Anti- Arrythmic Drugs Pt.1 Flashcards
Cardiac condxn system
- SA node fires
- Excitation spreads through atrial myocardium
- AV node fires
- Excitation spreads through AV bundle
- Purkinje fibers distribute excitation through ventricular myocardium
‘ACTION POTENTIAL IN FAST-RESPONSE FIBERS VENTRICULAR MYOCYTES, HIS-PURKINJE SYSTEM
Phase 0- 4
A) Phase 0: Rapid depolarization
-Inward current of Na+
B) Phase 1: Partial repolarization
- Na+ current is inactivated
- There may also be a transient voltage-sensitive outward current
C) Phase 2: Plateau
- Inward Ca2+ current
-Small outward potassium channel
D) Phase 3: Repolarization
- Delayed outwardly rectifying K+ current
E) Phase 4: Return of membrane to resting potential
(Ca2+ in, K + out)
ACTION POTENTIAL IN SLOW-RESPONSE FIBERS SA NODE, AV NODE
- Phase 0: Depolarization
• Inward current: L-type Ca Channels and T-type Ca channels - Phase 3: Repolarization
• Delayed rectifier K+ current - Phase 4: pacemaker current
• Slope will determine pacemaker activity i.e. at the SA node
• Inward Na+ current hyperpolarization-activated channel
•Inward Ca2+ current • Outward K+ current
DISTURBANCES OF CARDIAC RHYTHM
Classified according to:
Site of origin e.g.
- Atrial - Ventricular
Rate
- Increased rate (tachycardia) e.g.
•Atrial fibrillation
• Ventricular fibrillation
- Decreased rate (bradycardia) e.g.
• Heart block
• Asystolic arrest
ANTI-ARRHYTHMIC DRUGS
Class I-IV
Class I: Na+ channel blockers
Class II: Beta-blockers
Class III: K+ channel blockers
Class IV: Ca2+ channel blockers
‘CLASS I: Na+ CHANNEL BLOCKERS ‘USE-DEPENDENT’
-Na+ channels move between 3 states
Closed: Resting potential
-Activation (a) gate is closed and hinge (h) gate is open
Open: Activated by electrical signal causing depolarization
- Both gates are open
C), Inactivated (refractory): at the peak of the AP the channels are inactivated by closing the (h) gate, gate (a) remains open
-CLASS I I: Na+ CHANNEL BLOCKERS ‘USE-DEPENDENT
, Inhibit /,,
-Inhibit action potential propagation in excitable
cells
Reduce the maximum rate of depolarization at
phase 0 in non-nodal cells
- Use-dependent Na+ channel blockade
M Bind to activated and inactivated rather than closed
- Hyperkalemia causes increased toxicity for all
class I drugs channels - Block high frequency excitation of the myocardium
without affecting beating of the heart at normal
frequencies
CLASS IA: Na+ CHANNEL BLOCKERS
, Mechanism of Action (and Adverse Effects)
- Preferentially block channels in the open or activated state
- Prolong repolarization (K+ channel blockade): less than class III
- Increase action potential duration (APD) and ERP
• QT interval prolongation associated with torsades and syncope - Intermediate dissociation
CLASS IA: Na+ CHANNEL BLOCKERS
Examples
- Quinidine
- Procainamide
- Disopryamide
Anti-cholinergic effects:
blurred vision, dry mouth, constipation, increased intraocular pressure, urinary retention, increase HR and AV conduction
- May need initial digitilization to slow AV conduction
- Useful in recurrent paroxysmal Afib triggered by vagal overactivity
Quinidine
AE
Anticholinergic (moderate)
-> cinchonism (blurred vision, tinnitus, headache, psychosis) cramping and nausea, enhances digitalis toxicity
Procainamide
AE
-anticholinergic (weak) , relatively short half- life
-> lupus like syndrome in 30% of pts.
Disopryamide
AE
Αnticholinergic (strong)
- negative inotropic effect
Most commonly used
Class 1A drugs clinical uses
Afib, flutter, supraventricular & ventricular tachyarrythmias
CLASS IB: Na+ CHANNEL BLOCKERS
Examples
lidocaine (IV), mexiletine (oral)
