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Quinapril


Quinapril

Article Author:
Nitin Tandan
Article Editor:
Manouchkathe Cassagnol
Updated:
5/6/2020 10:15:14 AM
For CME on this topic:
Quinapril CME
PubMed Link:
Quinapril

Indications

Quinapril is an angiotensin-converting enzyme (ACE) inhibitor that was developed in the 1980s and was approved by the FDA, in 1989, for the treatment of hypertension.[1] In this study, researchers determined that quinapril had a lower incidence of adverse events as compared to other ACE inhibitors like captopril and enalapril, as well as the thiazide diuretic, chlorthalidone.[1] Quinapril has demonstrated effectiveness in lowering systolic blood pressure by 13 mm Hg and diastolic blood pressure by 10 mm Hg in approximately two out of three individuals.[2][3][4]

Quinapril has also had non-approved FDA indications for chronic heart failure (CHF) and slowing the progression of renal disease in diabetic patients. According to the SOLVD trial, ACE inhibitors, as a class, have shown to be beneficial in chronic heart failure (CHF).[5] The primary therapeutic effects include reduction of heart failure hospitalizations, hospitalizations for any reason, and risk of death. Additionally, the HOPE trial found that patients taking ACE inhibitors reduce the risk of ischemic stroke, non-fatal myocardial infarction, and cardiovascular death.[6] As a class, ACE inhibitors have shown to reduce proteinuria in diabetic patients. More importantly, however, research has demonstrated quinapril to be an agent that reduced microalbuminuria in essential hypertension and diabetic patients without significantly affecting insulin effectiveness or lipid levels.[7]

Mechanism of Action

Quinapril is a non-sulphylhydryl ACE inhibitor that acts by blocking the action of ACE, which plays a vital role in the renin-angiotensin-aldosterone system (RAAS). Quinapril is metabolized into quinaprilat in the liver, from where the drug enters the circulation. After conversion, the liver releases quinaprilat into the peripheral circulation where it inhibits ACE; the enzyme is responsible for the conversion of angiotensin I to angiotensin II. Angiotensin II is the hormone that promotes the stimulation of the hormone aldosterone, which is responsible for salt and water retention.[8] A combination of salt and water retention, coupled with peripheral vasculature constriction, leads to the development of systemic hypertension. Quinapril (and its metabolite quinaprilat) decreases systemic (peripheral and renal) vascular resistance, thereby decreasing blood pressure. Distribution is widespread, except for brain tissue.[9] The renal system clears the majority of quinapril, and the maximum observable effect of ACE inhibitors takes place at 5 hours.[4][10]

Administration

The administration of quinapril is via the oral route. Plasma clearance of quinapril correlates to the creatinine clearance of a patient. The dosing range that researchers tested was between 0.625 to 80 mg orally once daily, but the most effective antihypertensive effects were noted at doses of 20 mg orally once daily.[3] Patients with mild to moderate hypertension should be initiated on a dose range between 5 and 40 mg orally once daily. In patients with renal impairment, doses should be reduced to between 2.5 and 20 mg orally once daily.[11] Interestingly, twice daily dosing has been noted to achieve a more significant blood pressure trough effect in hypertensive patients as opposed to a similar total dose administered daily. 

Adverse Effects

Adverse effects of quinapril include dry cough (as is typical among all ACE inhibitor class members), hyperkalemia, angioedema, dizziness, hypotension, and renal dysfunction.[12][13][14] Less common adverse effects include skin rash and dysgeusia.[14]

Angioedema is a rare but well-documented side effect of ACE inhibitors, which often presents as facial, tongue, and lip swelling. However, there may be unique instances when patients present with isolated swelling of the small bowel. This presentation, also called intestinal-type angioedema, may manifest in patients taking ACE inhibitors that present with abdominal pain, nausea, vomiting, and/or diarrhea.[15]

Contraindications

ACE inhibitors, including quinapril, are contraindicated in pregnancy since they counteract the RAAS, which is essential for fetal renal development.[14] Possible complications of use of quinapril in pregnancy may include but are not limited to fetal lung hypoplasia, fetal renal hypoplasia/failure, oligohydramnios, skeletal hypoplasia, hypotension, and death.

Quinapril is also contraindicated in patients presenting with hyperkalemia, history, or current presentation of angioedema (regardless of the ACE inhibitor used), bilateral renal artery stenosis, acute kidney injury leading to renal failure with prior ACE inhibitor use, and aliskiren use within the last 36 hours. 

Although there was one report of agranulocytosis in a neutropenic patient using quinapril, there are no other reports of agranulocytosis noted in the literature, as has been found in rare cases of captopril use, one of the original ACE inhibitors.

Monitoring

The most serious side effects that require monitoring are angioedema and hyperkalemia. Clinicians need to inform patients about potential facial, tongue, and lip swelling so that they monitor themselves for angioedema. Additionally, patients and physicians need to be cognizant of abdominal symptoms like abdominal pain, nausea, vomiting, and diarrhea, which may suggest intestinal-type angioedema.[15] Routine laboratory assessment, including a basic metabolic panel to monitor serum potassium levels and renal function, should be performed. The current recommendation is to monitor serum electrolytes and renal function 2 to 3 weeks after initiation and at every dose titration. 

