accupril reactions to coughing

Quinapril hydrochloride is chemically described as [3S-[2[R*(R*)], 3R*]]-2-[2-[[1-(ethoxycarbonyl)-3-phenylpropyl]amino]-1-oxopropyl]-1,2,3,4-tetrahydro-3-isoquinolinecarboxylicacid, monohydrochloride accupril reactions to coughing. Its empirical formula is C 25 H 30 N 2 O 5 ·HCland its structural formula is:

Quinapril hydrochloride is a white to off-white amorphous powder that is freelysoluble in aqueous solvents accupril reactions to coughing.

ACCUPRIL tablets contain 5 mg, 10 mg, 20 mg, or 40 mg of quinapril for oraladministration accupril reactions to coughing. Each tablet also contains candelilla wax, crospovidone, gelatin,lactose, magnesium carbonate, magnesium stearate, synthetic red iron oxide,and titanium dioxide accupril reactions to coughing.

CLINICAL PHARMACOLOGY
Mechanism of Action: Quinapril is deesterified to the principal metabolite,quinaprilat, which is an inhibitor of ACE activity in human subjects and animals accupril reactions to coughing. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin Ito the vasoconstrictor, angiotensin II accupril reactions to coughing. The effect of quinapril in hypertensionand in congestive heart failure (CHF) appears to result primarily from the inhibitionof circulating and tissue ACE activity, thereby reducing angiotensin II formation accupril reactions to coughing. Quinapril inhibits the elevation in blood pressure caused by intravenously administeredangiotensin I, but has no effect on the pressor response to angiotensin II,norepinephrine or epinephrine accupril reactions to coughing. Angiotensin II also stimulates the secretionof aldosterone from the adrenal cortex, thereby facilitating renal sodium andfluid reabsorption accupril reactions to coughing. Reduced aldosterone secretion by quinapril may result ina small increase in serum potassium accupril reactions to coughing. In controlled hypertension trials, treatmentwith ACCUPRIL alone resulted in mean increases in potassium of 0.07 mmol/L (seePRECAUTIONS ) accupril reactions to coughing. Removal of angiotensin II negative feedback on renin secretionleads to increased plasma renin activity (PRA) accupril reactions to coughing.

While the principal mechanism of antihypertensive effect is thought to be throughthe renin-angiotensin-aldosterone system, quinapril exerts antihypertensiveactions even in patients with low renin hypertension accupril reactions to coughing. ACCUPRIL was an effectiveantihypertensive in all races studied, although it was somewhat less effectivein blacks (usually a predominantly low renin group) than in nonblacks accupril reactions to coughing. ACE isidentical to kininase II, an enzyme that degrades bradykinin, a potent peptidevasodilator; whether increased levels of bradykinin play a role in the therapeuticeffect of quinapril remains to be elucidated accupril reactions to coughing.

Pharmacokinetics and Metabolism: Following oral administration, peak plasmaquinapril concentrations are observed within one hour accupril reactions to coughing. Based on recovery ofquinapril and its metabolites in urine, the extent of absorption is at least60% accupril reactions to coughing. The rate and extent of quinapril absorption are diminished moderately (approximately25-30%) when ACCUPRIL tablets are administered during a high-fat meal accupril reactions to coughing. Followingabsorption, quinapril is deesterified to its major active metabolite, quinaprilat(about 38% of oral dose), and to other minor inactive metabolites accupril reactions to coughing. Followingmultiple oral dosing of ACCUPRIL, there is an effective accumulation half-lifeof quinaprilat of approximately 3 hours, and peak plasma quinaprilat concentrationsare observed approximately 2 hours post-dose accupril reactions to coughing. Quinaprilat is eliminated primarilyby renal excretion, up to 96% of an IV dose, and has an elimination half-lifein plasma of approximately 2 hours and a prolonged terminal phase with a half-lifeof 25 hours accupril reactions to coughing. The pharmacokinetics of quinapril and quinaprilat are linear overa single-dose range of 5-80 mg doses and 40-160 mg in multiple daily doses accupril reactions to coughing. Approximately 97% of either quinapril or quinaprilat circulating in plasma isbound to proteins accupril reactions to coughing.

In patients with renal insufficiency, the elimination half-life of quinaprilatincreases as creatinine clearance decreases accupril reactions to coughing. There is a linear correlation betweenplasma quinaprilat clearance and creatinine clearance accupril reactions to coughing. In patients with end-stagerenal disease, chronic hemodialysis or continuous ambulatory peritoneal dialysishas little effect on the elimination of quinapril and quinaprilat accupril reactions to coughing. Eliminationof quinaprilat may be reduced in elderly patients (>/=65 years) and in thosewith heart failure; this reduction is attributable to decrease in renal function(see DOSAGE AND ADMINISTRATION ) accupril reactions to coughing. Quinaprilat concentrations are reduced inpatients with alcoholic cirrhosis due to impaired deesterification of quinapril accupril reactions to coughing. Studies in rats indicate that quinapril and its metabolites do not cross theblood-brain barrier accupril reactions to coughing.

