Nitroscot

Uses

Nitroscot Tablet is used for the prophylaxis of chronic stable angina pectoris.

Nitroscot Spray is used for acute relief of an attack or prophylaxis of angina pectoris due to coronary artery disease.

Nitroscot Injection is used for the treatment of peri-operative hypertension; for controlling of congestive heart failure in the setting of acute myocardial infarction; for treatment of angina pectoris in patients who have not responded to sublingual nitroglycerin and beta blockers and for induction of Intraoperative hypotension.

Nitroscot is also used to associated treatment for these conditions: Angina Attacks, Angina Pectoris, Chronic Anal Fissures, Congestive Heart Failure (CHF), Coronary Artery Spasm, Gastroesophageal variceal hemorrhage prophylaxis, Perioperative Hypertension, Esophageal spastic disorders

How Nitroscot works

Nitroscot is converted by mitochondrial aldehyde dehydrogenase (mtALDH) to nitric oxide (NO), an active substance which then activates the enzyme guanylate cyclase. The activation of this enzyme is followed by the synthesis of cyclic guanosine 3',5'-monophosphate (cGMP), activating a cascade of protein kinase-dependent phosphorylation events in smooth muscles. This process eventually leads to the dephosphorylation of the myosin light chain of smooth muscles, causing relaxation and increased blood flow in veins, arteries and cardiac tissue.. The above processes lead to decreased work of the heart decreased blood pressure, relief of anginal symptoms, and increased blood flow to the myocardium.One in vitro study using mouse aorta suggests that nitric oxide (an activated metabolite of nitroglycerin) targets the natriuretic peptide receptors.

Dosage

Nitroscot dosage

Tablet or Capsule-

Adults and Elderly Patients: Dosage should be adjusted to the requirements of the individual patient but will usually be 1 or 2 tablets taken three times daily. The lowest effective dose should be used.

Spray-

At the onset of an attack, 1 or 2 metered sprays should be administered under the tongue. No more than 3 metered sprays are recommended within a 15-minute period. If the chest pain persists, prompt medical attention is recommended. NitroscotSpray may be used prophylactically 5 to 10 minutes prior to engaging in activities which might precipitate an acute attack.

Intravenous Infusion-

Nitroscot injection is a concentrated, potent drug which must be diluted in dextrose (5%) injection or sodium chloride (0.9%) injection prior to its infusion. Nitroscot injection should not be mixed with other drugs. This is not for direct intravenous injection.

Initial Dilution: Aseptically transfer the contents of one nitroglycerin ampoule (containing 50 mg of nitroglycerin) into a 500 ml glass bottle of either Dextrose (5%) Injection or Sodium Chloride Injection (0.9%). This yields a final concentration of 100mcg/ml.

Maintenance Dilution: It is important to consider the fluid requirements of the patient as well as the expected duration of infusion in selecting the appropriate dilution of Nitroscot Injection. After the initial dosage titration, the concentration of the solution may be increased, if necessary, to limit fluids given to the patient. The nitroglycerin concentration should not exceed 400 mcg/ml.

Side Effects

Side-effects include facial flushing, headache, dizziness and postural hypotension which may be associated with reflex tachycardia or paradoxical bradycardia. Toxic effects of Nitroscot include vomiting, restlessness, cyanosis, methaemoglobinaemia and syncope.

Toxicity

LD50 information The oral LD50 of nitroglycerin in rats is 105 mg/kg and the LD50 of the intravenous form in rats is 23.2 mg/kg.

Overdose information An overdose of nitroglycerin can lead to a variety of hemodynamic effects. General effects may include vertigo, fever, flushed skin, and diaphoresis. Cardiorespiratory symptoms may include syncope, dyspnea, decreased heart rate, or palpitations. Neurologic manifestations can include paralysis, seizures, coma, and death. There are no known antidotes to an overdose of nitroglycerin, and it is not known whether its metabolites can be removed from the circulation. If hypotension occurs due to an overdose with nitroglycerin, elevate the lower limbs and administer an intravenous infusion of normal saline or other fluids if necessary to maintain central fluid volume.

Precaution

Only the smallest dose required for effective control of the acute anginal attack should be used. Excessive use may lead to the development of tolerance. This drug should be used with caution in patients who may be volume-depleted or are already hypotensive.

