Anti-Arrhythmia Drugs

Question 1

3 Strategies to Combat Arrhythmia from Inc Automaticity

Answer 1

1- dec slope phase 4 (dec If or Na+ channels)

2- hyperpolarize resting membrane pot

3- make the phase 0 threshold potential higher (takes longer to reach)

Question 2

3 Strategies to Combat Arrhythmia from Re-entry

Answer 2

1- Suppress PACs or PVCs to begin with

2- Slow anterograde conduction in slow path

3- Inc refractory period in either limb

Question 3

How to Combat EADs and DADs

Answer 3

EADs - underlying metabolic problem or stop offending drug

DADs- prevent Ca++ overload in cell

Question 4

Class I Drugs in General

Answer 4

Na++ channel blockers

1a- moderate (also K+ blocking effects so long QT, anti-chol, anti alpha and neg ionotropy effects)
-dec slope of phase 0 and inc AP/ERP - long QT

1b- mild (only Na+ channels so no long QT; all hepatic; good post MI)
-dec slope of phase 0 but actually dec AP duration

1c- strong (DO NOT USE if structural heart disease - CAST)
-Significantly dec slop of phase 0

**All have CNS effects b/c Na+ channels there

Question 5

Class III Drugs in General

Answer 5

K+ channel blockers; variable group so think about in clumps

All prolong QT

Amiodarone/Dronedarone - works on all receptors; liver

Sotalol - non specific beta blocker; renal

Dofetilide/Ibutilide - purely K+ blockers

Question 6

Digoxin (uses, mechanism, side effects)

Answer 6

• Used to treat SVTs
• Mechanism - blocks Na-K ATPase so inc Na+ in cell —> compensate by inhibiting Na-Ca exchanger —> inc Ca++ in cell —> Ca-induced Ca release —> inc contractility —> inc SV which triggers baroreceptors —> inc parasympathetic/ dec sympathetic input to nodes (DEC HR AND CONDUCTION VEL)
• Side Effects -
  
  • GI, green/yellow halos in vision
  • Can cause tachy or brady arrhythmias
    
    • Why? higher resting membrane potential (less Na+) may inc automaticity (closer to threshold), slower upstroke b/c some Na+ channels deactivated now which may cause variation in depolarization which allow re-entry, more Ca++ in cell (DADs), dec refractory period so more time when vulnerable to EAD

Question 7

Adenosine (uses, mechanism, side effects)

Answer 7

• Used to dx specific SVT by slowing AV node so you can clearly see what is happening above
• Use for AVNRT to delay re-entrant circuit
• Mechanism-
  
  • Activates K + channels - inc efflux (hyper polarize cell); dec automaticity
  • Inhibits adenylyl cyclase —> dec cAMP —> dec funny channel; dec automaticity
  • Inhibits protein kinases —> dec Ca++ influx; slows AV node conduction

*Side effects - full coronary arteries (chest pain), full cutaneous arteries (flushing), full meningeal arteries (headache); can induce bronchospasm in those w/ asthma

Question 8

3 Class Ia Agents (comparison)

Answer 8

Quinidine - LIVER; cinchonism (tinnitus, headache)
**anti-chol so may accelerate AV node - give w/ beta blocker or Ca++ channel blocker

Procainamide - LIVER AND RENAL; acetylated –> NAPA (also EP sig; can become toxic if slow acetylator) reversible SLE/hypersensitivity

Disopyramide - RENAL; most potent anti-chol and neg inotropic; constipation/urinary retention/dry mouth
**avoid if L ventricular dysfunction

Question 9

2 Class 1b Agents (comparison)

Answer 9

Lidocaine- LIVER; usually IV; used if digoxin toxicity

Mexilitine - LIVER; oral version so also GI effects

**Both contra-indicated if CHF liver congestion (toxicity)

Question 10

2 Class Ic Agents (comparison)

Answer 10

Flecainide - LIVER AND RENAL; pro-arrhythmia and CNS effects

Propafenone- LIVER; generally less effects than flecainide

**DO NOT USE EITHER IF STRUCTURAL HEART DISEASE (post MI)

Question 11

Amiodarone

Dronedarone

Answer 11

-Class III agents but work on multiple receptors

Amiodarone - lipophilic (long half life; stays in tissues); risk of liver fibrosis (check LFTs); cornea deposits, blue skin pigmentation, hyper or hypo thyroid; CNS (some Na+ block)

Dronedarone - oral version and generally less effects but also less potent than amiodarone

Question 12

Sotalol

Answer 12

• Non-selective beta blocker w/ K+ block activity
• Renal excretion
• PR and QT prolongation and bradycardia from beta blockage (esp in women and those w/ CHF); can be pro-arrhythmia

Question 13

Ibutilide

Dofetilide

Answer 13

Both purely K+ blockers

Ibutilide - RENAL; careful of torsades de point; also activate slow Na channels

Dofetilide - RENAL

Question 14

3 Ways to Treat Digoxin Toxicity

Answer 14

• Correct hypokalemia/hypomagnesium (exacerbates)
• Lidocaine - suppress DADs and V tach
• Digibind - digoxin specific antibody

Question 15

When should digoxin be avoided? (3)

Answer 15

• Renal insufficiency
• AV node conduction disease
• Meds that alter drug clearance (ex - amiodarone, quinidine)