nitrates including GTN

see also:

• vasodilators
• acute pulmonary oedema (APO)
• acute coronary syndromes
• nitrate and nitrate toxicity / overdose
• Western Health policies (intranet only):
  • Glyceryl Trinitrate (GTN) Infusion protocol (docx)
  • Medicated Transdermal Patches - Safe Management (docx)

• nitrates are direct-acting vasodilators acting on veins primarily at low dose, and also on arteries at higher doses, resulting in:
  • reduced pre-load on the heart and reducing LV end-diastolic volume and reduces myocardial oxygen demand
  • at higher doses, arterial vasodilation results in reduced arterial blood pressure, reduced after-load with further reduced myocardial oxygen demand, but also in combination with venous pooling, increases risk of postural hypotension.
  • in addition, the arterial dilatation of coronary vessels helps to improve coronary blood flow in patients with angina, reducing myocardial ischaemia.
• nitrates release free nitric oxide which activates guanylate cyclase in vascular smooth muscle, increasing formation of c-GMP leading to dephosphylation of myosin light chains and smooth muscle relaxation.

• known hypersensitivity to nitrates
• hypotension or uncorrected hypovolaemia
• constrictive pericarditis or cardiac tamponade
• aortic stenosis
• significant Left Main coronary artery narrowing
• hypertrophic cardiomyopathy (HCM or HOCM)
• glaucoma
• raised intracranial pressure

• generally dose related.
• almost all reported are a result of vasodilatory actions:
  • headaches
  • hypotension / postural hypotension
  • tachycardia or bradycardia
  • sweating
  • nausea AND vomiting, abdominal pain;
  • restlessness, muscle twitching, dizziness and palpitations.
• toxicity causes methaemoglobinaemia

• concomitant use with tricyclic antidepressants, anticholinergic agents, Viagra (sildenafil), vasodilators such as hydralazine and antihypertensive agents such as calcium channel blockers, beta blockers, diuretics and ACE inhibitors may potentiate the hypotensive effect of glyceryl trinitrate.

• GTN sublingual tablets or spray
  • eg. Anginine
  • onset of action 1-3 minutes
  • dose 0.5-1 tablet under tongue, or 1 sublingual spray (can repeat in 5 minutes if no relief)
  • headache, flushing and severe postural hypotension may occur and last for 15-20 minutes after dose
• isosorbide dintrate sublingual tablet
  • onset of action 2-5 minutes
  • 5-10mg every 2-3 hours
  • lasts 1-2hrs

• long lasting transdermal patches
• onset of action may be > 4hrs
• usually 25mg or 50mg
• apply for 12-14 hours, and remove for 10-12hours each night to avoid tolerance developing
• various supplier systems are not of equal dosing

• see below

• isosorbide dinitrate
  • onset of action 25-40min, lasts 4-6 hours
  • dose: 3-30mg qid

• isosorbide mononitrate:
  • onset of action 1-2hr, lasts 24hrs
  • dose: 30-60mg once daily (max. 120mg/d)

• uncontrolled ischaemic chest pain
• acute pulmonary oedema (APO)
• to control hypertension peri–operatively in patients with ischaemic heart disease, coronary angioplasty and arteriography
• relief of coronary artery spasm, as well as improved blood flow with increased coronary artery size
• acute hypertension

• 50mg G.T.N in 30% v/v ethanol BP, 30%v/v propyleneglycol BP and water for injection to 10ml

• rapidly hydrolysed in the liver and also metabolised by enzymes in the blood
• has a short half life estimated at 1–4 minutes
• therapeutic effect is apparent within 1 – 2 minutes of intravenous administration

• PVC giving sets may be used despite theoretical absorption of GTN onto PVC, HOWEVER, infusions must NOT use PVC bags but use Baxter 500ml non PVC BAGS or 100ml glass bottle.
• recommended concentrations:
  • always use 5% dextrose
  • 30mg in 500ml (1mcg/min = 1ml/hr)
  • patients with fluid restriction may benefit from either:
    • “Double Strength”: 60mg in 500ml
    • “Triple Strength”: 90mg in 500ml
    • “10x strength”: 60mg in 100ml (10mcg/min = 1ml/hr)
  • choice depends on the clinical need of the patient.
• infusion rate:
  • infusion rate in ml/hr = required dose (mcg/min) x 60 (min/hr) / Infusion concentration (mcg/ml)
  • start infusion at 20 mcg/min
    • increasing by 10 mcg/min every 5 – 10 minutes until relief of symptoms achieved.
    • maximum of 200 mcg/min
  • BP and HR are to be checked prior to, and 3–5 minutes after commencing infusion and titration of infusion.
  • if hypotension occurs, halve the rate, if it persists then cease.

• once a pain-free state has been established for greater than 2 hours, weaning can commence
• GTN should be decreased by 10 mcg / min at ½ hourly interval if the patient remains pain free
• topical vasodilators (eg. GTN patch 50mg) are to be initiated when G.T.N is less than 20 mcg/min and 30 minutes prior to GTN infusion being ceased