๐Ÿฉบ MedAtlax

Search

SearchSearch

nitrates & nitrites

Aug 24, 20254 min read

Organic nitrates and nitrites:

Inorganic nitrates are ineffective

Classification:

  1. Short-acting nitrates:
  • Amyl nitrite (inhalation)
  • Nitroglycerine (SL)
  • Isosorbide dinitrate (SL)
  • i.v. nitroglycerin
  1. Long-acting nitrates:
  • Isosorbide dinitrate or
  • mononitrate (Oral)
  1. Transdermal patches

Pharmacokinetics:

Absorption: nitrates are rapidly absorbed from buccal membrane, GIT, and bronchioles.

Metabolism: in the liver:

  • If given oral โ†’ extensive first-pass hepatic metabolism (oral bioavailability <10%).
  • If given sublingual โ†’ no first-pass metabolism โ†’ high bioavailability.

Excretion: via the kidney.

Mechanism of action:

acts by causing systemic venodilation by causing liberation of the free radical nitric oxide (NO) which is identical to the endothelial derived relaxing factor (EDRF) โ†’ โ†‘ cGMP โ†’ โ†“ Ca2+ influx into the vascular sm ms โ†’ VD (more on the veins).

Pharmacological effects:

CVS:

  • Blood vessels: VD of the venous (and to lesser extent to the arterial) side leading to โ†“ preload . So, Reducing myocardial wall tension and oxygen requirements

    Dilating the epicardial coronary vessels leading to increased coronary blood flow

    • Increasing blood flow in collateral vessels
    • VD of the arteries in the face and neck leading to flushing.
    • VD of meningeal arteries leading to throbbing headache. ย 

  • Heart: Reflex tachycardia (in high dose) 2ry to โ†“ BP.

  • BP: High doses cause โ†“ in both systolic and diastolic BP.

Smooth ms:

  • relaxation of bronchial, GIT, uterine, and biliary sm ms. ย  Respiration:
  • reflex tachypnea (โ†‘ resp rate) due to hypotension. ย  Blood:
  • Methemoglobinemia in high doses due to oxidation of Hb into met-Hb.

Therapeutic uses:

1-Angina pectoris:

  • Nitrates are used for treatment of all types of angina both for relieving the acute attack and for prophylaxis.

These effects will lead to: A-Reduction of myocardial O2 demand through:

  • Venodilatation โ†’ โ†“ venous return (preload) .
  • Arteriolodilatation โ†’ โ†“ peripheral resistance (afterload). ย  B-Enhancement of myocardial perfusion through:
  • Coronary VD.
  • Redistribution of blood from large epicordial vessels to ischemic subendo-cardial vessels.

2-Myocardial infarction: to โ†“ the area of myocardial damage. ย  3-Acute heart failure: to โ†“ preload and afterload. ย  4-Treatment of cyanide poisoning: cyanide has high affinity for metHb more than normal Hb. ย  5-Biliary colic. ย  6-Management of constriction ring during labor.

Side effects:

  1. Hypotension and reflex tachycardia: may aggravate angina.

  2. Throbbing headache: with nitroglycerin, due to VD of meningeal arteries.

  3. Flushing of the face.

  4. Tolerance to its effect: with long acting preparation due to:

    • Depletion of sulfhydryl (-SH) containing enzymes necessary for liberation of NO from nitrates โ†’ โ†“ formation of NO โ†’ โ†“ VD effect.
    • Reflex sympathetic activation (due to hypotension), this will cause VC.
    • Prevention of tolerance: make a daily nitrate-free interval (8-10โ€“12 h) to give chance for the SH- containing enzymes to regenerate.
    • During this period, give another anti-anginal drug (e.g. beta-blocker or CCBs).

  5. Methemoglobinemia in high doses (rare).

  6. Never to be combined with other drugs causing vasodilation (Viagraยฎ) or hypotension - would result in irreversible hypotension

Precautions during nitrate therapy:

  • Tablet should be held under tongue until dissolved. Avoid eating, drinking, or smoking until tablet is dissolved.
  • Advise patient to sit down.
  • Relief should occur in 1 to 3 minutes
  • Use the smallest effective dose to avoid hypotension and reflex tachycardia.
  • The patient should consult his doctor if anginal pain does not improve after taking 3 SL tablets of NG during 15 min (may be MI). May be repeated every 5 minutes for 3 doses.
  • Nitroglycerine tablets should not be put in direct sunlight or with cotton .
  • The expiry date (60 days) should be checked (active tablets have burning taste).
  • Sudden withdrawal may cause acute MI.

Sustained Released Tablet

Administer dose 1 hour before or 2 hours after meal with a full glass of water for faster absorption.

Nitroglycerine Patch

  • Place the patch on a hairless area of chest or upper arm each day.
  • Move patch to a different place on your body each day to prevent skin irritation.
  • Remove the patch for 8 to 12 hours each night and put on a fresh patch each day.
  • Patches โ€“ takes 40 minutes to an hour to start working
  • Place the patch on a hairless area of chest or upper arm each day.
  • Move patch to a different place on your body each day to prevent skin irritation.
  • Remove the patch for 8 to 12 hours each night and put on a fresh patch each day.
  • Patches โ€“ย  takes 40 minutes to an hour to start working

Nitroglycerine Ointment

Acute Coronary Syndrome

  • The resulting vasodilation of veins and peripheral and coronary arteries may reduce excessive cardiac preload and afterload.

  • Route: Intravenous nitroglycerin is preferred

  • Indications: The first 24 to 48 hours of acute MI and heart failure , large anterior MI, persistent ischemia , or hypertension.

Graph View

Backlinks