Nitroglycerin / Glyceryl Trinitrate (GTN)

(nye troe gli' ser in)

PCaution when used during lactation / LCaution when used during lactation : Caution - pregnancy &  lactation (breast feeding)

Molecule Info

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Indication(s) & Dosage

Nitroglycerin (GTN) is indicated for acute relief and prophylaxis of angina pectoris from coronary artery disease (CAD).

Tablet should be used sublingually (under tongue) or in buccal pouch at onset of acute anginal attack. Doses can be repeated approx. after 5 minutes until relief is obtained. Seek immediate medical attention if pain persists after 15 minutes with 3 oral formulations taken, or even if pain is felt somewhat different than usual. Prophylactic use can be considered 5 to 10 minutes prior to activity involvement and patient should be at rest. Renal failure patients doesn't need dosage adjustment.

Stable angina pectoris

Adult: As modified release (MR) preparation: 12.8 mg t.i.d. (max)
Acute phase
Adult: As MR tablet: 300-600 mcg Sublingually, repeat if necessary. Seek medical assistance ifpain persists after a total of 3 doses within 15 minutes. As aerosol spray: 1-2 sprays of 400 mcg each directed onto or under tongue, closing mouth after spraying. No more than 3 metered-doses to be taken at any one time and min of 15 minutes interval between consecutive treatments. 

Buccal preparation
Acute phase
Adult: 2-5 mg t.i.d, placed between gum and upper lip, increased if necessary. If buccal tablet is accidentally swallowed, place another tablet in buccal cavity. 

Buccal preparation
Heart failure (HF)
Adult: 5 mg placed between gum and upper lip, repeated until symptoms are controlled. For chronic heart failure: 5-10 mg t.i.d may be used. 

Intravenous (IV) preparation
Heart failure
Adult: Start with 5-25 mcg/minute.
Intravenous (IV) preparation
Acute myocardial infarction (AMI)
Adult: Start with 5-25 mcg/minute, adjust according to patient's response. Usual range: 10-200 mcg/minute. Max: 400 mcg/minute. 
Intravenous (IV) preparation
Induction of hypotension or control of hypertension during surgery
Adult: Start with 5-25 mcg/minute, adjust according to patient's response. Usual range: 10-200 mcg/minute. Max: 400 mcg/minute.

Intravenous (IV) preparation
Unstable angina
Adult: Start with 5-10 mcg/minute. Usual range: 10-200 mcg/minute.

Transdermal preparation
Management of stable angina
Adult: Apply 1 patch (releasing 2.5-20 mg/24 hrs) onto chest, upper arms, thigh, abdomen or shoulder. Replace with a new patch each 24 hrs and rotate sites of application with each new patch. Max: 20 mg daily.
Transdermal preparation
Prophylaxis of extravasation secondary to venous cannulation & phlebitis
Adult: Apply one 5 mg patch distal to IV site, replace patch at a different skin site either daily or after 3-4 days depending on patch; continue for as long as IV infusion is maintained.

Topical/Cutaneous preparation
Management of stable angina
Adult: As 2% ointment: Apply 0.5-2 inches (to chest, arm, thigh or back) 3-4 times daily or each 3-4 hrs, if necessary. 
Rectal preparation
Pain due to chronic anal fissure
Adult: As a 0.4% ointment: Apply 1.5 mg intra anally 12 hourly for up to 8 weeks.

Incompatibility: Alteplase, levofloxacin. Hydralazine, phenytoin.

Overdose Symptoms include decreased cardiac output and hypotension, vasodilatation, venous pooling. There may be also throbbing headache, confusion and moderate fever; vertigo; palpitation;nausea, vomiting; syncope; air hunger and dyspnoea, increased intracranial pressure, visual disturbance.
Contraindications Concomitant use with phosphodiesterase type 5 inhibitor. Hypersensitivity. Heart failure, marked anaemia, severe hypotension, hypertrophic obstructive cardiomyopathy, cerebral haemorrhage or head trauma, low cardiac output secondary to hypovolaemia, inferior MI with right ventricular involvement, raised intracranial pressure.
Special Precautions
  • Marked hepatic/renal impairment, malnutrition, hypothermia, hypothyroidism.
  • CV disease, lung disease or cor-pulmonale.
  • Pregnancy, lactation, glaucoma, mitral valve prolapse, cardiac tamponade, syncope.

