Quinapril (Brand name: Accupril) is an angiotensin converting enzyme inhibitor (ACE inhibitor).
ACE inhibitors work by widening blood vessels in the body, which can lower pressure in the blood vessels.
Quinapril is used in the treatment of hypertension and heart failure.
 BRAND NAMES
- Australia: Accupril Consumer Medicine Information
- Italy: Accuprin, Acequin, Quinazil
- U.S.: Accupril PI
 MECHANISM OF ACTION
Quinapril is an ACE inhibitor. (Angiotensin Converting Enzyme Inhibitor) ACE inhibitors acts by:
- Inhibiting the formation of angiotensin II from the inactive angiotensin I. Angiotensin II is a potent vasoconstrictor that leads to increased blood pressure.
- ACE catalyses the breakdown of bradykinin (a powerful vasodilator). Therefore, ACE inhibitors, by inhibiting bradykinin metabolism, increase bradykinin levels, which can contribute to the vasodilator activity
- Angiotensin II promotes aldosterone release which normally acts to retain sodium and water. Due to reduced angiotensin production, plasma concentrations of aldosterone are also reduced, resulting in increased excretion of sodium in the urine and increased concentrations of potassium in the blood.
Quinapril is converted to its principal active metabolite, Quinaprilat by hepatic cleavage of the ester group.
- Treatment of hypertension, alone or in combination with other antihypertensive agents, especially thiazide-like diuretics. (ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks)
- Management of heart failure as adjunctive therapy when added to conventional therapy including diuretics and/or digitalis.
- Hypertension: The recommended initial dose in patients not on diuretics is 10-20 mg once a day. Dosage should be adjusted according to blood pressure response. Most patients have required dosages of 20, 40, or 80 mg/day, given as a single dose or in two equally divided doses. in some patients, treated once daily the antihypertensive effect may diminish toward the end of the dosing interval. In such patients, daily dosage should be given in two equally divided doses.
- Patients whose blood pressures are not adequately controlled with quinapril monotherapy may instead be given quinapril HCl/hydrochlorothiazide 10/12.5 or 20/12.5. Further increases of either or both components could depend on clinical response. The hydrochlorothiazide dose should generally not be increased until 2 to 3 weeks have elapsed. Patients whose blood pressures are adequately controlled with 25 mg of daily hydrochlorothiazide, but who experience significant potassium loss with this regimen, may achieve blood pressure control with less electrolyte disturbance if they are switched to quinapril HCl/hydrochlorothiazide 10/12.5 or 20/12.5.
- Heart failure: The recommended initial dose is 5 mg twice daily. if the initial dosage is well tolerated, patients should then be titrated at weekly intervals until an effective dose, usually 20 to 40 mg daily given in two equally divided doses, is reached or undesirable hypotension, orthostatis, or azotemia prohibit reaching this dose.
- Hypersensitivity to Quinapril
- Patients with a history of angioedema related to previous treatment with an angiotensin converting enzyme inhibitor.
- Coadministration of aliskiren in patients with diabetes.
- Pregnancy and lactation
Anaphylactoid and Possibly Related Reactions
Head and Neck Angioedema: Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with ACE inhibitors and has been seen in 0.1% of patients receiving Quinapril. Angioedema associated with laryngeal edema can be fatal. If laryngeal stridor or angioedema of the face, tongue, or glottis occurs, treatment with Quinapril should be discontinued immediately, the patient treated in accordance with accepted medical care, and carefully observed until the swelling disappears. In instances where swelling is confined to the face and lips, the condition generally resolves without treatment; antihistamines may be useful in relieving symptoms. Where there is involvement of the tongue, glottis, or larynx likely to cause airway obstruction, emergency therapy including, but not limited to, subcutaneous epinephrine solution 1:1000 (0.3 to 0.5 mL) should be promptly administered. Patients taking concomitant mTOR inhibitor (e.g. temsirolimus) therapy may be at increased risk for angioedema.
Intestinal Angioedema Intestinal angioedema has been reported in patients treated with ACE inhibitors. These patients presented with abdominal pain (with or without nausea or vomiting); in some cases there was no prior history of facial angioedema and C-1 esterase levels were normal. The angioedema was diagnosed by procedures including abdominal CT scan or ultrasound, or at surgery, and symptoms resolved after stopping the ACE inhibitor. Intestinal angioedema should be included in the differential diagnosis of patients on ACE inhibitors presenting with abdominal pain.
Patients with a history of angioedema Patients with a history of angioedema unrelated to ACE inhibitor therapy may be at increased risk of angioedema while receiving an ACE inhibitor.
Rarely, ACE inhibitors have been associated with a syndrome that starts with cholestatic jaundice and progresses to fulminant hepatic necrosis and (sometimes) death. The mechanism of this syndrome is not understood. Patients receiving ACE inhibitors who develop jaundice or marked elevations of hepatic enzymes should discontinue the ACE inhibitor and receive appropriate medical follow-up.
