Anti-arrythmic drugs

Question 1

Anti-Arrythmic drugs

Answer 1

 Class I: Na+ channel blockers
 Class II: Beta-blockers
 Class III: K+ channel blockers
 Class IV: Ca2+ channel blockers

Question 2

——————- : is the period in which the heart cannot start a new depolarisation cycle. This prevents ectopic beats (irreglualr heart beat) from happening

Answer 2

ERP (Effective Refractory Period

Question 3

MoA of Class I: Na+ channel
blockers “Use-Dependent”

Answer 3

-Inhibit AP propagation in excitable cells.
-They reduce the max depolarisation rate at phase 0.
-Bind to activated and inactivated (rather than closed channels).
-Block high frequency excitation of the myocardium w/o affecting HR at normal frequencies!

Question 4

Contraindications of Class I: Na+ channel
blockers “Use-Dependent”

Answer 4

Hyperkalaemia
–> causes increased toxicity for all class I
drugs

Question 5

Class IA: Na+ channel
blockers Examples

Answer 5

Procainamide (weak Anticholinergic- short half-life)
Quinidine (Moderate Antichlinergic)
Disopyramide (Strong Anticholinergic)
(Pro-Qui-Di)

Question 6

MoA of Class IA: Na+ channel
blockers

Answer 6

-They mostly block channels in the open or activated state.
-Prolong repolarisation ( K+ CHANNEL BLOCKED , less than class III).
-Increase APD & ERP

Question 7

AE of Class IA: Na+ channel
blockers (generally not each drug)

Answer 7

QT interval associated w/ torsade and syncope
(because class IA cause prolonged repolarization so they prolong QT interval)

* torsade –> (Polymorphic ventricular arrythmias)

Question 8

Clinical uses of Class IA: Na+ channel
blockers

Answer 8

Atrial flutter, fibrillation, Supraventricular and ventricular Tachyarrthmias

Question 9

AE of Procainamide

Answer 9

Lupus-like sy in
25-30% of patients

Question 10

AE of Quinidine

Answer 10

Cinchonism (blurred vision, tinnitus, headache, psychosis)

Question 11

AE of Disopyramide

Answer 11

Negative intropic effects = Less contraction force and HR
contraindicated in HF

Question 12

Class IB: Na+ channel blockers Examples

Answer 12

1) Lidocaine (IV)
2) Mexiletine (Oral)

Question 13

MoA of Class IB: Na+ channel blockers

Answer 13

• Bind selectively to inactivated channels in ventricular and Purkinje fiber cells
• Decrease APD
• supresses excitability in hypoxic areas of the heart
• Block preamture beats

Question 14

Clinical uses of Class IB: Na+ channel blockers

Answer 14

• Ventricular arrythmias, particularly post-MI
• Digoxin toxicity

Question 15

AE of Class IB: Na+ channel blockers

Answer 15

1) Drowsiness,
2) disorientation,
3) convulsions (seizures)
4) CV depression
5) tremor

Question 16

Class IC: Na+ channel
blockers Examples

Answer 16

Flecainide (oral)
Propafenone

Question 17

MoA of Class IC: Na+ channel
blockers

Answer 17

• Inhibit conduction through His Purkinje system.
• Suppress ventricular ectopic beats
• No effect on APD or on ANS

Question 18

AE of Class IC: Na+ channel
blockers

Answer 18

Increased risk of sudden death when:
-Vfib after MI
-VT
* no longer used

Question 19

Clinical uses of Flecainide

Answer 19

Prophylaxis against paroxysmal atrial fibrillation (for patients w/o structural and ishemic heart disease- dilated cardiomyopathy).

* Class IC: Na+ channel blockers

Question 20

AE of Flecainide (oral)

Answer 20

Limited use as it is a Proarrythmic –> increased risk in sudden death post MI and when used prophylactically in VT

*Class IC: Na+ channel

Question 21

Contraindications of Flecainide (oral)

Answer 21

HF -> structural and Ischemic heart disease (Dilated cardiomyopathy)

Class IC: Na+ channel blockers

Question 22

Clinical uses of Propafenone

Answer 22

SVT & VT w/o sturctural ischemia
(supraventricular tavhyarrthmias and ventricualr tachyarrythmias)

* Class IC: Na+ channel blockers

Question 23

Contraindiactions of Propafenone

Answer 23

HF –> β-blocking and Ca+ channel blocking activity can worsen HF

* Class IC: Na+ channel blocker

Question 24

Class II: B-Blockers Examples

Answer 24

Propranolol (non-selective), with minor class I activity
Metoprolol (β1-selective)
Esmolol - IV (β1-selective: used in acute SVT via IV route: very short-acting)

Question 25

MoA of Class II: B-Blockers

Answer 25

* **Decrease SA and AV nodal activity**. * Decrease slope of phase 4 (diastolic currents) of AP in pacemakers * increase cAMP

Question 26

Clinical uses of Class II: B-blockers

Answer 26

- Reduce mortality following MI (prophylaxis) - SVTs

Question 27

Contraindications of Class II: B-Blockers

Answer 27

1) Caution in diabetics since it may **mask hypoglycaemia** 2) **WPWS**

Question 28

Class III: K+ channel blockers Examples

Answer 28

**AMIODARONE (IV)** Dronedarone Sotalol

Question 29

MoA of Class III: K+ channel blockers

Answer 29

- **Block K+ channels including the outward rectifier current** - **Prolong APD (QT interval)** - Greater refractory period may interrupt **reentrant arrhythmias** and suppress ectopic beats - Especially active in Purkinje and ventricular fibers

