Download Drugs for Dysrhythmias

Antiarrhythmic Drugs
Drug/MOA
Class IA
Quinidine
Alpha-blocker
Blocks Na AND K
channels.
Disopyramide
Na blocker
Procainamide
Na (primary) and K
(secondary) blockade
Class IB
Lidocaine
Fast on-off block of
Na channels
Class IC
Flecainide
Na channel block
Fluorinated congener
of procainamide
Propafenone
Na channel block
Beta blocking
Effects/Facts
Adverse Effects (proarrhythmia is common)
-Direct vasorelaxant
-May cause orthostasis and reflex sinus tachycardia
-No negative inotropic effect, even w/ left ventricular dysfunction.
-Most common – diarrhea
-Most lethal – torsades de pointes
-Cinchonism – headache, dizziness, tinnitus
-Significant anticholinergic effect
-Significant negative inotropic effect
-Effective drug for vagally mediated AF
-Effective drug for AF in hypertrophic cardiomyopathy
-Decreases both contractility and obstruction in the ventricle!
-Slows CV and pacemaker rate b/c of Na blockade
-Prolongs APD
-Direct depressant effects on SA and AV nodes
Clinical Applications:
-Most atrial and ventricular arrhythmias
-2nd DOC for sustained ventricular arrhythmias associated w/ MI
-DOC in pre-excited atrial fibrillation w/ rapid ventricular response.
PK: IV, IM, eliminated by hepatic metabolism to NAPA and renal elimination
Fast and slow acetylator phenotypes exist and are genetically determined.
-NAPA implicated in torsades de pointes in pts w/ renal failure
-Lupus-related symptoms w/ long term therapy
(arthralgias, myalgias, serositis, pulm infiltrates, hepatomegaly)
(less common w/ rapid acetylators)
-Hypotension w/ IV dosing due to ganglion blocking properties
-Worsening of CHF in 10 %
-GI (25 %), rash, Raynaud phenomenon, agrnulocytosis,
neuromuscular effects in pts w/ myasthenia gravis, depression,
ANA in 80%, Histone Ab in 2/3
-Shortens APD duration
-Lidocaine and oral congener (Mexilitene) act largely by slowing conduction
-Second line therapies for refractory ventricular arrhythmias
Mainly neurological
-Significant negative inotropic effect esp at higher doses
-Proarrhythmia (VT and SVT)
-Positive use dependence: More effective at higher HR, due to slow unbinding kinetics
(check graph in ppt to understand)
-Levels elevated by amio
-Don’t use in LV dysfunction or CHF
-Plasma half life 13-19 hrs/ 2/3rd metabolized in liver
-FDA approval for tx of SVT
-Usually used w/ AV nodal blocking agent
-Similar antiarrhythmic profile to flecainide
-Drug rapidly absorbed w/ bioavailability of 50 %, elimination half-life being 2-10 hrs in
normal subjects and 12-32 hours in poor metabolizers
Metabolism: CYP2D6
-Extensive metabolizers: less parent drug = less beta blocker effect
-Poor metabolizers: more parent drug = more beta blocker effect
Neuro and GI
Class II - Beta Blockers (check ppts for MOAs)
-Esmolol onset is within seconds!
Propranalol
-Check powerpoint for all facts – we’ve learned most of these already.
Esmolol
-Multiple drug interactions
-Nausea, dizziness, metallic taste, blurry vision, paresthesias, liver
test abnormalities, exacerbation of asthma
-Strongly inhibited by quinidine
Class III
FOR ALL: prolong QT, no effect on CV (predominant effect is through prolonging repolarization)
-Initiated or re-initiated in hospital
Dofetilide
K channel block
Sotalol
K channel block
Ibutilide
K channel block
Amiodarone
K channel block
Dronedarone
CI: A LOT of drugs – know ketoconazole, azithromycin,
-Dose should be adjusted based on renal function (how its excreted)
fluoroquinolones
-Drugs used for maintaining sinus rhythm in pts w/ paroxysmal AF and CHF?
DOFETILIDE AND AMIODARONE!!!!!!!!!
