59 - Ischaemic Heart Disease Flashcards
Ways that the heart can increase coronary artery blood supply
1)
2)
1) Dilate coronary arteries
2) Reduce heart rate (blood fills coronary arteries only during diastole)
Angina pectus
Insufficient O2 to meet cardiac muscle needs
Reduced perfusion rather than inadequate blood [O2]
Stable angina
Chest pain with exertion, stress
Associated with coronary artery disease
Variant angina
Coronary vasospasm at rest.
Unknown mediator
Unstable angina
Angina at rest and with effort
Potential for thrombus formation
Aims of stable angina treatment
1)
2)
3)
1) Prevent attacks
2) Relieve symptoms
3) Prevent progression to heart attacks
What does drug treatment for stable angina aim to do?
Increase O2 supply to heart, reduce heart O2 consumption
Why might dilation of coronary arteries be difficult in stable angina?
Atheromatous arteries difficult to dilate.
Arteries might already be maximally-dilataed
Ways to decrease heart O2 demand
1)
2)
3)
1) Decrease cardiac output (stroke volume, heart rate)
2) Reduce preload (dilate veins, reduce venous return)
3) Reduce afterload (dilate arterioles, decrease resistance)
Drugs with which preload can be decreased in stable angina
Nitrates
Drugs with which afterload can be decreased in stable angina
Ca2+ channel blockers
Drugs with which cardiac output can be decreased in stable angina
1)
2)
3)
1) Ca2+ channel blockers
2) Beta-adrenoceptor antagonists
3) Ivabradine
All these affect myocardium
Nitrates mechanism of action 1) 2) 3) 4) 5)
1) Drug undergoes biotransformation, releases NO
2) NO stimulates guanylate cyclase in cell
3) Guanylate cyclase increase cGMP levels in cell
4) cGMP inhibits Ca2+ entry into cell, preventing Ca2+ activating myosin light chain kianse, which activates myosin light chain.
5) Relaxation of vascular smooth muscle
Effects of nitrates on angina
1)
2)
3)
1) Relaxation of veins leads to decreased preload
2) Relaxation of large arteries leads to decreased afterload
3) Relaxation of coronary arteries leads to no increase in flow with fixed stenosis, and no diversion of blood from ischaemic area
Short-acting nitrate
Glyceryl trinitrate (GTN)
Why must glyceryl trinitrate be given IV, transdermally or sublingually?
Subject to extensive first-pass metabolism
What can glyceryl nitrate not be stored in?
Plastic, as adsorbs to plastic, is unstable.
When is glyceryl trinitrate given sublingually?
For acute attack, if anticipating effort
Longer-acting nitrate
Isosorbide dinitrate
Isosorbide dinitrate administration
Administrated orally.
First-pass metabolism converts into active metabolite (isosorbide-5-mononitrate)
Adverse effects of nitrates 1) 2) 3) 4)
1) Affects other smooth muscle (relaxation of airways, gut). Not clinically significant.
2) Postural hypotension (venous pooling)
3) Headache, flushing (arterial dilation)
4) Reflex tachycardia
How is reflex tachycardia from nitrate use dealt with?
Often used in combination with beta-adrR or cardiac-selective Ca2+ blockers to minimise reflex tachycardia
Drug contraindicated with nitrates
Sildenafil (viagra).
Viagra is a phosphodiesterase inhibitor, reduces cGMP breakdown.
Tolerance to nitrates 1) 2) 3) 4)
1) Depletion of tissue thiols required for NO production from glyceryl trinitrate
2) Increased release of, sensitivity to vasoconstrictors (EG: angiotensin II)
3) Increased endothelial free radical scavenging NO, reducing bioavailability of NO
4) Reduced or abnormal activity of muscle mitochondrial ALDH2, decreased NO activity
What is required to minimise nitrate tolerance
Drug-free period.
Remove patch overnight
Example of a cardiac-specific Ca2+ channel blocker
Nifedipine (14-times more cardioselective than vasoselective)
Effect of Ca2+ blockers on angina
Decreased HR, SV, CO, reduced demand.
Arterial dilation, reduced afterload.
Ca2+ blockers mostly prescribed for angina
Verapamil, diltiazem
How are Ca2+ blockers used to treat angina?
Prophylactically
Drug that is never taken with a beta blocker
Verapamil
Effect of beta blockers on angina
1)
2)
1) Decreases contractility, stroke volume - Decreased cardiac output and demand
2) Decreases heart rate (affects SA, AV nodes) - Increased diastole time, increased coronary perfusion
First-line prophylactic therapy for angina
Beta-blockers (atenolol is cardiac-selective)
Are nitrates, Ca2+ blockers and beta-blockers disease-modifying?
No.
Novel angina therapy
Ivabradine
Ivabradine effect
Decreases heart rate.
Reduces myocardial oxygen demands, increases diastole time.
Ivabradine mechanism
Selectively inhibits Na+/K+ If current in SA node.
This decreases the frequency of atrial depolarisation
Below what heart rate does Ivabradine cease to have an effect?
70bpm
Is Ivabradine disease-modifying?
Yes. Decreases risk of myocardial infarct
Adverse effects of Ivabradine
1)
2)
1) Brightness in visual field
2) Conduction abnormalities
Precautions to take with Ivabradine
Antibiotics, antifungals can increase Ivabradine levels
Angina drugs that decrease heart rate
1)
2)
3)
1) Ivabradine
2) Beta-blockers
3) Ca2+ channel blockers
Angina drugs that decrease stroke volume
1)
2)
1) Beta-blockers
2)
Angina drugs that decrease afterload
1)
2)
1) Ca2+ channel blockers
2) Nitrates (not so much)
Angina drug that decreases preload
Nitrates
How is variant angina treated?
1)
2)
3)
1) Short acting nitrate relieves coronary spasm
2) Dihydropyridine (Ca2+ channel blocker) prophylaxis
3) Don’t use beta-AdrR antagonists (contraindicated)
Treatment for unstable angina
Same as for stable angina, but include aspirin to prevent thrombosis
Why can some antibiotics and antifungals increase Ivabradine half-life?
Ivabradine metabolised in liver through cytochrome P450.
If antibiotics or antifungals are also metabolised in this wal, can slow metabolism.
