Drugs used in angina and MI Flashcards
Define angina pectoris
Chest pain when blood supply to part of the myocardium is inadequate for its needs. Usually caused by atheroma
Causes of angina
- Coronary atheroma
- Aortic stenosis
- Severe anaemia Infection (arteritis, syphillis)
- Absent coronary circulation
- Toxins
Strategies to prevent and treat angina
Reduce CV risk factors: BP, Cholesterol, smoking, LVH
Decrease metabolic demand of LV
Increase coronary blood flow
Major determinants of LV work
Heart rate
Arterial pressure
Ventricular size
Drugs relieve angina work by reducing the metabolic demands of the heart, which means reducing the work of the LV.
Drugs which reduce ventricular dimension
Nitrovasodilators e.g. glyceryl nitrate, isosorbide mononitrate, amyl nitrate.
These relax smooth muscle and preferentially affect veins. Leads to increase in venous capacitance with small falls in arteriolar resistance. This reduces the heart size
Mechanism of nitrovasodilators
Broken down or metabolised to nitric oxide in endothelial cells. This activates guanylate cyclase in vascular smooth muscle to cause an increase in cGMP, reducing [Ca}i and causing vascular relaxation.
Effect of organic nitrates on circulation
Increase in venous capacitance
Fall in CVP
Small decrease in arteriolar resistance
Reduction in cardiac size
Reduced CO
Fall in CO and TPR = Reduced LV work
Administration or nitrates in angia
GTN: given sublingually, when swallowed undergoes extensive first pass metabolism in the liver and is inactive. When sucked it is rapidly absorbed in the buccal mucosa into the systemic circulation. Action within 1-2mins that lasts for 15-20mins
Isosorbide mononitrate: sublingual or oral. Isosorbide DI-nitrate is converted to mononitrate in the liver by first pass metabolism. Long acting drugs that last for several hours.
Unwanted effects of nitrovasodilators
Vascular headaches as a result of dilation of the muscular intracranial arteries.
Prolonged exposure to nitrates results in tolerance. vsmc becomes resistant to dilator effects and following withdrawal may result in abnormal constriction.
Reflex tachycardia in response to vasodilation which offsets some of the benefit of the drugs.
Potential for dilating sites of atheroma leading to further reduction in coronary circulation
Drugs given to reduce heart rate
Beta blockers - slow the heart rate and attenuate increase in heart rate in respone to exercise and stress
Ivabradine - slows the heart by inhibiting If ion channels in the SA node but does not affect contractility of ventricles. Used in patients intolerant of beta blockers
Ca2+ channel blockers - slow the heart rate by reducing Ca2+ entry into pacemaker cells.
Efffects of beta blockers on the heart
Blocks b1 receptors of the sympathetic nervous system.
Reduces HR increases with exercise and other stress
Reduces contractility and arterial pressure
Reduces oxygen needs of the myocardium at a given level of exercise or stress
Reduces the metabolic needs of the heart.
Unwanted effects of beta blockers
Increase LV size which increases LV work, offsets benefits of the drugs.
Slows heart rate
Leads to cold peripheries (acts of b3Rs)
Contraindicated in asthmatics (causes bronchoconstriction)
Effects of Ca2+ channel blockers
Reduce calcium entry to cells through L-type VG-Ca2+ channels.
Reduced Ca2+ entry into pacemaker cells reduces the heart rate
Reduced Ca2+ entry into cardiac myocytes reduces the force of contraction
Reduce Ca2+ entry to vascular myocytes, resistance arteries relax, systemic vascular resistance decreases, bp falls.
Unwanted effects of Ca2+ channel blockers
Heart: Bradycardia, Heart failure, Oedema
Arterial pressure: Flushing, headaches, ankle swelling, reflec tachycardia (nifedipine only)
Drugs given to reduce arterial pressure
Ca2+ channel blockers: Nifedipine, Diltiazem, Verapamil
Work by reducing Ca2+ influx through VG-Ca2+ channels in peripheral vasculature. Leads to relaxation of resistance vessels and a fall in TPR.
Heart has to pump against a lower pressure so the work of the heart is reduced.
Ca2+ channel antagonists also prevent calcium entry in coronary vessels and may prevent vaso-spasm
Potassium channel openers
e.g. Nicorandil
Drugs that open K-ATP channels in vascular smooth muscle. This hyperpolarises the cell, closing Ca2+ channels. Low Ca2+ causes vessel relaxation.
