Drug Treatment of Ischaemic Heart Disease Flashcards
How can oxygen supply to heart be increased?
Either by dilating coronary arteries or by decreasing the heart rate which allows the heart to spend longer time in diastole (the phase when the heart can be perfused)
How can oxygen demand of the heart be decreased?
By decreasing HR, SV, preload (dilate veins) or afterload (dilate arteries)
What are the three types of angina?
stable angina, variant angina, unstable angina
What is stable angina?
Chest pain on exertion
What is variant angina?
Unpredictable - occurs at rest - mediator unknown
What is unstable angina?
Occurs at rest and with effort - pain intensifies - potential for thrombus
What is the mechanism of stable angina?
Coronary arteries are partially occluded so are maximally dilated even at rest - so during exertion there is no reserve and so the increase in demand can’t be met
What is the mechanism of nitrates?
Nitrates undergo biotransformation to release NO once absorbed, NO stimulates guanlyate cyclase, guanlyate cyclase converts GTP into cGMP, cGMP dephosphorylates myosin light chain which prevents interaction with actin which causes relaxation
On which part of the cardiovascular system do nitrates predominantly act?
On venous circulation - decreases preload but also has effects on arterial circulation to decrease afterload
What is glyceryl trinitrate?
A short acting nitrate
How is glyceryl trinitrate given?
sublingual for acute attack, transdermal for prophylaxis, i.v. for emergency
What is is isosorbide trinitrate?
A longer acting nitrate
How is isosorbide trinitrate given?
taken orally where it undergoes metabolism to be converted to the active isosorbide-5-mononitrate - taken in anticipation of effort or prophylactically
What are the adverse effects of nitrates?
postural hypotension, headache, flushing, reflex tachycardia
How do viagra and nitrates interact?
Viagra is a phosphodiesterase inhibitor which decreases the breakdown of cGMP, if taken in combination could lead to too much cGMP and a severe drop in blood pressure which could be fatal if having a heart attack
Why is there reduced effectiveness of nitrates with continuous use?
Because of depletion of tissue thiols required for NO production from nitrates, or because or increased release or sensitivity to constrictors or because of increased scavengers of NO, or because of reduced activity of ALDH2 leading to less NO production
What is verapamil?
A calcium channel blocker for both vascular and cardiac muscle
What is nifedipine?
A calcium channel blocker that is selective for vascular muscle
What is the mechanism of calcium channel blockers?
Blocks calcium entry via L-type calcium channels to reduce contraction
Why are calcium channel blockers used in angina?
Reduces HR to increase supply, reduce HR and SV to decrease demand and dilate arteries to reduce after load to decrease demand
What are the adverse effects of all calcium channel blockers?
flushing, headache, oedema
What are the adverse effects of verapamil specifically?
bradycardia and AV block - never take with a beta blocker
What are the adverse effects of nifedepine specifically?
hypotension and reflex tachycardia - may take with a beta blocker
Why are beta blockers taken for angina?
Decrease HR to increase supply, decrease heart rate, contractility and SV to decrease demand
What is ivabradine?
A drug which specifically targets heart rate by selective inhibition of the inward sodium current If in the sinus node
What is the result of using ivabradine for angina?
Slows heart rate to increase oxygen supply and decrease demand
What are the adverse effects of ivabradine?
Brightness in visual field, conduction abnormalities
What is the only drug for angina which decrease the risk of MI?
Ivabradine
What is the treatment for variant angina?
relief with a nitrate, prophylaxis with a vascular selective calcium channel blocker
What is the treatment for unstable angina?
The same as for stable angina but with additional aspirin to prevent clotting