Gradual withdrawal in patients who have received prolonged high dose infusions. Avoid prolonged excessive hypotension. Nitrate-free interval is recommended in patients on continuous treatment with nitrates to decreaserisk of tolerance.

Adverse Drug Reaction(s)

Tachycardia, throbbing headache and tolerance, facial flushing & dizziness. Vomiting, restlessness, hypotension, syncope, rarely cyanosis and methaemoglobinaemia, impaired respiration, bradycardia may result from large doses.

IV admininstration: IV preparation contains substantial quantities of alcohol and alcohol intoxication can occur.

Sublingual Tabs/Spray preparation: Dry mouth, localised burning sensation.

Topical preparation: Contact dermatitis, erythema, local irritation.

Transdermal patches: Contact dermatitis, metal-containing patches should be removed before cardioversion, defibrillation, diathermy. Buccal oral formulations: Delayed dissolution, may be swallowed by mistake.

Serious ADR: Paradoxical bradycardia, impaired respiration, syncope and collapse, hypotension, .

Drug Interactions Dihydroergotamine bioavailability enhance. Infusion may extend pancuronium-induced neuromuscular blockade, decrease efficacy of heparin, alteplase and noradrenaline when used together. Buccal and sublingual preparations' efficacy may be decreased by drugs that can cause dry mouth due to decreased dissolution. Aspirin and other NSAIDs may decreasetherapeutic response to glyceryl trinitrate.
Serious: Concommitant use of calcium channel blockers, antihypertensives, phenothiazines and TCAs may result in Orthostatic hypotension. Please consult detailed drug interactions before prescribing.
Pregnancy Category (US FDA) Category C: Animals studies have revealed adverse effects on foetus and there are no controlled studies in women are not available. When potential benefit overweighs the risk to foetus this medication can be considered.
Storage Store at 15-30°C. 
Pharmacology Nitroglycerin (GTN) relaxes vascular smooth muscle cells. Nitroglycerin (GTN) results dilation of both arterial and venous beds (dose-dependent), predominantly venous. Peripheral pooling of blood results from dilation of postcapillary vessels including large veins, decreases venous return and reduces preload (left ventricular end-diastolic pressure). Nitroglycerin (GTN) also results arteriolar relaxation, thereby reducing afterload (peripheral vascular resistance and arterial pressure) and dilates large epicardial coronary arteries. Systolic, diastolic and mean arterial BP (blood pressure) may be reduced in therapeutic doses. Coronary perfusion pressure may be reduced if BP (blood pressure) falls significantly or increased heart rate reduces diastolic filling time. Increased central venous and pulmonary capillary wedge pressures, pulmonary and systemic vascular resistance are also decreased in therapeutic doses. , Presumably due to a compensatory response to fall in blood pressure, heart rate is usually increased nominally. The Cardiac indices may changed, myocardial oxygen demand is decreased and a favorable supply demand ratio can be availed.

Mode of Action

Guanylate cyclase is activated by a free radical, nitric oxide (NO) created by Nitroglycerin (GTN) resulting increased cGMP (cyclic GMP) in smooth muscle and other tissues. De-phosphorylation of myosin light chains from these events, regulate smooth muscle contraction and produce vasodilatation.

Pharmacodynamics

In alignment with angina relief (symptomatic), digital plethysmography indicates that onset of vasodilatory effect occurs approximately 1 to 3 minutes after sublingual nitroglycerin (GTN) administration and reaches a maximum by 5 minutes after dose. Effects persist for at least 25 minutes following Nitroglycerin (GTN) administration.

