Quinapril

Quinapril is an antihypertensive agent belonging to angiotensin-converting enzyme (ACE) inhibitors.

Quinapril is approved for the treatment of Hypertension and Heart failure with reduced ejection fraction. It is also used to treat Diabetic Nephropathy.

High-fat meal reduces absorption with approx 60% of an oral dose absorbed and enters breast milk with small amounts and Plasma protein binding of approx 97%. It is hepatically hydrolyzed to form Quinapril (active metabolite) and inactive metabolites.

And gets excreted via urine and feces, and terminal half-life: 3 hr.

The more common side effect that can occur with Quinapril includes cough, runny or stuffy nose; Muscle or joint pain; Dizziness, headache, tired feeling, Nausea, vomiting, diarrhea, or Mild skin itching or rash. Etc,.

Quinapril is available in the form of dosage forms as tablets.

Quinapril is available in India, China, Italy, and the USA.

Quinapril is a prodrug of quinaprilat. It is a competitive inhibitor of ACE. It prevents the conversion of angiotensin I to angiotensin II (a potent vasoconstrictor), resulting in lower levels of angiotensin II, which causes an increase in plasma renin activity and a reduction in aldosterone (a hormone that causes water and Na retention) secretion. This promotes vasodilation and BP reduction.

Quinaprilat prevents the conversion of angiotensin I to angiotensin II by inhibition of angiotensin-converting enzyme, and also reduces the breakdown of bradykinin.1,2 Reduced levels of angiotensin II lead to lower levels of PAI-1, reducing the risk of thrombosis, especially after a myocardial infarction.

The onset of action of Quinapril occurs within 1 hour.

The Duration of action of Quinapril in the body is 24 hours.

The Tmax was found within 4 hours following the administration of Quinapril, and Cmax was reached within 302.64±0.07 ng/mL.

Quinapril is available in the form of tablets.

Quinapril tablets are to be swallowed whole with water.

Quinapril is approved for the treatment of Hypertension and Heart failure with reduced ejection fraction. It is also used to treat Diabetic Nephropathy.

Quinapril is an angiotensin-converting enzyme (ACE) inhibitor. It works by blocking a substance in the body that causes blood vessels to tighten. As a result, Quinapril relaxes the blood vessels. This lowers blood pressure and increases the supply of blood and oxygen to the heart.

Quinapril is approved for the use in the following clinical indication.

Heart failure with reduced ejection fraction:

Treatment of heart failure.

Hypertension:

It is used in the treatment of hypertension. It may be used alone or in Combination with thiazide diuretics.

Quinapril is available in the form of tablets in potencies of 5 mg, 10 mg, 20 mg, 40 mg.

Hypertension

Initial: 10-20 mg taken orally quarterly ; may administer 5 mg in patients receiving diuretic therapy if the diuretic is continued

Maintenance: 20-80 mg taken orally quarterly or divided every 12 hour

Congestive Heart Failure

Initial: 5 mg taken orally every 12 hour

Maintenance: 20-40 mg taken orally quarterly or divided every 12 hour

Diabetic Nephropathy (Off-Label)

Slows rate of progression of renal disease in patients with HTN, DM, and microalbuminuria

Initial: 10-20 mg taken orally quarterly

Maintenance: 20-80 mg taken orally quarterly or divided every 12 hour

Quinapril can be administered orally after meals. The dosage and the duration of treatment should be as per the clinical judgment of the treating physician).

Quinapril is available in various dosage strengths as 5 mg, 10 mg, 20 mg, 40 mg.

Quinapril is available in the form of tablets.

• Dose Adjustment in the pediatric patient:

Hypertension:

Children and Adolescents:

Oral: Initial: 5 mg once daily; may titrate every 2 weeks; maximum daily dose: 80 mg/day; for younger patients or those who are small for age, begin at the lower end of range. A pharmacokinetic analysis of a 0.2 mg/kg single-dose in 24 pediatric patients <7 years of age, reported similar serum concentrations to those in adults who received a single 10 mg dose; long-term, weight-based efficacy and safety data are lacking.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Quinapril is approved for the treatment of Heart failure with reduced ejection fraction and Hypertension. It is also used to treat HIV-associated Nephropathy.

Hypertension: It has been observed that the low-salt Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure. Sometimes after a few weeks, its effects on blood pressure become noticeable.

