Drugs used in angina and MI

Question 1

Define angina pectoris

Answer 1

Chest pain when blood supply to part of the myocardium is inadequate for its needs. Usually caused by atheroma

Question 2

Causes of angina

Answer 2

• Coronary atheroma
• Aortic stenosis
• Severe anaemia Infection (arteritis, syphillis)
• Absent coronary circulation
• Toxins

Question 3

Strategies to prevent and treat angina

Answer 3

Reduce CV risk factors: BP, Cholesterol, smoking, LVH

Decrease metabolic demand of LV

Increase coronary blood flow

Question 4

Major determinants of LV work

Answer 4

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.

Question 5

Drugs which reduce ventricular dimension

Answer 5

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

Question 6

Mechanism of nitrovasodilators

Answer 6

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.

Question 7

Effect of organic nitrates on circulation

Answer 7

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

Question 8

Administration or nitrates in angia

Answer 8

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.

Question 9

Unwanted effects of nitrovasodilators

Answer 9

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

Question 10

Drugs given to reduce heart rate

Answer 10

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.

Question 11

Efffects of beta blockers on the heart

Answer 11

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.

Question 12

Unwanted effects of beta blockers

Answer 12

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)

Question 13

Effects of Ca2+ channel blockers

Answer 13

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.

Question 14

Unwanted effects of Ca2+ channel blockers

Answer 14

Heart: Bradycardia, Heart failure, Oedema

Arterial pressure: Flushing, headaches, ankle swelling, reflec tachycardia (nifedipine only)

Question 15

Drugs given to reduce arterial pressure

Answer 15

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

Question 16

Potassium channel openers

Answer 16

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

Question 17

Ranolazine

Answer 17

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.

Question 18

Treatment for stable angina

Answer 18

First line: beta blocker or calcium channel blocker

If not tolerated: Long acting nitrate, ivabradine, nicorandil, ranolazine

Question 19

Treatment for unstable angina

Answer 19

Antiplatelt treatment asap. Aspirin (clopidogrel 2nd line)

Antithrombin treatment: Heparin or direct thrombin inhibitor

Nitrates

Question 20

Treatment immediately following MI

Answer 20

Rapid admission to coronary care unit

Early clot-busting treatment (PTCA, thrombolysis)

Aspirin (anti-platelet)

Beta blockers

Prevent thrombo-embolism

Question 21

Aims of treatment post-MI

Answer 21

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

Question 22

Common abnormalities in ECG of patients with acute MI

Answer 22

LBBB

Anterior ST elevation

Posterior ST elevation

ST depression

Normal

Question 23

Treatment of a patient with acute MI but no ECG evidence

Answer 23

Pain relief: morphine, anti-emetic

Aspirin: to reduce risk of further clot formation

Rapid transfer to hospital

Question 24

Contraindications for clot-busting drugs

Answer 24

Previous harmorrhagic stroke

Recent major surgery

Peptic ulceration/internal bleeding

Oesophageal varices

Pregnancy

Any stroke within 6 months

Question 25

Drug interventions to prevent recurrent MI

Answer 25

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

Question 26

Risks of using streptokinase

Answer 26

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.

Question 27

Briefly describe the fibrinolytic pathway

Answer 27

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.

Question 28

Name 3 clot-busting drugs

Answer 28

Streptokinase

urokinase

tPA

reteplase

Question 29

Why are beta blockers given as an early treatment in acute MI?

Answer 29

Reduces SNS drive

Prevents cardiac rupture

Less risk of ventricular fibrillation

Infarct size decreased

Question 30

What is coronary steal?

Answer 30

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.

Question 31

What is a complication increasing coronary flow in atheromatous vessels and how can it be reduced?

Answer 31

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

Question 32

Drug strategy for treating acute MI

Answer 32

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)

Question 33

Two commonest types of tachyarrhythmia

Answer 33

Atrial fibrillation - heart beat is completely irregular

Supraventricular tachycardia - heart beat is rapid but regular.