Pharmacokinetics 

Absorption

Nitroglycerin (GTN) is rapidly absorbed following sublingual administration of Nitroglycerin (GTN) oral formulations. Mean peak nitroglycerin (GTN) plasma concentrations occur at a mean time of approximately 6 to 7 minutes after dose (Chart-1). Maximum plasma nitroglycerin (GTN) concentrations, Cmax and area under plasma concentration time curves, AUC increase dose dependently following 0.3 to 0.6 mg Nitroglycerin. The absolute bioavailability of nitroglycerin (GTN) from oral formulations is approximately 40% but due to factors influencing drug absorption (sublingual hydration and mucosal metabolism) it tends to be variable.

Chart

PARAMETER MEAN NITROGLYCERIN (SD) VALUES
2 x 0.3 MG Nitroglycerin (GTN) TABLET 1 x 0.6 MG Nitroglycerin (GTN) TABLET
Cmax, ng/ml 2.3 (1.7) 2.1 (1.5)
Tmax, mins 6.4 (2.5) 7.2 (3.2)
AUC, mins 14.9 (8.2) 14.9 (11.4)
t½, mins 2.8 (1.1) 2.6 (0.6)
Distribution

Volume of distribution of nitroglycerin (GTN) is 3.3 L/kg following IV (intravenous) administration. Plasma proteins binding is approximately 60% when plasma concentrations is between 50 and 500 ng/mL.

Metabolism

A liver reductase enzyme is of primary importance in metabolism of nitroglycerin (GTN) to glycerol di- and mononitrate metabolites and ultimately to glycerol and organic nitrate. Known sites of extrahepatic metabolism include red blood cells and vascular walls. In addition to nitroglycerin (GTN), 2 major metabolites 1, 2- and 1,3-dinitroglycerin (GTN), are found in plasma. Mean peak 1,2- and 1,3-dinitroglycerin (GTN) plasma concentrations occur at approximately 15 minutes after dose. The elimination half-life of 1,2- and 1,3-dinitroglycerin (GTN) is 36 and 32 minutes, respectively. The 1,2- and 1,3-dinitroglycerin (GTN) metabolites have been reported to possess approximately 2% and 10%, respectively, of pharmacological activity of nitroglycerin (GTN). Higher plasma concentrations of dinitro metabolites, along with their nearly 10-fold longer elimination half-lives, may contribute significantly to duration of pharmacologic effect. Glycerol mononitrate metabolites of nitroglycerin (GTN) are biologically inactive.

Excretion

Nitroglycerin (GTN) plasma concentrations decrease rapidly, with a mean elimination half-life of 2 to 3 minutes. Half-life values range from 1.5 to 7.5 minutes. Clearance (13.6 L/min) greatly exceeds hepatic blood flow. Metabolism is primary route of drug elimination.

ATC Classification C05AE01 and C01DA02 - glyceryl trinitrate and  class of organic nitrate vasodilators respectively

 