The dietary restriction should be individualized as per patient requirements.

Quinapril may be contraindicated in the following:

Hypersensitivity to Quinapril or any component of the formulation; angioedema related to previous treatment with an ACE inhibitor;

Concomitant use with aliskiren in patients with diabetes mellitus; concomitant use with neprilysin inhibitor (eg, sacubitril) or within 36 hours of switching to or from neprilysin inhibitor.

Documentation of allergenic cross-reactivity for ACE inhibitors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows

Concerns related to adverse effects:

• Cholestatic jaundice: A rare toxicity associated with ACE inhibitors includes cholestatic jaundice, although there are no published reports with Quinapril.

• Hypersensitivity reactions: Anaphylaxis/nonimmune anaphylaxis can occur with ACE inhibitors. Severe nonimmune anaphylaxis may be seen during hemodialysis (eg, CVVHD) with high-flux dialysis membranes (eg, AN69), and rarely, during low density lipoprotein apheresis with dextran sulfate cellulose. Rare cases of nonimmune anaphylaxis have been reported in patients undergoing sensitization treatment with Hymenoptera (bee, wasp) venom while receiving ACE inhibitors.

• Hypotension/syncope: Symptomatic hypotension with or without syncope can occur with ACE inhibitors (usually with the first several doses). Effects are most often observed in volume-depleted patients; correct volume depletion prior to initiation. Close monitoring of patient is required, especially with initial dosing and dosing increases. Blood pressure must be lowered at a rate appropriate for the patient’s clinical condition. Although dose reduction may be necessary, hypotension is not a reason for discontinuation of future ACE inhibitor use, especially in patients with heart failure where a reduction in systolic blood pressure is a desirable observation.

Disease-related concerns:

• Aortic stenosis: Use with caution in patients with severe aortic stenosis; may reduce coronary perfusion resulting in ischemia.

• Ascites: Generally, avoid use in patients with ascites due to cirrhosis or refractory ascites; if use cannot be avoided in patients with ascites due to cirrhosis, monitor BP and renal function carefully to avoid rapid development of renal failure

• Cardiovascular disease: Initiation of therapy in patients with ischemic heart disease or cerebrovascular disease warrants close observation due to the potential consequences posed by falling blood pressure (eg, MI, stroke). Fluid replacement, if needed, may restore blood pressure; therapy may then be resumed. Discontinue therapy in patients whose hypotension recurs.

• Hypertrophic cardiomyopathy with left ventricular outflow tract obstruction: Use with caution in patients with hypertrophic cardiomyopathy and left ventricular outflow tract obstruction since reduction in afterload may worsen symptoms associated with this condition.

• Renal impairment: Use with caution in patients with renal impairment; dosage adjustment may be needed. Avoid rapid dosage escalation which may lead to further renal impairment.

Special populations:

• Race/Ethnicity: In Black patients, the BP-lowering effects of ACE inhibitors may be less pronounced. The exact mechanism is not known; differences in the renin-angiotensin-aldosterone system, low renin levels, and salt sensitivity more commonly found in Black patients may contribute (Brewster 2013; Helmer 2017).

• Surgical patients: In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension; however, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent (Hillis 2011). Based on current research and clinical guidelines in patients undergoing non-cardiac surgery, continuing ACE inhibitors is reasonable in the perioperative period. If ACE inhibitors are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible.

Drinking alcohol while taking the Quinapril can increase drowsiness and dizziness, which in turn increases the risk of accidental injury.

Quinapril use in breastfeeding patients is not recommended.

Pregnancy Category D

The use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Quinapril as soon as possible. These adverse outcomes are usually associated with the use of these drugs in the second and third trimester of pregnancy. Most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. Appropriate management of maternal hypertension during pregnancy is important to optimize outcomes for both mother and fetus.

In the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. Perform serial ultrasound examinations to assess the intra-amniotic environment. If oligohydramnios is observed, discontinue Quinapril, unless it is considered life-saving for the mother. Fetal testing may be appropriate, based on the week of pregnancy. Patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. Closely observe infants with histories of in utero exposure to Quinapril for hypotension, oliguria, and hyperkalemia.

