Pharmacology of the heart

Question 1

How can the heart be targeted and what will it affect?

Answer 1

Directly by targeting SANodal cells to alter rate, rhythm and force.
Indirectly by affecting vasculature to alter blood volume and composition.

Question 2

What is an arrhythmia?

Answer 2

Abnormal generation or conduction leading to an abnormal rhythm or disruptive rate. Classified by location and rate. Improved by directly affecting the SANodal cells.

Question 3

What is the effect of anti-arrhythmic drugs?

Answer 3

To change the ion currents to modify the membrane potential and control the rate and rhythm.

Question 4

What is a class I anti-arrhythmic drug and what is its mechanism?

Answer 4

Voltage gated Na channel blockers e.g. Lidocaine

Reduce rate of depolarisation and slow HR

Question 5

What is a class II anti-arrhythmic drug and what is its mechanism?

Answer 5

Beta Blocker e.g. propanolol
Reduces sympathetic effect and slow HR and targets the pacemaker potential to reduce the rate at which it reaches the threshold.

Question 6

What is a class III anti-arrhythmic drug and what is its mechanism?

Answer 6

K channel blockers e.g. aminodarone, sotalol

Prolong the AP by preventing repolarisation to create a longer refractory period.

Question 7

What are the side effects of using aminodarone?

Answer 7

Contains iodine so can alter thyroid function as an off target effect.

Question 8

What is a class IV anti-arrhythmic drug and what is its mechanism?

Answer 8

L-type Ca channel blocker e.g. Verapamil

Affects the depolarisation of SA and AV nodal cells which require Ca for depolarisation. Cardioselectivity to L-type.

Question 9

What is a class V anti-arrhythmic drug and what is its mechanism?

Answer 9

Non classified drugs

e. g. Adenosine = Acts at receptors on nodal cells to open K channels for hyperpolarisation and a longer refractory period to slow conduction
e. g. Cardiac glycosides - Digoxin targets CNS to increase vagal activity and reduce AV conducting rate and ventricular rate. Decreased the rate to normalise rhythm.

Question 10

What is the main use of digoxin?

Answer 10

Atrial fibrillation

Question 11

Why does caffeine cause palpitations?

Answer 11

It is an adenosine antagonist, exciting the cells

Question 12

What is the s.e of all anti-arrhythmic drugs?

Answer 12

Can cause arrhythmias themselves

Question 13

When are drugs that alter inotropy required?

Answer 13

For a pt in heart failure or during anaphylaxis using autonomic drugs e.g. Ad

Question 14

What determines the force of contraction?

Answer 14

Extracellular Ca influx causes release of Ca from SR. Actin-myosin interactions are Ca dependent. Both extracellular and SR act as a source.

Question 15

What happens to the Ca after a contraction?

Answer 15

Some Ca is resequesterd and some is excreted by Na/Ca antiporter.

Question 16

What is the aim of an inotropic drug?

Answer 16

To increase contractility, by increasing [Ca] during cardiac failure

Question 17

Name the 3 main inotropic drugs.

Answer 17

Sympathomimetics
Cardiac glycosides
Phosphodiesterase inhibitors

Question 18

What is the mechanism of action of cardiac glycosides?

Answer 18

e.g. Digoxin partially inhibits Na/K ATPase to slow the mechanism and increase intracellular Na and therefore reduce the gradient for the Na/Ca antiporter. Ca remains in the cell, creating an inotropic effect.

Question 19

What are the s.e of glycosides?

Answer 19

Cause ionic disturbance for increased excitation = arrhythmias
Can affect nervous system Na/K ATPase = neurological disturbances
Affect GIT smooth muscle
Gynaecomastia in an off target affect by activating oestrogen receptors.

Question 20

What are the contraindications for glycosides?

Answer 20

Interacts with diuretics to cause hypokalaemia by competing with the K at the ATPase and increasing the digoxin effect even further.

Question 21

What is the mechanism of action of phosphodiesterase inhibitors?

Answer 21

e.g. Milrinone, enoximone
Inhibiting cAMP breakdown allows Ca channels to stay open for longer. More cAMP = more force of contraction as more intracellular Ca.

Question 22

What is the cardioselectivity of phosphodiesterase inhibitors?

Answer 22

PDE 3 is specific to cardiac myocytes so target their cAMP without affecting other cell types.

Question 23

What are the adverse effects of phosphodiesterase inhibitors?

Answer 23

Arrhythmias from increased excitability

Only given in emergencies due to its short half life.

Question 24

What drugs are used for cardiac failure?

Answer 24

ACEi
beta Blockers (redued HR)
ARBs
Diuretic (reduce blood volume)
Vasodilator (increase systemic volume)
Ivabradine (reduce HR by targeting pacemaker channels)