Pharmacodynamics and Clinical Effects
Hypertension: Single doses of 20 mg of ACCUPRIL provide over 80% inhibitionof plasma ACE for 24 hours accupril reactions to coughing. Inhibition of the pressor response to angiotensinI is shorter-lived, with a 20 mg dose giving 75% inhibition for about 4 hours,50% inhibition for about 8 hours, and 20% inhibition at 24 hours accupril reactions to coughing. With chronicdosing, however, there is substantial inhibition of angiotensin II levels at24 hours by doses of 20-80 mg accupril reactions to coughing.

Administration of 10 to 80 mg of ACCUPRIL to patients with mild to severe hypertensionresults in a reduction of sitting and standing blood pressure to about the sameextent with minimal effect on heart rate accupril reactions to coughing. Symptomatic postural hypotension isinfrequent although it can occur in patients who are salt- and/or volume-depleted(see WARNINGS ) accupril reactions to coughing. Antihypertensive activity commences within 1 hour with peakeffects usually achieved by 2 to 4 hours after dosing accupril reactions to coughing. During chronic therapy,most of the blood pressure lowering effect of a given dose is obtained in 1-2weeks accupril reactions to coughing. In multiple-dose studies, 10-80 mg per day in single or divided doseslowered systolic and diastolic blood pressure throughout the dosing interval,with a trough effect of about 5-11/3-7 mm Hg accupril reactions to coughing. The trough effect represents about50% of the peak effect accupril reactions to coughing. While the dose-response relationship is relatively flat,doses of 40-80 mg were somewhat more effective at trough than 10-20 mg, andtwice daily dosing tended to give a somewhat lower trough blood pressure thanonce daily dosing with the same total dose accupril reactions to coughing. The antihypertensive effect of ACCUPRILcontinues during long-term therapy, with no evidence of loss of effectiveness accupril reactions to coughing.

Hemodynamic assessments in patients with hypertension indicate that blood pressurereduction produced by quinapril is accompanied by a reduction in total peripheralresistance and renal vascular resistance with little or no change in heart rate,cardiac index, renal blood flow, glomerular filtration rate, or filtration fraction accupril reactions to coughing.

Use of ACCUPRIL with a thiazide diuretic gives a blood-pressure lowering effectgreater than that seen with either agent alone accupril reactions to coughing.

In patients with hypertension, ACCUPRIL 10-40 mg was similar in effectivenessto captopril, enalapril, propranolol, and thiazide diuretics accupril reactions to coughing.

Therapeutic effects appear to be the same for elderly (>/=65 years of age)and younger adult patients given the same daily dosages, with no increase inadverse events in elderly patients accupril reactions to coughing.

Heart Failure: In a placebo-controlled trial involving patients with congestiveheart failure treated with digitalis and diuretics, parenteral quinaprilat,the active metabolite of quinapril, reduced pulmonary capillary wedge pressureand systemic vascular resistance and increased cardiac output/index accupril reactions to coughing. Similarfavorable hemodynamic effects were seen with oral quinapril in baseline-controlledtrials, and such effects appeared to be maintained during chronic oral quinapriltherapy accupril reactions to coughing. Quinapril reduced renal hepatic vascular resistance and increased renaland hepatic blood flow with glomerular filtration rate remaining unchanged accupril reactions to coughing.

A significant dose response relationship for improvement in maximal exercisetolerance has been observed with ACCUPRIL therapy accupril reactions to coughing. Beneficial effects on theseverity of heart failure as measured by New York Heart Association (NYHA) classificationand Quality of Life and on symptoms of dyspnea, fatigue, and edema were evidentafter 6 months in a double-blind, placebo-controlled study accupril reactions to coughing. Favorable effectswere maintained for up to two years of open label therapy accupril reactions to coughing. The effects of quinaprilon long-term mortality in heart failure have not been evaluated accupril reactions to coughing.

INDICATIONS AND USAGE
Hypertension
ACCUPRIL is indicated for the treatment of hypertension accupril reactions to coughing. It may be used aloneor in combination with thiazide diuretics accupril reactions to coughing.

Heart Failure
ACCUPRIL is indicated in the management of heart failure as adjunctive therapywhen added to conventional therapy including diuretics and/or digitalis accupril reactions to coughing.

In using ACCUPRIL, consideration should be given to the fact that another angiotensin-convertingenzyme inhibitor, captopril, has caused agranulocytosis, particularly in patientswith renal impairment or collagen vascular disease accupril reactions to coughing. Available data are insufficientto show that ACCUPRIL does not have a similar risk (see WARNINGS ) accupril reactions to coughing.

Angioedema in black patients: Black patients receiving ACE inhibitor monotherapyhave been reported to have a higher incidence of angioedema compared to non-blacks accupril reactions to coughing. It should also be noted that in controlled clinical trials ACE inhibitors havean effect on blood pressure that is less in black patients than in non-blacks accupril reactions to coughing.

CONTRAINDICATIONS
ACCUPRIL is contraindicated in patients who are hypersensitive to this productand in patients with a history of angioedema related to previous treatment withan ACE inhibitor accupril reactions to coughing.

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