Drug Treatment of Ischaemic Heart Diesase Flashcards
Explain oxygen supply to the heart? How would you increase flow to the heart?
Coronary arteries supply blood to cardiac muscle
- O2 supply depends on coronary artery flow - To increase flow - dilate coronary arteries - decrease heart rate - arteries less compressed
What does oxygen demand depend upon?
O2 demand depends on cardiac workload
- cardiac output - HR x SV - preload - degree of stretch pre-contraction - afterload - resistance heart pumps against
Explain the condition Angina Pectoris
- Ischaemic Heart disease causes Angina
→ imbalance between O2 supply/O2 needs
→ insufficient O2 to meet cardiac demand
→ reduced perfusion rather than inadequate blood O2
What are some different types of angina?
- There are varying types:
- Stable angina (classic, effort)
- chest pain with exertion, stress
- associated with coronary artery disease
- Variant angina (vasospastic, Prinzmetal’s)
- coronary vasospasm at rest
- mediator unknown
- Unstable angina (crescendo, rest)
- angina at rest and with effort
- potential for thrombi formation
- Stable angina (classic, effort)
What are some of the aims of treatment of angina?
- treat to:
- prevent attacks
- relieve symptoms
- prevent progression to heart attack
What are angina drugs designed to do?
- increase O2 supply
- dilate coronary arteries
– under local metabolic control
– may be maximally dilated already
– difficult to dilate atheromatous arteries - reduce heart rate
– heart spends longer in relaxation phase
– coronary arteries have longer to fill
- dilate coronary arteries
- reduce O2 demand
- decrease cardiac output
– reduce heart rate
– reduce stroke volume - reduce preload
– dilate veins, reduce venous return - reduce afterload
– dilate arterioles, decrease resistance
- decrease cardiac output
Which angina drugs affect preload?
Nitrates
Which angina drugs affect afterload?
calcium channel blockers
Which angina drugs affect the myocardium?
- calcium channel blockers
- beta adrenoceptor blockers
- ivabradine
Explain the mechanism of nitrates.
drug undergoes biotransformation ↓ releases NO ↓ stimulates guanylate cyclase in vascular smooth muscle ↓ GTP converted to cGMP ↓ ↓ myosin LC-PO4 → myosin LC ↓ vascular relaxation
What is the site of action of nitrates?
relaxation of all vessels
- veins –> decrease preload (major)
- large arteries –> decrease afterload
- coronary arteries –> no increase in flow with fixed stenosis & no diversion of flow from ischemic area
What are some short acting nitrates?
Short acting
- glyceryl trinitrate (GTN)
- 1st pass metabolism
- inactive metabolite so not given orally
- sublingual for acute attack, anticipation of effort
- transdermal for prophylaxis
- i.v. for emergency
- care needed with storage – adsorbed by plastic, unstable
What are some longer acting nitrates?
Longer acting
- isosorbide dinitrate
- 1st pass metabolism
- isosorbide-5-mononitrate = active metabolite
- oral for anticipation of effort or prophylaxis
What are some adverse effects of nitrates?
- effects on other smooth muscle
– brief relaxation of gut, airways
– not clinically significant - postural hypotension - venous pooling
- headache, flushing - cerebral, head, neck arterial dilatation
- reflex tachycardia – usually used in combination with βblockers or cardiac-selective calcium channel blocker to minimise this
What are some drug interactions of nitrates?
- potential problems if cGMP increases too much, ie/ GTN can interact with Viagra
- -> Viagra is a phosphodiesterase inhibitor which stops the breakdown of cGMP. With GTN, there is a massive increase of cGMP which could massively increase vasodilation and lower BP massively. This would increase hypoxia to already infarcted heart.