-Initiated or re-initiated in hospital w/ EKG monitoring
-Dose should be adjusted based on renal function (how its excreted)
-Blocks rapid component of delayed rectifier current (Ikr)
-Most significant: incidence of TdP – 4 %
-Lower concentrations drug also activates inward sodium current
-2 % require cardioversion
-Increases APD and ERP, thus increasing QT and QTc intervals
-In almost all pts, onset of arrhythmia was within 40 mins of
-Acute prolongation of atrial ERP leading to rapid termination of AF and AFL
commencement of drug infusion
-Only IV drug approved by FDA to convert AF or AFL of recent onset
EFFECTS:
Additive effect w/ beta blockers and CCB
Metabolism – slow absorption from GI tract
Dosage need not be adjusted in renal failure
SIDE EFFECTS:
1. Frequency of hypotension low
2. Pulmonary (5-15 %) – dyspnea, cough, fever, pleuritic CP, CXR findings
Acute – Subacute – Chronic (look at ppt for details)
Pathology – inflammatory cell infiltrate, fibrosis, macrophages, etc.)
3. Hepatic (15-50 %)
4. Thyroid (2-24 %) –
Hypo – Worff-Chaikoff Effect – block of thyroid gland iodine uptake and thyroid hormone biosynthesis
Hyper
-Thyrotoxicosis incidence 2-12 %
-Type I amiodarone-induced thyrotoxicosis – unmasking of prior thyroid abnormality; pts w/ nodular goiter, nodules, or graves’
-Type II amiodarone-induced thyrotoxicosis – follicle cytotox w/ inflammation, IL-6 levels markedly elevated
Tx: stop amio vs. medical and/or surgical therapy
5. Photosensitivity (25-75 %) - discoloration
6. Blue skin (<10 %)
7. Corneal microdeposits (>90 %) – reversible
8. Ocular Toxicity: halo vision, bilateral loss w/ gradual onset due to optic neuritis
Pathology – intracytoplasmic lamellar bodies in corneal epithelium, opacities in anterior subscapscaular region of lens (irreversible), disk edema leading to optic
neuropathy
Dx: slit lamp exam, acuity testing
Tx: stop drug if possible for vision loss
CI: Increases digoxin, Coumadin, and cyclosporine
9. Neuro: symptoms include tremor, gait, peripheral neuropathy
Pathology: accumulation in myelinated and unmyelinated axons w/ inclusions
Dx: EMG, clinical syndrome
Tx: responds well to dosage reduction
-Neuro tox most common at higher doses and in elderly, can usually be ameliorated w/ doses reduction.
K channel block; Young Padawan; DON’T GIVE TO PEOPLE W/ CHF
Class IV
Verapamil
Diltiazem
L-type Ca channel
OTHERS:
Adenosine
Activation of outward
K current in atria, SA,
and AV nodes (not
ventricles)
Digoxin
Central and
peripheral actions to
increase vagal activity
Ranolazine
Na channel block
AND repol phase
Ivabradine
Inhibits If current
-Decreases phase 0 depolarization – so sinus node automaticity is slowed
-Increase AV nodal refractory periods – thus decreasing number of impulses that travel
through AV node
-Used for rate control in AF and AFL
-DON’T USE IN PATIENTS WITH HEART FAILURE
-AV node – drug depresses nodal action potential
-SA node – sinus rate slows
-Proarrythmias (tosades, faster AF, new AF)
-Diagnostic uses (WPW, AVNRT)
-Therapeutic uses – rapid termination of most narrow complex tachycardias
-DON’T GIVE TO HEART TRANSPLANT PATIENTS
-AV – delay in conduction and increase in ERP, which slows ventricular response in AF
and AFL
-No direct anti-fibrillatory actions of drug
-Used largely for control of ventricular response in AF
-Renally excreted
-Not useful for rate control of AF in ambulatory state
-Approved for angina.
-Utilized w/ very food effects to treat ventricular arrhythmias.
-Acts on both depol and repol stage
-Creates uniform level of repolarization – good for rhythm control
-FUNNY current
-Used to treat sinus tachycardia
-Effective in treatment of angina pectoris and in tx of heart failure
CI: dipyridamole, theophylline