Usage
- Imidapril is prescribed for the treatment of hypertension (high blood pressure), congestive heart failure, and diabetic nephropathy (kidney damage caused by diabetes).
- Pharmacological classification: Angiotensin-Converting Enzyme (ACE) inhibitor.
- Mechanism of Action: Imidapril, a prodrug, is converted in the liver to its active metabolite, imidaprilat. Imidaprilat blocks the action of the angiotensin-converting enzyme (ACE), which prevents the conversion of angiotensin I to angiotensin II. Angiotensin II is a potent vasoconstrictor (narrows blood vessels) and also stimulates the release of aldosterone, which causes the body to retain sodium and water. By blocking the formation of angiotensin II, imidapril lowers blood pressure and reduces strain on the heart.
Alternate Names
- Imidapril hydrochloride is the chemical name.
- Brand Names: Tanatril, Vascor, Prilium.
How It Works
- Pharmacodynamics: Imidapril lowers blood pressure by reducing peripheral vascular resistance (the resistance to blood flow in the arteries) without significantly altering heart rate or cardiac output. It improves renal blood flow and reduces proteinuria (protein in the urine) in patients with diabetic nephropathy.
- Pharmacokinetics: Imidapril is well-absorbed after oral administration, is extensively metabolized by the liver to imidaprilat. Peak plasma concentration of imidaprilat is reached within 7 hours. It has a biphasic elimination half-life, with an initial half-life of 7-9 hours and terminal half-life exceeding 24 hours, reaching a steady-state concentration after 5 days of dosing. About 85% of imidapril and 53% of imidaprilat are protein bound. Elimination occurs through renal (40%) and hepatobiliary (50%) routes. Reduced renal function significantly impacts imidaprilat pharmacokinetics, necessitating dosage adjustments, while hepatic dysfunction only slightly impacts pharmacokinetics. Food, especially fatty meals, can decrease imidapril absorption.
- Mode of Action: Imidaprilat competitively binds to and inhibits ACE, reducing the conversion of angiotensin I to angiotensin II. This leads to decreased vasoconstriction, reduced aldosterone secretion, and subsequently lower blood pressure and sodium retention.
- Elimination pathways: Primarily renal (40%) and hepatobiliary/fecal (50%) excretion.
Dosage
Standard Dosage
Adults:
- Initial dose: 5 mg once daily, taken orally about 15 minutes before a meal.
- Maintenance dose: If blood pressure remains uncontrolled after 3 weeks, increase to 10 mg once daily. Maximum dose: 20 mg once daily.
Children:
- Safety and efficacy not established in children.
Special Cases:
- Elderly Patients: Initial dose: 2.5 mg once daily. Maximum dose: 10 mg once daily.
- Patients with Renal Impairment: Creatinine Clearance 30-80 mL/min: Initial dose: 2.5 mg once daily, titrated cautiously. Creatinine Clearance <30 mL/min: Not recommended.
- Patients with Hepatic Dysfunction: Initial dose: 2.5 mg once daily.
- Patients with Comorbid Conditions (e.g., heart failure, cerebrovascular disease, angina pectoris): Initial dose: 2.5 mg once daily with close monitoring. Patients at risk for first-dose hypotension: Initial dose: 2.5 mg once daily.
Clinical Use Cases
- Imidapril’s primary clinical use is in the management of hypertension, heart failure, and diabetic nephropathy. Dosage adjustments are made according to the standard dosage guidelines and patient-specific factors. Its use in intubation, surgical procedures, mechanical ventilation, ICU, or emergency situations isn’t routinely indicated.
Dosage Adjustments
- Adjust dosage based on renal function, hepatic function, and response to therapy. Close monitoring is essential, particularly in patients with comorbidities.
Side Effects
Common Side Effects
- Cough, dizziness, headache, fatigue, nausea, diarrhea.
Rare but Serious Side Effects
- Angioedema (swelling of face, lips, tongue, or throat), hyperkalemia (high potassium levels), renal impairment, hypotension (low blood pressure), neutropenia (low white blood cell count), hepatic dysfunction (including jaundice).
Long-Term Effects
- Chronic kidney disease worsening, electrolyte imbalances.
Adverse Drug Reactions (ADR)
- Angioedema, severe hypotension, acute renal failure, hepatic necrosis.
Contraindications
- Hypersensitivity to imidapril or other ACE inhibitors.
- History of angioedema related to ACE inhibitor therapy.
