Nadic

Uses

Nadic is a non-selective beta-adrenergic antagonist used for the management of arrhythmias, angina pectoris, and hypertension.

Nadic is indicated to treat angina pectoris and hypertension. Another product formulated with bendroflumethiazide is indicated to treat hypertension.

Nadic is also used to associated treatment for these conditions: Angina Pectoris, Atrial Fibrillation, Gastroesophageal variceal hemorrhage prophylaxis, High Blood Pressure (Hypertension), Migraine, Thyrotoxicosis

How Nadic works

Although nadolol is described as a non selective beta blocker, it does not interact with beta 3 adrenal receptors. Antagonism of beta-1 and beta-2 adrenoceptors in the heart inhibits cyclic AMP and its signalling pathway, decreasing the strength and speed of contractions as well as the speed of relaxation and conduction. Antagonism of beta-2 adrenoceptors in the smooth muscle cells of the vasculature inhibits their relaxation, leading to an increase in peripheral vascular resistance and reducing the risk of severe hypotension. The increase in peripheral vascular resistance may contribute to the decrease in insulin sensitivity associated with nadolol use. Antagonism of beta-1 adrenoceptors in the juxtaglomerular apparatus of the kidney inhibits the release of renin, and therefore angiotensin II mediated vasoconstriction, aldosterone mediated water retention, and the release of epinephrine. Antagonism of beta-2 adrenoceptors in the liver and skeletal muscle inhibits glycogenolysis, in the lungs prevents bronchodilation, and in the pancrease inhibits insulin release.

Toxicity

The oral LD₅₀ in mice is 4500mg/kg.

Patients experiencing an overdose may present with bradycardia, cardiac failure, hypotension, and bronchospasm. An overdose may be treated with atropine for bradycardia, digitalis and diuretics for cardiac failure, vasopressors for hypotension, and beta-2 stimulants for bronchospasms, as well as gastric lavage and hemodialysis.

Food Interaction

• Avoid alcohol.
• Avoid natural licorice.
• Take with or without food. The absorption is unaffected by food.

[Moderate] GENERALLY AVOID: Coadministration with green tea may significantly decrease the plasma concentrations of nadolol.

The mechanism of interaction has not been established, but may involve inhibition of OATP1A2-mediated uptake of nadolol in the intestine by catechins in green tea.

In a study with ten healthy volunteers, administration of a single 30 mg oral dose of nadolol following repeated consumption of green tea (700 mL

The renal clearance of nadolol was not altered.

Green tea also markedly reduced the effects of nadolol on systolic blood pressure.

MANAGEMENT: Based on available data, patients should be advised to limit their consumption of green tea and green tea extracts during treatment with nadolol.

Nadic Alcohol interaction

[Moderate]

Many psychotherapeutic and CNS-active agents (e.g., anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, alcohol, muscle relaxants) exhibit hypotensive effects, especially during initiation of therapy and dose escalation.

Coadministration with antihypertensives and other hypotensive agents, in particular vasodilators and alpha-blockers, may result in additive effects on blood pressure and orthostasis.

Caution and close monitoring for development of hypotension is advised during coadministration of these agents.

Some authorities recommend avoiding alcohol in patients receiving vasodilating antihypertensive drugs.

Patients should be advised to avoid rising abruptly from a sitting or recumbent position and to notify their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or tachycardia.

Nadic Cholesterol interaction

[Moderate] Beta-adrenergic receptor blocking agents (aka beta-blockers) may alter serum lipid profiles.

Increases in serum VLDL and LDL cholesterol and triglycerides, as well as decreases in HDL cholesterol, have been reported with some beta-blockers.

Patients with preexisting hyperlipidemia may require closer monitoring during beta-blocker therapy, and adjustments made accordingly in their lipid-lowering regimen.

Nadic multivitamins interaction

[Moderate] ADJUST DOSING INTERVAL: Concurrent administration with calcium salts may decrease the oral bioavailability of atenolol and possibly other beta-blockers.

The exact mechanism of interaction is unknown.

In six healthy subjects, calcium 500 mg (as lactate, carbonate, and gluconate) reduced the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of atenolol (100 mg) by 51% and 32%, respectively.

The elimination half-life increased by 44%.

Twelve hours after the combination, beta-blocking activity (as indicated by inhibition of exercise tachycardia) was reduced compared to that with atenolol alone.

However, during a 4-week treatment in six hypertensive patients, there was no difference in blood pressure values between treatments.

The investigators suggest that prolongation of the elimination half-life induced by calcium coadministration may have led to atenolol cumulation during long-term dosing, which compensated for the reduced bioavailability.

It may help to separate the administration times of beta-blockers and calcium products by at least 2 hours.

Patients should be monitored for potentially diminished beta-blocking effects following the addition of calcium therapy.

Nadic Drug Interaction

Moderate: furosemide, furosemide, alprazolam, alprazolamMinor: levothyroxine, levothyroxineUnknown: duloxetine, duloxetine, omega-3 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, pregabalin, pregabalin, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol, rifaximin, rifaximin, cetirizine, cetirizine

Nadic Disease Interaction

Major: bradyarrhythmia/AV block, cardiogenic shock/hypotension, CHF, diabetes, hemodialysis, hypersensitivity, ischemic heart disease, PVD, renal dysfunction, asthma/COPDModerate: cerebrovascular insufficiency, glaucoma, hyperlipidemia, hyperthyroidism, myasthenia gravis, pheochromocytoma, psoriasis, tachycardia, Prinzmetal's variant angina

Volume of Distribution

In healthy subjects, the volume of distribution of nadolol is 147-157L.

Elimination Route

Oral doses of nadolol are approximately 30% absorbed. In healthy subjects, nadolol has a T_max of 2.7h with a C_max or 69±15ng/mL following a 60mg oral dose and 132±27ng/mL after a 120mg oral dose. The AUC following a 60mg oral dose was 1021ng*h/mL and following a 120mg oral dose was 1913±382ng*h/mL.

Half Life

The half life of nadolol is 20 to 24 hours.

Clearance

In healthy subjects, the total body clearance of nadolol is 219-250mL/min and the renal clearance is 131-150mL/min.

Elimination Route

Nadic is not metabolized in the liver and excreted mainly in the urine. In healthy subjects, following intravenous dosing, 60% of a dose is eliminated in the urine and 15% in the feces after 72 hours. The remainder of the dose is expected to be eliminated in the feces afterwards.

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