Quinapril: Angiotensin-converting enzyme inhibitor, Accupril, Acenor 10, Quinapril 5, Tapzill

2021-06-21 04:17 AM

Quinapril lowers blood pressure by reducing total peripheral vascular resistance and renal vascular resistance, but with little or no change in heart rate, cardiac indices, and renal blood flow.

International generic name: Quinapril

Type of drug: Angiotensin-converting enzyme inhibitor.

Drug form and strength

Tablets: 5 mg, 10 mg, 20 mg, 40 mg on quinapril base.

Pharmacology and mechanism of action

Quinapril is an angiotensin-converting enzyme inhibitor used to treat high blood pressure and heart failure. In the body, quinapril is converted to the active substance quinaprilat. Angiotensin-converting enzyme (ACE) converts angiotensin I into angiotensin II, a vasoconstrictor. At the same time, angiotensin II also stimulates the adrenal cortex to secrete aldosterone, increasing the reabsorption of sodium and water in the kidneys. By inhibiting ACE activity, quinapril reduces angiotensin II formation and aldosterone. In addition to the above effect, ACE inhibitors also prevent the breakdown of bradykinin - a potent vasodilator peptide. As a result, quinapril dilates blood vessels, reduces peripheral resistance, reduces sodium and water retention, and lowers blood pressure. However, due to a decrease in aldosterone secretion, quinapril may cause mild hyperkalemia (mean increase of 0.07 mmol/l), while increased bradykinin levels are responsible for some of the ADRs of ACE inhibitors. dry cough).

Treatment of hypertension: Quinapril is used as monotherapy or in combination with other antihypertensive agents. In a single dose of 20 mg as monotherapy, quinapril inhibited more than 80% of blood ACE activity for 24 hours. In doses of 10 to 80 mg in mild to severe hypertension, quinapril reduced sitting and standing blood pressure to a similar extent, but with little effect on heart rate. Orthostatic hypotension is rare, but may occur in individuals with hyponatremia and/or hypovolemia. The antihypertensive effect begins within 1 hour, is strongest 2 to 4 hours after oral administration, and persists for 24 hours. With prolonged treatment, the antihypertensive effect reaches its peak after 1-2 weeks.

Quinapril did not lose potency with prolonged use and there was no recurrence of severe disease upon discontinuation of the drug.

Quinapril lowers blood pressure by reducing total peripheral vascular resistance and renal vascular resistance, but little or no change in heart rate, cardiac index, renal blood flow, glomerular filtration rate, or fraction filter.

Co-administration of quinapril with thiazide diuretics resulted in greater hypotension than monotherapy.

Treatment of congestive heart failure: As with other angiotensin-converting enzyme inhibitors, quinapril is the first-line drug for the treatment of stage I (asymptomatic) to stage IV (severe) congestive heart failure. In addition to increasing dose beta-adrenergic receptor blockers, it is recommended to be administered with ACE inhibitors, while diuretics and digitalis are used in cases of edema and/or tachycardia, i.e. in stages II-III.

The mechanism of action of quinapril, like that of other ACE inhibitors, is vasodilation, thereby reducing afterload and preload, reducing the burden on the heart. Long-term use, ACE inhibitors also reduce myocardial hypertrophy, thereby protecting the heart.

Treatment of diabetic nephropathy and general renal failure: This has been confirmed by numerous clinical trials. Particularly for renal failure, the dose should be reduced when the serum creatinine level is higher than 200 micromol/liter because too low blood pressure can aggravate renal failure.

Pharmacokinetics

Following oral administration, quinapril is approximately 60% absorbed, reaching peak plasma concentrations within 1 hour. The presence of food does not affect the extent of absorption but may increase the time to peak drug concentrations. The rate and extent of absorption of quinapril is reduced by about 25 to 30% when taken with a high-fat meal.

After absorption, quinapril is extensively metabolized in the liver to the main active metabolite quinaprilat (approximately 38% of the oral dose) and other inactive metabolites. Peak concentrations of quinaprilat are reached within 2 hours of oral administration. Approximately 97% of quinapril or quinaprilat is bound to plasma proteins. After taking a single dose of quinapril, the effect begins within 1 hour, peaks in 2-4 hours, and lasts 24 hours.

