Arrhythmias

Question 1

In order what are the five major landmarks of cardiac conduction?

Answer 1

Sinoatrial node
atrioventricular node
Bundle of His
Left/Right branches of that bundle
Perkinje Fibres

Question 2

What’s the bundle of His?

Answer 2

Receives the signal from the AV node and starts propagation through the ventricles; it is basically the PRE-BRANCHED bunch of nerves that disperse to bring about ventricular contraction.
The first branching is into the left and right bundle fibres.

Question 3

For a non-pacemaker cell, what makes the mV shoot upward transiently?

Answer 3

Opening v-gated sodium channels.

Question 4

In the resting state of a non-pacemaker cell, what ions are waiting to influx and what ions to efflux?

Answer 4

More sodium and calcium outside,

More potassium inside.

Question 5

What prolongs the +mV (refractory state) in a non-pacemaker cell?

Answer 5

Steady influx of Ca2+ through L-TYPE calcium channels.
[A mixture of that with endplasmic Ca2+ release].
L-Ca2+ channels opened in response to +mV brought on by rapid Na+ influx.
These two factors strongly compete with the repolarising effect of K+ efflux.

Question 6

What ultimately resolves the action potential (repolarises) in a non-pacemaker cell?

Answer 6

POTASSIUM EFFLUX
In response to increasing potassium efflux, the L-type Ca2+ channels back off. (I.e. close in response to lowered mV, as well as resequestration of Ca2+ in the ER).

Question 7

Why doesn’t the potassium quickly repolarise the cell?

Answer 7

Ca2+ is influxing, but also the K+ channels take time to open.
Potassium really gets a handle on things once the channels are predominantly open and all the it’s boys have arrived.

Question 8

What factor predominates during the resting mV in a non-pacemaker cell?

Answer 8

K+ pumps continually keeping intracellular [K+] low.

Question 9

What are steps 0-4 of a myocyte action potential?

Answer 9

0: v-gated Na+ channels open.
1: Transient outward K+ current (Kv Ito channels)
2: L-type Ca2+ channels open.
3: K+ channels start predominating, pulling the mV back down. Ca2+
4: resting potential, maintained by K/Na pump.

Question 10

The main K+ here relevant through the whole process are the K+ channels. What’s that other K+ transporter involved in myocyte APs? What stage is it significant?

Answer 10

The v-gated K+ channel called an Ito channel (t.o. for transient outward, and “I” just referring to current).
It is active in stage ONE.
It has a very narrow +mV open range, and predominates the mV immediately (but very transiently after stage 0.

Question 11

Myocytes are also called M-dependent cells, while pacemaker cells are called N-dependent cells, based on what ion is responsible for depolarisation.

Answer 11

Myocytes: Na+
Pacemaker: Ca2+

Question 12

Long QT and Torsade-de-points are examples of…

Answer 12

… EARLY afterdepolarisation (EAD)

Question 13

Early afterdepolarisation arises from stages B or C.

Answer 13

2 or 3.

Question 14

What are two types of impulse generation fuck ups?

Answer 14

Autorrhythmia problems (e.g. ectopic pacemakers)
Triggered potentials (EAD or DAD).

Question 15

What drug can cause EAD?

Answer 15

K+ channel blockers.

Question 16

Which class of Na+v blockers has both the quickest 0-depolarisation AND the quickest ERP to resolve? 
I.e. the weakest effect.

Answer 16

IB.

Question 17

Tell me the strengths of sodium blockade and ERP prolongation for each of the Class I groups.
Nah, I’m blocking you from driving. Call a cab mate.

Answer 17

Sodium blockade: IC>IA>IB

ERP lengthening: IA>IC>IB

Question 18

Which group of Class I actually shortens the ERP?

Answer 18

Class IB

Question 19

Which class I subgroup prefers (is more suited to) ischaemic tissue?

Answer 19

Class IB

Question 20

Which class I subgroup prefers ischaemic tissue but only marginally?

Answer 20

Class IC.

Question 21

Class I shows mostly Y clearance.

Answer 21

Class I: HEPATIC clearance.

Question 22

What two special side effects do class IA drugs have compared to the class as a whole?

Answer 22

1. Atropine-like effects

2. Negative inotropy.

Question 23

Tell me again four atropine-like side effects?

Answer 23

blurred vision, dry mouth, urinary retention, constipated

Question 24

What are the four main headings for Class I side effects?

Answer 24

Heart
Blood
GI
Neuro

Question 25

What is the point of beta blocking drugs?

Answer 25

To reduce sympathetic transmission to the SA and AV nodes.

Question 26

What drugs are particularly good at decreasing AV refractoriness?

Answer 26

Beta blockers (Class II).

Question 27

There’s an arrhythmic problem where impulses generated in the low atria are causing tachycardia in the ventricles. That’s supraventricular tachychardia. What drugs are well suited to this problem?

Answer 27

-Class II (Beta blockers).
Bonus: they block the AV nodes preferentially.

-Class IV

Question 28

For class II, which of the following describes the relative block: 
SA>AV or SA

Answer 28

SA

Question 29

Name four side effects of Beta blockers. One is logical, one depends on selectivity, one is a consequence of its function, one seems to just keep popping up.

Answer 29

Bradycardia, fatigue, bronchospasm, negative inotropy.

Question 30

Name four side effects of Beta blockers. No prompts.

Answer 30

Bradycardia, fatigue, bronchospasm, negative iontropy.

Question 31

Which class’s job is [AP and] ERP prolongation? What is the ECG effect of this?

Answer 31

Class III - K+ channel blockade.

Results in LENGTHENED QT.

Question 32

In class III, what’s the risk of lengthening the QT interval?

Answer 32

Risk of Torsades-de-pointes.

Question 33

Of the two class III drugs mentioned, which is renally cleared and which is hepatically cleared? 
Prompt: it's easier to write one of their names on a kidney, the other one you'd need a liver to fit all the letters on.

Answer 33

Hepatic: amiodarone
Renal: sotalol

Question 34

Which class III drugs has a strong tendency to accumulate over repeated doses and why?

Answer 34

Amiodarone - because of extensive albumin binding and long half life.

Question 35

With beta blockers and calcium blockers we always see that they reduce heart rate and the force of contraction. Briefly account for both.

Answer 35

By reducing sodium and calcium currents, it takes longer for the autorhythmic cells to depolarise, lengthening the overall autorhythmic cycle, meaning fewer impulses per minute.
By reducing the slope of depolarisation, we’ve reduced the velocity with which the excited myocytes contract the myocardium in unison, providing less force to propel blood out. This reduces cardiact output.

Question 36

Use dependence is exemplified by:

Reverse use-dependence is exemplified by:

Answer 36

UD: class I
RUD: class III

Question 37

Ugh so basically anything mentioned in the lecture affects AV conduction and likes to inhibit the AV node more than the SA node. Okay.

Answer 37

Yep.

That’s pretty much anything from the lecture except Classes II and III. I.e. anything that acts on Ca2+-dependent cells.

Question 38

Which classes from the lecture are aimed mainly at myocytes (Na+-dependent ones)

Answer 38

Class I Na+ channel blockers.

Class III K+ channel blockers.

Question 39

Sotalol - out a hole.

Amiodarone - on your own.

Answer 39

Sotalol - renal clearance.

Amiodarone - hepatic.

Question 40

What are amiodarones side effects?

inc. 3 x eye and thyroid both ways.

Answer 40

Hepatisis, blue skin, optical neuritis, photosensitivity, corneal deposits, pulmorary fibrosis, hyperthyroidism, hypothyroidism.