Angiotensin-converting enzyme Inhibitor: Lisinopril
Indication
Lisinopril is used in adults to treat systemic hypertension and as an adjunctive therapy in patients with congestive heart failure and left ventricular dysfunction after a myocardial infarction. In pediatric patients, it is also used to treat systemic hypertension and congestive heart failure; additionally, it is used in congenital heart disease patients who have single ventricle anatomy, atrioventricular valve regurgitation, and aortic valve regurgitation.
Mechanism of Action
Lisinopril is a competitive inhibitor of angiotensin-converting enzyme; therefore, it blocks the conversion of angiotensin I to angiotensin II. Angiotensin II is a strong vasoconstrictor, therefore, reducing its blood level leads to less vasoconstriction. In addition, plasma renin levels are increased and aldosterone secretion reduced.
Dosing
Neonates (premature and full term), infants, and children younger than 6 years: no dosing information is available; because of this, the manufacturer recommends not using lisinopril in patients younger than 6 years of age
Children older than 6 years: initial or “test” dose 0.07 mg/kg/dose P.O./N.G. Dose once per 24 hours. Maximum initial dose, 5 mg once daily. Increase dose at 1- to 2-week intervals for desired effect. No data are available on doses greater than 0.61 mg/kg or greater than 40 mg
Adults:
Oral: initial or “test” dose, 10 mg/dose P.O./N.G. administered once daily. Increase dose by 5 to 10 mg/day at 1- to 2-week intervals for desired
effect. Usual dose, 20 to 40 mg/dose administered once daily. Maximum daily dose reported is 80 mg/day
For adults with congestive heart failure: initial or “test” dose, 5 mg/dose P.O./N.G. administered once daily. Increase dose by at most 10 mg/dose by at least 2-week intervals based on clinical response. Usual dose is 5 to 10 mg/ dose administered once daily. Maximum dose is 40 mg/day
Note: Dosing for all age groups should be titrated to an individual patient’s response, and the lowest dose that achieves this response should be chosen. Lower doses are appropriate for patients who are also being treated with diuretics and are water and sodium depleted, those with renal impairment and severe congestive heart failure, and patients with systemic arterial obstruction (e.g., coarctation of the aorta, renal artery stenosis). For additional dosing precautions in neonates.
Dosing adjustment for renal impairment:
Clcr greater than 30 mL/min/1.73m2: usual dose, 10 mg once daily
Clcr 10 to 30 mL/min/1.73m2: initial dose, 5 mg once daily
Clcr less than 10mL/min/1.73m2: initial dose,2.5mg once daily
In adults with renal impairment, dose titration should be performed cautiously. In addition, lower doses (e.g., one-half those listed) should be used for patients with hyponatremia,hypovolemia, severe congestive heart failure, reduced renal function, or if receiving diuretics. Use is not recommended in children who have a Clcr less than 30mL/min/1.73m2.
Pharmacokinetics
Onset of action: 1 hour (blood pressure lowered)
Absorption:
Children (6-16 years): 28%
Adults: 25% (6-60%)
Maximum effect: 6 to 8 hours
Half-life: 11 to 13 hours; increased with renal dysfunction
Duration: 24 hours
Protein binding: 25%
Clearance: time to peak serum concentration:
Children (6-16 years): 6 hours
Adults: 7 hours
Elimination: in urine as unchanged drug. Can be removed by hemodialysis
Monitoring Parameters
Blood pressure, blood urea nitrogen, serum creatinine,white blood cell count, and serum potassium. Monitoring for blood pressure should be conducted with knowledge that the maximum effect is 6 to 8 hours after dosing.
Contraindications
Hypersensitivity to lisinopril (any component) or other angiotensin-converting enzyme inhibitors. Also contraindicated in patients with a history of idiopathic or hereditary angioedema or angioedema with previous angiotensin-converting enzyme use.
Adverse Effects
Cardiovascular: hypotension, chest discomfort, orthostatic hypotension,
tachycardia, syncope
Respiratory: cough, dyspnea, eosinophilic pneumonitis
Central nervous system: headache, dizziness, fatigue
Gastrointestinal: diarrhea, nausea, vomiting, loss of taste perception,
intestinal angioedema (rare) Hepatic: cholestatic jaundice, hepatitis, fulminant hepatic necrosis (rare, but potentially fatal)
Renal: elevated blood urea nitrogen and serum creatinine
Endocrine/metabolic: hyperkalemia
Hematological: neutropenia, agranulocytosis, eosinophilia. The risk of neutropenia is increased in patients with renal dysfunction
Cutaneous/peripheral: rash, angioedema. The risk of angioedema is higher in the first 30 days of use and is greater for lisinopril and enalapril than
Other: anaphylactoid reactions
Precautions
Note: Dosing for all age groups should be titrated to an individual patient’s response, and the lowest dose that achieves this response chosen. Lower doses are appropriate for patients who are also being treated with diuretics and are water and sodium depleted, those with renal impairment and severe congestive heart failure, and patients with systemic arterial obstruction (e.g., coarctation of the aorta, renal artery stenosis).
Angioedema may occur in the head, neck, extremities, or intestines (rare). Airway obstruction can occur with swelling of the tongue, larynx, or glottis, especially in patients who have a history of airway surgery. For patients at higher risk of airway obstruction, equipment to establish airway patency and medications to relieve airway swelling (e.g., epinephrine) should be available.
Drug-Drug Interactions
In patients who are also receiving potassium supplements or a potassium-sparing diuretic (e.g., spironolactone), an additive hyperkalemic effect may occur. In patients who are also receiving indomethacin or a NSAID, the antihypertensive effect of enalapril maybe diminished, and renal dysfunction maybe exacerbated (usually reversible). Enalapril may increase serum lithium levels.
Compatible Diluents/Administration
Only available for oral/enteral administration. Lisinopril may be administered without regard to ingestion of food.
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