Quinapril is eliminated mainly in the urine and partly in the faeces in three forms: Quinaprilat, other metabolites, and unchanged drug.

The pharmacokinetics of quinapril and quinaprilat are affected in renal or hepatic impairment. The elimination half-life of quinapril is 0.8 hours and that of quinaprilat is 3 hours. The plasma concentrations and half-life of quinaprilat are increased when Clcr < 40 ml/min. The drug is excreted slowly in the elderly due to a decrease in physiological renal function with age. In cirrhotic patients, quinapril is poorly hydrolyzed, so quinaprilat blood levels decrease. Hemodialysis has little effect on the elimination of quinapril or quinaprilat.

Small amounts of quinapril are distributed into breast milk.

Indications

Hypertension (used as monotherapy or in combination with other antihypertensive drugs (thiazide diuretics, calcium channel blockers...).

Congestive heart failure (as monotherapy or in combination with diuretics and/or digitalis).

Diabetic nephropathy with hypertension, with microalbuminuria.

Contraindications

Hypersensitivity to quinapril or any of the ingredients.

aliskiren in combination with quinapril should not be used in diabetic patients with hypertension.

History of angioedema associated with ACE inhibitor therapy.

Pregnant woman.

Use should be avoided in patients with known or suspected renal vascular disease such as bilateral renal artery stenosis or renal artery stenosis in a single kidney, renal transplant recipients, peripheral vascular disease or severe systemic atherosclerosis.

Caution

There is cross-sensitivity between ACE inhibitors. Patients who are sensitive to an ACE inhibitor may also be sensitive to other drugs in this class.

ACE inhibitors, including quinapril, can cause angioedema, especially after the first dose. If angioedema is accompanied by laryngeal edema, it can be fatal. Therefore, if there is swelling in the face, tongue, or glottis of the larynx, laryngeal stridor, the drug must be stopped immediately, treated appropriately, and closely monitored. Intestinal angioedema may occur in patients receiving ACE inhibitors (usually unrelated to a history of facial angioedema or C1 complement elevation.) Intestinal angioedema usually presents with abdominal pain (with or without nausea, vomiting), usually diagnosed by CT scan, ultrasound, or abdominal surgery, this side effect resolves with discontinuation of the ACE inhibitor. The possibility of intestinal angioedema should be considered in patients with other diagnoses but present. abdominal pain while taking ACE inhibitors.

Caution should be exercised in patients with hereditary or idiopathic angioedema due to the increased risk of angioedema associated with ACE inhibitors.

Caution should be exercised in patients with a history of angioedema unrelated to ACE inhibitors.

People with severely reduced kidney function. Due to inhibition of the renin-angiotensin-aldosterone (RAA) system, decreased renal function and renal failure with or without a fatal outcome in hypertensive patients (particularly in patients with activity-dependent renal function). RAA system, as in patients with congestive heart failure). Manifestations of impaired renal function are expressed by increased blood urea, increased creatinine in patients taking ACE inhibitors, especially in hypertensive patients with unilateral or bilateral renal artery stenosis, patients with pre-existing renal failure that has been or is being combined with diuretics.

This ADR is reversible upon discontinuation of the ACE inhibitor and/or combination diuretic.

There is a risk of severe hypotension that can cause syncope with ACE inhibitors in patients with heart failure, hyponatremia, high dose diuretics, renal dialysis, or severe hypovolemia and/or salt depletion.

Severe hypotension with oliguria and/or uremia and fatal acute renal failure may occur in patients with congestive heart failure. In these patients, close monitoring is required during the first dose and during the first 2 weeks of treatment. If hypotension is excessive, an intravenous infusion of 0.9% sodium chloride solution is required.

Concomitant use of potassium-sparing diuretics or potassium-sparing diuretics in patients with diabetes and renal insufficiency increases the risk of quinapril hyperkalemia.

Check renal function and electrolytes before dosing and during treatment with quinapril.