Brand/Product Info


Total Products : 25                         
Brand Name Manufacturer/Marketer Composition Dosage Form Pack Size & Price
ANGICARD Drug International Ltd Glyceryl trinitrate (Nitroglycerine) 0.5mg Tablet 100's: 300.00 MRP
ANGIST SR The Acme Laboratories Ltd. Glyceryl trinitrate (Nitroglycerine) 2.6mg Tablet (sustained release) 30's: 120.30 MRP
ANRIL 0.5 Square Pharmaceuticals Ltd. Nitroglycerin 0.5mg Sublingual Tablet 3x10's: 90.30 MRP
ANRIL INJ Square Pharmaceuticals Ltd. Nitroglycerin 5mg/ml IV Injection 4x1's: 302.00 MRP
ANRIL SPRAY Square Pharmaceuticals Ltd. Nitroglycerin 400 mcg/spray Spray 200 sprays: 216.45 MRP
ANRIL SR-TAB Square Pharmaceuticals Ltd. Nitroglycerin 2.6mg SR Tablet 5x10's: 201.50 MRP
GTN 2.6 SR Eskayef Bangladesh Ltd Nitroglycerin BP 2.6mg Tablet (sustained release) 50's MRP: 200.00
NIDOCARD Retard Drug International Ltd Glyceryl trinitrate (Nitroglycerine) 2.6mg Tablet (sustained release) 100's: 400.00 MRP
NIDOCARD Retard-6.4 Drug International Ltd Glyceryl trinitrate (Nitroglycerine) 6.4mg Tablet (sustained release) 50's: 350.00 MRP
NIDOCARD Spray Drug International Ltd Glyceryl trinitrate 400mcg/Met. Dose, 200 MD unit Spray 200 doses/unit: 200.00 MRP
NITRIN SR Healthcare Pharmacuticals Ltd. Nitroglycerin USP 2.6mg Tablet 60's MRP 300 Tk
NITRO-SR Unimed & Unihealth Manufacturers Ltd. Glyceryl trinitrate (Nitroglycerine) 2.6mg Tablet (sustained release) 30's: 120.00 MRP
NITROCAP Orion Pharma Ltd. Glyceryl trinitrate (Nitroglycerine) 2.6mg Capsule 30's: 150.60 MRP
NITROCARD Aristopharma Ltd. Glyceryl trinitrate (Nitroglycerine) 2.6mg Tablet 50's: 200.00 MRP
NITRODIL Medimet Pharmaceuticals Ltd Glyceryl trinitrate (Nitroglycerine) 2.6mg Capsule 50's: 232.50 MRP
NITROMINT Retard City Overseas Glyceryl trinitrate (Nitroglycerine) 2.6mg Tablet (Controlled Release) 30's: 147.00 TP
NITROMINT Spray City Overseas Glyceryl trinitrate 400mcg/Met. Dose, 200 MD unit Spray 180 doses/unit: 205.00 TP
NITROSOL Beximco Pharmaceuticals Ltd Glyceryl Trinitrate BP 400mcg/actuation Spray 200MD: 225.00 MRP
NITROVAS Popular Pharmaceuticals Ltd. Glyceryl trinitrate (Nitroglycerine) 4mg/gm, Sublingual Ointment 30gm: 130.49 MRP
NITROVAS SR Popular Pharmaceuticals Ltd. Glyceryl trinitrate (Nitroglycerine) 2.6mg Tablet (sustained release) 30's: 120.62 MRP
PACTORIN Retard ACI Ltd. Glyceryl trinitrate (Nitroglycerine) 2.6mg Tablet retard 50's: 201.00 MRP
RECTOCARE OINT Square Pharmaceuticals Ltd. Nitroglycerin 0.4% Ointment 15 gm: 65.45 MRP
Trocer SR 2.6 Incepta Pharmaceuticals Limited Nitroglycerin BP 2.6mg Tablet 10x3's:MRP 120 Tk
TROCER SR Capsule Incepta Pharmaceuticals Limited Nitroglycerin USP 2.6mg Capsule 30's: 120.00 MRP
XYNOCARD SR The White Horse Pharma Glyceryl trinitrate (Nitroglycerine) 2.6mg Tablet (sustained release) 50's: 150.00 MRP

Gen. MedInfo

Why is this medication suggested? 

This medication, Nitroglycerin (GTN) formulations are in the class of vasodilators, used in people who have coronary artery disease (CAD) i.e narrowing of blood vessels that supply blood to the heart muscle to treat episodes of angina or chest pain. Being vasodilator, it relaxes blood vessels, supply more blood for heart muscles and thereby reduces the stress of the heart. Different GTN formulations (spray / oral) can be taken as well to prevent angina attack, before the activities which might produce episodes of angina. The extended-release Nitroglycerin (GTN) formulations can be used to prevent angina attack but not when the attack already started.

How should this medicine be used?

There might be different Nitroglycerin (GTN) formulation - sublingual tablet (placed under the tongue), extended-release capsule/tablet and spray. Sublingual or buccal (placed between teeth & gum) must not chewed or swallowed rather should be kept in mouth to be slowly dissolved; it may give burning or tingling sensation which is normal.

