Treatment of Ischaemic Heart Disease (IHD) Flashcards
What is variant or vasospastic angina?
Coronary spasm at rest, unpredictable
Unknown mediator, difficult to treat
What is the concern in crescendo angina?
Thrombus formation leading to MI
What happens to arterioles when there is arterial occlusion?
They are maximally dilated even at rest;
tf very little coronary reserve to respond to increased O2 demands of cardiac muscle –> angina, MI
What are the aims in treating stable angina?
- prevent attacks and progression to MI
- relieve symptoms by
- increasing O2 (-HR = more time in diastole = more coronary filling)
- reduce O2 demand (-CO, -SV, -HR, -preload through venous dilation, -afterload through arteriole dilation and -resistance)
What is the mechanism of nitrates in angina tx?
target: preload; prophylactic and symptom-relieving
- biotransformation
- release NO from endothelium into vascular SM
- stimulates guanylate cyclase:
- CTP –> cGMP
- cGMP dephosphorylates myosin light chain (can’t int w/actin)
- vascular relaxation
cGMP causes
relaxation of all vessels
major effect on veins (tf -preload)
minor effect on large arteries (-afterload), coronary arteries (no effects if stenosed)
what is coronary steal?
dilation of coronaries causes increased blood supply to already perfused areas, away from poorly perfused areas
glyceryl trinitrate (GTN, nitroglycerin)
- angina
- short acting
- 1st-pass metabolism (i.e. broken down by liver)
- tf admin sublingual in acute attack, anticipation of effort
- transdermal for prophylaxis
- i.v. for emerge
- absorbed by plastic, unstable, light-sensitive
isosorbide dinitrate
- angina: prophylactic, anticipation of exertion
- longer acting
- 1st pass metabolism
- taken orally –> active compound isosorbide-5-mononitrate
- dilates veins
What are the adverse effects of nitrates in angina tx?
- cGMP –> non-significant SM relaxation in gut, airways
- postural hypotension
- venous pooling
- reflex tachycardia to drop in BP (tf co-Rx w/b-blockers or cardiac-selective Ca2+ channel blocker to -HR)
- headache, flushing (cerebral, head, neck, arterial dilation)
why is GTN/nitroglycerin contraindicated with viagra?
- viagra is a phosphodiesterase inhibitor
- inh the breakdown of cGMP, cAMP
- GTN ++cGMP
- viagra –breakdown cGMP
- +++relaxation in SM
- fatal decrease in BP
What is the mechanism of GTN tolerance in angina tx?
classic:
- -tissue thiols req’d for NO production from GTN
- prevented by co-Rx w/N-acetyl cysteine
new:
- increased sensitivity to vasoconstrictors (ANGII, catecholamines) making it harder to dilate
- increase in endothelial ROS, scavening NO
- reduced/abnormal activity in ALDHS (mitochondrial enzyme) leading to -NO and +ROS
verapamil
- Ca2+ channel blocker
- equally selective for vascular and cardiac Ca2+ channels
- contraindicated in heart failure
nifedipine
- Ca2+ channel blocker
- selective for vascular Ca2+ channels
- can be used for hypertension, angina treatment
What is the mechanism of cardioselective Ca2+ channel blockers in angina tx?
- -Ca2+ entry to heart (SA, AV, muscle) through L-type channels
- -HR (+O2 supply)
- -SV, -CO, -O2 demand
- mostly verapamil and diltiazem
What is the mechanism of vascular-selective Ca2+ channel blockers in angina tx?
- block Ca2+ entry into vessels via L-type & receptor-operated channels
- +arterial dilation
- -afterload
- -O2 demand
- e.g. nifedipine, felodipine
What are the adverse effects of Ca2+ blockers in angina tx?
- prophylactic use
- verapamil:
- flushing, headache, oedema
- oedema bc CCB’s only target arterial SM and cause dilation; don’t get accommodating venodilation
- bradycardia, AV block
- **contraindicated w/B-blockers
- flushing, headache, oedema
- nifedipine:
- flushing, headache, oedema ^^
- hypotension
- reflex tachycardia
- **co-Rx w/B-blockers
What is the mechanism of beta-blockers in angina tx?
prophylactic use
- block effects of SNS on cardiac B1-aRs
- -HR @ SA, AV
- -contractility, SV @ muscle
- +diastole
- +coronary perfusion
- +O2 supply
- -CO
- -O2 demand
What are the adverse effects of beta-blocker use in angina tx?
- first-line therapy for prophylaxis is atenolol and propranolol
- atenolol is cardio-B1 selective
- propranolol is non-selective (B1, B2)
- tf get effects of bronchoconstriction and fatigue in skeletal muscle
How does ivabradine function to decrease HR?
- blocks the Ifunny current at the leaky Na+-in K+-out channel in the SA node
- reduces the slope of the diastolic depolarization
- increases time to threshold
- increased time between beat
- increased dialstolic coronary filling time
- tf -myocardial O2 demand, +O2 supply
What is the benfit of ivabradine?
- decreases HR without affecting:
- myocardial contractility and relaxation
- AV conduction
- ventriular repolarization
- tf cardiac function and BP are maintained
- compared to atenolol (blocks all B1-mediated cardiac effects, and verapamil which -contractility and rate)
- preserves endothelium-mediated vasodilation at rest and exercise
- +exercise toleramce +coronary blood flow
- compared to atenolol which can cause reflex vasoconstriction in coronary arteries at the A1-aRs due to a drop in BP
What additional benefit does ivabradine offer that other angina tx do not?
has been shown to decrease risk of MI and need for revascularization in pt with IHD and LV dysfunction
(if bpm > 70)
What are the adverse effects of ivabradine?
- If current in retina tf get birghtness in visual field
- conduction abnormalities
What is the treatment for variant angina?
- short-acting nitrates (GTN) for acute coronary spasm
- prophylaxis w/dihydropyridine Ca2+ channel blocker
- contraindicates B-blocker use
- vasospasm via a-adrenoceptor may be worsened if B2-mediated coronary dilation is blocked
- contraindicates B-blocker use
What is the tx for unstable angina?
- same as classic
- plus aspirin to prevent thrombosis
What are the revascularisation tx for angina?
- PCI - percutaneous coronary intervention
- CABG - coronary artery bypass graft
