drug treatments for ischaemic heart disease

Question 1

what are the defining features of ischaemic heart disease? 3

Answer 1

• imbalance in demand and supply
• increased myocardial oxygen demand due to work rate and workload
• decreased myocardial oxygen supply due to thrombus, atheroma, vasoconstriction

Question 2

how do we regulate coronary blood flow?

Answer 2

• endothelium-derived relaxing factor (NO)

Question 3

how do we regulate cardiac workload? 4

Answer 3

• end diastolic volume (preload) regulated by the sympathetic system and RAAS
• heart rate regulated by the sympathetic system and Ca2+
• contractility regulated by the sympathetic system and Ca2+
• TPR regulated by sympathetic system and RAAS

Question 4

what is stable angina?

what is the aim of drug treatment?

Answer 4

• a predictable pattern of pain during exercise that is relieved by rest
• decrease the work done by the heart and increase the blood supply and treat risk factors

Question 5

what do nitrates do?

example?

Answer 5

dilate arteries and veins

glyceryl trinitrate

Question 6

what are the side effects of nitrates? 4

Answer 6

• postural hypotension
• headache
• dizziness
• reflex tachycardia- due to the activation of the sympathetic nervous system. if treatment causes reflex tachycardia, then look to block effects of the nervous system using a beta blocker such as bisoprolol

Question 7

what do beta blockers do?

name one?

Answer 7

• decrease cardiac output and inhibit renin release from the kidneys, therefore inhibiting RAAS
• bisoprolol

Question 8

what are the side effects of beta blockers? 3

Answer 8

• bronchoconstriction
• fatigue
• contraindicated in patients with peripheral vascular disease

Question 9

what do Ca2+ channels antagonists do?

name 2?

Answer 9

decrease cardiac workload by decreasing frequency and force of contraction and increasing dilation of arterioles
-verapamil, diltiazem

Question 10

what is important about asthmatics and Ca2+ channel antagonists? 2

Answer 10

• where beta blockers are contraindicate then calcium channel blockers can be used
• mixtures of cardiac selective calcium channel blockers and beta blockers can cause severe bradycardia and even heart block

Question 11

describe the frequency and force of contraction with calcium channel antagonists? 3

Answer 11

• CCBs can reduce heartbeat by blocking L-type channels in the SA and AV nodes
• this will slow the rate of depolarisation and therefore reduce the rate of action potential generation
• they also decrease the force of contraction of the ventricles by reducing calcium entry through L-type channels

Question 12

what does ivabradine do?

side effects? 3

Answer 12

blocks the pacemaker current (Ih/f) in the nodal tissue of the heart

• luminous phenomena in retina
• blurred vision
• dizziness

Question 13

what does blocking the pacemaker current do? 3

Answer 13

• decrease the heart rate
• reduce the Na+ entry though If channels and slow the rate of depolarisation of the SA node cells and reduce firing frequency
• it will not directly alter the force of contraction of the heart

Question 14

what is the secondary prevention treatment to reduce hypercholesterolaemia? 4

Answer 14

• drugs designed to either inhibit uptake from the GI tract or reduce production in the liver
• frontline treatment are statins
• aspirin- anti-platelet agents (aspirin/clopidogrel)
• ACE inhibitors and ARBs. for decreased workload of the heart

Question 15

how do statins work? 3

Answer 15

• HMG CoA reductase is important in the production of cholesterol and can be inhibited by statins
• this stimulates the liver cells to express LDL receptors and allows the liver cells to scavenge LDL cholesterol from the plasma
• this reduces the plasma LDL cholesterol levels

Question 16

what is the mechanism of action of some key anti-platelet agents? 6

Answer 16

• platelet activation occurs when the endothelial cells become damaged
• this releases ADP which acts on P2Y12 receptors to stimulate the platelet to express GPIIb/IIIa receptors
• fibrinogen binds to these receptors to cross link different patients
• activation of COX also helps platelet activation through the production of thromboxane A2
• aspirin inhibits COX irreversibly
• clopidogrel and prasugrel are ASP antagonists and block P2Y12 receptors

Question 17

what is the common treatment for a myocardial infarction? 7

Answer 17

• pain relief: diamorphine-gamma-opioid receptors, decreases pain, anxiety, sympathetic drive
• oxygen
• aspirin
• clot busting drugs- tececteplase
• beta blockers- decrease cardiac workload, prevents arrhythmias- metoprolol is short acting for the hospital, bisoprolol is longer acting for community use
• ACE inhibitors- decrease cardiac workload, prevent remodelling development of heart failure- ramipril
• anticoagulant in case of long term bed rest- prevents thrombus formation, warfarin/apixaban

Question 18

what is the common drug treatment for heart failure? 3

Answer 18

• digoxin binds to the N+/K+ATPase and inhibits its action
• this will increase levels of Na+ inside the heart muscle cells
• this will increase in turn, inhibit the Na+/Ca2+ exchanger which will lead to a build-up of Ca2+ inside the muscle cell and a stronger contraction

Question 19

how dow e treat dysrhythmias? 2

Answer 19

• amiodarone

- K+ channel blocker that increases the refractory period of ventricular myocytes and can terminate arrhythmia