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DRUGS
• Electrophysiology
• Terminology of arrhythmia
• Classification of arrythmic agents
• Explanation of each
ELECTROPHYSIOLOGY OF NORMAL
CARDIAC RHYTHM
• To understand how antiarrhythmic
drugs work, need to understand
electrophysiology of normal K++ Na, Ca
contraction of heart
– Caused by unequal distribution of
ions inside vs. outside cell
• Na+ higher outside than inside cell
• Ca+ much higher outside than inside
• K+ higher inside cell than outside
Repolarization of
Contraction
ventricles
of atria
FACTORS PRECIPITATING CARDIAC
ARRHYTHMIAS:
1. Ischemia
pH & electrolyte abnormalities
80% – 90% asstd with MI
2. Excessive myocardial fiber stretch/ scarred/ diseased
cardiac tissue
3. Excessive discharge or sensitivity to autonomic
transmitters
4. Excessive exposure to foreign chemicals & toxic
substances
20% - 50% ----- General Anesthesia
10% - 20% ----- Digitalis toxicity
5. Two mechanisms: one or both
• Disturbance of impulse conduction
• Disturbance of impulse formation
DISORDERS OF IMPULSE CONDUCTION
Alter Suppress
↓/↑ conduction
excitability of abnormal
velocity
cardiac cells automaticity
ANTI-ARRHYTHMIC DRUGS
• Supraventricular: • Ventricular:
• Lidokain
– Metabolisme di hati ekstensif harus diberikan IV
– Indikasi: hanya utk pengobatan aritmia ventrikel yg
disebabkan oleh IMA, bedah jantung terbuka, digitalis
– ES: SSPdisosiasi, parestesia, mengantuk, agitasi. Dosis
tinggi: gangguan pendengaran, disorentasi, kejang, henti
napas
• Fenitoin
– IV intermiten dpt sebabkan flebitis. T ½ panjang
Oral: dimulai dgn dosis tinggi diturunkan hingga dosis
pemeliharaan
– Indikasi: aritmia atrium & ventrikel krn digitalis, aritmia
krn bedah jantung terbuka & infark miokard
– ES: SSP nystagmus, mengantuk, vertigo, ataksia, mual-
muntah
Antiaritmia Kelas Ic (1)
• Similar to lidocaine
• Oral route - resistant to first-pass hepatic metabolism
• Usage: ventricular arrhythmias
• t½ = 8 to 20 hrs
• Dosage: Mexiletene – 600 to 1200 mg/day
Tocainide – 800 to 2400 mg/day
• Side effect: tremors, blurred vision, lethargy, nausea, rash,
fever, agranulocytosis
Other CLASS IB: PHENYTOIN
• Anti-convulsant with anti-arrhythmic properties
• Suppresses ectopic pacemaker activity
• Useful in digitalis-induced arrhythmia
• Extensive, saturable first-pass hepatic metabolism
• Highly protein bound
• Toxicity: ataxia, nystagmus, mental confusion, serious
dermatological & BM reactions, hypotension, gingival
hyperplasia
• D/I: Quinidine, Mexiletene, Digitoxin, Estrogen, Theophyllin,
Vitamin D
CLASS IC: FLECAINIDE
• Action = flecainide
• (+) weak β-blocking activity ---- slows
conduction in all cardiac tissues
• t½ = 5 to 7 hrs.
• Dosage: 450 – 900 mg TID
• Usage: supraventricular arrhythmias, broad
spectrum antiarrhythmic agents
• SE: metallic taste, constipation, arrhythmia
exacerbation
CLASS IC: MORICIZINE
IBUTILIDE
• Slows repolarization
• Prolong cardiac action potentials
• Mech of action: ↑ inward Na+ current, blocking Ikr-
channel or both
• routes: Oral, IV (1 mg over 10min)
• Clin. Uses: atrial flutter, atrial fibrillation
• Toxicity: Torsades de pointes
DOFETILIDE
ADENOSINE
• A nucleoside that occurs naturally in the body
• t½ ≈ 10 seconds
• MOA: enhances K+ conductance & inhibits cAMP-induced Ca++ influx
→ results in marked hyperpolarization & suppression of Ca++-
dependent AP
• IV bolus: directly inhibits AV nodal conduction & ↑ AV nodal
refractory period
ADENOSINE
• DOC for prompt conversion of paroxysmal SVT to sinus
rhythm due to its high efficacy & very short duration of
action
• Dosage: 6-12 mg IV bolus
• D/I:
– theophylline, caffeine – adenosine receptor
blockers
– Dipyridamole – adenosine uptake inhibitor
• Toxicity: flushing, SOB or chest burning, atrial
fibrillation, headache, hypotension, nausea,
paresthesia
MAGNESIUM
• Effective in patients with recurrent episodes of torsades de pointes
(MgSO4 1 to 2 g IV) & in digitalis-induced arrhythmia
• MOA: unknown → influence Na+/K+ ATPase, Na+ channels, certain
K+ and Ca++ channels
POTASSIUM
• Developed because
Potassium channel blocker some patients
• Amiodarone – prolongs action potential by delaying K+ efflux
• Ibutilide – slows Na inward movement and delaying K + influx. negatively sensitive to
• Bretylium – first developed to treat hypertension but found to also suppress Na channel blockers
III ventricular fibrillation associated with myocardial infarction (they died!)
• Dofetilide - prolongs action potential by delaying K+ efflux with no other • Delay repolarization
effects
(phase 3)
• Increase APD and ERP
BASIC MECHANISM OF ANTI-
ARRHYTHMIC
Condition Drug