nitroglycerin; NTG; TNG (Tridil, NitroBid, Nitrol, Nitrostat, Deponit, Minitran, NitroDur, Nitropaste, Rectiv)

Indications

• hypertension
• acute relief of angina pectoris, unstable angina
• prophylaxis for angina pectoris
• preferred vasodilator for treatment of heart failure in the setting of acute myocardial infarction
• may also be useful in treatment of cardiogenic pulmonary edema
• ointment for symptomatic treatment of anal fissures

Contraindications

• severe bradycardia or tachycardia
• concurrent use of phosphodiesterase 5 inhibitors
  • sildenafil (Viagra) within 24 hours
  • tadalafil (Cialis) within 48 hours

Caution:

• hypovolemia
• constrictive pericarditis
• hypertension & hypotension
• increased intracranial pressure

pregnancy category = c

safety in lactation = ?

Dosage

• IV (infusion): Tradenames: Tridil, NitroBid.
  • mix 50 mg (5 mg/mL, 10 mL) in 250 mL D5W (200 ug/mL)
  • start at 5 ug/min (1.5 mL/min), max 200 ug/min.
• ointment
  • 2% (Nitropaste): Tradenames Nitro-bid, Nitrol.
    • 0.5-5 inches every 4-8 hours
    • remove every 8/day (to avoid tolerance)
    • (15 mg/inch). (30 g, 60 g)
  • 0.2% & 0.4% (Reactiv) for anal fissures
• sublingual: Tradename: Nitrostat.
  • 0.4 mg SL (if no relief after 5 min, call 911)
• sustained-release: Tradename: NitroBid.
  • start 2.5 mg PO BID/TID, titrate upward as needed.
• spray: Tradename: Nitrolingual.
  • 1-2 oral sprays PRN.
• transdermal:
  • 1 patch QD.
  • Deponit: 0.2, 0.4 mg/hr.
  • Minitran: 0.1, 0.2, 0.4, 0.6 mg/hr.
  • Nitro-Dur: 0.1, 0.2, 0.3, 0.4, 0.6, 0.8 mg/hr.
  • Nitrodisc: 0.2, 0.3, 0.4 mg/hr.
  • Transderm-Nitro: 0.1, 0.2, 0.4,0.6, 0.8 mg/hr.

Conversion: ointment < 1 inch patch 0.4 mg/hr dinitrate 20 mg TID

Injection: 5 mg/mL (10 mL)

Tabs: (sublingual) 0.15, 0.4, 0.4, 0.6 mg. {tablets useable until expiration date}

Tabs: (sustained-release) 2.5, 6.5, 9 mg.

Storage

• store in orginal container (reason unclear)

Pharmacokinetics

• onset of action
  • immediately following IV administration
  • within 2 minutes after sublingual administration
  • 20-40 minutes after SR capsule
  • 15-60 minutes after application of ointment
  • 30-60 minutes after application of patch
• peak effect
  • immediately following IV administration
  • within 4-8 minutes after sublingual administration
  • 45-120 minutes after SR capsule
  • 30-120 minutes after application of ointment
  • 60-180 minutes after application of patch
• duration of action
  • 3-5 minutes following IV administration
  • 30-60 minutes after sublingual administration
  • 4-8 hours after SR capsule
  • 2-12 hours after application of ointment
  • 18-24 hours after application of patch
• extensive 1st pass metabolism limits systemic absorbtion
• metabolized by liver
• long-term administration may saturate metabolic capacity of the liver, resulting in accumulation & tolerance
• 1/2life is 2-3 hours

elimination via liver

1/2life = 1-3 minutes

Adverse effects

• common (> 10%)
  • headache, flushing, lightheadedness, dizziness, weakness, orthostatic hypotension
• less common (1-10%)
  • rash, exfoliative dermatitis
• uncommon (< 1%)
  • nausea/vomiting, methemoglobinemia (overdose), reflex tachycardia, perspiration & collapse, bradycardia, coronary vasculature insufficiency, arrhythmias, allergic contact dermatitis, alcohol intoxication
• other
  • may cause tolerance & dependence with prolonged use
  • tingling or burning under the tongue NOT a reliable indicator of potency of sublingual form

• drug adverse effects of antihypertensive agents

Drug interactions

• may cause additive hypotension in combination with antihypertensive agents

• drug interaction(s) of nitrates with phosphodiesterase-5-inhibitors
• drug interaction(s) of phosphodiesterase-5-inhibitor with nitrates
• drug interaction(s) of NSAIDs & antihypertensives

Mechanism of action

• converted to nitric oxide (NO, EDRF) by vascular endothelium
• NO activates guanylate cyclase
• increases cGMP
• decreases intracellular Ca+2
• direct relaxation of smooth muscle, including that in the arteries & veins
• low concentrations of nitroglycerin produce dilation of the veins that predominates over that of arterioles
• venodilation results in decreased left & right end diastolic pressures (decreased preload)
• coronary blood flow increases transiently
• may inhibit platelet aggregation

Notes

• Nitroglycerin was first synthesized in 1846 by Sobero, who observed that a small quantity of the oily substance placed on the tongue elicited a severe headache
  • In 1879, William Murrell established the use of sublingual nitroglycerin for relief of acute angina.

More general terms

• nitrate

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4510