Drugs Affecting the Heart

Question 1

How can drugs affect the heart?

Answer 1

Directly - affects rate/rhythm and force of contraction

Indirectly - vasculature (+blood volume/composition - renal)

Question 2

Why do we need drugs that affect rate/rhythm?

Answer 2

arrhythmias

= disorders of rate or rhythm (or both)

Question 3

What are the types of arrhythmias?

Answer 3

Define by location - atrial, junctional, ventricular

Define by rate - tachycardia, bradycardia

Question 4

How are antiarrythmic drugs classified?

Answer 4

Classified by mechanism of action 
Class I, II, III, IV
Sometimes those without a class are said to be in Class V but they all have different mechanisms of action

Question 5

Give examples of drugs in class I and their mechanism of action.

Answer 5

Class I e.g. Lidocaine, Flecainide

• blocks voltage gates sodium channels
• all affect depolarisation phase
• shifts tilt of ventricular action potential to the right

Question 6

Give examples of drugs in class II and their mechanism of action

Answer 6

Class II e.g. propanolol

• beta blockers
• decreases sympathetic affect
• targets pacemaker potential
• takes longer to get to threshold
• decreases excitability

Question 7

Give examples of drugs in class III and their mechanism of action

Answer 7

Class III e.g. amiodarone (can affect thyroid function), sotalol (also a beta-blocker but this is main action)

• prolongation of AP
• could be due to K+ channel block
• shifts ventricular action potential right and so increases refractory period

Question 8

Give examples of drugs in class IV and their mechanism of action

Answer 8

Class IV e.g. verapamil
- blocks Ca2+ channels (L-type)
- relative cardio-selectivity –> targets cardiomyocytes
- shifts ventricular action potential to the right
-

Question 9

Give 2 examples of none classified antiarrythmic drugs and their mechanism of action

Answer 9

1. Adenosine (caffeine has similar action –> palpitations)
   - K+ channel opens, receptors for adenosine on SA/AV
   - hyperpolarisation, further from threshold
   - increased refractory period, nodal conduction slowed
2. cardiac glycosides e.g. digoxin
   - CNS - increase vagal activity
   - decreases AV conduction rate
   - decreases ventricular rate

Question 10

What are the adverse effects of antiarythmic drugs?

Answer 10

can cause arrhythmias! Because they are so diverse with so many mechanisms. Each arrhythmia is due to a particular ion so need to ensure correct drug is chosen.
Dose? needs to be carefully controlled
Pharmacokinetic issues - interactions with other drugs, affect metabolic enzymes e.g. in liver

Question 11

Why might we need drugs to affect force of contraction?

Answer 11

• anaphylaxis - CV collapse
• heart failure? - cardiac output is insufficient for the metabolic needs of the body
• many therapeutic options

Question 12

How is the force of cardiac muscle contraction usually determined?

Answer 12

• multiple determinants
• Starling forces, stretch, venous return
• Intracellular Ca2+

Question 13

What are inotropic drugs?

Answer 13

Work to increases contractility

+ve inotropic drugs increase intracellular calcium and subsequently increase force of contraction

Question 14

What are the three classes of inotropic drugs?

Answer 14

sympathomimetics (autonomic lecture)
cardiac glycosides
phosphodiesterase inhibitors

Question 15

What is the mechanism of action of digoxin?

Answer 15

CARDIAC GLYCOSIDE
Partial inhibition of Na+K+ATPase 
Increases intracellular Na+
Reduces gradient for sodium exit
Na+/Ca2+ transporter works less
Ca2+ is retained
Intracellular Ca2+ is increased

Question 16

State and explain the adverse effects of cardiac glycosides such as digoxin.

Answer 16

Ionic disturbance - increase excitability –> arrhythmias
Neurological disturbance, GIT disturbance (smooth muscle)
Gynaecomastia - off target effect, nothing to do with action on Na+K+ATPase, drug has large steroid component. In a few patients this can trick oestrogen receptors

Question 17

Is there a clinical use for digoxin?

Answer 17

Only used in a subset of heart failure of patients
Needs individual dose tailoring
High incidence of drug interaction
- some diuretics decrease potassium, this increases effect of digoxin due to competition for receptor –> increased adverse effects

Question 18

Give examples of phosphodiesterase inhibitors

What is their mechanism of action?

Answer 18

e.g. milrinone, enoximone
Phosphodiesterase breaks down cAMP and cGMP (signalling molecules)
Normally NorArenaline acts on B1 receptors and increases cAMP via a G-protein, this increases Ca2+ influx.
Phosphodiesterase inhibitors prolong action of g protein.
Increase cAMP –> increase inotropy
–> increase force of contraction

Question 19

What are the side effects of PDE inhibitors?

Do they have a clinical use?

Answer 19

increased excitability can lead to arrythmias
PDE type 3 are specific to the heart so systemic effects are decreased

Clinically

• emergencies only
• some studies suggest decreased survival in heart failure
• short half life

Question 20

What other drugs can be used for cardiac failure?

Answer 20

diuretics - blood volume
vasodilators - systemic volume
ACE inhibitors - blood pressure
beta blockers - decrease heart rate
ivabradine - targets PMP channels