Canonical Question
Anti-anginal
Master answer
Myocardial ischaemia
- Occurs when myocardial oxygen demand is not met by oxygen delivery
- Type I
- Due to atherosclerotic disease – plaque rupture, or coronary artery spasm
- Type II
- Due to increased metabolic demand of myocardium (e.g. tachycardia, hypertensive crisis)
- Type I
- Determinants of myocardial oxygen demand
- Basal metabolism of heart
- Heart rate
- Contractility
- External work
- Wall tension
| METOPROLOL | GLYCERYL TRINITRATE | |
|---|---|---|
| β1 selective adrenoceptor antagonist | Nitrate | |
| MoA | β1 adrenoceptor = GsPCR In Myocardium – Inhibition → Decreased activation of adenylyl cyclase → Decreased intracellular [cAMP] → Decreased activation of protein kinase A → Decreased phosphorylation and activation of intracellular enzymes → Decreased intracellular [Ca2+] – Decreased inotropy and decreased chronotropy → Decreased myocardial oxygen consumption → Relief of ischaemia | Nitrate groups activated by thiols to nitric oxide In vascular smooth muscle (veins > arteries) – → Diffuses intracellularly and activated guanylyl cyclase → increased intracellular [cAMP] → Decreased intracellular [Ca2+] → decreased vascular tone → venodilation and vasodilation – → Decreased preload and decreased afterload – → Decreased myocardial O2 consumption → Relief of ischaemia |
| A/E | CVS – Bradycardia – Hypotension – Arrhythmia – Decompensation of acute heart failure → Cardiogenic shock – Rebound myocardial ischaemia on abrupt cessation Resp – Bronchospasm if reactive airways disease CNS – Vivid dreams – Lethargy Other – Dyslipidaemia – Hyperglycaemia | CVS – Hypotension – Reflex tachycardia – If preload dependent cardiac output → decreased cardiac output → shock Resp – Methaemoglobin → decreased O2 delivery – Bronchodilation → V/Q mismatch CNS – Increased cerebral blood flow Other – Tolerance |
Sakurai 2016
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2010A Q16 | Define the mechanisms of action and adverse effects of metoprolol and glyceryl trinitrate when used to manage myocardial ischaemia. | historical_member | — |