More targeted towards arteries and arterioles which have a higher smooth musle tone.
May also cause headaches, flushing and dizziness. Used in conjuction with beta blockers to limit reflex tachycardia
Ranolazine
Blocks late inward sodium currents in cardiomyocytes. In ischemic myocardium, late inward sodium currents contribute to an elevation in [Na]i which increases [Ca]i via the Na/Ca exchanger.
Ca2+ overload in ishemic cells leads to impaired relaxation and compresses microcirculation in the walls of the ventricle. Coronary blood flow is reduced and ischemia worsens.
Blocking late inward sodium currents reduces Ca levels, therefore stress on the heart and improves coronary flow.
Also inhibits fatty acid oxidation, promotes carbohydrate metabolism.
Treatment for stable angina
First line: beta blocker or calcium channel blocker
If not tolerated: Long acting nitrate, ivabradine, nicorandil, ranolazine
Treatment for unstable angina
Antiplatelt treatment asap. Aspirin (clopidogrel 2nd line)
Antithrombin treatment: Heparin or direct thrombin inhibitor
Nitrates
Treatment immediately following MI
Rapid admission to coronary care unit
Early clot-busting treatment (PTCA, thrombolysis)
Aspirin (anti-platelet)
Beta blockers
Prevent thrombo-embolism
Aims of treatment post-MI
Reduce morbidity:
- Relieve pain
- Minimise size of infarct
- Prevent recurrence of heart attack
- Treat heart failure
- Anticipate and treat arrhythmias
- Improve hyper-coagulable state
Reduce mortality:
- arrhythmias
- heart attack
- embolism (venous or arterial)
Reduce complications
Common abnormalities in ECG of patients with acute MI
LBBB
Anterior ST elevation
Posterior ST elevation
ST depression
Normal
Treatment of a patient with acute MI but no ECG evidence
Pain relief: morphine, anti-emetic
Aspirin: to reduce risk of further clot formation
Rapid transfer to hospital
Contraindications for clot-busting drugs
Previous harmorrhagic stroke
Recent major surgery
Peptic ulceration/internal bleeding
Oesophageal varices
Pregnancy
Any stroke within 6 months
Drug interventions to prevent recurrent MI
Anti-platelet treatment - prevent clotting
Beta blockers - reduce heart rate, reduce blood pressure
ACE-inhibitors/ARBs - reduce fluid retention
Statins - reduce cholesterol
Lifestyle interventions: Diet, weight reduction, stop smoking
Risks of using streptokinase
Re-perfusion arrhythmia
Development of neutralising antibodies (no re-use after 1 year of treatment)
Allergic reaction
Not to be used if patient has had recent streptococcal infection.
Briefly describe the fibrinolytic pathway
Plasminogen is made in the liver and is incorporated into a fibrin clot as it forms. t-PA is released from the surrounding endothelium and cleaves plasminogen to plasmin. Plasmin cleaves the fibrin mesh into fragments which are cleared by proteases, kidney and the liver.
Name 3 clot-busting drugs
Streptokinase
urokinase
tPA
reteplase
Why are beta blockers given as an early treatment in acute MI?
Reduces SNS drive
Prevents cardiac rupture
Less risk of ventricular fibrillation
Infarct size decreased
What is coronary steal?
Occurs as a complication of using vasodilator drugs.
Attempts may be made to dilate the narrowed artery to increased blood flow, however in atheroma there is a fixed narrowing which does not respond to drugs. The vasodilators may then dilate other more healthy vessels and decrease blood flow through the narrowed vessel making ischemia worse.
What is a complication increasing coronary flow in atheromatous vessels and how can it be reduced?
Some atheromatous vessels may go into spasm when coronary flow is increased, reducing blood flow and precipitating an attack of angina.
Occurs when platelets and white cells adhere to the damaged vesel wall.
Anti-anginal drugs prevent vasospasm by causing vasodilation or preventing platelet activation
Drug strategy for treating acute MI
Restore coronary blood flow:
- Dilate coronary arteries
- Inhibit vasospasm
- Coronary thrombolysis
- Inhibit clotting and platelet activation
Decrease myocardial oxygen consumption:
(decrease HR and contractility)
Pain management (analgesics)
Post MI:
Inhibit cardiac remodelling (inhibit sympathetic system and angiotensin)
Two commonest types of tachyarrhythmia
Atrial fibrillation - heart beat is completely irregular
Supraventricular tachycardia - heart beat is rapid but regular.