Patients with renal insufficiency or autoimmune disease, especially diseases of the collagen vascular system such as systemic lupus erythematosus, scleroderma, and bone marrow failure: Increased risk of neutropenia or agranulocytosis seeds of quinapril. Instruct the patient to go to the doctor immediately when there are signs of infection, fever, sore throat... because it may be due to neutropenia. The number of white blood cells in the patient's blood should be checked periodically.

During major surgery or during anesthesia with antihypertensive agents, it should be noted that quinapril blocks the formation of angiotensin II, causing secondary renin release, leading to a marked decrease in blood pressure, which should be corrected by volume expansion.

Quinapril should be used with caution in patients with severe or symptomatic arterial stenosis (due to the risk of hypotension) and in patients with myocardial hypertrophy.

Impaired liver function: Patients should be closely monitored because they may cause obstructive jaundice, hepatocellular necrosis.

Impaired renal function: Caution should be exercised when quinapril is used in patients with renal impairment. Hyperkalemia and other adverse events often occur, requiring a reduction in the dose of the drug.

In hypertensive patients, renal function is often reduced with the use of ACE inhibitors. Efficacy and safety have not been established in patients with glomerular filtration rates less than 10 ml/min.

Pregnancy period

ACE inhibitors cross the placenta. The use of ACE inhibitors during the first trimester of pregnancy increases the risk of congenital abnormalities in the fetus, and during the second and third trimesters of pregnancy can cause increased mortality and morbidity. The incidence in fetuses and neonates includes hypotension, renal failure, anuria, craniocervical hypoplasia. Low amniotic fluid in the mother may be due to decreased renal function of the fetus.

ACE inhibitors should be discontinued as soon as possible when pregnancy is detected.

Breastfeeding period

Small amounts of quinapril are excreted in human milk, and caution should be exercised during lactation.

Quinapril should not be used for several weeks postpartum, especially in preterm birth, because of the risk of hypotension in the infant. If it is necessary to administer the drug to a nursing mother, the infant's blood pressure should be monitored.

Adverse Effects (ADRs)

When treating hypertension, ADRs are usually mild and transient. Cases of stopping treatment because of ADR were about 4.7% in hypertensive patients, 6.8% in patients with congestive heart failure.

Common, ADR > 1/100.

Persistent dry cough: Usually occurs during treatment, lasts throughout the treatment period, and resolves within a few days after stopping the drug.

Headache.

Increased serum creatinine and urea nitrogen (BUN) (more increased in patients taking quinapril in combination with diuretics).

Hyperkalemia ( 5.8 mmol/l) occurs in approximately 2% of patients receiving quinapril, but in less than 0.1% of patients discontinuing therapy because of hyperkalemia.

Uncommon, 1/1 000 < ADR < 1/100

Cardiovascular: Hypotension (especially after initial dose in hyponatremic or hypovolemic patients, or in congestive heart failure), palpitations, tachycardia.

Neurological: Somnolence, syncope, insomnia, agitation, depression, paresthesia.

Gastrointestinal: Nausea, taste disturbance, flatulence, dry mouth and throat, diarrhea or constipation, abdominal pain.

Skin: Skin rash, itching.

Genital: Impotence.

Musculoskeletal: Joint pain, back pain, muscle pain.

Eyes: Decreased vision, visual disturbances.

Other: fever, fatigue, weakness, edema, sweating, hair loss, pharyngitis.

Rarely, ADR < 1/1000

Cardiovascular: Angioedema, chest pain (often accompanied by severe hypotension), angina, orthostatic hypotension, arrhythmia, cardiogenic shock, vasculitis.

Gastrointestinal: Pancreatitis, gastrointestinal bleeding.

Liver: Increased liver enzymes, cholestatic jaundice, hepatitis, paroxysmal hepatic necrosis.

Skin: Exfoliative dermatitis, photosensitivity, dermatitis, and polymyositis.

Urinary: Acute renal failure, worsening of renal failure, increased creatinine, increased blood urea.

Respiratory: Eosinophilic infiltrates lung disease, sinusitis, rhinitis, sore throat, bronchospasm.

Hematologic: Neutropenia or agranulocytosis (fever, chills), hemolytic anemia, thrombocytopenia.

