| Structure |
Nitric and nitrous acid of alcohols |
| Pharmacodynamics |
- Taken up by vascular smooth muscle cells (and not cardiac, or skeletal muscle)
- Denitrited by glutathione-S-transferase
- Nitric oxide is then released. NO activates cGMP and reduces intracellular Ca2+.
- This leads to vasodilation.
- Organ system effects
- Vasodilation – low dose leads to vasodilation first. Larger dose causes arteriolar dilation, leading to reduced BP and reduced afterload à this reduces myocardial oxygen demand.
- Also causes a redistribution of blood flow in ischaemic cardiac tissues, leading to relief of angina symptoms.
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| Absorption/administration |
- Multiple routes – S/L, I/V, Buccal, Nasal, Patch, oral (for example, isosorbide mononitrate)
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| Distribution |
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| Metabolism |
- The liver contains a high capacity organic nitrate reductase à this ultimately inactivates the drug (extensive first pass)
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| Excretion |
- Via kidneys
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| Indications |
- Angina of effort
- Variant/Prinzmetal’s angina (coronary vasospasm)
- Unstable angina
- Mainly important because GTN reduces preload, and therefore reduces cardiac well tension and therefore, myocardial oxygen demand.
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| Contraindications |
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| Interactions |
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| Special precautions |
- Hypotensive patients
- Those patients with inferior/posterior MI
- Patients which cannot increase cardiac output to compensate (e.g. severe AS, tamponade)
- AVOID DRUG IN RICP
- Significant tachycardia/bradycardia
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| Adverse effects |
- Tachycardia and hypotension
- Headache (note that the drug is safe in raised intra-ocular pressure)
- Lightheadedness and dry mouth
- Lightheadedness and dry mouth
- Tachyphylaxis
- This is probably due to a decrease in tissue sulfhydryl groups and can be partially prevented/reversed with a sulfhydryl-regenerating agent.
- Methaemaglobinemia
- Nitrite groups react with haemoglobin to form methaemaglobin (but remember that in adults, this tends to be insignificant)
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| Dosing/administration |
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| Toxicology |
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| Withdrawal syndrome |
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