amiodarone, drug of the month
TRANSCRIPT
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Amiodarone Drug Of The Month
Presenter
Praveen upta
Moderator
Santhosh Satheesh
Head of Department,Department of Cardiology,
JIPMERPondicherry, India
Date26-04-2016
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AmiodaroneIntroduction
Complex antiarrhythmic agent
Benzofuran derivative
Labeled only for life threatening VT
Iodine-containing compound
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Clinical Pharmacology
Pharmacokinetics
Bioavailability- 22 to 95 percent.
Absorption is enhanced with food
Lipid soluble and is stored in high concentrations in fat and muscle, liver,
lungs, & skin
Routine monitoring of plasma level not recommended.
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Clinical Pharmacology
Pharmacokinetics
Plasma peak concentrations, 3 to 7 hours after single oral dose.
Minimal first-pass effect
Elimination by hepatic excretion
Extensive hepatic metabolism with desethylamiodarone as a metabolite.
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Clinical Pharmacology
Pharmacokinetics
Myocardium concentration 10 to 50 times of plasma
Plasma clearance is low, and
Renal excretion is negligible
Doses modification not requried in renal disease.
Amiodarone and desethylamiodarone not dialyzable
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Clinical pharmacology
Pharmacokinetics
Large Volume of distribution (60 liter/kg)
Highly protein bound (96%)
Crosses the placenta
Measurable levels in breast milk
desethylamiodarone have antiarrhythmic properties
Elimination half-life is 58 days
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Electrophysiologic effects
Class III drug
Prolongs the QT interval
Slows heart rate and
atrioventricular nodal
conduction
Prolongs refractoriness (via
potassium and sodium channel
blockade)
Slows intracardiac conduction
(via sodium channel blockade).
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Indications
Long-term treatment
Secondary prevention of life-threatening VT.
For patients who have survived sustained VT & with left ventricular
dysfunction
For primary prevention of SCD
As an adjunct to reduce the frequency of ICD shocks
Treatment of atrial fibrillation, although the FDA has not approved this
indication.
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Indications
Long-term treatment
Hypertrophic cardiomyopathy
Nonischemic dilated cardiomyopathy
Asymptomatic ventricular arrhythmias after myocardial infarction
Ventricular tachyarrhythmia during and after resuscitation from cardiac
arrest
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Acute treatment
IV amiodarone for the emergency treatment of VT
Onset of action with IV therapy in less than 30 minutes
ACLS recommended for the initial treatment of hemodynamically stable
wide-complex tachycardia
In patients who require long-term treatment, intravenous dosing should be
switched to oral dosing
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Acute treatment
Hemodynamically unstable atrial fibrillation
AF with rapid ventricular rates
AF with impaired renal function
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Amiodarone indication
Junctional tachycardia
AV node /AV entry
Before open heart surgery as well as postoperatively to decrease the
postoperative atrial fibrillation
60% to 80% effective for supraventricular tachyarrhythmias
40% to 60% for ventricular tachyarrhythmias
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Dosage of amiodarone
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Amiodarone in stable monomorphic VT
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Role of Amiodarone in cardiac arrest
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Amiodarone in AFProposed treatment algorithm for the use of dronedarone in the therapy of patients with atrial fibrillation.
Atrial fibrillation: Dronedarone and amiodarone—the safety versus efficacy debateEric N. Prystowsky, Nature Reviews Cardiology 7, 5-6 (January 2010) doi:10.1038/nrcardio.2009.221
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Adverse Effects
75% of patients over 5 years
Compel stopping of the drug in 18% to 37%
Most frequent ,Pulmonary and gastrointestinal
Reversible with dose reduction or cessation of treatment
Common when therapy is long term and at higher doses
Pulmonary toxicity, most serious
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Amiodarone effect on thyroid gland
Inhibit the peripheral conversion of T4 to T3
Slight increase in T4, reverse T3, and thyroid-stimulating hormone (TSH)
and a slight decrease in T3 levels
Reverse T3 concentration, used as an index of drug efficacy
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Amiodarone effect on thyroid gland
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Amiodarone effect on thyroid gland
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Amiodarone induced thyrotoxicosis
Approach to the Patient with Amiodarone- Induced ThyrotoxicosisFausto Bogazzi, Luigi Bartalena, and Enio Martino
Department of Endocrinology (F.B., E.M.), University of Pisa, 56124 Pisa, Italy; and Department of Clinical Medicine (L.B.), University of Insubria, 21100 Varese, ItalyJ Clin Endocrinol Metab, June 2010, 95(6):2529–2535 jcem.endojournals.org
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Amiodarone-Induced Hypothyroidism(AIH)
More than amiodarone induced thyrotoxicosis (AIT) in iodine-sufficient
Areas
More in females
Patients are older than AIT
AIH usually develops earlier than AIT
Presence of anti-thyroid peroxidase (TPO) antibodies is risk AIH
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Amiodarone-Induced Hypothyroidism(AIH)
Baseline elevation of TSH risk factor for AIH
Thyroid gland with Hashimoto’s thyroiditis, unable to escape from the acute
Wolff-Chaikoff effect after an iodine load and to resume normal thyroid hormone
synthesis
Patients without underlying thyroid abnormalities and with negative thyroid
autoantibody tests, subtle defects in iodine organification and thyroid hormone
synthesis are likely cause AIH
May spontaneously remit after discontinuation of amiodarone
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Monitoring of thyroid function for patient on amiodarone
Thyroid function tests, every 3 months for first year
Once or twice yearly, thereafter
Sooner ,if symptoms develop, that are consistent with thyroid dysfunction
During hypothyroidism, the TSH level increases greatly
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Amiodarone effect on thyroid gland Algorithm for management of amiodarone-induced thyroid disease. Amiodarone-induced thyroid disease can be diagnosed based on classic signs and symptoms of either hypothyroidism or hyperthyroidism or, more commonly, by routine (every 3-6 months) thyroid function testing. Any single abnormal TSH concentration (>10 mIU/l), an indication of clinical hypothyroidism (AIH),
should be confirmed and treated with levothyroxine. AIT management depends upon the severity and duration of clinical signs or symptoms. Mixed type 1 and type 2 AIT may require combination therapy with thionamides and corticoid steroids. Abbreviations:
AIH, amiodarone-induced hypothyroidism; AIT, amiodarone-induced thyrotoxicosis.
