Gyceryl Trinitrate

NITRATES:
  • Prodrugs that are sources of nitric oxide (NO)
  • Drugs include: Glyceryltrinitrate (nitroglycerin), isosorbidemononitrate and isosorbidedinitrate
MECHANISM OF ACTION:
  • Organic nitrates lead to the formation of the reactive gaseous free radical NO and related NO-containing compounds
  • NO can activate guanylylcyclase, increase the cellular level of cyclic GMP, activate PKG, and modulate the activities of cyclic nucleotide phosphodiesterases
  • In smooth muscle, the net result is reduced phosphorylation of myosin light chain, reduced Ca2+ concentration in the cytosol, and relaxation
  • Glyceryl trinitrate is given by sublingual route because of Hepatic first pass metabolism
  • Transdermal patch can be used for GTN
ACTION:
  • Promote relaxation of vascular smooth muscle
  • Low concentrations of nitroglycerin preferentially dilate veins more than arterioles
  1. decreases venous return, leading to a fall in left and right ventricular chamber size and end-diastolic pressures
  2. Systemic arterial pressure may fall slightly
  • Higher doses of organic nitrates cause:
  1. Further venous pooling and may decrease arteriolar resistance as well, thereby decreasing blood pressure and cardiac output
  2. Causing pallor, weakness, dizziness, and activation of compensatory sympathetic reflexes
  • Reduces myocardial O demand
  • decreasing both preload and afterload
  • Dilating coronary arteries and thereby increasing coronary blood flow mechanisms not entirely clear
  • Limits platelet aggregation/adhesion
  • Bronchial smooth muscle is relaxed irrespective of the preexisting tone
  • The muscles of the biliary tract, including those of the gallbladder, biliary ducts, and sphincter of Oddi, are effectively relaxed
  • Smooth muscle of the GI tract, including that of the esophagus, can be relaxed and its spontaneous motility decreased
  • Long term use of nitrates lead to decreased effect because of SH group in the enzyme
  • Relaxes ureteral and uterine smooth muscle
USES:
  • Stable angina pectoris
  • CCF
  • Unstable angina pectoris and NSTEMI
  • Acute myocardial infarction
  • Prinzmetal angina
  • Portal hypertension
  • Asthma and as a diuretic (obsolete)
  • Cyanide poisoning
  • Esophageal spasm
PORTAL HYPERTENSION:
  • Nitroglycerin has been used in combination with vasopressin to control acute variceal bleeding. The rate of infusion of nitroglycerin is 50 to 400 μg/min, provided that the systolic blood pressure > 90 mmHg
  • Nitrates are no longer recommended, either alone or in combination with a ß blocker, for primary prophylaxis to prevent first variceal bleeds
  • For secondary prophylaxis (to prevent varicealrebleeding), isosorbidemononitrate may be added to a beta blocker if the beta blocker alone has not resulted in an appropriate decrease in HVPG
DOSE:
NITROGLYCERINE DOSE:
ROUTE DOSE DURATION
Sublingual 0.3-0.6 to 1.5mg 10 min
spray 0.4mg 10min
Ointment 2%6x6" 15x15cm7.5 to 40mg 7hrs
Transdermal 0.2-0.8mg/hr every 12hr 8-12hr intermittent
Oral sustained release 2.5-13mg 4-8 hrs
Intravenous 5-200mcg/min 7-8 hrs
ADVERSE EFFECT:

  • Headache
  • Transient episodes of dizziness, weakness, and other manifestations associated with postural hypotension may develop
  • High doses of organic nitrates causes postural hypotension, facial flushing, and tachycardia(blocked by beta blocker)
  • Prolonged therapy causes endothelial dysfunction
  • Vasodilatation,Methamoglobinemia
  • Aggravation of symptoms of angina in a patient when given nitrates is seen in Idiopathic hypertrophic subaortic stenosis
INTERACTION:
  • Phosphodiesterase V inhibitors such as sildenafil, tardenafil, and vardenafil potentiate the action of the nitrates.
  • To preclude the dangerous hypotension that may occur, this combination is contraindicated.
Exam Question
  • CCF, Esophageal spasm & Cyanide poisoning can be treated by Nitrates 
  • Nitroglycerine causes Methamoglobinemia,Vasodilatation, Hypotension and Tachycardia
  • Role of nitrates in congestive cardiac failure is due to Decrease preload
  • Nitrates decrease myocardial oxygen consumption by direct reduction of oxygen consumption of the myocardial cell,dilation of the capacitance vessels & decreasing the size of heart
  • Long term use of nitrates lead to decreased effect because of SH group in the enzyme
  • Glyceryl trinitrate is given by sublingual route because of Hepatic first pass metabolism
  • Treatment of stable angina include Nitrates,CCBs
  • Agent of first choice in an acute attack of Prinzmetal's angina is Nitrates
  • Aggravation of symptoms of angina in a patient when given nitrates is seen in Idiopathic hypertrophic subaortic stenosis
  • Best time to administer long term nitrates for nocturnal angina Evening
  • Transdermal patch can be used for GTN
  • Tachycardia due to nitrates in a patient with angina pectoris is blocked by Beta blocker

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