Metabolic: Severe hyperkalemia, irregular heartbeat

Other: Positive antinuclear antibody reaction, photosensitivity, fever, back pain.

Instructions on how to handle ADR

When angioedema is present with limited swelling of the face, oral mucosa, lips, and extremities, discontinuation of the drug usually requires no treatment, although an H1-antagonist may relieve symptoms.

When capillary edema occurs in the trachea, face, tongue, or throat, emergency treatment is required as follows:

Stop the drug immediately and take the patient to the hospital.

Inject 0.3 - 0.5 ml of adrenaline solution 1/1000 immediately under the skin.

Intravenous hydrocortisone.

Management of severe hypotension: If hypotension occurs while taking the drug, the patient should be placed in the supine position, intravenous infusion of 0.9% sodium chloride solution. If hypotension is symptomatic with hemodynamic compromise, dose reduction or discontinuation of quinapril or diuretics may be required.

If blood urea nitrogen (BUN) and serum creatinine are increased, the dose of the ACE inhibitor should be reduced and/or the diuretic discontinued.

Dosage and Administration

Dosage: The dose of quinapril must be tailored to each patient, on the basis of tolerability and clinical response to the drug.

The safety and efficacy of quinapril in children have not been established.

Oral quinapril is the salt form of quinapril hydrochloride, but the dose is expressed as the base. 10.8 mg of quinapril hydrochloride is equivalent to 10.0 mg of quinapril.

Dosage for adults:

Treatment of high blood pressure:

In non-diuretics, the usual starting dose of quinapril is 10 mg once daily. In patients 65 years of age and older, the starting dose is 2.5 mg once daily. In patients with dehydration and hyponatremia due to pre-existing diuretic use, the starting dose of quinapril is 5 mg once. Because in some people there may be a sharp drop in blood pressure when starting treatment with ACE inhibitors, the first dose should be started at bedtime. Adjust dose according to patient response, but usually slowly, at intervals of at least 2 weeks.

The usual maintenance dose is 20-40 mg/day, administered once or in two equally divided doses. Up to 80 mg/day may be used. If necessary, a potassium-sparing diuretic may be added.

Concomitant Diuretic Therapy: To reduce the risk of possible hypotension in patients taking diuretics, the diuretic should, if possible, be discontinued 2 to 3 days before initiating quinapril.

Thereafter, if quinapril alone does not provide adequate control of blood pressure, the diuretic may be reintroduced cautiously.

If diuretics cannot be discontinued, an initial dose of 2.5 mg quinapril/day should be given under close medical supervision for several hours, until blood pressure is stabilized.

Treatment of congestive heart failure:

Because of the risk of severe hypotension, patients should be closely monitored when initiating quinapril therapy, considering recent diuretic use and the possibility of severe hypovolemia and/or hyponatremia in the patient. patient. Patients with congestive heart failure with or without renal impairment should be closely monitored during the first 2 weeks of treatment with quinapril and whenever the dose of quinapril and/or diuretics is increased.

The usual starting dose in adults with congestive heart failure with normal serum sodium levels and renal function is 5 mg orally twice a day. After the initial dose, the patient should be closely monitored for at least 2 hours for signs of hypotension (≤ 90/60 mmHg) or orthostatic hypotension. If present, wait for blood pressure to stabilize and adjust the initial standard dose of quinapril or reduce the diuretic dose. Adjust weekly dose to an effective dose, usually, a maintenance dose of 10-20 mg/day, administered once or in two equally divided doses. The dose may be increased to a maximum of 40 mg/day.

In patients with congestive heart failure receiving digitalis and/or diuretics, if the patient is volume and sodium hypovolemic, a lower starting dose of quinapril should be used, possibly starting at 2.5 mg.

In patients unable to take oral quinapril, quinaprilat can be administered intravenously, usually 1.25 mg - 10 mg twice daily.

