A3.1

Question 1

Describe membrane potential Phases

Answer 1

phase 0 - M gate moves/ Na flows in (moves +ve) = depolarization
phase 1 - opening K channel, K efflux (moves -ve)
phase 2 - plateau: Ca opens, Ca influx (+ve charge)
phase 3 - moves -ve as Ca shuts & K efflux = repolarization
phase 4 - MP restored back to rest by Na/K ATPase bringing K back in & Na out

(In pacemaker cells
phase 4 - MP spontaneous depolarizes again)

Question 2

describe

1. SA node & AV node cells
2. Atrium, Bundle of His & ventricle cells

Answer 2

1. slow conductors - use Ca channels mainly in AP upstroke
   (blocked by Ca channel blockers e.g. Verapamil)
2. fast conducting that use Na channels mainly in their AP upstroke
   (thus blocked by Na channel blockers (quinidine, lidocaine and propafenone)

Question 3

define

1. Absolute Refractory Period

2. Relative Refractory Period

Answer 3

1. Na+ channels are inactivated & no stimulus will re-open channel to allow Na+ in/ depolarise membrane AP threshold
2. Some Na+ channels re-opened from inactivation but the threshold is higher than normal making it more difficult for the activated Na+ channels to raise the membrane potential to the threshold of excitation.

Question 4

Name classes of anti-arrhythmic drugs & where do they act

Answer 4

Class I - Na channel blocker (phase 0 (inhibit upstroke of AP)) 
class II - Beta blockers (phase 2 (shorten plateau) & phase 4 increase rate of pacemaker potentials) 
class III - K channel blocker (phase 3 effect recovery of AP) 
class IV - Ca channel blocker (phase 2 affect pacemaker potential)

Question 5

Procainamide

Answer 5

Class 1A
decreasing membrane responsiveness (more difficult to generate AP)
(moderate inhibition of Na channels)

Question 6

Flecainide

Answer 6

Class IC
antiarrhythmics Inhibition of Na channels
major inhibition of membrane responsiveness (increases generation of AP?)

Question 7

Beta-blockers

Answer 7

Class II
Decrease cardiac automaticity and contractility, partly by blocking beta-adrenergic receptors (& partly by direct effects on cardiac cell membranes)
Antagonize the effects of catecholamines on Ca channels (reduce automaticity and slow conduction in partially depolarized cells and decrease myocardial contractility)

Question 8

Amiodarone

Answer 8

Class III
(but also has Class I, II and IV effects)
A ‘dirty drug’, inhibits K channels, (delays repolarization), Na channels and Ca channels (slight), blocks beta-receptors non-competitively, blocks alpha receptors, potent suppressor of ectopic automaticity.
Approved for ventricular tachycardia, ventricular fibrillation & paroxysmal supraventricular tachycardia used in other arrhythmia as well, has anti-anginal properties
Extremely long, biphasic, half life (initial ~10 days, terminal about 50 days) metabolized in liver

Question 9

Verapamil

Answer 9

Class IV
Blocks mainly L-type calcium channels
Decreases SA and Purkinje fiber automaticity, slows conduction through and increases refractory period of AV node
? Useful mainly in supraventricular arrhymias or ventricular arrthymias caused by cornary spasm

Question 10

Diltiazem

Answer 10

Class IV
Blocks mainly L-type calcium channels
Decreases SA and Purkinje fiber automaticity, slows conduction through and increases refractory period of AV node
? Useful mainly in supraventricular arrhymias or ventricular arrthymias caused by cornary spasm

Question 11

what does

1. Digoxin
2. Digitoxin do

Answer 11

are Inotropic drugs

1. slows conduction in the AV node
2. slows conduction in the AV node but more powerful

Question 12

describe mechanism of action of Digoxin

& indirect effects

Answer 12

Increase the contractile force.
Inhibits the Na+/K+-ATPase, which is responsible for Na+/K+ exchange across the muscle cell membrane -> incr [Na+]in -> incr [Ca2+]in -> incr force of myocardial contraction.
common in patients with atrial fibrillation

indirect: increases vagal activity and facilitates muscarinic transmission to the heart.
i. Slows HR
ii. Slows atrioventricular conductance.
iii. Prolongs the refractory period of the atrioventricular node.