Lopril - General Information:A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Lopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [PubChem]
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Pharmacology:Lopril, an angiotensin-converting enzyme (ACE) inhibitor, is used to treat hypertension, congestive heart failure, and renal syndromes such as diabetic nephropathy and scleroderma. The adverse effect and pharmacokinetic limitations of captopril stimulated the development enalapril and subsequent ACE inhibitors.
Lopril for patients
Patients should be advised to immediately report to their physician any signs or symptoms suggesting angioedema (e.g., swelling of face, eyes, lips, tongue, larynx and extremities; difficulty in swallowing or breathing; hoarseness) and to discontinue therapy.
Patients should be told to report promptly any indication of infection (e.g., sore throat, fever),which may be a sign of neutropenia, or of progressive edema which might be related to proteinuria and nephrotic syndrome.
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.
Patients should be advised not to use potassium-sparing diuret-ics, potassium supplements or potassium-containing salt substitutes without consulting their physician.
Patients should be warned against interruption or discontinuation of medication unless instructed by the physician.
Heart failure patients on captopril therapy should be cautioned against rapid increases in physical activity.
Patients should be informed that captopril should be taken one hour before meals.
Hypotension ó Patients on Diuretic Therapy: Patients on diuretics and especially those in whom diuretic therapy was recently instituted, as well as those on severe dietary salt restriction or dialysis, may occasionally experience a precipitous reduction of blood pressure usually within the first hour after receiving the initial dose of captopril.
The possibility of hypotensive effects with captopril can be minimized by either discontinuing the diuretic or increasing the salt intake approximately one week prior to initiation of treatment with captopril (captopril tablets, USP) or initiating therapy with small doses (6.25 or 12.5 mg). Alternatively, provide medical supervision for at least one hour after the initial dose. If hypotension occurs, the patient should be placed in a supine position and, if necessary, receive an intravenous infusion of normal saline. This transient hypotensive response is not a contraindication to further doses which can be given without difficulty once the blood pressure has increased after volume expansion.
Agents Having Vasodilator Activity: Data on the effect of concomitant use of other vasodilators in patients receiving captopril for heart failure are not available; therefore, nitroglycerin or other nitrates (as used for management of angina) or other drugs having vasodilator activity should, if possible, be discontinued before starting captopril. If resumed during captopril therapy, such agents should be administered cautiously, and perhaps at lower dosage.
Agents Causing Renin Release
Captoprilís effect will be augmented by antihypertensive agents that cause renin release. For example, diuretics (e.g., thiazides) may activate the renin-angiotensin-aldosterone system.
Agents Affecting Sympathetic Activity
The sympathetic nervous system may be especially important in supporting blood pressure in patients receiving captopril alone or with diuretics. Therefore, agents affecting sympathetic activity (e.g., ganglionic blocking agents or adrenergic neuron blocking agents) should be used with caution. Beta-adrenergic blocking drugs add some further antihypertensive effect to captopril, but the overall response is less than additive.
Agents Increasing Serum Potassium
Since captopril decreases aldosterone production, elevation of serum potassium may occur. Potassium-sparing diuretics such as spironolactone, triamterene, or amiloride, or potassium supplements should be given only for documented hypokalemia, and then with caution, since they may lead to a significant increase of serum potassium. Salt substitutes containing potassium should also be used with caution.
Inhibitors Of Endogenous Prostaglandin Synthesis
It has been reported that indomethacin may reduce the antihypertensive effect of captopril, especially in cases of low renin hypertension. Other nonsteroidal anti-inflammatory agents (e.g., aspirin) may also have this effect.
Increased serum lithium levels and symptoms of lithium toxicity have been reported in patients receiving concomitant lithium and ACE inhibitor therapy. These drugs should be coad-ministered with caution and frequent monitoring of serum lithium levels is recommended. If a diuretic is also used, it may increase the risk of lithium toxicity.
In a study of young healthy male subjects no evidence of a direct pharmacokinetic captopril-digoxin interaction could be found.
Loop Diuretics: Furosemide administered concurrently with cap-topril does not alter the pharmacokinetics of captopril in renally impaired hypertensive patients.
In a study of healthy male volunteers no significant pharmacokinetic interaction occurred when captopril and allop-urinol were administered concomitantly for 6 days.
Drug/Laboratory Test Interaction
Captopril may cause a false-positive urine test for acetone.
Captopril is contraindicated in patients who are hypersensitive to this product or any other angiotensin-converting enzyme inhibitor (e.g.,a patient who has experienced angioedema during therapy with any other ACE inhibitor).
Additional information about LoprilLopril Indication: For the treatment of hypertension. It may be used alone or in combination with thiazide diuretics.
Mechanism Of Action: Lopril competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II. As angiotensin II is a vasoconstrictor and a negative feedback mediator for renin activity, lower angiotensin II levels results in a decrease in blood pressure, an increase in renin activity, and stimulation of baroreceptor reflex mechanisms. Kininase II, an enzyme which degrades the vasodilator bradykinin, is identical to ACE and may also be inhibited.
Drug Interactions: Amiloride Increased risk of hyperkaliemia
Drospirenone Increased risk of hyperkaliemia
Lithium The ACE inhibitor increases serum levels of lithium
Potassium Increased risk of hyperkaliemia
Spironolactone Increased risk of hyperkaliemia
Tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor
Triamterene Increased risk of hyperkaliemia
Food Interactions: Avoid alcohol.
Avoid salt substitutes containing potassium.
Take on empty stomach: 1 hour before or 2 hours after meals, food decreases absorption by 30 to 55%.
Avoid natural licorice.
Do not take calcium, aluminum, magnesium or Iron supplements within 2 hours of taking this medication.
Generic Name: Captopril
Synonyms: Captoprilum [Inn-Latin]; Captopryl; L-Captopril
Drug Category: Angiotensin-converting Enzyme Inhibitors; Antihypertensive Agents
Drug Type: Small Molecule; Approved
Other Brand Names containing Captopril: Acediur; Aceplus; Acepress; Acepril; Alopresin; Apopril; Capoten; Captolane; Captoril; Cesplon; Dilabar; Garranil; Hipertil; Hypertil; Lopirin; Lopril; Tenosbon; Tensobon; Tensoprel;
Absorption: 75% without food (the presence of food in the gastrointestinal tract reduces absorption by about 30 to 40 percent).
Toxicity (Overdose): Symptoms of overdose include coma, lethargy, low blood pressure, sluggishness, and stomach and intestinal irritation and hyperactivity.
Protein Binding: About 25-30% of the circulating drug is bound to plasma proteins
Half Life: Less than 3 hours
Dosage Forms of Lopril: Tablet Oral
Chemical IUPAC Name: (2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid
Chemical Formula: C9H15NO3S
Captopril on Wikipedia: http://en.wikipedia.org/wiki/Captopril
Organisms Affected: Humans and other mammals
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