Dosage in renal failure:

In hypertensive patients with renal impairment, the dose must be adjusted according to the degree of renal impairment, and the risk of neutropenia of quinapril must be considered. The recommended starting dose of quinapril in patients with renal impairment is as follows:

Creatinine clearance (ml/min)

Maximum starting dose per day in the treatment of hypertension

Maximum starting dose per day in treatment

> 60 ml/min 10 mg  
> 30 ml/min - 60 ml/min 5 mg  5 mg
10 ml/min - 30 ml/min 2.5 mg 2.5 mg
< 10 ml/min Not enough data to recommend  

 

Subsequent doses should be adjusted according to the individual patient's tolerance and blood pressure response, usually over an interval of at least 2 weeks.

In patients with heart failure with renal failure, the starting dose of quinapril is 5 mg if Clcr > 30 ml/min and 2.5 mg if Clcr is 10 - 30 ml/min, closely monitor the patient. If well tolerated on the first day, then use quinapril twice daily for the following days. In the absence of excessive hypotension or further deterioration of renal function, the weekly dose of quinapril may be increased based on hemodynamic and clinical response.

No dose adjustment of quinapril is required when co-administered with hydrochlorothiazide diuretics in patients with glomerular filtration rate greater than 30 mL/min. In patients with severe renal impairment, the diuretic hydrochlorothiazide should be replaced with a loop diuretic, not the combination of quinapril and hydrochlorothiazide in these patients.

Drug interactions

Concomitant use of alcohol, diuretics, or other antihypertensive agents with ACE inhibitors may enhance the hypotensive effect.

Severe and sudden hypotension may occur within 1 to 5 hours after the initial dose of ACE inhibitors, particularly in patients with hypovolemic and diuretic-induced hyponatremia. Discontinuing diuretics or increasing salt intake cautiously 2 to 3 days before starting quinapril, or a lower starting dose of quinapril will limit this effect. If the patient is taking a diuretic dose greater than 80 mg of furosemide, close monitoring is required when starting the first dose of quinapril, in some patients reducing or discontinuing the minimum diuretic before taking quinapril 24. hours (but cannot be stopped in patients with heart failure due to the risk of pulmonary edema). If high-dose diuretics cannot be discontinued, the patient should be closely monitored for a minimum of 2 hours when quinapril is started or until blood pressure stabilizes.

The use of potassium-sparing diuretics or potassium-containing salts, potassium supplements, and ACE inhibitors increase the risk of hyperkalemia, requiring frequent monitoring of blood potassium levels.

Nonsteroidal anti-inflammatory drugs, especially indomethacin, reduce the antihypertensive effect of ACE inhibitors, increasing the risk of kidney damage.

Allopurinol, cytostatics, procainamide, corticosteroids, or bone marrow inhibitors may increase the risk of developing ADRs with ACE inhibitors, such as neutropenia and/or agranulocytosis, which can be fatal. Concomitant use of ACE inhibitors with lithium results in a reversible increase in serum lithium concentrations and increased lithium toxicity.

Sympathomimetics reduces the antihypertensive effect of ACE inhibitors.

Quinapril may reduce the effect of quinolone antibiotics and tetracycline derivatives.

Tetracycline or other drugs that interact with magnesium when used concurrently with quinapril may be reduced absorption. Absorption of tetracyclines is reduced by about 28-37%, possibly due to the high magnesium content in quinapril tablets.

The effect of quinapril can be reduced by antacids, aprotinin, NSAIDs, salicylates, yohimbine.

Stability and preservation

Store in tightly closed packaging, protected from light, at a temperature of 15 - 30 degrees Celsius.

Overdose and treatment

There are insufficient data on quinapril overdose in humans. Doses of quinapril 1 440 - 4 280 mg/kg caused significant mortality in mice and rats.

Most clinical manifestations are symptoms of severe hypotension.

Treatment of overdose includes volume expansion and treatment of dehydration and electrolyte imbalance.

Hemodialysis and peritoneal dialysis have little effect on the elimination of quinapril and quinaprilat. Angiotensin II is predictable as a specific antidote-antagonist in the treatment of quinapril overdose but has only been used in some studies. Because the hypotensive effect of quinapril is due to vasodilation and hypovolemia, treatment of quinapril overdose is with an infusion of 0.9% sodium chloride solution.

Tradenames

Accupril; Acenor 10; Quinapril 5; Tapzill.