Excessive hypotension is rare in patients with uncomplicated hypertension treated with Quinapril alone. Patients with heart failure given Quinapril commonly have some reduction in blood pressure, but discontinuation of therapy because of continuing symptomatic hypotension usually is not necessary when dosing instructions are followed.
Another ACE inhibitor, captopril, has been shown to cause agranulocytosis and bone marrow depression rarely in patients with uncomplicated hypertension, but more frequently in patients with renal impairment, especially if they also have a collagen vascular disease, such as systemic lupus erythematosus or scleroderma. Agranulocytosis did occur during Quinapril treatment in one patient with a history of neutropenia during previous captopril therapy. Available data from clinical trials of Quinapril are insufficient to show that, in patients without prior reactions to other ACE inhibitors, Quinapril does not cause agranulocytosis at similar rates. As with other ACE inhibitors, periodic monitoring of white blood cell counts in patients with collagen vascular disease and/or renal disease should be considered.
Impaired renal function
As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients with severe heart failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone system, treatment with ACE inhibitors, including Quinapril, may be associated with oliguria and/or progressive azotemia and rarely acute renal failure and/or death. In clinical studies in hypertensive patients with unilateral or bilateral renal artery stenosis, increases in blood urea nitrogen and serum creatinine have been observed in some patients following ACE inhibitor therapy. These increases were almost always reversible upon discontinuation of the ACE inhibitor and/or diuretic therapy. In such patients, renal function should be monitored during the first few weeks of therapy. Some patients with hypertension or heart failure with no apparent preexisting renal vascular disease have developed increases in blood urea and serum creatinine, usually minor and transient, especially when Quinapril has been given concomitantly with a diuretic. This is more likely to occur in patients with preexisting renal impairment. Dosage reduction and/or discontinuation of any diuretic and/or Quinapril may be required. Evaluation of patients with hypertension or heart failure should always include assessment of renal function (see DOSAGE AND ADMINISTRATION).
Hyperkalemia and potassium-sparing diuretics
In clinical trials, hyperkalemia (serum potassium ≥5.8 mmol/L) occurred in approximately 2% of patients receiving Quinapril. In most cases, elevated serum potassium levels were isolated values which resolved despite continued therapy. Less than 0.1% of patients discontinued therapy due to hyperkalemia. Risk factors for the development of hyperkalemia include renal insufficiency, diabetes mellitus, and the concomitant use of potassium-sparing diuretics, potassium supplements, and/or potassium-containing salt substitutes, which should be used cautiously, if at all, with Quinapril.
Presumably due to the inhibition of the degradation of endogenous bradykinin, persistent non-productive cough has been reported with all ACE inhibitors, always resolving after discontinuation of therapy. ACE inhibitor-induced cough should be considered in the differential diagnosis of cough.
In patients undergoing major surgery or during anesthesia with agents that produce hypotension, Quinapril will block angiotensin II formation secondary to compensatory renin release. If hypotension occurs and is considered to be due to this mechanism, it can be corrected by volume expansion.
Angioedema, including laryngeal edema can occur with treatment with ACE inhibitors, especially following the first dose. Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) and to stop taking the drug until they have consulted with their physician.
Patients should be cautioned that lightheadedness can occur, especially during the first few days of Quinapril therapy, and that it should be reported to a physician. If actual syncope occurs, patients should be told to not take the drug until they have consulted with their physician. All patients should be cautioned that inadequate fluid intake or excessive perspiration, diarrhea, or vomiting can lead to an excessive fall in blood pressure because of reduction in fluid volume, with the same consequences of lightheadedness and possible syncope. Patients planning to undergo any surgery and/or anesthesia should be told to inform their physician that they are taking an ACE inhibitor.
Patients should be told not to use potassium supplements or salt substitutes containing potassium without consulting their physician
Patients should be told to report promptly any indication of infection (eg, sore throat, fever) which could be a sign of neutropenia. NOTE: As with many other drugs, certain advice to patients being treated with Quinapril is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.
- Patients on diuretics may experience an excessive reduction of blood pressure.
- Caution is advised if non steroidal antiinflammatory drugs NSAIDs are prescribed with ACE inhibitors. (Concomitant use of NSAIDS may result in decreased ACE inhibitor effectiveness). In some patients with compromised renal function who are being treated with NSAIDS, the co-administration of ACE inhibitors may result in further deterioration of renal function. Cases of acute renal failure, usually reversible, have also been reported.
- Potassium-sparing diuretics (eg, spironolactone, triamterene, or amiloride) and potassium supplements may have an additive effect on potassium retention, resulting in hyperkalemia.
