Liver amiodarone

Amiodarone Tremor, ataxia, pareslfresia, insomnia, corneal microdeposits, optic neuropathy/neuritis, nausea, vomiting, anorexia, constipation, TdP (<1%), bradycardia or AV block (IV and oral use), pulmonary fibrosis, liver function test abnormalities, hepatitis, hypothyroidism, hyperthyroidism, photosensitivity, bluegray skin discoloration, hypotension (IV use), phlebitis (IV use)... 

Amiodarone is the preferred antiarrhythmic during cardiac arrest according to the 2005 guidelines. Hypotension occurs frequently but can generally be reversed by decreasing the infusion rate. Other acute effects include fever, elevated liver function tests, confusion, nausea, and thrombocytopenia. 

WARNING Co administration w/ ritonavir assoc w/ Hep hepatic decomp w/ fatalities. D/C w/ S/Sxs of H Uses HIV 1 Infxn w/ highly Tx-experienced pts or HIV 1 strains resistant to multiple protease inhibitors. Must be used w/ ritonavir 200 mg Action Antiretroviral HIV-1 protease inhibitor Dose 500 mg PO bid w/ food, administer w/ ritonavir 200 mg PO bid Caution [C, -] Sulfa aU gy, Uvct Dz Contra Mod-severe hepatic insuff concomitant use w/ amiodarone, astemizole, bepridil, cisapride, ergots, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, rifampin, simvastatin, terfenadine, triazolam, St. John s wort Disp Caps SE HA, GI distress, rash, fati e, fat redistribution, hyperglycemia, Hep, liver Dz, lipid elevations Interactions T Effects OF anticoagulants, antipits, azole antifun-... 

Amiodarone is slowly and poorly absorbed after oral administration. It is metabolised slowly in liver to active metabolite. 

Simvastatin (Zocor) [Anrilipemic/HMG-CoA Reductase Inhibitor] Uses X Cholesterol Action HMG-CoA reductase inhibitor Dose Adults. 5-80 mg PO w/ meals X in renal insuff Peds. 10-17 y 10 mg, 40 mg/daily max Caution [X, —] Avoid concurrent use of gemfibrozil Contra PRG, liver Dz Disp Tabs 5,10, 20, 40, 80 mg SE HA, GI upset, myalgia, myopathy (muscle pain, tenderness or weakness w/ creatine kinase 10 x ULN), Hep Interactions T Effects OF digoxin, warfarin T risk of myopathy/iiiabdomyolysis W/ amiodarone, cyclosporine, CYP3A4 inhibitors, fibrates, HIV protease inhibitors, macrolides, niacin, verapamil, grapefruit juice X effects W/ cholestyramine, colestipol, fluvas-tatin, isradipine, propranolol EMS T Effects of warfarin use amiodarone and... 

Kodawara, T., et al. 2002. Organic anion transporter oatp2-mediated interaction between digoxin and amiodarone in the rat liver. Pharm Res 19 (6) 738. 

An initial increase in cardiac arrhythmias (proarrhythmic effect) may occur when class III drugs are instituted. The most important proarrhythmia is known as torsades de pointes, which is a form of ventricular tachycardia that can be fatal.11,40 Specific class III agents are associated with various other side effects. Amiodarone, for example, is associated with pulmonary toxicity and liver damage. Other class III drugs may have a more favorable side-effect profile but may not be as effective as amiodarone in controlling arrhythmias. Side effects of class HI drugs there-... 

Adverse effects Amiodarone shows a variety of toxic effects. After long-term use, more than one half of the patients receiving the drug show side effects sufficiently severe to prompt its discontinuation. Some of the more common effects include interstitial pulmonary fibrosis, gastrointestinal tract intolerance, tremor, ataxia, dizziness, hyper- or hypothyroidism, liver toxicity, photosensitivity, neuropathy, muscle weakness, and blue skin discoloration caused by iodine accumulation in the skin. As noted earlier (see p. 166) recent clinical trials have shown that amiodarone did not reduce incidence of sudden death or prolong survival in patient with congestive heart failure (CHF). 

Disposition in the Body. Slowly and incompletely absorbed after oral administration distributed to the tissues where it is strongly bound. Metabolised by V-dealkylation to monodesethylamiodarone which is the major plasma metabolite during chronic dosing. High concentrations of amiodarone and monodesethylamiodarone are found in the liver, lungs, and adipose tissue. Enterohepatic circulation may occur. Only a small amount is excreted in the urine as unchanged drug. 

Loratadine is well absorbed after oral administration, with peak plasma concentrations at approximately 1.5 hours. Clinically significant relief of symptoms is usually obtained within 2 to 4 hours of the first dose. Excretion of loratadine occurs almost equally through the urine and feces.This dual mechanism of secretion provides a measure of safety in patients with liver or kidney disease, but caution should be exercised in both groups. Also, torsades de pointes may occur with the concurrent use of loratadine and amiodarone. Desloratadine is a metabolite of loratadine. 

Pharmacokinetics. Amiodarone is effective given orally its enormous apparent distribution volume (701/kg) indicates that little remains in the blood. It is stored in fat and many other tissues and the t) of 54 days after multiple dosing signifies slow release from these sites (and slow accumulation to steady state means that a loading dose is necessary, see Table 24.1). The drug is metabolised in the liver and eliminated through the biliary and intestinal tracts. 

Hepatic fibrosis or cirrhosis may be caused by therapeutic use of methotrexate, e.g. for psoriasis in the latter case the risk is lessened by giving a large dose weekly rather than a smaller dose daily and by monitoring progress by liver biopsy after every 1.5-2 g of methotrexate. Chronic exposure to amiodarone may lead to cirrhosis this drug can also cause an alcoholic hepatitis-like picture. 

However, amiodarone can also canse liver damage, which nsnaUy takes the form of a hepatitis associated with phosphohpid deposition, and there can be changes similar to those of alcoholic hepatitis (171-173). In some cases there is progression of cirrhosis (174). The risk of hepatic impairment in patients taking amiodarone is not known, bnt relatively severe hver damage can occnr even in the absence of sjmptoms and with only minor associated changes in liver fnnction tests. 

Chronic liver damage with amiodarone is much more common than acute hepatitis, but cholestatic jaundice is one of the relatively rare presentations (SEDA-19, 193) (178,179). 

It has been suggested that liver injury due to amiodarone is either due to a direct biochemical action or perhaps metabolic idiosyncrasy. Because there have been cases in which oral administration has not led to a recurrence, it has also been suggested that the vehicle in which amiodarone is usually dissolved, polysorbate (Tween) 80, is responsible rather than the amiodarone itself (SEDA-18, 202). 

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