Interaction

Orthostatic hypotension may occur with the combined use of calcium channel blockers, antihypertensive agents, phenothiazine, and tricyclic antidepressants. Use of alcohol with nitroglycerin may produce severe hypotension and collapse. Oral nitroglycerin may enhance the bioavailability of dihydroergotamine.

Food Interaction

• Avoid alcohol.

Nitroscot Alcohol interaction

[Minor] The ethyl alcohol and propylene glycol vehicle of some intravenous nitroglycerin preparations may cause sedation and hypotension.

Sedation and hypotension also may result when one of these preparations is coadministered with ethanol.

Management consists of monitoring mental status.

Nitroscot Drug Interaction

Minor: aspirin, aspirinUnknown: fluticasone / salmeterol, rosuvastatin, apixaban, omega-3 polyunsaturated fatty acids, insulin glargine, furosemide, atorvastatin, metoprolol, metoprolol, polyethylene glycol 3350, clopidogrel, albuterol, pantoprazole, levothyroxine, acetaminophen, cyanocobalamin, ascorbic acid, cholecalciferol

Nitroscot Disease Interaction

Major: AMI, anemia, hemodialysis, hypotension, intracranial pressure, pericarditisModerate: hypertrophic cardiomyopathyMinor: glaucoma

Volume of Distribution

The volume of distribution of nitroglycerin is 3 L/kg.

Elimination Route

Nitroscot is rapidly absorbed and is often used in emergency situations for this reason. After a sublingual dose of 0.5 mg of nitroglycerin, peak concentration was reached by an average of in 4.4 minutes after administration and was measured to be 2.56 ng/ml.

Cmax following a 0.6mg dose of sublingual nitroglycerin was measured to be 2.1 ng/mL and AUC was 14.9 minutes, and Tmax was 7.2 minutes. Absolute bioavailability after the administration of sublingual nitroglycerin tablets is about 40%. The bioavailability of nitroglycerin depends on factors such as mucosal metabolism and hydration status, which both affect the absorption of sublingual drugs.

Half Life

In a pharmacokinetic study, the plasma half-life of intravenously administered nitroglycerin was 2.8 ± 0.9 minutes. The FDA label for the intravenous form of nitroglycerin indicates a similar plasma half-life of about 3 minutes. A pharmacokinetic study using sublingual nitroglycerin estimated the plasma half-life to be approximately 6 minutes. The elimination half-lives of 1,2- and 1,3-dinitroglycerin (metabolites of nitroglycerin)range between 32-26 minutes.

Clearance

The FDA label for the intravenous form of nitroglycerin estimates clearance to be 1 L/kg/min. Apparent clearance after a sublingual dose was measured to be 21.9 L/min in a pharmacokinetic study of 22 patients with ischemic heart disease and angina.

Elimination Route

Metabolism is the main route by which nitroglycerin is eliminated from the body.

Pregnancy & Breastfeeding use

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Nitroscot should be given to pregnant women only if clearly needed.

Nursing Mothers: It is not known whether nitroglycerin is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Nitroscot spray is administered to a nursing woman.

Contraindication

Hypersensitivity to nitrates. Obstructive hypertrophic cardiomyopathy. Low cardiac output secondary to hypovolemia. Inferior myocardial infarction with right ventricular involvement. Raised intracranial pressure. Mitral valve propalpse. Glaucoma.

Special Warning

Use in neonates: Safety and efficacy for use in infants and children have not been established.

Use in children: Safety and efficacy for use in children has not been established.

Acute Overdose

Symptoms: Hypotension, reflex tachycardia, pallor, sweating, diarrhoea, weak pulse, collapse, syncope, dizziness, headache, asthenia, nausea, vomiting, methaemoglobinaemia. Bradycardia, psychosis and resp depression may occur in severe poisoning.

Management: Increase central fluid volume through passive elevation of patient’s legs. IV infusion of normal saline or similar fluid may also be necessary. Methylene blue infusion may be given in case of methaemoglobinaemia. Administer oxygen if necessary.

Storage Condition

Store between 15-30° C. Protect from light and moisture. Keep away from the reach of children.

Innovators Monograph

You find simplified version here Nitroscot