Cardiology

Question 1

What are the two effects of local anaesthetics?

Answer 1

Anaesthetic properties on sensory nerves and antidysrhythmics due to action on cardiac Na channels.

Question 2

What are the 5 types of anaesthetic application?

Answer 2

Surface, infiltration, intrathecal, nerve block and epidural.

Question 3

Tetrodotoxin

Answer 3

Blocker of neuronal VG Na channels. Mutations in Glu387 of S6 of domain I leads to loss of TTX binding.

Question 4

Batrachotoxin

Answer 4

Blocks VG Na channels. Acts on intracellular portion to prevent inactivation and to move the membrane potential to more negative potential so channels open more readily.

Question 5

Alpha-scorpion toxin

Answer 5

Blocks VG Na channels. Acts from outside of the Na channel to inhibit inactivation. In combination with batrachotoxin leads to near permanent opening.

Question 6

Benzocaine and lidocaine

Answer 6

Local anaesthetics. Must be uncharged to cross the membrane and become charged in the cell, gaining access to the intracellular portion of the VG Na channel. Can act in uncharged (hydrophobic) form as it crosses the cell membrane. Exhibit use dependence - the more the channel is open, the more likely it is to be blocked.

Question 7

What do local anaesthetics mainly do?

Answer 7

Prolong/enhance inactivation of the channel. The S6 region of domain IV confers anaesthetic selectivity.

Question 8

Dihydropyridines

Answer 8

L-type Ca channel antagonists. General consensus is that they bind to pore-lining region of domain IV. Binding is enhanced by depolarisation of the cell membrane, suggesting binding to the inactivated channel. Do not show use dependence.

Question 9

Nifedipine

Answer 9

Dihydropyridine - L-type Ca channel antagonist.

Question 10

BAY K 8644

Answer 10

Dihydropyridine - L-type Ca channel agonist.

Question 11

What effect do catecholamines have on the heart?

Answer 11

Stimulate beta-2 receptors. L-type Ca channels are phosphorylated by PKA - activated. Ryanodine receptors sensitised - positive ionotropic effect. Current at which If is activated shifts to a more positive potential so more frequent contractions - positive chronotropic effect. Various delayed rectifier K+ channels producing depolarisation are enhanced - positive chronotropic effect.

Question 12

What effect does ACh have on the heart?

Answer 12

M2 receptors localised in nodal tissue. Gi coupled so decrease in cAMP. Negative chronotropic effect due to decreased Ca currents but little effect on ionotropic effect as receptors localised to nodal tissue. Negative chronotropic effect due to If current activation shift to more negative potentials. I(K-ACh) also activated - hyperpolarise cell so more difficult to elicit APs.

Question 13

Why is the SAN the dominant pacemaker in the heart?

Answer 13

It has a higher frequency discharge than other pacemaker tissues (70 min-1). Stimulates other pacemaker cells to fire before their If current elicits an action potential.

Question 14

What is an ectopic pacemaker?

Answer 14

A pacemaker at a site other than the SAN.

Question 15

How is the heartbeat well organised?

Answer 15

3D branching arrangement of conduction fibres. Collision of fibres that extinguish each other. Channels become refractory preventing re-excitation at an inappropriate time.

Question 16

What can disrupt the electrical properties of the heart?

Answer 16

SAN not functioning properly so ectopic foci develop. Damage to the myocardium.

Question 17

What is the difference between a myocardial infarction and angina pectoris and the damage caused?

Answer 17

Myocardial infarction - part of the myocardium becomes hypoxic and loses function. Replaced by connective, non-conductive tissue. Angina pectoris - part of the myocardium becomes ischaemic and cannot operate efficiently but the tissue is still conductive.

Question 18

What do class IA antidysrthymics do?

Answer 18

Block VG Na channels. Intermediate association/dissociation rate. Increased affinity for the open state - exhibit use dependence. Increase AP duration - but AP length has no effect on the action. E.g. Quinidine.

Question 19

What do class IB antidysrthymics do?

Answer 19

Block VG Na channels. Fast association/dissocation. Greater affinity for inactivated states than activated states. Influenced by the length of the AP. Most effective in tissues with high firing rates, RMP at which the membrane is depolarised and in parts of the heart where the AP is the longest. E.g. lidocaine

Question 20

What do class IC antidysrythmics do?

Answer 20

Block VG Na channels. Slow association/dissocation rates. Good at suppressing entropic beats but also good at suppressing everything. Pro-dysrhythmic. e.g. flecainide

Question 21

What do Class II antidysrthymics do?

Answer 21

Beta-1 antagonists. Decrease the effect of catecholamines onto the heart. Negative chronotropic and negative ionotropic effects. Can be used in myocardial infarction where myocardium can become sensitised to catecholamines. E.g, atenolol

Question 22

What do class III antidysrhythmics do?

Answer 22

Ca channel blockers e.g. amiodarone. Mechanism unclear. Prolong AP and refractory period. Shown to effect both outward and inward currents.

Question 23

What do class IV antidyrhythmics do?

Answer 23

Ca-channel antagonists. E.g. verapamil. Must not be given excessively as would inhibit the contraction due to Ca importance in excitation-contraction coupling.

Question 24

How is nifedipine helpful in myocardial salvage?

Answer 24

Nifedipine blocks L-type Ca channels, reducing Ca loading into the cell which can lead to cell death. Also has vasodilator effects, decreasing the oxygen demand of the tissue.

Question 25

Adenosine

Answer 25

Anti-Dysrhythmic - binds to A1 receptors which are Gi coupled. Decreases cAMP and activates I (K-ACh) hyper polarising cardiac pacemaker and conductive tissue. Used in supra ventricular tachycardia.

Question 26

Cardiac glycosides

Answer 26

Anti-dysrythmic - increase vagal activity by action in the CNS. Inhibition at the AV node. Also affects the AP refractory period.