 - 362 mL/min [oral administration]

Elimination Route

Perindopril is extensively metabolized following oral administration, with only 4 to 12% of the dose recovered unchanged in the urine.

Pregnancy & Breastfeeding use

Perindopril should not be used during pregnancy & lactation.

Contraindication

Perindopril is contraindicated in patients with a history of hypersensitivity to Perindopril. This drug is contraindicated in case of management of hypertension of Children, during Pregnancy & Lactation.

Acute Overdose

Symptoms: Hypotension, bradycardia, circulatory shock, renal failure, hyperventilation, electrolyte disturbances, tachycardia, palpitations, dizziness, anxiety, and cough.

Management: Symptomatic and supportive. IV infusion of NaCl 0.9%. Treatment with angiotensin II infusion and/or IV catecholamines may also be considered. Haemodialysis may be beneficial.