- Lithium carbonate: Increased serum lithium levels and symptoms of lithium toxicity has been reported when used in combination with ACE inhibitors.
 PREGNANCY AND LACTATION
- Pregnancy Category D (US). ACE inhibitors can cause fetal and neonatal morbidity and mortality when administered to pregnant women (espacially in the second and third trimester of pregnancy). When pregnancy is detected, Quinapril should be discontinued as soon as possible.
- Nursing Mothers: Because Quinapril is secreted in human milk, caution should be exercised when this drug is administered to a nursing woman.
 SIDE EFFECTS
ACE inhibitors are usually well tolerated. Possible side effects include: Dry irritant cough attributable to accumulation of bradykinin, dizziness, impotence, hypotension (especially during the first days of therapy), chest pain, fatigue, headache and diarrhea.
- Risk of hyperkalaemia due to potassium retention (rarely and especially in patients with renal dysfunction)
- Angioedema of the face, extremities, lips, tongue, glottis, and larynx has been reported in patients treated with ACE inhibitors (rare but potentially fatal).
- Skin rashes (rare)
 RELATED LINKS
|ACE inhibitors||Benazepril (Lotensin) • Captopril (Capoten) • Cilazapril • Delapril • Enalapril (Renitec, Vasotec) • Fosinopril (Monopril) • Lisinopril (Prinivil, Zestril) • Moexipril (Univasc) • Perindopril (Aceon) • Quinapril (Accupril) • Ramipril (Altace, Triatec) • Trandolapril (Mavik) • Zofenopril (Bifril, Zopranol)|
|Angiotensin II receptor antagonist||Azilsartan (Edarbi) • Candesartan (Atacand) • Eprosartan (Teveten) • Irbesartan (Aprovel, Avapro, Karvea) • Losartan (Cozaar) • Olmesartan (Benicar, Olmetec) • Telmisartan (Micadis) • Valsartan (Diovan, Tareg)|
|Renin inhibitors||Aliskiren (Rasilez, Tekturna)|
|Alpha-1 blockers||Doxazosin (Cardura) • Prazosin (Minipress) • Terazosin (Hytrin)|
|Alpha-2 agonists (centrally acting)||Clonidine (Oral route) • Clonidine (Transdermal) (Catapresan) • Guanfacine (Tenex) • Methyldopa (Aldomet)|
|Calcium channel blockers||Dihydropyridines||Amlodipine (Norvasc) • Barnidipine (Vasexten) • Felodipine (Plendil) • Isradipine (Dynacirc) • Lacidipine (Lacipil, Motens) • Lercanidipine (Zanidip) • Manidipine • Nicardipine • Nifedipine (Adalat) • Nisoldipine • Nitrendipine|
|Benzothiazepine||Diltiazem (Cardizem, Taztia XT, Tiazac, Tildiem)|
|Phenylalkylamine||Gallopamil • Verapamil (Calan)|
|Beta blockers||Beta1 selective (cardioselective)||Acebutolol (Sectral) • Atenolol (Tenormin) • Betaxolol (Kerlon) • Bisoprolol (Concor) • Celiprolol (Cordiax) • Metoprolol (Betaloc, Lopressor, Toprol-XL) • Nebivolol (Bystolic, Lobivon, Nebilox)|
|Nonselective (Beta1 and Beta2 blockers)||Oxprenolol (Trasitensin) • Propranolol (Inderal) • Timolol (Blocadren)|
|Nonselective (Beta1, Beta2 and Alpha1 blockers)||Carvedilol (Dilatrend) • Labetalol (Trandate)|
|Beta blocker with intrinsic sympathomimetic activity (ISA)||Acebutolol (Sectral) • Celiprolol (Cordiax)|
|Lipophilic Beta blockers||Propranolol (Inderal) • Metoprolol (Betaloc, Lopressor, Toprol-XL) • Oxprenolol (Trasitensin)|
|Diuretics||Carbonic anhydrase inhibitors||Acetazolamide (Diamox)|
|Loop diuretics||Bumetanide • Etacrynic acid • Furosemide (Lasix) • Piretanide • Torasemide (Demadex)|
|Thiazide diuretics||Chlorothiazide (Diuril) • Hydrochlorothiazide (Esidrex)|
|Thiazide-like diuretics||Chlortalidone (Hygroton) • Indapamide (Lozol, Lozide) • Metolazone|
|Potassium-sparing diuretics|| Epithelial sodium channel blockers: Amiloride (Midamor) • Triamterene (Dyrenium) |
Aldosterone receptor antagonists: Potassium canrenoate • Eplerenone (Inspra) • Spironolactone (Aldactone)
|Combination therapy||Amiloride/Hydrochlorothiazide (Moduretic) • Spironolactone/Hydrochlorothiazide (Aldactazide)|