Question 30

AE of Class III: K+ channel blockers

Answer 30

Prolonging APD may lead to **torsade de pointes**

Question 31

Contraindications of Class III: K+ channel blockers

Answer 31

1) **antipsychotics**. 2) Increased risk with **hypokalaemia**, 3) **hypercalcaemia** 4) hereditary **prolonged QT** | * Monitor electrolyte levels, especially K+

Question 32

MoA of Amiodarone

Answer 32

* K+/ Ca+2 channel blocker --> decreases AV activity * prolongs APD --> Prolongs QT interval --> torsade ->**Long half-life = 10-100 days!** --> Because it accumulates in the body (can cause toxicity) | * Class III: K+ channel blockers

Question 33

Clinical uses of Amiodarone

Answer 33

1) Tachycardia associated w/ Wolf-Parkinson-White Syndrome 2) SVT/ VT

Question 34

Administration of Amiodarone

Answer 34

**IV** | *Class III: K+ channel blockers (

Question 35

*** AE of Amiodarone

Answer 35

- **Photosensitive skin rashes (phototoxicity)** - **blue pigmentation of the skin** - **Thyroid dys.** - **Pulmonary fibrosis** - **Corneal deposits** - **Heapatic necrsosis** - bradycardia, heart block, heart failure. - Rarely VT or torsade de pointes | *Class III: K+ channel blockers

Question 36

Clinical uses of Dronedarone

Answer 36

Used instead of Amiodarone as it has less sever AE (New drug) | *Class III: K+ channel blockers

Question 37

Clinical uses of Sotalol

Answer 37

**Life threatening VT** (Less effective than amiodarone in preventing chronic VT) | * Class III: K+ channel blockers

Question 38

AE of Sotalol

Answer 38

can cause **Torsades de pointes** | * Class III: K+ channel blockers

Question 39

Class IV: Ca+ channel blockers Examples

Answer 39

**Verapamil (oral/IV)**

Question 40

MoA of Class IV: Ca+ channel blockers

Answer 40

1) Decrease phases 0 and 4 (decreases HR) in the SA and AV nodes = **increases ERP** 2) Decrease phase 2 in fast response fibres: ° shorten AP plateau, ° **decrease contractility**, ° reduces after depolarisation→ **suppresses premature ectopic beat**

Question 41

AE of Class IV: Ca+ channel blockers

Answer 41

1) **Constipation (Verapamil)** 2) dizziness 3) flushing 4) hypotension 5) **AV block** 6) Oedema

Question 42

Clinical uses of Verapamil?

Answer 42

Prevention of paroxysmal **SVT (Atrial tachy)** and **Afib** | *CCB

Question 43

Contraindications of Verapamil

Answer 43

1) Wolff-Parkinson-White Syndrome; 2) VTs; 3) Beta-blockers --> AV block 4) Digoxin --> displaces digoxin from tissue -binding sites (Digoxin toxicity)

Question 44

Anti-Arrythmic drugs NOT CLASSIFIED +clinical uses

Answer 44

1) **Atropine (IV)** (M2 receptor Antagonist) --> sinus Bradycardia 2) **Adenosine (IV)**- short half-life --> Acute SVT 3) **Digoxin** --> Afib

Question 45

AE of Atropine

Answer 45

- Dry mouth - Constipation - Urinary retention - Mydriasis (pupil dilatation) - Tachycardia - Blurred vision

Question 46

AE of Digoxin

Answer 46

**Yellow vision**

Question 47

MoA of Adenosine

Answer 47

* **Increase K outward** current (IKAch) and **decreases Ca2+ inward** current * Activates Adenosine receptors: causes Gi-coupled **decreases in cAMP** * Shorter lived than Verapamil, thus safer, only lasts **20-30s after a bolus**.

Question 48

AE of Adenosine

Answer 48

1) Chest pain, 2) **SOB (shortness of breath),** 3) dizziness, 4) nausea, 5) flushing.

Question 49

Contraindications of Adenosine

Answer 49

Important interactions: 1) **Theophylline and other xanthines (caffeine)** block adenosine receptors and thus inhibit the actions of adenosine. 2) **Dipyrimadole (anti-platelet)** blocks the nucleoside uptake mechanism, prolonging the adverse effects of adenosine

Question 50

Ivabradine Class?

Answer 50

Selective inhibitor of "If" channles | *if : funny channels

Question 51

MoA of Ivabradine

Answer 51

Selective demandsor of “If” channels: - prolongs slow depolarisation phase - Decreases SA node firing - **Reduces oxygen demands**

Question 52

Clinical uses of Ivabradine

Answer 52

1) Chronic stable angina. 2) Chronic HF for patients: - in sinus rhythm - HR>70bpm - LVEF<35% - **who have a B-blocker contraindication**

Question 53

AE of Ivabradine

Answer 53

1) Bradycardia, 2) visual disturbances, 3) hypertension 4) **Long QT** 5) Atrial fibrillation