Arrythmia new class drugs

Question 1

What is the list of the 8 Anti Arrythmytic drugs

Answer 1

• class 0 - Targeting the SA node
• Class 1D- Targeting the late Na current
• Class 2 - target AVN
• Class 3- limiting the arrythmia to the atria

-Class 4- Targeting calcium handling

-Class 5- Targetting the stretch sensitive cation channels

-Class 6- Improved cell- cell communcications

-Class 7- Target the environment and the remodelling

Question 2

Class 0

Answer 2

Target the SAN which encodes HCN1 & HCN4
targets the HCN channels to inhibit the If current
Ivabradine

Question 3

Class 1D

Answer 3

The Nav1.5 are the Na channels that get transiently activated and then they close rapidly.
Howevever, sometimes they dont close completely and generate a late Na current

This Na feeds into the NCX that causes cell depolaristaion and can cause delayed early depolaristaion (DAD)

drugs to inhibit the late current

Question 4

Class 2

Answer 4

Targeting the AVN
AVN- adenosine receptor A1

drugs that prolong AVN conduction
and reduce the frequency of ventricular contraction

Question 5

Class 3

Answer 5

Targeting Atria

KV1.5 found only in the atria
causes prolonged repolarisation & a longer effective refractory period

Question 6

Class 4

Answer 6

Calcium handling:

excess calcium causes delayed early depolarisation

Regulate RYR activity
Inhibit NCX inhibitor

Question 7

Class 5

Answer 7

target stretch sensitive cation channels that cause depolarisation

Question 8

class 6

Answer 8

target cell- cell connections
drugs that stabilise connexins (gap junctions)
which allow for the propogation of action potentials

Question 9

Class 7

Answer 9

Target the environment and the remodelling

target the Na/H exchanger, which reduces the Na build up in the cell.
less Na feeds into the Na/Ca exchanger
less calcium influx into the cell
less depolarisation

target atrial remodelling
antinflammatories
statins.

Question 10

Arrythmia mechanism- 1.

Answer 10

Increased automaticity is one mechanism by which arrhythmias can occur.

• Increased automaticity occurs when cardiac cells depolarise spontaneously.
  -This occurs when the cells in the pacemaker become damaged or
• The cardiac cells become increasingly sensitive to electrical impulses
• Epinepherine binds to the B1 adrenergic receptors in the atria, this stimulates Gs proteins that result in the phosphorylation of Calcium channels and release calcium.
• The release of calcium allows the cells to reach the threshold to reach depolarisation quicker, which result in more frequent pacemaker potentials and therefore tachycardias.

Question 11

Arrythmia mechanism- 2

Answer 11

Triggered automaticity is another mechanism by which arrhythmias can occur.

-Early after depolarisation (before repolarisation phase)
-Delayed after depolarisation (After the repolarisation phase)

-These are caused by damage to the cardiac cells
-The cardiac cells become ischemic
-Increased levels of cations then the membrane potential can not rest- can quickly reach threshold for the cell to become depolarised. This may lead to unwanted events.— TACCHYCARDIA

Question 12

Arrythmia mechanism –3

Answer 12

Rentry mechanism:

• When an area of the cardiac tissue becomes ischemic and damaged
• This results in a unidirectional block of electrical impulse conduction and creates an area of slow conduction
• This causes the electrical impulse to circulate around this damaged area, creating a loop
• This stimulates and excites the area of the heart again, causing it to contract rapidly and irregularly
• Resulting in tacchycardias

Question 13

Vaugh Williams classification of drugs

Answer 13

Class I drugs aim to reduce ectopic atrial and ventricular automaticity.
- Reduce delayed after depolarisation
- Prevent R-entry mechanisms that cause circus movement

How: Inhibiting Na+ channels - reduce the Phase 0 slope, reduce the transmission of the action potential to adjacent myocytes.
Class IA also inhibits K+ channels which prolongs the refractory period and prevents repolarisation, this indirectly reduces Na channel activity that will result in depolarisation.

Limitations of Class 1:
- they do not heal ischemic tissue and can result in the damage of cardiac tissue
- They can cause asystole
- prolonging the refractory period can result in risk of early after depolarisations

Answer 14

Class IA: Inhibit Na channels and K+. Red. Phase 0 slope, Prolonged refractory period and delayed repolarisation

Class 1B: Ischemic patients: Inhibit inactivated Na channels. Shorted refractory period. Early repolarisation

Class IC: Inhibit rapid Na+ channels, no effect on K+ channels. reduce phase 0 slope.

Class 2: Red sympathetic activity on the heart- Block B1 adrenergic receptors- reduce contractility

Class 3: Block K+ channels- prolong repolarisation - increased refractory period–
lim: risk of early after depolarisation
- prolonged refractory period is pro arrythmias

Class 4: Block Ca2+ channels- particularly useful in the SAN/AVN node - to slow phase 0 depolarisation slope. lim: Bradycardia