While extended-release formulations can be taken by mouth 3-4 times daily, other preparations including spray are taken as required, either 5-10 minutes prior activities or at the onset of chest pain (Angina).

You need to strictly adhere with the prescription & guidance of the Doctor. It is advisable to sit down and take a nitroglycerin (GTN) dose when the attack starts. Your doctor may instruct you to take a 2nd dose after 5 minutes if chest pain persists and even a 3rd dose after another 5 minutes if required. But after 3rd dose if the pain still persists you’ll need immediate medical attention straight away.

How to use Nitroglycerin (GTN) spray?

  • First of all, take a sit if possible. Hold the container & remove plastic cap, no need to shake.
  • Container should be held upright and pointed away from yourself and others and to prime the container press button 10 times – if you are first time user. Otherwise, press button 2 times to re-prime container if you haven’t used it for last 6 weeks or more.
  • Place the upright container close to your mouth and with your forefinger press button firmly to release spray into your mouth. You cannot inhale the spray.
  • Keep your mouth closed with the medication for 5-10 minutes.
  • Close the container with plastic cap.
  • Hold container upright and check liquid level in the container time to time to ensure that you have enough medication on hand. The container may not dispense sufficient medication dose, if the liquid level remains at bottom.

Never try to open container of nitroglycerin (GTN) spray as it may catch fire and even should not be used closed to flame or fire.

What protections should be taken?

Prior to intake of Nitroglycerin (GTN),

  • inform your doctor if the individual allergic to any kind of nitroglycerin (GTN) formulations or any other medications.
  • inform your doctor if the individual taking Phospho Di Esterase inhibitors (PDE-5) like sildenafil (Viagra), tadalafil and vardenafil. In that cases you may not take Nitroglycerin (GTN).
  • inform your doctor if the individual taking or plan to take medications like- aspirin; beta blockers (atenolol, labetalol, metoprolol, nadolol, propranolol, sotalol, timolol etc); calcium channel blockers; bromocriptine; cabergoline; dihydroergotamine; ergotamine, methylergonovine, methysergide etc; heparin; medications for hypertension or heart failure. Use of these medications might require Nitroglycerin dosage adjustment.
  • if the individual takes preparations like antihistamines that cause dry mouth, sublingual /buccal nitroglycerin (GTN) may not adequately dissolve in the mouth. Other medication that might cause dry mouth are antidepressants including amitriptyline, amoxapine, clomipramine (Anafranil), desipramine, doxepin, imipramine (Tofranil), nortriptyline, protriptyline and trimipramine; ipratropium or medications for irritable bowel disease, motion sickness, parkinson's disease, ulcers, or urinary problems. In that case, the individual may need to take artificial saliva product or chew gum to produce sufficient saliva to dissolve nitroglycerin tablet.
  • inform your doctor if the individual had a heart attack on recent time or have anemia. Nitroglycerin (GTN) should not be taken in any condition that causes increased intracranial pressure. Also, the doctor should know beforehand, if the individual is dehydrated, had heart failure low blood pressure, or hypertrophic cardiomyopathy.
  • inform the doctor if the individual is pregnant or plan to become pregnant, or breast-feeding.
  • if the individual having surgery, including dental surgery, inform the dentist that the individual taking nitroglycerin (GTN).
  • Nitroglycerin (GTN) may cause dizziness, lightheadedness and fainting while getting up quickly from a lying position. So it is advisable to get up slowly, resting the feet on floor for a few minutes and then stand up.
  • Nitroglycerin (GTN) may cause headaches and this is not unusual. To avoid headaches recommended doses should not be reduced otherwise the medication may not work as it should be.

This information is provided for reference only and not a replacement for and should only be used in conjunction with full consultation with a registered medical practitioner. It may not contain all available information you require and cannot substitute professional medical care, nor does it take into account all individual circumstances. Although great effort has been made to ensure content accuracy, mph-bd shall not be held responsible or liable for any claims or damages arising from use or misuse of information contained herein, its contents or omissions, or otherwise.

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