Session 7 ILOs - Arrhythmias and CVS drugs

Question 1

Describe the classes of anti-arrhythmic drugs, their mechanism of action and the principles of their therapeutic use

Answer 1

4 main classes :

1. Voltage sensitive Na+ channel blockers e.g. Lidocaine
   - Use-dependent block of open or inactive Na+ channels
   - Works preferentially in damaged depolarised myocardium
   - Slows upstroke and shortens AP
2. Beta AR antagonists e.g. Propranolol, Atenolol
   - Block sympathetic action at B1 AR in heart
   - Decreases slope of pacemaker potential and rising phase of AP
   - Can prevent supra-ventricular tachycardias
   - Used following myocardial infarction (reduced O2 demand)
3. K+ channel blockers e.g. Amiodarone
   - Prolongs the AP by blocking K+ channels
   - However can be pro-arrhythmic, but Amiodarone has other actions in addition to blocking K+ channels
   - Used to treat tachycardia associated with Wolff-Parkinson-White syndrome
   - Effective for suppressing ventricular arrhythmia post MI
4. Ca2+ channel blockers e.g. Verapamil, Dilitiazem
   - Decreases the slope of the AP at SAN and decreases AVN conduction
   - Also decreases the force of contraction

Question 2

Describe the therapeutic uses of β-adrenoreceptor antagonists

Answer 2

Beta AR antagonists e.g. Propranolol, Atenolol

1. Can prevent supra-ventricular tachycardias
   - Slow conduction at the AVN
   - Slows ventricular rate in patients with atrial fibrillation
2. Used following myocardial infarction (reduced O2 demand)
   - MI often causes increased sympathetic activity which may because arrhythmias (so these prevent ventricular arrhythmias)

Question 3

Define the term ‘inotropic’ drug and the circumstances under which these drugs can be used

Answer 3

Inotropic - drug that alters the force of contraction of the heart

Generally, inotropic drugs are used to increase contractility and are given for conditions associated with a low cardiac output

1. Cardiac glycosides e.g. Digoxin
   - Works by blocking Na+/K+ ATPase, leads to a rise in intracellular Na+ so decreased Na/Ca exchanger activity and more Ca2+ remains in the cell
2. Beta-adrenergic agonist e.g. Dobutamine
   - Selective B1 AR agonist
   - Used in cardiogenic shock
   - Used in acute but reversible heart failure (e.g. following cardiac surgery)

Question 4

Describe how drugs can be used in the treatment of heart failure and hypertension

Answer 4

Drugs for heart failure AND hypertension: ACE-inhibitors, angiotensin II receptor blockers and diuretics

1. ACE-inhibitors e.g. Perindopril
   - Inhibits the action of angiotensin converting enzyme to prevent the actions of angiotensin II
   - Helps to decrease vasomotor tone decreasing blood pressure, which reduces afterload
   - Also decreases fluid retention to reduce blood volume which reduces preload
   = reduces heart workload
2. Angiotensin II receptor blockers e.g. Losartan
   - Prevents the actions of angiotensin II, which are: vasoconstriction, Na+ reabsorption and aldosterone release (Na+ reabsorption)
3. Diuretics e.g. Furosemide
   - Esp. loop diuretics in congestive heart failure
   - Reduces pulmonary and peripheral oedema by acting on the loop of Henley to reduce Na+ reabsorption

Drugs for JUST hypertension (not heart failure): Calcium channel blockers

1. Ca2+ channel blockers e.g. Nifedipine
   - Dihydropyridine Ca2+ channel blockers act on vascular smooth muscle
   - Other Ca2+ channel blockers work on the heart to reduce workload of heart by reducing the force of contraction
   - However, with the exception of amlodipine, Ca2+ channel blockers should be avoided in heart failure as they can further depress cardiac function and exacerbate symptoms

Question 5

Explain the mechanism by which organic nitrates alleviate angina

Answer 5

Organic nitrates e.g. GTN spray (short acting) and Isosorbide dinitrate (longer acting)
- React with thiols (-SH groups) in vascular smooth muscle which causes NO2- to be released which is converted to NO
- NO is a powerful vasodilator particularly on the veins (NOT arterioles)
- Causes guanylate cyclase to convert GTP to cGMP and activate protein kinase G which decreases intracellular calcium
= reduced preload so heart fills less, which reduces contraction, which reduces the O2 demand of cardiac tissue (secondary action of dilating coronary collateral arteries to improve O2 delivery)

Question 6

Name some cardiovascular conditions which have an increased risk of thrombus formation and describe the pharmacological agents used to minimise this risk

Answer 6

Cardiovascular conditions with increased risk of thrombus formation:

1. Atrial fibrillation - blood pooling increases clot formation
2. Acute myocardial infarction - platelet rich clots in coronary arteries
3. Mechanical prosthetic heart valves - increased risk of thrombus forming on the valves

Pharmacological agents:

1. Anticoagulants - prevention of venous thromboembolism
   e. g. Heparin inhibits thrombin action
   e. g. Warfarin antagonises the action of vitamin K
   e. g. Dabigatran which is a direct oral thrombin inhibitor
2. Antiplatelets - prevention of platelet rich arterial thrombus formation
   e. g. Aspirin or Clopidogrel - given following acute MI or high risk MI