clinical pharmacology of stable coronary artery disease Flashcards
what are the acute coronary syndromes?
MI- STEMi and NSTEMI
unstable angina pectoris
what are the two stable coronary artery diseases?
angina pectoris
silent ischaemia
what are the risk factors for coronary artery disease?
hypertension smoking hyperlipidaemia hyperglycaemia male post-menopausal females
in what general situation would stable coronary artery disease cause angina?
anything which increases HR, stroke volume or blood pressure
what is silent ischaemia?
non-typical form of angina where there is no chest pain, just symptoms such as SOB or fatigue
what are determinants of demand which if increased will cause demand ischaemia?
- HR
- systolic BP
- myocardial wall stress
- myocardial contractility
what arevthe determinants of supply which if altered cause supply ischaemia?
- coronary artery diameter and tone
- collateral blood flow
- perfusion pressure
- heart rate (duration of diastole)
which arteries does atherosclerosis normally affect?
muscular arteries such as coronary and cerebral vessels
what are the general wyays that drugs can treat myocardial ischaemia?
- decreasing myocardial oxygen demand by reducing cardiac workload
- increasing the supply of oxygen to ischaemic myocardium
what are the 3 ways that drugs decrease the myocardial oxygen demand?
decreasing myocardial workload:
- reduce heart rate
- reduce myocardial contractility
- reduce afterload
what are the general aims of treatments of stable coronary artery disease?
- relieve symptoms
- halt the disease process
- regression of the disease process
- prevent myocardial infarction
- prevent death
what are the rate-limiting drug therapies for stable coronary artery disease?
Beta-blockers
ivabradine
calcium channel blockers
what are the vasodilating drugs used to treat stable coronary artery disease?
Calcium channel blockers
Nitrates (oral and sublingual)
what are the 2 beta blockers used to treat stable angina?
Bisoprolol
atenolol
what are the actions of Beta Blockers?
- decrease heart rate
- decrease the force of myocardial contraction
- decrease cardiac output
- decrease velocity of contraction
- decrease blood pressure
- protect cardiomyocytes from oxygen free radicals during ischaemic episodes
what is the “rebound phenomenon” associated with beta Blocker cessation?
sudden cessation of Beta Blockers may precipitate MI.
Best to slowly wean off the treatment.
what are the contraindications of Beta blockers?
asthma peripheral vascular disease raynauds syndrome heart failure bradycardia heart block
what are the adverse drug reactions associated with Beta blockers?
tiredness lethargy impotence bradycardia bronchospasm
what are the drugs that Beta blockers can interact with and what is the negative effect causes?
- hypotensive agents: hypotension
- other rate imiting drugs ;like verapamil and diltiazem: bradycardia
- negative inotropic agents such as veramipril, di;tiazem or disopyramide: cardiac failure
- antagonism of anti hypertensive actions of Beta blockers by NSAIDs
- exaggerates hypoglycaemic actions of insulin and hypoglycaemics but also masks them
what are the calcium channel blockers used in the treatment if stable coronary disease?
rare limiting: diltiazem verapamil vasodilating: amlodipine nifedipine
what are 2 rate limitng CCBs?
diltiazem
verapamil
what are 2 vasodilating CCBs?
nifadipine
amlodipine
what do vasodilating CCBs do?
reduce vascular tree tone and produce vasodilatation and reduce afterload
what do rate limiting CCBs do?
reduce heart rate and and the force or myocardial contractility
which form of nifedipine is never used for stable coronary artery disease?why?
immediate release, evidence suggests it may precipitate acute MI or stroke
why is immediate release nifedipine never used in post MI and unstable angina patients?
increases morbidity and mortality in post MI patients and increases the risk of infarction and death in unstable angina patients
what are the adverse drug reactions of calcium channel blockers?
ankle oedema (doesnt respond to diuretucs)
headache
flushing
palpitations
what are the three nitrovasodilators?
glyceryl trinitrate (GTN)
isosorbide mononitrate
isosorbide dinatrate
what forms does GTN come in?
sublingual, buccal, transdermal
what is the route of administration of isosorbide dinitrate and isosorbide mononitrate?
sustained release formulation tablets
which form of nifedipine is used for the treatment of acute coronary syndrome?
slow release
what do nitrates do to blood vessels to treat stable coronary disease?
- increases arteriolar dilatation, reducing cardiac afterload
- increased venodilatation so reducing venous return, reducing preload
- relieves coronary spasm
- redistributes myocardial blood flow to ischaemic areas of myoiocardium
in what situation is GTN used?
rapid treatment of angina pain
in what situations are oral nitrates used?
-once a day sustained release so used in prophylaxis to prevent treatments
in what situations are IV nitrates used?
main stay in the treatment of unstable angina where they are used in combination with heparin
what is nitrate tolerance? and how is it avoided?
tolerance to the effects of nitrate therapy. Can occur rapidly. overcome y giving asymmetric doses of nitrate at 8 am and 2 pm
what are the adverse drug reactions of nitrate?
headache
hypotension (GTN syncope)
what us the action of the stable coronary artery drug, Nicorandil?
- ischaemic precondition of myocardium
- dilation of coronary resistance arterioles
- vasodilation of coronary epicardial arteries
what is the action of ivabridine?
selective sinus node If channel inhibitor, so slows heart rate and myocardial oxygen demand
what side effects does nicorandil have?
produces Crohn’s like symptoms
what is the action of ranolizine?
reduces tension in heart wall leading to decreased oxygen requirements for the muscle
what are the indications of aspirin treatment in stable coronary syndrome?
- adults unable to tolerate or with a contraindication to the use of Beta blockers
- or in combination with Beta blockers when Beta blockers on their own are inadequate
what can aspirin do to prognosis in acute MI?
reduce mortality
and in combination with streptokinase can reduce mortality and reinfarction
what can aspirin do to prognosis in unstable angina?
reduce MI and death risk
why is aspirin used in secondary prevention?
reduce reinfarction and combined vascular event risk
what is the most common cause of admission to hospital with GI bleed?
low dose aspirin
which antiplatelets are used in stable coronary artery disease?
aspirin
clopidogrel
ticagrelor
what is the advantage of clopidogrel over aspirin?
same bleeding but less GI bleeding
what are the 3 cholesterol lowering drugs commonly used in treatment of stable coronary artery disease?
simvastatin
pravastatin
atorvastatin
describe a common treatment regimen?
- Beta blocker
- rate limiting CCB (if Beta blocker contraindicated or not adequate)
- dihydropiridine (vasodilating) CCB
- Ivabradine/ ranolazine
- aspirin
- statin
- long acting nitrate
- nicorandil
- PCI
what is a normal treatment regime for the relief of angina symptoms?
- short acting GTN plus Beta blocker and/or CCB
- Ivabradine, long-acting nitrates, nicorandil, ranolazine, trimetazidine
- consider PCI or CABG
what is a normal treatment regime for the prevention of cardiovascular events from stable coronary artery disease?
- lifestyle management, control of risk factors
2. aspirin (clopidogrel if aspiin intolerence), statins, consider ACEI or ARBs (angiotensin receptor blockers.
