Antiarrythmic Flashcards
Procainamide
Class IA
Cardiac Effects - slows upstroke of AP, slows conduction, prolongs QRS, prolongs APD by non-specific blockade of K channels
Extracardiac Effects - ganglion-blocking properties, hypotension
Toxicity - Excessive AP prolongation, QT-interval prolongation which can lead to torsades de pointes. Long term use can cause syndrome like lupus
Pharmacokinetics - drug metabolite (NAPA) - class 3 activity. Hepatic metabolism. NAPA has longer half-life than procainamide
T.U. - most A and V arrythmias
Quinidine
Class IA
Cardiac Effects - slows upstroke of AP, slows conduction, prolongs QRS, prolongs APD by non-specific blockade of K channels, antimuscarinic effects
Extracardiac Effects - Adverse GI effects, cinchonism at toxic concentrations
Toxicity - excessive QT prolongation -> torsades de pointes
PK - readily absorbed from GI tract an eliminated by hepatic metabolism, renal excretion
T.U. - rarely used because cardiac and extracardiac S.E.
Disopyramide
Class IA
Cardiac Effects - slows upstroke of AP, slows conduction, prolongs QRS, prolongs APD by non-specific blockade of K channels, antimuscarinic effects
Extracardiac Effects - Atropine like activity -> urinary retention, dry mouth, blurred vision, constipation
Tox - excessive QT prolongation -> torsades. May precipitate to heart failure
PK - loading doses not recommended because of heart failure. Hepatic metabolism and renal excretion
T.U. - effective for supraventricular arrythmias but only approved for ventricular arrythmias in USA
Lidocaine
Class IB
Cardiac Effects - selective depression of conduction in depolarized cells. Little effect on ECG
Extracardiac Effects -
Tox - Least cardiotoxic class I drugs. Paresthesia, tremor, nausea, light headedness, slurred speech
PK - extensive first pass hepatic metabolism -> only 3% appears in plasma -> give parenterally
T.U. - agent of choice for termination of ventricular tachycardia and prevention of v.fib after cardioversion in setting of acute ischemia. NO PROPHYLACTIC
Mexiletine
Class IB
Cardiac Effects - orally active congener of lidocaine. Selective depression of conduction in depolarized cells
Extracardiac Effects - relieves chronic pain
Tox - tremor, blurred vision, lethargy, nausea
PK - hepatic metabolism, renal excretion. half life = 8-20 hrs
T.U. - ventricular arrythmias
Tocainide
Class IB
Cardiac Effects - selective depression of conduction in depolarized cells.
Tox - lidocaine analog
PK - glucuronidation metabolism -> renal excretion
T.U. - not sold in USA
Flecainide
Class IC
Cardiac Effects - slows upstroke of AP, slows conduction, potent blocker of Na and K channels with slow unblocking potential
Tox - severe exacerbation of arrythmia when normal doses administered to preexisting v. tachyarrythmias
PK - metabolism and elimination both hepatic and renal
T.U. - supraventricular arrythmias. Effective in suppressing PVC
Propafenone
Class IC
Cardiac Effects - slows upstroke of AP, slows conduction, WEAK beta-blocking activity
Tox - metallic taste and constipation, some arrythmia exacerbation
PK - hepatic metabolism and renal excretion
T.U. - supraventricular arrythmias
Moricizine
Class IC
Cardiac Effects - slows upstroke of AP, slows conduction, does not prolong AP duration
PK - extensive first pass metabolism
T.U. - ventricular arrythmias, no longer sold in USA
Propranolol
Class II (beta-blocker)
Non-selective beta-blocker. Reduces chronotropic, inotropic, and vasodilator responses to beta-adrenergic stimulation by competing for binding sites
Tox - GI, dizziness, fatigue, bradychardia, hypotension
PK - extensive liver metabolism
T.U. - hypertension, akathasia, tremor, CHF
Acebutolol
Class II (beta-blocker)
Cardioselective, beta-adrenergic receptor blocker (beta-1)
Tox - Same as other beta-blockers
PK - hepatic metabolism (diacetolol - active metabolite), both renal and non-renal excretion
T.U. - same
Esmolol
Class II (beta-blocker)
Short-acting cardioselective adrenergic blocker, selective to beta-1 receptors. At higher doses it affects beta-2
Tox - same
PK - metabolized by RBCs (esterases), renal excretion
T.U. - other beta-blockers
Sotalol
Class II (beta-blocker)
Blocks beta-adrenergic receptors and cardiac action potential duration prolongation
Tox - overdose predisposes patients to torsades and ventricular arrythmias
PK - liver (no significant metabolism), renal excretion
T.U. - atrial and ventricular dysrhythmias
Class I Na Blockers
Binds to and blocks FAST Na channels
- leads to decreased phase 0 (decreased amplitude)
- decreases conduction velocity
Class IA
Moderate Na blockers
Increase the ERP (non-specific activity of K channels)
Class IB
Weak Na blockers
Decrease ERP
Class IC
Strong Na blockers
no effect on ERP
Class II: beta-blockers
- Used to prevent supraventricular arrythmias and reduce ventricular ectopic depolarizations
- inhibit sympathetic activation of cardiac automaticity and conduction
- slow HR, decrease AV node conduction velocity, increase AV node refractory period
K channel blockers
blocks K channels = slows the repolarization during phase 3
- increases AP duration and ERP
- will lengthen the QT interval
Amiodarone
Class III (also has class I and beta blocking activity)
- prolongs AP (also potent Na blocker and weak beta blocker and Ca blocker –> slows HR and AV node conduction)
- causes peripheral vasodilation
Tox - bradychardia and heart block with preexisting SA or AV node disease, accumulates in tissues. Blocks peripheral conversion of thyroxine (T4) to Triiodothyronine (T3) and source of inorganic iodine
PK - hepatic metabolism –> bioactive metabolite. Has complex elimination which results in half life lasting 1-3 months. substrate for CYP3A4 –> can cause increased level of other drugs (warfarin)
TU - v tach, a fib or a flutter
Most important adverse effect of amiodarone
dose related pulmonary toxicity
- OTHERS
- abnormal liver function
- skin deposits –> photodermatitis
- corneal microdeposits –> halos in peripheral visual fields
- hypo- and hyperthyroidism
Dofetilide
Class III
- selective K channel blocker, prolongs AP, increase QT interval
- Tox - life-threatening v arrhythmias
PK - 100% bioavailable, hepatic metabolism via CYP3A4
TU - maintenance and restoration of normal sinus rhythm in a fib. contraindicated in long QT, bradychardia, hypokalemia
Ibutilide
Class III
- prolongs AP, also slows inward Na activator –> increases ERP
Tox - excessive QT interval prolongation –> torsades
PK - hepatic metabolism
TU - acute conversion of a flutter and fib to normal sinus rhythm (more effective in flutter)
Class IV Drugs
- bind to L-type Ca channels located in vascular smooth muscle, cardiac myocytes, and SA/AV node
- smooth muscle = relaxation
- cardiac myocytes = shortens phase 2 of AP, reduce force of contraction
- nodal cells = decreased HR, decreased conduction velocity
- DON’T give with a beta-blocker!!!!
