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What is the MOA of amiodarone?
Class III antiarrhythmic: blocks K+ channels which prolongs the repolarization and refractory period in the atrial and ventricular tissue
Also has same MOA as all other drugs (Na+, BB, CCB)
What are some common uses for amiodarone?
- Supraventricular and ventricular tachycardia (VT, VF, A fib or flutter)
- Cardiac arrerst
- Prevention of post-operative AF during cardiothoracid surgery
Where does amiodarone typically concentrate?
What type of absorption does amiodarone have?
Slow and incomplete
Does food enhance or decrease the rate and extent of absorption? (AUC and Cmax)
Enhance: Increase AUC and Cmax
What is the bioavailability of oral amiodarone?
What type of circulation does amiodarone undergo?
What percentage of amiodarone is protein bound?
What two proteins does amiodarone bind with?
- alpha-1-acid glycoprotein
What is the approximate volume of distribution of amiodarone?
What are the major sites of distribution for amiodarone?
_________ cocentration 10-400 times greater than ________ concentrations
Does amiodarone follow a one or two compartment model?
What is the active metabolite of amiodarone?
Is the process of amiodarone being distributed to the tissues slow or fast?
What is a major enzyme that metabolizes amiodarone?
What enzyme(s) and/or transporter (s) is/are inhibited by amiodarone?
Does amiodarone need to be adjusted in renal dysfunction?
What is the 1/2 life for chronic oral dosing of amiodarone?
What is the 1/2 life for IV amiodarone?
9 to 36 days
Is the half life of N-DEA greater, less than, or equal to amiodarone?
Greater than or equal
What are two factors that alter the clearance of amiodarone?
- Cirrhosis: decreases formation of DEA
- Elderly: decreased clearance
What effect does renal failure, heart failure, or dialysis have on amiodarone?
What is the onset of action of amiodarone?
What is the duration of amiodarone?
What is the therapeutic range of amiodarone?
When is the peak concentration of amiodarone?
What is the oral LD for amiodarone?
1.2-1.8 g/day in divided doses up to 10 grams
What is the IV LD for amiodarone?
5-7 mg/kg over 30-60 minutes, then 1.2-1.8 g/day continuous infusion up to 10 grams
What is the maintenance dose for amiodarone?
If the patient has been on IV therapy for < 1 week, what is the oral LD that should be given?
800-1600 mg/day for 1-2 weeks followed by a MD
If the patient has been on IV therapy for 1 to < 3 weeks, what is the oral LD that should be given?
600-800 mg/day for 1-2 weeks followed by a MD
If the patient has been on IV therapy for > 3 weeks, what is the oral LD that should be given?
None, go ahead and start with the MD
When switching from oral to IV amiodarone, how should the dose be adjusted?
Give 50% of oral dose when switching to IV
Which drugs can caused a prolonged QT interval when used with amiodarone?
- Azole antifungals
- Macrolides (erythromycin, clarithromycin)
Which drugs can cause delayed AV node conduction when used with amiodarone?
When using digoxin and amiodarone together, what adjustment should be made?
Decrease the digoxin dose by 50%
When using warfarin and amiodarone together, what adjustments hould be made?
Decrease the warfarin dose by 25%
What drugs may have increased concentrations when administered with amiodarone?
What drugs will decrease amiodarone levels?
- St. Johns Wort
What drugs will increase amiodarone levels?
- Grapefruit Juice
- Protease inhibitors
Approximately how much of an increase in amiodarone levels would you expect to see when administered with grapefruit juice?
If amiodarone is given too quickly through an IV what are some AE that can happen?
In order to prevent phlebitis, what is the cut off for giving central line amiodarone?
> 2 mg/nL
What are some toxicites that can occur due to the MOA of amiodarone?
- Sinus bradycardia
- Atrioventricular block
- QT prolongation (rarely torsades)
What are some proposed etiologies of toxicity related to chronic therapy?
- Long 1/2 life : accumulation of amiodarone and iodine
- Lipophilic distribution into adipose tissues of multiple organs
- Phospholipidosis : abnormal lipid storage
- Free radical formation
At what dose do most toxicites occur?
> 400 mg/day
What types of pulmonary toxicites are possible with amiodarone?
- Pulmonary fibrosis
- Hypersensitivity Pneumonitis
- Pulmonary inflammation
- Interstitial or alveolar Pneumonitis
What is the MOA of pulmonary toxicity with amiodarone?
Abnormal phospholipid storage in lysosomal cells leading to membrane stiffness and cell damage
Is pulmonary toxicity independent or depending on dose and/or duration of therapy?
Does pre-existing pulmonary disease increase the risk of pulmonary toxicity?
No, but it may worsen the prognosis
What are some signs and symptoms of pulmonary toxicity?
- Nonproductive cough
- Pleuritic chest pain
- Weight loss
- CSR: interstitial or alveolar infiltrates and/or extensive pulmonary fibrosis
What types of hepatic toxicity are seen with amiodarone?
- Transient elevation in LFTs
- Clinical hepatitis and cirrhosis
What are the signs and symptoms of hepatic toxicity?
- Typical signs of liver failure (side pain, jaundice)
What is the MOA of hepatic toxicity?
- Direct toxic effects
Is it more common to see HYPOthyroidism or HYPERthyroidism with amiodarone?
What is the MOA of thyroid toxicity with amiodarone?
- Excess iodine intake
- Amiodarone blocks conversion of T4 to T3 --> inactive thyroid hormonres
- Also leads to decreased synthesis of T4
Is thyroid toxicity dependent or independent of dose/duration?
What are two ocular toxicities that occur due to amiodarone?
- Corneal microdeposits
- Opetic neuropathy
What are symptoms of corneal microdeposits?
- Present with corneal cysts or abscesses
What is the MOA of corneal microdeposits?
Secretion of amiodarone by the lacrimal glands and deposits on the surface of the cornea
What are two dermatologic toxicites of amiodarone?
- Blue-gray skin discoloration
What is the MOA of blue-gray skin?
Photosensitive reaction resulting in lipofuscion deposits instead of melanin and pigment
In what patient population are neurologic toxicities more common? Is it independent or dependent of dose?
Are corneal microdeposits related or non-related to drug dose/duration?
What should you monitor at baseline for amiodarone use?
- Eye exam
What tests should be ordered at 6 months post amiodarone?
What tests should be ordered annually?
- PFTs (symptoms only)
- CXR (symptoms)
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