Define myocardial infarction.
List some risk factors for MI.
What is coronary artery disease?
What is a vulnerable plaque?
Irreversible necrosis of heart muscle secondary to prolonged ischemia. 7/10 survive now.
Hypertension, high blood cholesterol, diabetes (can double risk), family history of premature CHD.
Coronary arteries hardered and narrowed, plaque containing cholesterol + SM cells + alive and dead inflammatory cells. Plaques can be stable, can grow, and can rupture and expose blood to plaque contents -> platelets react and stick together -> thrombus.
A lot more prone to rupture: thinner capsule and more contents.
What does a tPA (thrombolytics) do?
Facilitates the conversion of plasminogen to plasmin which dissolves fibrin (clot). Used to be used after MI. Now only used for dangerous pulmonary emboli/places where can't get people to hospital quickly. Lots of agents tried e.g. urokinase
What is asprin?
What happens when low-dose aspirin is ingested?
When should asprin be given?
One of most useful drugs for heart disease. Blocks thromboxane A2 (most potent stimulator for platelets coagulation and thrombus initiation). Irreversible inhibitor of COX. Platelets can't make new protein (lack nucleus) so stops thromboxane production. Thus platelets inhibited for their life (7-10d)
Inhibits platelets in portal blood, is rapidly destroyed in systemic circulation by liver so SEs minimised. ALL OTHER NSAIDS CAN INCREASE RISK OF CDV EVENTS! Secondary to an increase in BP. Naproxen best tolerated. Short-courses best treated.
Aspirin should be given to all cases of confirmed or suspected STEMI unless significant contraindication exists.
Who should aspirin not be given to and why?
Children <16y (unless MI or Kawasaki disese) due to small risk of fulminant liver failure
Breast-feeding because small amounts in breast milk -> Reye's syndrome
People with liver or renal disese
How do beta blockers work?
Describe their effects in:
a) the kidney
b) the heart
c) central and peripheral NS
Competitive antagonist of sympathetic NS or circulating catecholamines at beta-adrenoceptors. Beta1-receptors in heart (and kidney) and beta2 on lung, periperal BV and skeletal muscle.
Kidney: block beta1 receptors and inhibit renin release from JG cells = reduced RAAS activity
Heart: block beta1 receptors in SAN (reduce HR) and myocardium (reduce cardiac contractility)
Central and peripheral NS: block beta receptors in BS and periphery = inhibit NT release and decrese sympathetic NS activity
What happens if high doses of beta blockers are given?
Many beta blockers have properties which influence choice. Give 2 examples.
When should beta blockers not be prescribed?
"Cardioselective" agents such as bisoprolol, atenolol and metoprolol predominantly work on beta1 receptors, but at high doses = loss of receptor selectivity
1) Pindolol - partial agonisy activity, blocks when awake and stimulates when asleep
2) Sotalol - local anaesthetic and anti-arythmic effect
Pregnancy (concerns about foetal well-being), breast-feeding, renal disease (some)
What is cholesterol?
What is HMG CoA reductase?
How do statins fit in?
What are some non-cholesterol effects of statins?
Fatty steroid made 10 in liver (90%), needed for hormone synthesis, can be in cell membranes
Enzyme that catalyses rate limiting step in cholesterol synthesis.
Statins = competitive natural or synthetic inhibitors of HMG CoA, main effect = lower cholesterol.
Anti-inflammatory in terms of plaque contents (SM maturation, macrophage numbers, oxidative stress, CRP, cytokines and TF expression decrease etc.)
STATINS V. IMP FOR PREVENTING 20 CORONARY ARTERY DISEASE
Why aren't stents alone enough to treat CAD?
How do ACE-Is work?
Briefly, what happens to the heart after an MI?
Stents treat lesions selected on luminal stenosis. CAD is diffuse and progressive. Statins directly alter CAD via lipid lowering and other cellular effects. Newer ones acheive plaque regression and stabilisation.
Competitive inhibitor of plasma ACE (most in lungs, some in tissues), prevents conversion of angiotensin I (inactive) to II (active). Prevents angiotension II constriction -> vasodilation. (ARBs too)
Ventricular remodelling (can lead to progressive regional myocardial dysfunction): myocyte necrosis + fibrotic scar -> elongation of infarcted segment -> dilation and hypertrophy of border zone. ACE-Is are thought to reduce this = survival benefit after MI.
Aside from aspirin, beta blockers, statins and ACE-Is, what other 2 drugs may be used after an acute MI, and how do they work?
Clopidogrel: P2Y12a inhibitor - further inhibits platelet aggregation. (ADP from dense bodies acts on P2Y12 platelet receptor to promote activation and aggregation).
GTN: NO donor -> vasodilator - relieves any residulal exertional chest pain by vasodilating coronary arteries to improve flow to heart. Symptomatic use only.
List some side effects of the following:
c) beta blockers
a) hemorrhage esp. intracerebral. Can try and reverse it's effects
b) can cause asthma in NSAID-prone asthma, bleeding, gastritis (less gastric mucus produced). Common overdose drug.
c) Bronchospasm, bradycardia, hypotension, erectile dysfunction
d) Muscle toxicity, increases liklihood of developing diabetes, sleep disturbance
e) Dry, irritant cough, hyperkalaemia
NB: now trialing methotrexate (commonly used for RA)