Brands, Medical Use, Clinical Data
- Cardiotonic Agents
- Antihypertensive Agents
- Angiotensin-converting Enzyme Inhibitors
Brands / Synonyms
Acercomp; Inhibril; Linopril; Lisinopril and Hydrochlorothiazide; Lisinopril Dihydrate; Lisipril; Lysinopril; Noperten; Presiten; Prinivil; Prinzide; Renacor; Sinopril; Zestoretic; Zestril; Zestril
For the treatment of hypertension, heart failure and acute myocardial infarction. It may be used alone or in combination with thiazide diuretics
Lisinopril, an angiotensin-converting enzyme (ACE) inhibitor, is used to treat hypertension, congestive heart failure (CHF), postmyocardial infarction, and diabetic nephropathy or retinopathy. Although it is the lysine ester of enalaprilat, the active form of the prodrug enalapril, lisinopril is active unchanged.
Mechanism of Action
Lisinopril competes with angiotensin I for its binding site on the angiotensin-converting enzyme (ACE), an enzyme which converts angiotensin I to angiotensin II. As angiotensin II is a vasoconstrictor and a negative feedback mediator for renin activity, lower angiotensin II plasma levels result in decreased blood pressure and increased plasma renin activity. Baroreceptor reflex mechanisms, stimulated by the fall in blood pressure, release kininase II, an enzyme identical to ACE that degrades bradykinin, a vasodilator.
Approximately 25%, but widely variable between individuals (6 to 60%)
hypotension, LD50= 2000 mg/kg(orally in rat)
Biotrnasformation / Drug Metabolism
Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine
PRINIVIL is contraindicated in patients who are hypersensitive to this product and in patients with a
history of angioedema related to previous treatment with an angiotensin converting enzyme inhibitor and in patients
with hereditary or idiopathic angioedema.
Hypotension - Patients on Diuretic Therapy: Patients on diuretics, and especially those in
whom diuretic therapy was recently instituted, may occasionally experience an excessive reduction of blood pressure
after initiation of therapy with PRINIVIL. The possibility of hypotensive effects with PRINIVIL can be minimized by
either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with PRINIVIL. If it
is necessary to continue the diuretic, initiate therapy with PRINIVIL at a dose of 5 mg daily, and provide close
medical supervision after the initial dose until blood pressure has stabilized. When a diuretic is added to the
therapy of a patient receiving PRINIVIL, an additional antihypertensive effect is usually observed. Studies with ACE
inhibitors in combination with diuretics indicate that the dose of the ACE inhibitor can be reduced when it is given
with a diuretic.
Non-steroidal Anti-inflammatory Agents: In some patients with compromised renal function who
are being treated with non-steroidal anti-inflammatory drugs, the co-administration of lisinopril may result in a
further deterioration of renal function. These effects are usually reversible.
Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors, including
lisinopril. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE
In a study in 36 patients with mild to moderate hypertension where the antihypertensive effects of
PRINIVIL alone were compared to PRINIVIL given concomitantly with indomethacin, the use of indomethacin was
associated with a reduced antihypertensive effect, although the difference between the two regimens was not
Other Agents: PRINIVIL has been used concomitantly with nitrates and/or digoxin without
evidence of clinically significant adverse interactions. This included post myocardial infarction patients who were
receiving intravenous or transdermal nitroglycerin. No clinically important pharmacokinetic interactions occurred
when PRINIVIL was used concomitantly with propranolol or hydrochlorothiazide. The presence of food in the stomach
does not alter the bioavailability of PRINIVIL.
Agents Increasing Serum Potassium: PRINIVIL attenuates potassium loss caused by thiazide-type
diuretics. Use of PRINIVIL with potassium-sparing diuretics (e.g., spironolactone, triamterene, or amiloride),
potassium supplements, or potassium-containing salt substitutes may lead to significant increases in serum potassium.
Therefore, if concomitant use of these agents is indicated because of demonstrated hypokalemia, they should be used
with caution and with frequent monitoring of serum potassium. Potassium sparing agents should generally not be used
in patients with heart failure who are receiving PRINIVIL.
Lithium: Lithium toxicity has been reported in patients receiving lithium concomitantly with
drugs which cause elimination of sodium, including ACE inhibitors. Lithium toxicity was usually reversible upon
discontinuation of lithium and the ACE inhibitor. It is recommended that serum lithium levels be monitored frequently
if PRINIVIL is administered concomitantly with lithium.