Cardio: Antiarrhythmics

Question 1

Na⁺ Channel blockers - Antiarrhythmics

Block fast Na+ channels
thereby reducing the rate of Phase 0 depolarization
prolonging the effective refractory period
increasing the threshold of excitability
and reducing Phase 4 depolarization

Answer 1

• (3) Class I antiarrhythmics
  
  • Class IA
  • Class IB
  • Class IC

Question 2

Class IA: Drugs

Answer 2

• Quinidine (Muscarinic and α antagonist = Atropine)
  
  • SEx: reflex tacycardia
  • Used for Atrial Fibrillations
  • Digitilize pt.** w/ Digoxin to slow AV node conduct.**
• Procainamide
• Disopyramide
• “The Queen Proclaims Diso’s pyramid”

Question 3

Class IA: Mechanism

Answer 3

• Moderate block of Na⁺ channels; prolong APs
• Fast Na⁺ Channels
• *Slow Conduction →
• ↑** APD - action potential duration
• ↑ ERP = effective refractory period
• *Prolongation of the QRS and * QT interval
  
  • ​→ Torsades
• Possible Heart block
• At low doses, anticholinergic (vagolytic) effects predominate, and may increase conduction velocity in the AV node and accelerate HR

Question 4

Class 1A: Clinical Use

Answer 4

• Both Atrial Fibrillation to prevent passage to ventricular arrhythmias (use w/ Digoxin)
• especially re-entrant and ectopic SVT and **VT **and can be used to maintain Sinus rhythm

Question 5

Class IA: Toxicity

Answer 5

• Cinchonism (Quinidine = tinnitus, ringing of the ears and dizziness, headache, GI dysfunction, ocular disfunction)
• Procainamide = Reversible SLE-like syndrome (w/ slow acyelators = +ANA, +Antihistone)
  
  • Hematotoxity (CBCs monitored), Torsades
• Heart Failure (Disopyramide)
• Thrombocytopenia
• Torsades de pointes due to increased QT interval
  
  • “Twisting of the spikes”
• ​w/ Digoxin → monitor ECG
• w/ Hyperkalemia → enhances effects

Question 6

Class IB: Drugs

Answer 6

• **Lidocaine **(Only used IV due to first-pass)
  
  • Post-MI
  • Open-Heart Surgery
  • Digoxin toxicity
  • SEx: CNS toxicity, Least Cardiotoxic!!
• Mexiletine (Oral)
• Tocainide (Oral)

Question 7

Class IB: Mechanism

Answer 7

• Fast Na⁺ Channels (↓ I_Na)
• Shorten the duration of the Refractory period
  → Blocks inactivated channels (slow conduction in hypoxic and ischemic heart)
  → ↓ APD - due to slow Na channels during the plateau phase - plateau gets shorter - more narrow
• Preferentially affect ischemic or depolarized Purkinje and Ventricular tissue
• Phenytoin can also fall into the class IB category

Question 8

Class IB: Clinical Use

Answer 8

• Suprress Acute ventricular arrhythmias
  (especially post-MI)
  
  • IB is Best post-MI
• Little effect on conduction velocity so it has little effect on atrial function
• Digitalis-induced arrhythmias

Question 9

Class IB: Toxicity

Answer 9

• CNS stimulation / depression
• Cardiovascular depression

Question 10

Class IC: Drugs

Answer 10

• Flecainide (Tambocor)
  
  • Limited use because of its proarrhythmogenic effects leading to sudden cardiac death
• Propafenone
• Class IC:
• “Can I have Fries** P**lease”

Question 11

Class IC: Mechanism

Answer 11

• Strongly blocks fast Na⁺ and K⁺ channels
  
  • especially His-Purkinje tissue
  • No effect on APD
  • No ANS effects
• Significantly prolongs refractory period in AV node
• Minimal effect on AP duration

Question 12

Class IC: Clinical Use

Answer 12

• ULTIMATE - Last ditch use
• Treat SVTs
• Including Paroxysmal **Atrial fibrillation **and Atrial flutter
• Only as a last resort in refractory VT

Question 13

Class IC: Toxicity

Answer 13

• Flecainide = Proarrhythmic actions –> use of these drugs is limited, cautious use is recommended may cause SCD
• Contraindicated in post-MI
  
  • Structural and Ischemic
• IC is Contraindicated in structural and ischemic heart disease

Question 14

Class II: Drugs

Answer 14

ß-blockers

• Propranolol (non-selective)
• Carvedilol
• Metroprolol
• Esmolol (Selective)
• Atenolol
• Timolol
• “PC MEAT”

Question 15

Class II: Mechanism

Answer 15

• β-adrenoceptor antagonists and act by reducing sympathetic stimulation
• Depress automaticity
• ↓ SA and AV nodal activity by decreasing cAMP
• *decreased *Ca²⁺ currents
• ↓ slope of phase 4 (repolarization)
• AV node particularly sensitive
  
