Dr Sharon Rees @reesprescribe
Day 1: Discovered in 1847 as an early explosive, #glyceryltrinitrate, or GTN (also known as nitroglycerin) was used in blasting and smokeless gunpowder. In the UK, interest in amyl nitrite (no prescription use now) led to GTN usage for angina from 1867 (stable in solid medicinal form)
Dr Sharon Rees @reesprescribe
Day 2: #glyceryltrinitrate is a potent vasodilator. UK uses include angina treatment and prophylaxis, control of myocardial infarction and hypertension for cardiac surgery, anal fissure and prophylaxis of phlebitis (transdermal). Longer-acting nitrate agents can also treat left ventricular heart failure
Dr Sharon Rees @reesprescribe
Day 2 (cont): Sub-lingual spray 400mcg x 1-2/no more than three uses (shelf-life ~3yrs), sub-lingual tablet 300-600 mcg every 5 minutes up to 3 doses (tablets expire 8 weeks after opening), iv infusion 10-200 mcg/minute
Dr Sharon Rees @reesprescribe
Day 3: MOA #glyceryltrinitrate. Once in smooth muscle cells, denitration leads to release of nitric oxide. This activates guanylate cyclase and increases cGMP. Less Ca+ into cell allows smooth muscle relaxation. Powerful venodilation lowers cardiac preload. At higher doses, coronary artery vasospasm is relieved and there is lower afterload. All actions lower oxygen demand and relieve anginal pain
Dr Sharon Rees @reesprescribe
Day 4: Kinetics – GTN is a prodrug. Rapid absorption from sub-lingual and buccal mucosa > fast pain relief-effect but for < 30 mins. Extensive first pass metabolism limits formulations, t½ 1-3 minutes, but some metabolites can last longer (~30 mins). Metabolised in blood vessels/no elimination
Dr Sharon Rees @reesprescribe
Day 5: ADRs common: flushing, headache, postural hypotension, reflex tachycardia, nausea. Uncommon, circulatory collapse, tongue blistering (sub-lingual), exfoliative dermatitis (not exhaustive); NB potential to worsen angina if severe hypotension/reflex tachycardia
Dr Sharon Rees @reesprescribe
Day 5 (cont): Issues such as tolerance and avoiding sudden withdrawal as linked to rebound vasoconstriction; potential for angina, myocardial infarction and sudden death (caution for all nitrates) may depend on usage of GTN, especially with high continuous dose
Dr Sharon Rees @reesprescribe
Day 6: Drug-drug interactions #glyceryltrinitrate: All hypotensive agents including alcohol, tricyclic anti-depressants and neuroleptics, severe interaction with phosphodiesterase inhibitors eg sildenafil (not exhaustive). Note drugs with antimuscarinic effects can cause dry mouth and reduce the effectiveness of sublingual GTN tablets
Dr Sharon Rees @reesprescribe
Day 7: Mechanism for tolerance/cross tolerance to other nitrates largely unknown. Theories include: endothelial dysfunction, activation of counter cardiovascular reflexes eg renin angiotensin aldosterone system, elevation of opposing neurohormones, eg norepinephrine and lower nitrate metabolism (prodrug)
EARN YOUR CPD CERTIFICATE
With the help of Prescribing and Therapeutics Training Ltd and the Journal of Prescribing Practice, you can earn your 1-hour CPD certificate.
In addition to the tweets, read the BNF section on Nitrates and the monograph on glyceryl trinitrate. Another useful source is the Summary of Product Characteristics for glyceryl trinitrate, such as the link below for sub-lingual spray. Please submit the answers to reesprescribe@gmail.com with the name of the drug and as a numbered list with TRUE/FALSE or the correct A,B,C,D option (there is only one correct answer). If you achieve 8 or more out of ten on the questions, a CPD certificate will be emailed to you.
Further reading on #Glyceryltrinitrate
- Nitrates : https://bnf.nice.org.uk/treatment-summary/nitrates.html
- Glyceryl trinitrate : https://bnf.nice.org.uk/drug/glyceryl-trinitrate.html
- Glyceryl Trinitrate Spray 400 micrograms/metered dose, sublingual spray : https://www.medicines.org.uk/emc/product/674/smpc
- Glyceryl trinitrate (GTN) sub-lingual spray is an unstable compound, which expires quickly. TRUE or FALSE?
- The main use for GTN is for diastolic heart failure. TRUE or FALSE?
- Which is TRUE?
- The first pass metabolism for GTN is very high
- The first pass metabolism for GTN is very low
- GTN spray can be used for phlebitis
- There is an extensive renal elimination phase for GTN
- Once opened, GTN tablets expire in 8 weeks TRUE or FALSE?
- Which is TRUE?
- After nitrate groups are added, the compound dissolves into the endothelium and blocks potassium channels
- After accessing cardiac muscle cells, nitric oxide release leads to contraction
- After accessing smooth muscle cells in blood vessels, nitric oxide release leads to smooth muscle relaxation
- After denitration, there is a prolonged release of prostaglandins which relax the smooth muscle
- All nitrates should not be used in hypotensive conditions. TRUE or FALSE?
- At low doses, GTN has a greater effect on arteries than veins. TRUE or FALSE?
- Which is FALSE?
- Flushing and headache are common adverse drug reactions
- Alcohol should be avoided with GTN
- Relief of anginal pain is fast-acting but brief
- GTN is likely to cause hypertension
- A drug with anti-cholinergic actions or side-effects could affect sub-lingual tablet absorption. TRUE or FALSE?
- All nitrates can be linked to the development of tolerance, but this is more likely with the longer acting preparations. TRUE or FALSE?