Nitrates and other antianginals (nicorandil, ivabradine, perhexiline)
How nitrates relieve angina through nitric oxide, cGMP and preload reduction (with a worked wall stress example), why tolerance develops and nitrate-free intervals work, the PDE5 inhibitor interaction, and the distinct mechanisms and toxicities of nicorandil, ivabradine and perhexiline.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Angina is a mismatch between myocardial oxygen supply (coronary flow, mostly in diastole) and demand (heart rate, wall stress, contractility).
- Nitrates mainly cut demand by venodilation and also dilate epicardial coronaries and relieve spasm. Nicorandil adds K-ATP channel opening. Ivabradine slows the sinus rate. Perhexiline changes myocardial fuel use.
- Paper 1 tests the NO-cGMP pathway, preload and Laplace, tolerance, the PDE5 interaction, RV infarction, and the unusual toxicities of nicorandil, ivabradine and perhexiline.
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Sources
- Therapeutic Guidelines: Cardiovascular. Stable anginaAU/NZTherapeutic Guidelines Ltd, current eTG edition (version not verified)
- Vrints C, Andreotti F, Koskinas KC et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J 2024;45:3415-537European Society of Cardiology, 2024
- Brieger D, Cullen L, Briffa T et al. Australian clinical guideline for diagnosing and managing acute coronary syndromes 2025. Heart Lung Circ 2025;34(4):309-397AU/NZNational Heart Foundation of Australia and CSANZ, 2025
- Swedberg K, Komajda M, Böhm M et al. Ivabradine and outcomes in chronic heart failure (SHIFT). Lancet 2010;376:875-85Lancet, 2010
- Fox K, Ford I, Steg PG et al. Ivabradine in stable coronary artery disease without clinical heart failure (SIGNIFY). N Engl J Med 2014;371:1091-9N Engl J Med, 2014
- IONA Study Group. Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet 2002;359:1269-75Lancet, 2002
- Ashrafian H, Horowitz JD, Frenneaux MP. Perhexiline. Cardiovasc Drug Rev 2007;25:76-97Cardiovasc Drug Rev, 2007
- Ranolazine (Ranexa): Public Summary Document, March 2017 PBAC meeting (TGA registration approved 12 May 2016; listing not recommended)AU/NZPharmaceutical Benefits Advisory Committee, 2017
- Procoralan (ivabradine): EU summary of product characteristics, section 4.8 (luminous phenomena in 14.5% across trials)European Medicines Agency, current at November 2026
- Last updated
- 14 November 2026
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