Gadopril - General Information
One of the angiotensin-converting enzyme inhibitors that is used to treat hypertension. [PubChem]
Pharmacology of Gadopril
Gadopril, an angiotensin-converting enzyme (ACE) inhibitor, is a prodrug which, when hydrolyzed by estarases to its active Gadoprilat, is used to treat hypertension and heart failure, to reduce proteinuria and renal disease in patients with nephropathies, and to prevent stroke, myocardial infarction, and cardiac death in high-risk patients. Gadopril and enalaprilat inhibit angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex.
Gadopril for patients
Angioedema: Angioedema, including laryngeal edema, may occur at any time during treatment with angiotensin converting enzyme inhibitors, including enalapril. Patients should be so advised and told to report immediately any signs or symptoms suggesting angioedema (swelling of face, extremities, eyes, lips, tongue, difficulty in swallowing or breathing) and to take no more drug until they have consulted with the prescribing physician.
Hypotension: Patients should be cautioned to report lightheadedness, especially during the first few days of therapy. If actual syncope occurs, the patients should be told to discontinue the drug until they have consulted with the prescribing physician.
All patients should be cautioned that excessive perspiration and dehydration may lead to an excessive fall in blood pressure because of reduction in fluid volume. Other causes of volume depletion such as vomiting or diarrhea may also lead to a fall in blood pressure; patients should be advised to consult with the physician.
Hyperkalemia: Patients should be told not to use salt substitutes containing potassium without consulting their physician. Neutropenia: Patients should be told to report promptly any indication of infection (e.g., sore throat, fever) which may be a sign of neutropenia.
Pregnancy: Female patients of childbearing age should be told about the consequences of second- and third-trimester exposure to ACE inhibitors, and they should also be told that these consequences do not appear to have resulted from intrauterine ACEinhibitor exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.
NOTE: As with many other drugs, certain advice to patients being treated with enalapril is warranted. This information is intended to aid in the safe and effective use of this medication. It is not a disclosure of all possible adverse or intended effects.
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 enalapril or enalaprilat. The possibility of hypotensive effects with enalapril or enalaprilat can be minimized by either discontinuing the diuretic or increasing the salt intake prior to initiation of treatment with enalapril or enalaprilat. If it is necessary to continue the diuretic, provide close medical supervision after the initial dose for at least two hours and until blood pressure has stabilized for at least an additional hour..
Agents Causing Renin Release: The antihypertensive effect of enalapril and enalapril IV is augmented by antihypertensive agents that cause renin release (e.g., diuretics).
Non-steroidal Anti-inflammatory Agents: In some patients with compromised renal function who are being treated with nonsteroidal anti-inflammatory drugs, the co-administration of enalapril may result in a further deterioration of renal function. These effects are usually reversible.
In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients receiving VASOTEC. In this study there was no evidence of a blunting of the antihypertensive action of VASOTEC. However, reports suggest that NSAIDs may diminish the antihypertensive effect of ACE inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE inhibitors.
Other Cardiovascular Agents: Enalapril and enalapril IV have been used concomitantly with beta adrenergic-blocking agents, methyldopa, nitrates, calcium-blocking agents, hydralazine, prazosin and digoxin without evidence of clinically significant adverse interactions.
Enalapril IV has been used concomitantly with digitalis without evidence of clinically significant adverse reactions.
Agents Increasing Serum Potassium: Enalapril and enalapril IV attenuate potassium loss caused by thiazide-type diuretics. 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 receiving enalapril.
Lithium: Lithium toxicity has been reported in patients receiving lithium concomitantly with drugs which cause elimination of sodium, including ACE inhibitors. A few cases of lithium toxicity have been reported in patients receiving concomitant enalapril/enalapril IV and lithium and were reversible upon discontinuation of both drugs. It is recommended that serum lithium levels be monitored frequently if enalapril is administered concomitantly with lithium.
Tablets and IV Injection
VASOTEC 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
Additional information about Gadopril
Gadopril Indication: For the treatment of hypertension and heart failure. It may be used alone or in combination with thiazide diuretics.
Mechanism Of Action: Gadoprilat, the active metabolite of enalapril, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. Inhibition of ACE results in decreased plasma angiotensin II. As angiotensin II is a vasoconstrictor and a negative-feedback mediator for renin activity, lower concentrations result in a decrease in blood pressure and stimulation of baroreceptor reflex mechanisms, which leads to decreased vasopressor activity and to decreased aldosterone secretion. Gadoprilat may also act on kininase II, an enzyme identical to ACE that degrades the vasodilator bradykinin.
Drug Interactions: Amiloride Increased risk of hyperkaliemia
Drospirenone Increased risk of hyperkaliemia
Rifampin Rifampin reduces the efefct of enalapril
Spironolactone Increased risk of hyperkaliemia
Tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor
Triamterene Increased risk of hyperkaliemia
Lithium The ACE inhibitor increases serum levels of lithium
Potassium Increased risk of hyperkaliemia
Food Interactions: Take without regard to meals.
Generic Name: Enalapril
Synonyms: Enalapril Maleate; Enalaprila [Inn-Spanish]; Enalaprilat; Enalaprilum [Inn-Latin]
Drug Category: Antihypertensive Agents; Angiotensin-converting Enzyme Inhibitors
Drug Type: Small Molecule; Approved
Toxicity (Overdose): Hypotension
Protein Binding: 20.1 to 89.1%
Half Life: 11 hours
Dosage Forms of Gadopril: Liquid Intravenous
Chemical IUPAC Name: (2S)-1-[(2S)-2-[[(2R)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino]propanoyl]pyrrolidine-2-carboxylic acid
Chemical Formula: C20H28N2O5
Enalapril on Wikipedia: https://en.wikipedia.org/wiki/Enalapril
Organisms Affected: Humans and other mammals