Week 10- antianginal pharmacology Flashcards
what is angina pectoris?
When oxygen supply to myocardium is
insufficient for its needs, latin for tight chest
what is the pain feeling like?
intense, diffuse, gripping, constricting,
suffocating chest pain
“bear hug”
may radiate to arms, neck & jaw
difficult to distinguish from “heart burn”
what is athersclerosis?
a blockage in the coronary artery
what happens during athersclerosis?
atherosclerosis causes artery to narrow due to growth which will block the artery and the placque over time will become unstable and will rupture and will release plaque material and trigger platelet activation and clotting and will form a thrombus that will block the artery
what are the aims for treatment of angina?
Alleviate acute symptoms
Minimise frequency of ischaemia (lack of block and oxygen supply to cardiomyocytes)
Reduce progression of atherosclerosis
(secondary prevention – statins, aspirin, ACEI in
diabetes etc)
what are the triggers for angina?
when there is an unbalance in the oxygen needs and oxygen supply. limited o2 supply to cardiomycocytes causes angina
how to reduce oxygen demand?
-reduce cardia output e.g. rest, stress, smoking, weight -Reduce pre-load venodilator e.g. nitrates -Reduce afterload arterial dilator e.g. calcium channel blocker, nitrates -Reduce cardiac rate/contractility negative inotrope/chronotrope e.g b- blocker, calcium channel blocker -Improve efficiency of heart exercise, stop smoking
how to improve oxygen supply?
-increase coronary flow
arterial dilator eg calcium channel blocker, nitrate
surgery e.g. bypass, angioplasty, stent
what are the anti-anginal agents?
Organic nitrates – acute attacks Calcium channel blockers b-adrenoreceptor antagonists Slow heart rate so reduce metabolic demand Potassium channel activators Vasodilators
what are organic nitrates?
- Glyceryl trinitrate (nitroglycerin) explosive (Nobel) effective in angina quick onset/short duration of action - Isosorbide mononitrate longer duration of action
what is the mechanism of action of nitrates?
- Nitric oxide (NO) released from organic nitrates
Relaxes all smooth muscle
Main effects on CV system - Lower doses
marked dilatation of large veins
reduction in Central Venous Pressure (reduced pre-load)
reduction in Cardiac output & oxygen consumption
little effect on arterioles/little change in BP
-Higher doses/chronic use
arteriolar dilatation, fall in BP, reduced CO, headache
how is sheer stress and nitric oxide helping vaso dilation?
-nitric oxide is used in the CV system as a vasodilator and normally the endotheial cells will send sheer stress which will will trigger them to make nitric oxide which will diffuse across membrane and go to smooth muscle cellsa and cause vasodilation due to dephosphorylation of myosin light chain?
what are the effects of nitrates on the coronary circulation?
- Increase coronary flow in normal subjects
Reduction of vascular resistance - Dilation of coronary arteries despite a fall in BP
- Diverts blood from normal to ischaemic areas
Pharmacological “By pass” of narrowed segments
what is the pharmacokinetics and stability of Glycerol trinitrate (Nitroglycerin) ?
Absorbed sublingually (under the tongue) - rapid relief Rapidly metabolised in liver (30 min activity) Can’t be swallowed (1st Pass effect) -come as sprays, tablets glass bottles as volatile substances -patches
what does beta blcokers do for angina?
-reduce oxygen consumption only, so slow heart rate
-the depress the mycoardium
no effect on coronary arteries
provide secondary prevention
improve exercise capacity
contraindicated in coronary spasm
slow withdrawal (up-regulated receptors)
- Indications
Angina prophylaxis
Unstable angina
what are the 3 main classes of calcium channel blocker?
Phenylalkylamines eg verapamil
Dihydropyridines eg nifedipine, amlodopine
Benzothiazepines eg diltiazem
how do calcium channel blockers work?
Block calcium ions entering cells through preventing
opening of voltage-gated L-type calcium channels
Bind a1 subunit of the cardiac L-type calcium channels but at
different sites
what is the pharmacological effects of calcium channel blockers?
-Main effects on cardiac and vascular smooth muscle, inhibiting Ca2+
entry caused by depolarisation in these tissues
verapamil is relatively cardioselective
nifedipine is relatively smooth muscle selective
diltiazem is intermediate
what are the direct cardiac actions of calcium channel blockers?
Antidysrhythmic effects(mainly atrial tachycardia) because of impaired
atrioventricular conduction
Reduced contractility
Negative inotropic and chronotropic effect (but little effect on CO -due to
reduction in peripheral resistance)
Verapamil – contra-indication in heart failure
what are the direct vascual smooth muscle affects of CCB mainly nifedipine?
arteriolar dilatation – reduce blood pressure (reduce afterload)
coronary vasodilatation –used in patients with variant angina (spasm)