Glyceryl Trinitrate
NITRATES:
- Prodrugs that are sources of nitric oxide (NO).
Drugs include:
- Glyceryl trinitrate (Nitroglycerin/NTG).
- Isosorbide mononitrate.
- Isosorbide dinitrate
MECHANISM OF ACTION:
- Organic nitrates forms reactive gaseous free radical NO & it’s related NO-containing compounds.
NO activates guanylyl cyclase:
- Increases cellular cyclic GMP level, activates PKG, & modulates cyclic nucleotide phosphodiesterases activity.
ADMINISTRATION
- NTG given by sublingual route because of hepatic first pass metabolism
- Transdermal patch can be used for GTN.
AVAILABLE DRUGS:
- Pentaerythritol tetranitrate – Longest acting by inhalation route.
- Amyl nitrate – Shortest acting drug.
ACTION:
- Promote relaxation of vascular smooth muscle.
- Bronchial smooth muscle relaxed irrespective of preexisting tone.
- Relaxes ureteral & uterine smooth muscle.
- Muscles of biliary tract, including gallbladder, biliary ducts, & sphincter of Oddi – Effectively relaxed.
- Smooth muscle of GI tract, including oesophagus – Relaxed & decreases spontaneous motility.
Low concentrations of NTG:
- Dilates veins more than arterioles
- Decreases venous return.
- Reduces left & right ventricular chamber size.
- Systemic arterial pressure may fall slightly.
Higher doses of NTG:
- Further venous pooling.
- Decreases arteriolar resistance, blood pressure & cardiac output
- Results in pallor, weakness, dizziness, & activation of compensatory sympathetic reflexes.
Reduces myocardial O2 demand
- Decreases preload & afterload.
- Dilates coronary arteries & increases coronary blood flow.
- Limits platelet aggregation/adhesion.
- Long-term use of nitrates leads to tolerance (decreased efficiency).
- Due to its SH group in enzyme.
- Not seen with sublingual route.
- Melosidomine – Emerging non-tolerant drug.
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 – Mainly Amyl nitrate & sodium nitrate
- Oesophagal Spasm.
- DOSE:
NITROGLYCERINE DOSE:
| ROUTE | DOSE | DURATION |
| Sublingual | 0.3-0.6 to 1.5mg | 10 min |
| spray | 0.4mg | 10min |
| Ointment |
2%6×6″ 15x15cm 7.5 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.
- Manifestations of postural hypotension.
High doses of organic nitrates causes:
- Postural hypotension.
- Facial flushing.
- Tachycardia (blocked by beta blocker).
- Prolonged therapy causes endothelial dysfunction
- Vasodilatation.
Methemoglobinemia –
- Nitrates convert hemoglobin to methhemoglobin.
- High affinity for cyanide ions.
- Aggravation of angina symptoms in Idiopathic hypertrophic subaortic stenosis, on nitrate administration.
INTERACTION:
With Phosphodiesterase V inhibitors:
- Sildenafil & Vardenafil potentiates nitrates action.
- May result in dangerous hypotension.
- Due to excess cGMP by nitrates.
Exam Question
- CCF, oesophageal spasm & cyanide poisoning can be treated by Nitrates
- Nitroglycerine causes methemoglobinemia, vasodilatation, hypotension & tachycardia.
- Nitrates act in CCF by decreasing preload.
- Nitrates decrease myocardial oxygen consumption by direct reduction of myocardial oxygen consumption, dilation of capacitance vessels & decreasing heart size.
- Long-term nitrate usage decreases its own effect due to SH group in enzyme.
- NTG is given by sublingual route because of hepatic first-pass metabolism.
- Treatment of stable angina include nitrates & CCBs.
- DOC in an acute attack of Prinzmetal’s angina is Nitrates.
- Aggravation of angina symptoms is seen in Idiopathic hypertrophic subaortic stenosis on administering nitrates.
- Best time to administer long-term nitrates for nocturnal angina is evening.
- GTN can be used as “Transdermal patch”.
- Tachycardia due to nitrates with angina pectoris is blocked by Beta-blocker.
Don’t Forget to Solve all the previous Year Question asked on Glyceryl Trinitrate