Esradin (ANTIHYPERTENSIVES)

Uses

Esradin (ANTIHYPERTENSIVES) is used for the management of hypertension. It may be used alone or concurrently with thiazide-type diuretics.

Esradin (ANTIHYPERTENSIVES) is also used to associated treatment for these conditions: High Blood Pressure (Hypertension)

How Esradin (ANTIHYPERTENSIVES) works

Esradin (ANTIHYPERTENSIVES) belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, isradipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives isradipine additional arterial selectivity. At therapeutic sub-toxic concentrations, isradipine has little effect on cardiac myocytes and conduction cells.

Dosage

Esradin (ANTIHYPERTENSIVES) dosage

Adult: Initially, 2.5 mg bid, increase if necessary after 3-4 wk to 5 mg bid, or 10 mg bid as required.

Elderly: Initially, 1.25 mg bid. Maintenance: 2.5 or 5 mg once daily.

Hepatic Impairment: Initially 1.25 mg bid. Maintenance: 2.5 or 5 mg once daily.

Side Effects

Headache, dizziness, palpitations, tachycardia, peripheral oedema, flushing, dyspnoea, abdominal discomfort, rash, pruritus, polyuria, fatigue, malaise.

Toxicity

Symptoms of overdose include lethargy, sinus tachycardia, and transient hypotension. Significant lethality was observed in mice given oral doses of over 200 mg/kg and rabbits given about 50 mg/kg of isradipine. Rats tolerated doses of over 2000 mg/kg without effects on survival.

Precaution

Patients with CHF, severe aortic stenosis, hypertrophic cardiomyopathy with outflow tract obstruction. Hepatic impairment. Pregnancy and lactation.

Interaction

Concurrent admin with enzyme-inducing drugs (e.g. rifampicin, phenobarbital, carbamazepine) reduced plasma concentrations of isradipine. Increased bioavailability with cimetidine. May increase serum levels with CYP3A4 inhibitors (e.g. macrolides, HIV protease inhibitors, azole antifungals, delavirdine).

Food Interaction

• Take with or without food.

[Moderate] GENERALLY AVOID: The consumption of grapefruit juice may be associated with significantly increased plasma concentrations of some calcium channel blockers (CCBs) when they are administered orally.

The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

The interaction has been reported with the dihydropyridine CCBs (in roughly decreasing order of magnitude) felodipine, nisoldipine, nifedipine, and nimodipine, often with a high degree of interindividual variability.

Grapefruit juice caused more than twofold increases in felodipine, nifedipine, and nisoldipine AUCs.

MANAGEMENT: The manufacturers of nifedipine and nisoldipine recommend avoiding grapefruit juice.

Patients treated orally with other calcium channel blockers should be advised to avoid consumption of large amounts of grapefruits and grapefruit juice to prevent any undue fluctuations in serum drug levels.

Increased effects on blood pressure may persist for up to 4 days after the consumption of grapefruit juice.

Monitoring for calcium channel blocker adverse effects (e.g., headache, hypotension, syncope, tachycardia, edema) is recommended.

Esradin (ANTIHYPERTENSIVES) multivitamins interaction

[Moderate] Calcium-containing products may decrease the effectiveness of calcium channel blockers by saturating calcium channels with calcium.

Calcium chloride has been used to manage acute severe verapamil toxicity.

Management consists of monitoring the effectiveness of calcium channel blocker therapy during coadministration with calcium products.

Esradin (ANTIHYPERTENSIVES) Drug Interaction

Moderate: rasagiline, rasagiline, meperidine, meperidineUnknown: diphenhydramine, diphenhydramine, sulfamethoxazole / trimethoprim, sulfamethoxazole / trimethoprim, levothyroxine, levothyroxine, acetaminophen, acetaminophen, cyanocobalamin, cyanocobalamin, ascorbic acid, ascorbic acid, cholecalciferol, cholecalciferol, cetirizine, cetirizine

Esradin (ANTIHYPERTENSIVES) Disease Interaction

Major: cardiogenic shock/hypotension, coronary artery disease, liver diseaseModerate: CHF/AMI, GI narrowing

Elimination Route

Esradin (ANTIHYPERTENSIVES) is 90%-95% absorbed and is subject to extensive first-pass metabolism, resulting in a bioavailability of about 15%-24%.

Half Life

8 hours

Elimination Route

Approximately 60% to 65% of an administered dose is excreted in the urine and 25% to 30% in the feces.

Pregnancy & Breastfeeding use

Pregnancy Category C. Either studies in animals have revealed adverse effects on the foetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the foetus

Contraindication

Cardiogenic shock, within 1 mth of MI, unstable angina, treatment of hypertensive crisis.

Acute Overdose

Symptoms: Excessive peripheral vasodilation with subsequent marked and prolonged systemic hypotension and tachycardia.

Management: Symptomatic and supportive treatment. Emesis, gastric lavage, admin of activated charcoal followed in 30 min by a saline cathartic. A vasoconstrictor (e.g. epinephrine) may be useful in restoring normotensive state. Refractory hypotension or AV conduction disturbances may be treated with IV Ca salts or glucagon.

Storage Condition

Store below 30° C.

Innovators Monograph

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