- Hereditary or idiopathic angioedema.
- Pregnancy (especially second and third trimesters).
- Breastfeeding.
- Renal failure with creatinine clearance <30 mL/min.
- Concomitant use with aliskiren in patients with diabetes or renal impairment.
Drug Interactions
- Diuretics: Increased risk of hypotension.
- Potassium-sparing diuretics (e.g., spironolactone, amiloride, triamterene): Increased risk of hyperkalemia.
- Lithium: Increased lithium levels and toxicity.
- NSAIDs: Reduced antihypertensive effect.
- Rifampicin: Reduced imidapril effectiveness.
- Antidiabetic agents: Enhanced hypoglycemic effect.
- Allopurinol, procainamide, immunosuppressants: Increased risk of leukopenia.
- Other antihypertensives, nitrates, tricyclic antidepressants, neuroleptics: Enhanced hypotensive effect.
- Alcohol: May potentiate the hypotensive effect.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category C (first trimester), Category D (second and third trimesters). Imidapril can cause fetal harm and death when administered during pregnancy, especially in the second and third trimesters. It should be discontinued as soon as pregnancy is detected.
- Breastfeeding: Imidapril is excreted in breast milk and may affect the nursing infant. Breastfeeding should be discontinued or the drug avoided.
Drug Profile Summary
- Mechanism of Action: ACE inhibitor, reduces angiotensin II formation, lowers blood pressure.
- Side Effects: Cough, dizziness, fatigue, nausea, angioedema, hyperkalemia, renal impairment.
- Contraindications: Hypersensitivity, angioedema history, pregnancy, breastfeeding, renal failure.
- Drug Interactions: Diuretics, potassium supplements, lithium, NSAIDs, rifampicin, antidiabetics.
- Pregnancy & Breastfeeding: Contraindicated.
- Dosage: 5-20 mg daily (adults); initial dose 2.5 mg in elderly, renally or hepatically impaired.
- Monitoring Parameters: Blood pressure, renal function (serum creatinine, potassium), liver function tests.
Popular Combinations
- Imidapril is often combined with hydrochlorothiazide (a diuretic) for synergistic antihypertensive effects.
Precautions
- Monitor renal function, potassium levels, and blood pressure regularly.
- Caution in patients with renal or hepatic impairment, heart failure, and other comorbidities.
- Avoid in pregnancy and breastfeeding.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Imidapril?
A: Adults: Initial dose 5mg once daily, max 20 mg. Elderly: Initial 2.5 mg, max 10 mg. Renally/hepatically impaired: Initial 2.5 mg. Adjust based on response and renal function. Not for children.
Q2: What is the mechanism of action of Imidapril?
A: Imidapril is an ACE inhibitor that works by inhibiting the conversion of angiotensin I to angiotensin II, leading to vasodilation and reduced blood pressure.
Q3: What are the common side effects of Imidapril?
A: Cough, dizziness, headache, fatigue, nausea, and diarrhea.
A: Angioedema (swelling of the face, lips, tongue, or throat), severe hypotension (low blood pressure), acute renal failure, hepatic necrosis, and hyperkalemia.
Q5: Can Imidapril be used during pregnancy or breastfeeding?
A: No, Imidapril is contraindicated during pregnancy, especially in the second and third trimesters, due to the risk of fetal harm. It should also be avoided during breastfeeding.
Q6: Are there any drug interactions I should be aware of with Imidapril?
A: Yes, significant interactions exist with diuretics, potassium supplements, lithium, NSAIDs, rifampicin, and antidiabetic agents. Consult resources for comprehensive list.
Q7: How should I manage a patient experiencing hypotension after the first dose of Imidapril?
A: Place the patient in a supine position and consider administering intravenous fluids if necessary. Monitor vital signs and notify physician. Re-evaluate therapy and reduce dose as needed.
Q8: What should I do if my patient develops a persistent dry cough while on Imidapril?
A: Consider switching to an angiotensin receptor blocker (ARB) as an alternative antihypertensive medication, as cough is a common class effect of ACE inhibitors.
Q9: How should I monitor patients taking Imidapril long term?
A: Regularly monitor blood pressure, renal function (serum creatinine and potassium levels), and liver function tests. Assess for development of adverse effects.
Q10: Should Imidapril be taken with food?
A: No, Imidapril is best taken on an empty stomach, as food, especially high-fat meals, can reduce its absorption. Administration approximately 15 minutes prior to meals is recommended.
