Antiarrythmic Drugs I - Lee

Question 1

drugs affecting QRS

Answer 1

• affect the depolarization period
• most widen the QRS
• wider QRS –> prolonged phase o upstroke

Question 2

use dependent drugs

Answer 2

• bind better to activated or inactivated channels
• better drugs to use for a higher HR –> more of an effect
• risk of toxicity with high HR

Question 3

reverse use dependent drugs

Answer 3

• drugs bind better to resting channels

- more of an effect with lower HR

Question 4

Vaugh-Williams classes of antiarrhythmics

Answer 4

1. class I - Na+ channel blockers –> slow down conduction path
2. class II - beta blockers –>
3. class III - K+ channel blockers –> increase the refractory period
4. class IV - Ca2+ channel blockers

-prevent reentry by converting a unidirectional block to bidirectional

Question 5

Class 1a drugs

Answer 5

• prolong QRS and QT interval –> torsades de pointes*
• block Na+ and K+ channels
• slow phase 0 (even phase 3)

1. procainamide*
   - blocks Na+ and K+
   - for SHORT term atrial/ventricular arrhythmias
   - short duration of action (frequent dosing)
   - not for long term or renal failure
   - risk of torsades de pointes and lupus syndrome*
2. quinidine
   - block Na+ and K+
   - for atrial/AV junctional/ventricular arrhythmias
   - avoid with cinchonism, hemolysis, hypersensitivity
   - risk of torsades de pointes and cinchonisms*
3. disopyramide
   - anti-muscarinic effects –> dry eyes, urinary retention, constipation
   - for ventricular arrhythmias

Question 6

Class 1b drugs

Answer 6

• shorten phase 3 repolarization period
• short QT –> no risk of torsades de pointes
• CNS effects*

1. lidocaine
   - blocks Na+
   - WIDE therapeutic index*
   - for ventricular arrhythmia post MI or preventing V-fib following cardioversion*
   - only used as IV** (heavy 1st pass metabolism)
   - risks of CNS toxicity –> nystagmus, drowsy, speech, paresthesia, agitation/confused/convulsions*
2. mexilitine
   - ORAL**
   - NARROW therapeutic index* (easier to get toxicity)
   - for ventricular arrythmias
   - risk of CNS, nausea, vomiting

Question 7

Class 1c drugs

Answer 7

-markedly prolong QRS –> slower phase O than 1A –> risk of cardiac arrest bc more toxic

1. flecainide
   - block Na+ greatly
   - blocks K+**–> increased AP duration
   - for supraventricular arrhythmias and recurrent A-fib
   - not for preexisting VT or MI
   - risk of blurred vision, heart block, and proarrhythmic effects due to prolonged QRS*
2. propafenone
   - blocks Na+, but NO K+ blockage**
   - weak beta blocking activity** –> avoid in patients with asthma* –> risk of bronchospasm*
   - P-glycoprotien inhibitor*
   - for atrial arrhythmias - paroxysmal Afib/flutter and PSVT

Question 8

Class 3 antiarrhythmic drugs

Answer 8

• K+ channel blockers –> prolong phase 3 repolarization

- extend QT –> worry about torsades de pointes** in all

Question 9

amiodarone** - class 3

Answer 9

• predominant class 3 K+ channel blocker –> also class 1a (inactivated state), 2, 4 properties**
• for serious ventricular arrhythmias (V-tach)*, A-fib, and older patients
• base line testing before starting –> chest Xray, PFT, TFT, LFT*
• not used with sinus node dysfunction, bradycardia, or 1st/3rd AV block due to beta blocker properties*
• risk of hypo/hyperthyroidism, hypersensitivity hepatitis, photo dermatitis (blue man), corneal deposits, pulmonary fibrosis (fatal)***
• metabolized by CYP3A4, CYP2C8*
• highly lipid soluble –> high bile excretion (safe to use in renal disease)*
• very long half life (3-10 days, 58 days)*
• tissue levels detectable for up to 1 year

Question 10

dronederone - class 3

Answer 10

• for A-fib

- same as amiodorone except NO pulmonary or thyroid toxicity*

Question 11

sotalol - class 3

Answer 11

• L-sotalol –> class II properties
• D-sotalol –> class III properties –> prolong AP and QT
• for V-tach, Afib/flutter*
• beta blocker effects –> not used with asthma, sinus bradycardia, or 1st/3rd degree AV block*
• reverse use dependent*** –> binds to resting channels at lower HR (less effect with high HR)

Question 12

dofetilide - class 3

Answer 12

• pure K+ blocker***
• 1st line treatment for persistent A-fib, heart failure, coronary disease*
• risk of proarrhythmic effects

Question 13

ibutilide - class 3

Answer 13

• class 3 and 1a effects
• for chemical conversion of A-fib**
• only IV** –> heavy 1st pass metabolism
• high risk of arrhythmias

Question 14

CAST trials

Answer 14

• have antiarrhythmic drugs that can cause arrhythmias at same time
• flecainide used in trial –> less arrhythmias but increased mortality*
• why drugs are only used for severe arrhythmias