Patients should receive instruction to avoid high-potassium foods (i.e., alternative salt in hypertension, bananas, avocados), and advised against concurrent use of other agents that contribute to hyperkalemia (i.e., aldosterone antagonists). Patients that take many antihypertensives agents also need to be cautious as quinapril may contribute to significant hypotension, especially following administration of the first dose. 

Occasional or rare monitoring of liver function tests, as well as complete blood counts, may be warranted in quinapril as rare adverse effects such as agranulocytosis and/or hepatic enzyme elevation may occur.

If patients report a persistent, dry cough while taking quinapril, the clinician may consider a therapeutic switch to an angiotensin receptor blocking agent (ARB).

Toxicity

Overdosing on ACE inhibitors may lead to significant hypotension, renal failure, hyperkalemia, and hyponatremia.[12][13][14] After ingestion of 20-times of the daily amount, significant hypotension occurred within the first 6 hours of ingestion. Considerations can be made for activated charcoal if a patient were to present within an hour of ingestion.[16] To date, there is no true antidote for quinapril.

Enhancing Healthcare Team Outcomes

Since quinapril has been available on the market, it has been an effective medication for the treatment of hypertension and CHF. Key points to remember are that 1) average systolic blood pressure change is approximately 13 mm Hg while average diastolic blood pressure change is approximately 10 mm Hg with maximum effect at 5 hours, and 2) patients require close monitoring for adverse effects like hyperkalemia, renal dysfunction, and angioedema. [Level II]


References

[1] Frank GJ,Knapp LE,McLain RW, Overall tolerance and safety of quinapril in clinical trials. Angiology. 1989 Apr;     [PubMed PMID: 2650583]
[2] Sedman AJ,Posvar E, Clinical pharmacology of quinapril in healthy volunteers and in patients with hypertension and congestive heart failure. Angiology. 1989 Apr;     [PubMed PMID: 2539762]
[3] Maclean D, Quinapril: a double-blind, placebo-controlled trial in essential hypertension. Angiology. 1989 Apr;     [PubMed PMID: 2650581]
[4] Begg EJ,Robson RA,Bailey RR,Lynn KL,Frank GJ,Olson SC, The pharmacokinetics and pharmacodynamics of quinapril and quinaprilat in renal impairment. British journal of clinical pharmacology. 1990 Aug;     [PubMed PMID: 2144994]
[5] Yusuf S,Pitt B,Davis CE,Hood WB,Cohn JN, Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. The New England journal of medicine. 1991 Aug 1;     [PubMed PMID: 2057034]
[6] Smith WH,Ball SG, ACE inhibitors in heart failure: an update. Basic research in cardiology. 2000;     [PubMed PMID: 11192359]
[7] Dominguez LJ,Barbagallo M,Kattah W,Garcia D,Sowers JR, Quinapril reduces microalbuminuria in essential hypertensive and in diabetic hypertensive subjects. American journal of hypertension. 1995 Aug;     [PubMed PMID: 7576397]
[8] Raia JJ Jr,Barone JA,Byerly WG,Lacy CR, Angiotensin-converting enzyme inhibitors: a comparative review. DICP : the annals of pharmacotherapy. 1990 May;     [PubMed PMID: 2188439]
[9] Kaplan HR,Taylor DG,Olson SC,Andrews LK, Quinapril--a preclinical review of the pharmacology, pharmacokinetics, and toxicology. Angiology. 1989 Apr;     [PubMed PMID: 2539761]
[10] Squire IB,Macfadyen RJ,Lees KR,Hillis WS,Reid JL, Haemodynamic response and pharmacokinetics after the first dose of quinapril in patients with congestive heart failure. British journal of clinical pharmacology. 1994 Aug;     [PubMed PMID: 7981011]
[11] Miller MA,Texter M,Gmerek A,Robbins J,Shurzinske L,Canter D, Quinapril hydrochloride effects on renal function in patients with renal dysfunction and hypertension: a drug-withdrawal study. Cardiovascular drugs and therapy. 1994 Apr;     [PubMed PMID: 7918140]
[12] Quinapril 2012;     [PubMed PMID: 31643770]
[13] Canter D,Frank GJ,Knapp LE,McLain RW, The safety profile of quinapril: is there a difference among ACE inhibitors? Clinical cardiology. 1990 Jun;     [PubMed PMID: 2189620]
[14] Alderman CP, Adverse effects of the angiotensin-converting enzyme inhibitors. The Annals of pharmacotherapy. 1996 Jan;     [PubMed PMID: 8773167]
[15] Palmquist S,Mathews B, Isolated intestinal type angioedema due to ACE-inhibitor therapy. Clinical case reports. 2017 May;     [PubMed PMID: 28469880]
[16] Lucas C,Christie GA,Waring WS, Rapid onset of haemodynamic effects after angiotensin converting enzyme-inhibitor overdose: implications for initial patient triage. Emergency medicine journal : EMJ. 2006 Nov;     [PubMed PMID: 17057137]