  • *Increase *PR interval
  • Esmolol very short acting

Question 16

Class II: Clinical Use

Answer 16

• Prophylaxis post-MI - neg. inotropic effect ↓ O₂ demand
• SVTs
• Prevent reflex tachycardia produced by vasodilationg agents
• Used for Digitalis toxicity
• Esmolol (IV) in acute SVT
• Slowing ventricular rate during Atrial Fibrillation and Atrial Flutter

Question 17

Class II: Toxicity

Answer 17

• Bradycardia
• AV block
• CHF
• Impotence
• Exacerbation of COPD and Asthma (bronchospasm)
• CNS (Sedation, Sleep alterations)
• Masks sings of Hypoglycemia
• Metoprolol: can cause dyslipidemia
• Propanolo: exacerbate vasopasm in Prinzmetal angina
• Contraindicated: in cocaine users (unopposed
  α-adrenergic receptor agonist activity) Tx: glucagon

Question 18

Class III: Drugs

Answer 18

K⁺ channel blockers

• Amiodarone
  
  • Mimics classes I, II, III, IV
  • Used w/ ANY Arrhythmias
  • t_1/2 = 80 days, forever to reach half lives​
• Ibutilide
• Dofetilide
• Sotalol
• “Three(III) letters took him to his final resting place… AIDS”

Question 19

Class III: Mechanism

Answer 19

• **↓ I_K - ↓ outward K⁺ **- currents or slow inward Na⁺ currents
• *↑ *APD
• ↑ ERP
• Used when other antiarrhythmics fail
• Prolong QT interval

Question 20

Class III: Clinical Use

Answer 20

• Atrial fibrillation
• Atrial flutter
• Ventricular tachycardia (amiodarone, sotalol)

Question 21

Class III: Toxicity

Answer 21

• Amiodarone: Pulmonary fibrosis, Hepatotoxicity, Hypo/Hyper-thyroidism (40% iodine by weight), Corneal deposits, Blue/gray skin deposits - photodermatitis, neuro effects, constipation, cardio (bradycardia, heart block, CHF)
  
  • Remember to check PFTs, LFTs, and TFTs
  • Class I, II, III, and IV effects and alters lipid membrane - hapten - triggers immune responses
• Ibutilide: Torsades de pointes
• Dofetilide: None
• Sotabol: Torsades de pointes, excessive ß-blockade

Question 22

Class IV: Drugs

Answer 22

L-type Ca²⁺ Channel blockers

• Verapamil
• Diltiazem
• Use with SVTs

Question 23

Class IV: Mechanism

Answer 23

• Blocks Slow L-type Ca²⁺ channels
• ↓ Phase 0
• ↓ Phase IV
• ↓ SA, ↓ AV nodal activity
• Decrease conduction velocity
• ↑ ERP
• *↑ *PR interval

Question 24

Class IV: Clinical Use

Answer 24

• Reentrant Supraventricular Tachycardia (reSVT)
• Prevention of nodal arrhythmias (e.g. SVT)
• Rate control of Atrial fibrillation and Atrial Flutter

Question 25

Class IV: Toxicity

Answer 25

• Constipation (Verapamil)
• Flushing, dizziness
• Edema
• Additive AV blocks w/ β-blockers (↑ PR interval)
• Verapamil displaces digoxin from binding sites
• Sinus node depression)
• May be exacerbated in individuals taking β-adrenoceptor antagonists
• Should not be used w/ WPW pts.

Question 26

Adenosine antiarrhythmics

(Class V drugs)

Answer 26

• ↓ SA and AV nodal activity
• Acts through a specific Purinergic (P₁) receptor
• G_i-coupled *- ↑ *K⁺ efflux –> hyperpolarizaing the cell ↓ I_Ca(Calcium influx) –> Hyperpolarizes the cell
• Tx: DOC and paroxysmal Supraventricular tachycardia (pSVT) (WORST EVER) including WPWs
• Very short acting (~10 - 15 seconds)
• SEx: flusing, sedation, dyspnea (bronchospasm, must warn pts.), hypotension, angina
• Antagonized by Methylxanthines (Theophylline (COPDs) and Caffeine)

Question 27

Mg²⁺ antiarrhythmics

Answer 27

• Competes with Ca²⁺
• Tx: Torsades de pointes - ↓ K⁺ efflux - long complex
  
  • Drugs causing Torsades de pointes​
    
    • K⁺ channel blockers (‘AIDS’)
    • Antipsychotics (Thioridazine)
    • Tricyclic antidepressants
    • Anti-histimines
• Digoxin toxicity
• Seizures - Pregnancy

Question 28

Antiarrhythmic Classes

Answer 28

• Class I: Na⁺ channel blockers
• Class II: ß-blockers
• Class III: K⁺ channel blockers
• Class IV: Ca²⁺ channel blockers
• Others: Adenosine, Mg²⁺, Digoxin

Question 29

Atropine

Answer 29

• Blocks the effects of Acetylcholine
• Elevates Sinus rate and AV nodal and SA conduction
• Decreases refractory period
• Used to treat Bradyarrhythmias that accompany MI
• Adverse effects include:
  
  • Dry mouth, Mydriasis (dilation of pupil), and Cycloplegia (loss of accomodation of eye)
  • May induce arrthythmias