Lisinopril
General clinical considerations
Pregnancy Categories and Implications
use in pregnant women should only be considered for cases of hypertension refractory to other medications
Box warning
[US Boxed Warning]: Drugs that act on the renin-angiotensin system can cause injury and death to the developing fetus. Discontinue as soon as possible once pregnancy is detected.
Exposure to an angiotensin-converting enzyme (ACE) inhibitor during the first trimester of pregnancy may be associated with an increased risk of fetal malformations
Lisinopril crosses the placenta
Drug interactions
Monitor
ibuprofen
heparin
bupivacaine
aspirin
amphetamine
sodium phosphates
dose dependent
Avoid
sacubitril
grass pollen allergen extract
bromperidol
Toxicities
gasping syndrome
large amounts of benzyl alcohol
consists of:
cardiovascular collapse
hypotension
CNS dysfunction (including convulsions, intracranial hemorrhage)
gasping respirations
respiratory distress
metabolic acidosis
In neonates
Contraindications
pediatric patients 6 to 16 years of age with severe renal impairment
pediatric patients <6 years
concomitant use with ARBs or other ACE inhibitors in diabetic patients with end organ damage
concomitant use with aliskiren, angiotensin receptor blockers (ARBs), or other ACE inhibitors in patients with :
with heart failure who are hypotensive
hyperkalemia (>5 mmol/L)
moderate to severe renal impairment (GFR <60 mL/minute/1.73 m2)
coadministration with or within 36 hours of switching to or from a neprilysin inhibitor
Ex: sacubitril
concomitant use with aliskiren in patients with diabetes mellitus
idiopathic or hereditary angioedema
angioedema related to previous treatment with an ACE inhibitor
Hypersensitivity
Indications
Treatment of acute MI within 24 hours in hemodynamically stable patients to improve survival.
Hypertension:
Management of hypertension in adult and pediatric patients ≥6 years of age.
Adjunctive therapy to reduce signs and symptoms of systolic heart failure.
General dosages
Proteinuric chronic kidney disease (diabetic or nondiabetic)
Oral: Initial: 2.5 to 10 mg once daily depending on blood pressure
Posttransplant erythrocytosis (renal transplant recipients)
Oral: Initial: 2.5 or 5 mg once daily
Hypertension
Oral: Initial: 5 to 10 mg once daily
Heart failure with reduced ejection fraction:
Oral: Initial: 2.5 to 5 mg once daily
Acute coronary syndromes:
ST-elevation myocardial infarction:
Oral: Initial: 2.5 to 5 mg once daily initiated within 24 hours of presentation
Non-ST-elevation acute coronary syndrome
Oral: Initial: 2.5 to 10 mg once daily (depending on initial blood pressure)
Dental applications and considerations
Molecular Pharmacodynamics
vasoactive kallikreins may be decreased in conversion to active hormones by ACE inhibitors
reducing blood pressure
a CNS mechanism may also be involved in hypotensive effect as angiotensin II increases adrenergic outflow from CNS
results in lower levels of angiotensin II which causes
a reduction in aldosterone secretion
prevents conversion of angiotensin I to angiotensin II,
potent vasoconstrictor
Competitive inhibitor of angiotensin-converting enzyme (ACE)
Pharmacokinetics
Additional
Time to Peak
Long acting capsule (Inderal LA): 6 hours
Extended release capsule (Inderal XL, InnoPran XL): 12 to 14 hours
Infants: ≤2 hours (Hemangeol)
Immediate release: Adults: 1 to 4 hours
Half-Life Elimination
Adults: Immediate release formulation: 3 to 6 hours; Extended-release formulations: 8 to 10 hours
Infants (35 to 150 days of age): Median 3.5 hours; Children: 3.9 to 6.4 hours
Neonates: Possible increased half-life
Duration of Action
Extended-release formulations: ~24 to 27 hours
Immediate release: 6 to 12 hours
Onset of Action
Peak effect: Hypertension: A few days to several weeks.
Beta-blockade: Oral: 1 to 2 hours; IV: ≤5 minutes
Excretion
<1% excreted in urine as unchanged drug
Metabolites are excreted primarily in urine (96% to 99%)
Metabolism
4-hydroxypropranolol possesses beta-adrenergic receptor blocking activity and is a weak inhibitor of CYP2D6.
side chain oxidation is mainly via CYP1A2, but also CYP2D6
Note: Aromatic hydroxylation is catalyzed primarily by isoenzyme CYP2D6
the 4 primary metabolites include: Propranolol glucuronide, naphthyloxylactic acid, and sulfate and glucuronic acid conjugates of 4-hydroxy propranolol
the 3 main metabolic pathways include: Aromatic hydroxylation (primarily 4-hydroxylation), N-dealkylation followed by further side-chain oxidation and direct glucuronidation
Extensive first-pass effect, hepatically metabolized to active and inactive compounds
Distribution
crosses the blood-brain barrier
Vd: 4 L/kg in adults
Bioavailability
protein-rich foods increase bioavailability by ~50%
oral bioavailability may be increased in Down syndrome children
~25% reaches systemic circulation due to high first-pass metabolism
Absorption
Oral
Rapid and Complete