Potassium-Rich Foods: Bananas, sweet potatoes, nuts, and other foods rich in potassium when taken along with Quinapril, can be led to an increase in blood potassium levels.

Pleurisy Root: Pleurisy roots are not recommended with most heart medications due to the cardiac glycoside content of the root.

The adverse reactions related to molecule Quinapril can be categorized as

• Common Adverse effects:

Body aches or pain, Chills, Cough, Difficulty breathing, Ear congestion, Fever, Headache, Loss of voice, Nasal congestion, Runny nose, Sneezing, Sore throat, Unusual tiredness or weakness etc,

• Less Common adverse effect:

Bladder pain, bloody or cloudy urine, change in hearing, chest pain, cold, congestion, diarrhea, difficult, burning, or painful urination, dryness of the throat, earache or pain in the ear, ear drainage, etc.

• Rare adverse effects:

Agranulocytosis, bone marrow suppression, epistaxis, Raynaud’s phenomenon etc.

The clinically relevant drug interactions of Quinapril is briefly summarized here:

Additive hyperkalemic effects w/ K-sparing diuretics, K supplements, and other drugs that can cause hyperkalemia. Increased lithium concentrations and toxicity. May decrease absorption of tetracyclines. May increase nitritoid reactions of gold Na thiomalate.

Potentially Fatal: Increased risk of hypotension, hyperkalemia and nephrotoxicity w/ concomitant aliskiren in renally impaired and diabetic patients.

The common side of Quinapril include the following

Body aches or pain, Chills, Cough, Difficulty breathing, Ear congestion, Fever, Headache, Loss of voice, Nasal congestion, Runny nose, Sneezing, Sore throat, Unusual tiredness or weakness etc,

Race/Ethnicity:

In Black patients, the BP-lowering effects of ACE inhibitors may be less pronounced. The exact mechanism is not known; differences in the renin-angiotensin-aldosterone system, low renin levels, and salt sensitivity more commonly found in Black patients may contribute .

Surgical patients:

In patients on chronic ACE inhibitor therapy, intraoperative hypotension may occur with induction and maintenance of general anesthesia; use with caution before, during, or immediately after major surgery. Cardiopulmonary bypass, intraoperative blood loss, or vasodilating anesthesia increases endogenous renin release. Use of ACE inhibitors perioperatively will blunt angiotensin II formation and may result in hypotension; however, discontinuation of therapy prior to surgery is controversial. If continued preoperatively, avoidance of hypotensive agents during surgery is prudent . Based on current research and clinical guidelines in patients undergoing non-cardiac surgery, continuing ACE inhibitors is reasonable in the perioperative period. If ACE inhibitors are held before surgery, it is reasonable to restart postoperatively as soon as clinically feasible

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

There is no FDA guidance on the use of Quinapril in geriatric settings.

Symptoms: Severe hypotension.

Management: Supportive treatment and IV volume expansion.

Pharmacodynamics:

Quinapril is a prodrug of an angiotensin-converting enzyme (ACE) inhibitor used in the treatment of hypertension or adjunct in the treatment of heart failure. Quinapril has a wide therapeutic window and a long duration of action as it is given in doses of 10-80mg once daily. Quinaprilat prevents the conversion of angiotensin I to angiotensin II by inhibition of angiotensin-converting enzyme, and also reduces the breakdown of bradykinin. Reduced levels of angiotensin II lead to lower levels of PAI-1, reducing the risk of thrombosis, especially after a myocardial infarction.

Pharmacokinetics:

Absorption: High fat meal reduces absorption. Approx 60% of an oral dose is absorbed. Time to peak plasma concentration: Approx 2 hr (as quinaprilat).

Distribution: Enters breast milk (small amounts). Plasma protein binding: Approx 97%.

Metabolism: Hepatically hydrolyzed to form quinaprilat (active metabolite) and inactive metabolites.

Excretion: Via urine (50-60% as quinaprilat) and faeces. Terminal half-life: 3 hr (quinaprilat).

• https://www.rxlist.com/Quinapril -drug.htm
• https://reference.medscape.com/drug/Quinapril -ranQuinapril -Quinapril -342328
• https://go.drugbank.com/drugs/DB00492
• https://www.mayoclinic.org/drugs-supplements/Quinapril -oral-route/proper-use/drg-20069186
• https://www.drugs.com/mtm/Quinapril .html