Effects of Amiodarone Therapy on Thyroid Function: Amiodarone-related Adverse Effects Janna Cohen-Lehman, DO; Peter Dahl, MD; Sara Danzi, PhD; Irwin Klein, MD Faculty and DisclosuresCME Released: 11/24/2009; Valid for credit through 11/24/2010, Medsccap, Saturday, October 15, 2016
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Pulmonary toxicity
Frequency - 2 to 17%
Result from direct drug-induced phospholipidosis or immune-mediated
hypersensitivity
Subacute cough
Progressive dyspnea
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Pulmonary toxicity
ARDS-Can develop rapidly
Worsening dyspnea or cough, do prompt assessment
Congestive heart failure can mimic amiodarone pneumonitis and, must be
ruled out early in the evaluation
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Amiodarone induced pulmonary fibrosis
Patchy interstitial infiltrates on
chest radiographs
Reduced DLCO
HRCT chest
Lower incidence if dose 300
mg/day or less
Amiodarone lung, A.Prof Frank Gaillard et al◉
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Pulmonary toxicity
treatment
Withdrawal of amiodarone
Supportive care
Corticosteroids
Toxicity is reversible
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Cardiovascular adverse effects
Bradycardia and heart block occur in 1 to 3 %
Proarrhythmia occurs in less than 1 %
Prolongation of the QT interval
Polymorphic ventricular tachycardia (i.e., torsades de pointes) is rare
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Cardiovascular adverse effects
CI in patients with second- or third-degree heart block
IV amiodarone-heart block or bradycardia in 4.9%
Hypotension in 16 %
Infusion discontinued, or rate reduced, if patient develop complication
Phlebitis (Use central venous line when possible)
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Adverse effect of amiodarone
Corneal microdeposits
Occur in 100% of adults receiving
the drug longer than 6 months
Optic neuritis (Rare)
Optic atrophy (Rare)
Visual loss (Rare)
Amiodarone-Induced Vortex Keratopathy,Tommy C.Y. Chan, M.B.,
B.S.Vishal Jhanji, M.D., N Engl J Med 2015; 372:1656April 23, 2015DOI: 10.1056/NEJMicm1406501
Amiodarone induced skin discoloration Photosensitivity
Less frequently
phototoxicity
Blue–gray skin
Hyperpigmentation of
sunexposed areas
<10% of patients
Preferentially men
Q J Med 2011; 104:723–724, doi:10.1093/qjmed/hcq131, Advance Access Publication 30 July 2010
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Amiodarone induced skin discoloration
20 months of continuous treatment and a minimal cumulative dose of 160
g
Due to lysosomal dermal lipofuscin deposits
Treatment is reduction or cessation of therapy
Skin changes slowly abate
Skin discoloration persist for years
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Drug Interactions
Potent inhibitor of the hepatic and renal metabolism of several drugs
Inhibits metabolism through several cytochrome P450 pathways
CYP 2C9 ( warfarin )
CYP 2D6 ( beta blockers and narcotics)
CYP 3A4 (cyclosporine/CCB)
Interactions with digoxin
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Monitoring of Amiodarone
Followed regularly
Assess ongoing need
Efficacy of the drug
Appropriateness of dosage
Adverse effects
Potential drug interactions
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Take home message
Effective in patient with AF both short and long term use
Effective in patient with acute VT
Not effective in prevention of SCD in primary and secondary prevention trial
Helpful in prevention of no of ICD shock
Followed patient regularly
See for adverse effects
Look for potential drug interactions
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Reference
Amiodarone: Guidelines,for Use and Monitoring, LYLE A. SIDDOWAY,
M.D., York Hospital, York, Pennsylvania, December 1, 2003 / Volume 68,
Number 11 www.aafp.org/afp, American Family Physician
Images- Google image
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Thank you