Tiêu đề 18. ANTI-ARRHYTHMIC DRUGS.pdf ✅

PHARMD GURU Page 1 DEFINITION:  Arrhythmia is defined as the variation of heart from normal rhythm.  A disturbance in the rhythm, heart rate, impulse generation or conduction of electrical impulses is responsible for membrane depolarization. These changes can escort to alterations in overall cardiac function that can be life-threatening. MECHANISMS OF ARRHYTHMIAS:  Disturbances in generation of impulse may be due to: o Abnormal automaticity. o Delayed after depolarization.  Disturbances in conduction of impulse: o By causing repeated activation (re-entry), impulse may re-circulate in heart. o Blocks conduction. CLASSIFICATION OF ANTI-ARRHYTHMIC DRUGS: ANTI-ARRHYTHMIC DRUGS
PHARMD GURU Page 2 (or) CLASS-I: NA+ CHANNEL BLOCKER:  Bind to and block Na+ channels (and K+ also).  Act on initial rapid depolarisation (slowing effect).  Local Anaesthetic (higher concentration): block nerve conduction.  Do not alter resting membrane potential (Membrane Stabilisers).  At times, post repolarization refractoriness.  Bind preferentially to the open channel state.  Use Dependence: The more the channel is in use, the more drug is bound.
PHARMD GURU Page 3 CLASS IA: QUINIDINE:  D-isomer of quinine obtained from cinchona bark.  Historically first antiarrhythmic drug used. MECHANISM OF ACTION:  Blocks sodium channels.  Decreases automaticity, conduction velocity and prolong S repolarization.  Decreases phase 0 depolarization, increases action potential duration (APD) and effective refractory period (ERP). OTHER ACTIONS:  Decreases BP (α-block), skeletal muscle relaxation. CLINICAL PHARMACOKINETICS:  Well absorbed.  80% bound to plasma proteins (albumin).  Extensive hepatic oxidative metabolism.  3-hydroxyquinidine, is nearly as potent as quinidine in blocking cardiac Na+ Channels and prolonging cardiac action potentials.
PHARMD GURU Page 4 USES:  To maintain sinus rhythm in patients with atrial flutter or atrial fibrillation.  To prevent recurrence of ventricular tachycardia or VF. ADVERSE EFFECT: Non-cardiac:  Diarrhea, thrombocytopenia.  Cinchonism and skin rashes. Cardiac:  Marked QT-interval prolongation and torsades de pointes (2-8%).  Hypotension.  Tachycardia. DRUG INTERACTIONS:  Metabolized by CYP450.  Increases digoxin levels.  Cardiac depression with beta blockers.  Inhibits CYP2D6. DISOPYRAMIDE: MECHANISM OF ACTION: Disopyramide produces a negative ionotropic effects that is greater than weak effect exerted by quinidine and procainamide, and unlike the latter drugs, disopyramide causes peripheral vasoconstriction. ADVERSE EFFECTS:  Precipitation of glaucoma.  Constipation, dry mouth.  Urinary retention.  Myocardial depression.