L50: Treatment Of Angina Flashcards
Non-atherosclerotic causes of coronary artery obstruction
- Congenital
- Tumour
- Granulomas
- Scarring
- Myocardial bridges (coronary artery within myocardium —> contract —> no blood supply)
- Aortic dissection
What is variant angina (NOT stable/unstable angina)
- spasm in coronary artery (may/may not associate with atheromas)
- triggered by
—> cold weather
—> stress
—> vasoconstrictor drug
—> smoking
—> cocaine
Principles of anti-anginal drugs
- ↑ perfusion of myocardium by Dilating coronary vessels
- ↓ metabolic demand by Reducing cardiac workload
Why non-selective vasodilators are not used
Coronary steal phenomenon:
Narrowed coronary vessels are inherently maximally dilated to compensate for reduction in blood supply
—> non-selective vasodilator dilate ALL other coronary vessels
—> cause blood to be further shunted away from ischaemic region
Antianginal drugs
- Nitrates (Nitroglycerin, Isosorbide dinitrate)
- Ca channel blockers (vascular / cardiac-selective: Nifedipine, Amlodipine, Diltiazem, Verapamil)
- β blockers (Propranolol / Metoprolol)
- Metabolic modulators (Trimetazidine)
- Inhibitors of slowly inactivating Na current (Ranolazine)
- Direct bradycardiac agents (Ivabradine)
Nitrates
Nitroglycerin, Isosorbide dinitrate
- Veins dilation —> ↓ venous return —> ↓ cardiac workload
- Large arteries dilation —> ↓ afterload (peripheral vascular resistance) —> ↓ cardiac workload
- Collateral coronary artery dilation —> improve distribution of coronary flow
- ↓ coronary artery spasm (for variant angina)
Mechanism:
Nitrate —> nitric oxide —> cGMP —> dephosphorylation of myosin light chain —> relaxation
Pharmacokinetics:
- Rapid metabolism in liver —> low bioavailability
- Oral —> prophylaxis in patients frequent angina, sustained-release+higher dose
- Sublingual —> rapid onset for fast relief, prophylaxis prior to exercise, however dose limited due to excessive effect, also brief duration
- Cutaneous/Transdermal ointment —> slow onset, nocturnal angina
- Transmucosal/Buccal —> short term prophylaxis
- IV —> relief of coronary vasospasm, rapid and safe titration of dose
- Kidney excretion
SE:
- Tachyphylaxis —> nitrate free period —> 8-12 hours per day
- Dependence —> withdrawal —> risk of arteriospasm —> not withdraw abruptly
- headache
- postural hypotension
- tachycardia
Precaution:
- Reflex tachycardia / effects enhanced when use with PDE-5 inhibitor (Sildenafil), soluble guanylyl cyclase (Riociguat)
Ca channel blocker
- ↓ Force —> ↓ cardiac workload
- Vasodilators of arteries and arterioles —> ↓ afterload —> ↓ cardiac workload
- ↓ coronary artery spasm (for variant angina)
SE:
- vascular selective:
—> headache, flushing
—> hypotension (reflex tachycardia: may exacerbate angina symptoms)
—> peripheral oedema (arterial dilation > venous dilation)
- cardiac selective:
—> AV block —> heart failure
β blockers
- ↓ Force and ↓ HR —> ↓ cardiac workload + ↑ diastolic period —> ↑ coronary flow
- ↑ coronary artery spasm (AVOID in variant angina)
SE:
- bronchospasm (less with β1 selective)
- hypoglycaemia (less with β1 selective)
- arrhythmia / heart failure (less with pindolol)
- CNS disturbance (less with low lipid solubility β blocker)
- vasospasm (↓ vasodilation caution in severe peripheral vascular disease, less with β1 selective (cardiac selective) β blocker)
Trimetazidine
- inhibit long chain mitochondrial 3-KAT enzyme (3-ketoacyl CoA thiolase)
—> inhibit fatty acid β oxidation
—> shift to glucose oxidation
—> ↑ efficiency of cardiac oxygen utilisation - NO effect on HR/BP
SE: Mild, Parkinson syndrome (resolved after withdrawal, CI in Parkinson patient)
Ranolazine
Mechanism:
1. Inhibit late sodium current (selective action in areas of ischaemia)
—> ↓ Na influx
—> ↓ activation of Na/Ca exchanger
—> ↓ Ca influx
—> ↓ intracellular Ca
—> ↓ contractility —> ↓ cardiac workload
- ↓ oxygen demand by inhibiting fatty acid β oxidation
- ↑ coronary perfusion by inhibiting Na channel in vascular smooth muscle
—> ↓ intracellular Ca - NO effect on HR / BP
SE: Mild
Precaution:
- CYP450 enzyme (hepatic dysfunction, drug-drug interaction with inducer/inhibitor)
—> CI in strong CYP450 inhibitors e.g. itraconazole, clarithromycin
- modestly inhibit K current (↑ action potential duration, cautious with long QT syndrome)
- CI in Liver cirrhosis
Ivabradine
- Inhibitor of HCN channel (hyperpolarisation-activated cyclic nucleotide-gated channel)
—> selectively inhibit funny current in SA node
—> ↓ rate of spontaneous depolarisation
—> ↓ HR
—> ↓ cardiac workload and ↑ diastole (↑ coronary perfusion)
SE:
- bradycardia
- Phosphenes, blurred vision
- atrial fibrillation
- hypertension
Patient selection:
- resting HR > 70
- chronic stable angina
- normal sinus rhythm
- reserved for patients not responding to β blockers
- avoid in arrhythmia, QT-prolonging medication, Hypokalemic medication
- avoid in cardiac selective Ca blocker (Verapamil, Diltiazem)
CI:
- resting HR < 60
- BP < 90/50
- SA node dysfunction
- pacemaker dependence
- severe hepatic impairment
- strong CYP3A4 inhibitors
- pregnancy, lactation, child-bearing age women
Combination therapy
- CCB + nitrates
- β blockers + nitrates
- Dihydropyridine + nitrate (coronary steal: worsen angina symptoms)
Non-pharmacological therapy and other pharmacological therapy
- Coronary artery bypass grafting
- Percutaneous transluminal coronary angioplasty
- Anti-coagulants —> prevent thrombi
- Anti-platelets —> prevent thrombi
- Lipid-lowering drugs —> prevent atheroma
