Anti-arrythmic drugs Flashcards
Anti-Arrythmic drugs
Class I: Na+ channel blockers
Class II: Beta-blockers
Class III: K+ channel blockers
Class IV: Ca2+ channel blockers
——————- : is the period in which the heart cannot start a new depolarisation cycle. This prevents ectopic beats (irreglualr heart beat) from happening
ERP (Effective Refractory Period
MoA of Class I: Na+ channel
blockers “Use-Dependent”
-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!
Contraindications of Class I: Na+ channel
blockers “Use-Dependent”
Hyperkalaemia
–> causes increased toxicity for all class I
drugs
Class IA: Na+ channel
blockers Examples
Procainamide (weak Anticholinergic- short half-life)
Quinidine (Moderate Antichlinergic)
Disopyramide (Strong Anticholinergic)
(Pro-Qui-Di)
MoA of Class IA: Na+ channel
blockers
-They mostly block channels in the open or activated state.
-Prolong repolarisation ( K+ CHANNEL BLOCKED , less than class III).
-Increase APD & ERP
AE of Class IA: Na+ channel
blockers (generally not each drug)
QT interval associated w/ torsade and syncope
(because class IA cause prolonged repolarization so they prolong QT interval)
* torsade –> (Polymorphic ventricular arrythmias)
Clinical uses of Class IA: Na+ channel
blockers
Atrial flutter, fibrillation, Supraventricular and ventricular Tachyarrthmias
AE of Procainamide
Lupus-like sy in
25-30% of patients
AE of Quinidine
Cinchonism (blurred vision, tinnitus, headache, psychosis)
AE of Disopyramide
Negative intropic effects = Less contraction force and HR
contraindicated in HF
Class IB: Na+ channel blockers Examples
1) Lidocaine (IV)
2) Mexiletine (Oral)
MoA of Class IB: Na+ channel blockers
- Bind selectively to inactivated channels in ventricular and Purkinje fiber cells
- Decrease APD
- supresses excitability in hypoxic areas of the heart
- Block preamture beats
Clinical uses of Class IB: Na+ channel blockers
- Ventricular arrythmias, particularly post-MI
- Digoxin toxicity
AE of Class IB: Na+ channel blockers
1) Drowsiness,
2) disorientation,
3) convulsions (seizures)
4) CV depression
5) tremor
Class IC: Na+ channel
blockers Examples
Flecainide (oral)
Propafenone
MoA of Class IC: Na+ channel
blockers
- Inhibit conduction through His Purkinje system.
- Suppress ventricular ectopic beats
- No effect on APD or on ANS
AE of Class IC: Na+ channel
blockers
Increased risk of sudden death when:
-Vfib after MI
-VT
* no longer used
Clinical uses of Flecainide
Prophylaxis against paroxysmal atrial fibrillation (for patients w/o structural and ishemic heart disease- dilated cardiomyopathy).
* Class IC: Na+ channel blockers
AE of Flecainide (oral)
Limited use as it is a Proarrythmic –> increased risk in sudden death post MI and when used prophylactically in VT
*Class IC: Na+ channel
Contraindications of Flecainide (oral)
HF -> structural and Ischemic heart disease (Dilated cardiomyopathy)
Class IC: Na+ channel blockers
Clinical uses of Propafenone
SVT & VT w/o sturctural ischemia
(supraventricular tavhyarrthmias and ventricualr tachyarrythmias)
* Class IC: Na+ channel blockers
Contraindiactions of Propafenone
HF –> β-blocking and Ca+ channel blocking activity can worsen HF
* Class IC: Na+ channel blocker
Class II: B-Blockers Examples
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)
MoA of Class II: B-Blockers
- Decrease SA and AV nodal activity.
- Decrease slope of phase 4 (diastolic currents) of AP in pacemakers
- increase cAMP
Clinical uses of Class II: B-blockers
- Reduce mortality following MI (prophylaxis)
- SVTs
Contraindications of Class II: B-Blockers
1) Caution in diabetics
since it may mask hypoglycaemia
2) WPWS
Class III: K+ channel blockers Examples
AMIODARONE (IV)
Dronedarone
Sotalol
MoA of Class III: K+ channel
blockers
- 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
AE of Class III: K+ channel
blockers
Prolonging APD may lead to
torsade de pointes
Contraindications of Class III: K+ channel
blockers
1) antipsychotics.
2) Increased risk with hypokalaemia,
3) hypercalcaemia
4) hereditary prolonged QT
* Monitor electrolyte levels, especially K+
MoA of Amiodarone
- 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
Clinical uses of Amiodarone
1) Tachycardia associated w/ Wolf-Parkinson-White Syndrome
2) SVT/ VT
Administration of Amiodarone
IV
*Class III: K+ channel blockers (
AE of Amiodarone
- 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
Clinical uses of Dronedarone
Used instead of Amiodarone as it has less sever AE (New drug)
*Class III: K+ channel blockers
Clinical uses of Sotalol
Life threatening VT
(Less effective than amiodarone in preventing chronic VT)
* Class III: K+ channel blockers
AE of Sotalol
can cause Torsades de pointes
* Class III: K+ channel blockers
Class IV: Ca+ channel blockers Examples
Verapamil (oral/IV)
MoA of Class IV: Ca+ channel
blockers
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
AE of Class IV: Ca+ channel
blockers
1) Constipation (Verapamil)
2) dizziness
3) flushing
4) hypotension
5) AV block
6) Oedema
Clinical uses of Verapamil?
Prevention of paroxysmal SVT (Atrial tachy) and Afib
*CCB
Contraindications of Verapamil
1) Wolff-Parkinson-White Syndrome;
2) VTs;
3) Beta-blockers –> AV block
4) Digoxin –> displaces digoxin from tissue -binding sites (Digoxin toxicity)
Anti-Arrythmic drugs NOT CLASSIFIED +clinical uses
1) Atropine (IV) (M2 receptor Antagonist) –> sinus Bradycardia
2) Adenosine (IV)- short half-life –> Acute SVT
3) Digoxin –> Afib
AE of Atropine
- Dry mouth
- Constipation
- Urinary retention
- Mydriasis (pupil dilatation)
- Tachycardia
- Blurred vision
AE of Digoxin
Yellow vision
MoA of Adenosine
- 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**.
AE of Adenosine
1) Chest pain,
2) SOB (shortness of breath),
3) dizziness,
4) nausea,
5) flushing.
Contraindications of Adenosine
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
Ivabradine Class?
Selective inhibitor of “If” channles
*if : funny channels
MoA of Ivabradine
Selective demandsor of “If” channels:
- prolongs slow depolarisation phase
- Decreases SA node firing
- Reduces oxygen demands
Clinical uses of Ivabradine
1) Chronic stable angina.
2) Chronic HF for patients:
- in sinus rhythm
- HR>70bpm
- LVEF<35%
- who have a B-blocker contraindication
AE of Ivabradine
1) Bradycardia,
2) visual disturbances,
3) hypertension
4) Long QT
5) Atrial fibrillation
