Amiodarone derivative

Dronedarone Investigational amiodarone derivative multichannel actions, reduces mortality in patients with atrial fibrillation... 

Waldhauser KM, Torok M, Ha HR, Thomet U, Konrad D, Brecht K, Follath F, Krahenbuhl S (2006) Hepatocellular toxicity and pharmacological effect of amiodarone and amiodarone derivatives. J Pharmacol Exp Ther 319(3) 1413-1423 Wang Y, Singh R, Lefkowitch JH, Rigoli RM, Czaja MJ (2006) Tumor necrosis factor-induced toxic liver injury results from JNK2-dependent activation of caspase-8 and the mitochondrial death pathway. J Biol Chem 281(22) 15258-15267 Watkins PB (2005) Idiosyncratic liver injury challenges and approaches. Toxicol Pathol 33 (l) l-5... 

Amiodarone. Amiodarone, an iodinated benzofuran derivative that has stmctural similarities to the thyroid hormones (qv), was originally... 

Since alterations of thyroid fimction by amiodarone are related to the iodine substitution of the drug, the iodine-free derivative dronedarone has been developed with similar electrophysiological effects as amiodarone. It seems to act also as a T3-anatgonist, but does not provoke hyperthyreoidism [1]. 

Alcohol, amiodarone, didanosine, 1-asparaginase, piroxicam, stavudine, tamoxifen, tetracycline derivatives, valproic acid, and zidovudine... 

Amiodarone (11), a benzofuran derivative, was initially developed as a coronary vasodilator in the early 1960 s [11,12]. Several years later, the efficacy of the compound as an antiarrhythmic agent began to be exploited. The first clinical trials with amiodarone were reported in 1974 [13]. Amiodarone was effective in controlling the tachyarrhythmias of eleven patients with Wolff-Parkinson-White syndrome. Since that time the compound has been studied extensively [14,15]. Recently, in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial (CAMIAT), amiodarone was shown to reduce mortality during a mean 18 month period following myocardial infarction (13.8% deaths in placebo group vs. 2.1 % deaths in the treatment group) [16]. 

In addition to the amiodarone-related compounds, (81) and (82), described above, BASF has been exploring some novel heterocyclic compounds as Class III antiarrhythmic agents. A series of imidazo[l,2-c]pyrro-lo[l,2-a]quinazoline derivatives have been patented which are several times more potent than (-I- )-sotalol in lengthening QT interval of the electrocardiogram in the anaesthetized guinea-pig model [230], One of the most potent compounds is (85), which was 17-times more potent than the standard. These compounds represent one of the unique Class III structural types described to date. 

Hypersensitivity to any component of the product. Coadministration of nelfinavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (eg, amiodarone, quinidine, ergot derivatives, pimozide, midazolam, triazolam, lovastatin, simvastatin see Drug Interactions). 

Drugs that may be affected by fosamprenavir include the following Amiodarone, amitriptyline, benzodiazepines, calcium channel blockers, cisapride, contraceptives (oral), cyclosporine, ergot derivatives, HMG-CoA reductase inhibitors, imipramine, itraconazole, ketoconazole, lidocaine (systemic), methadone, pimozide, quinidine, rifabutin, sildenafil, tacrolimus, vardenafil, warfarin. 

Amiodarone (Cordarone) is an iodine-containing benzo-furan derivative identified as a class III agent because it predominantly prolongs action potentials. Amiodarone also blocks sodium and calcium channels and is a noncompetitive p-receptor blocker. Amiodarone is effective for the treatment of most arrhythmias. Toxicity associated with amiodarone has led the U. S. Food and Drug Administration (FDA) to recommend that it be reserved for use in patients with life-threatening arrhythmias. 

The corresponding 3,5-dibromo derivative is benzbromarone, which is less active. The last two compounds are, besides, powerful urico-eliminators 30a 2-ethyl-3-(3,4,5-trimethoxybenzoyl)benzofuran (23c)66 and 2-butyl-3-[3,5-diiodo-4-(2-diethylaminoethoxy)benzoyl]benzofuran or amiodarone (24) (or Cordarone67) are powerful angiotropics. 

Delavirdine should not be used in combination with drugs that are CYP3A4 substrates such as pimozide, midazolam, triazolam, amiodarone, propafenone and ergot derivatives. Inducers of the hepatic P-450 system, rifampin, rifabutin, pheno-barbital, phenytoin or carbamazepine, should not be used in combination with delaviridine. It also increases the plasma levels of HIV protease inhibitors. 

The pharmacokinetics of saquinavir is modified by agents that alter isoenzyme CYP3A4 of the cytochrome P-450 system and P-glycoprotein transporter. It should not be administered with midazolam, triazolam and ergot derivatives. The plasma concentrations of saquinavir are lower when coadministered with efavirenz, nevirapine or rifampin. Ritonavir reverses the effects of nevirapine on saquinavir. The coadministration of astemizole, terfenadine, amiodarone, bepridil, quinidine, propafenone or flecainide with saquinavir is also not recommended due to its potential for serious and/or life-threatening reactions. 

Ritonavir increases the plasma levels of triazolam, pimozide, midazolam, ergot derivatives, propafenone and amiodarone by delaying their elimination since it is a very potent inhibitor of CYP3A4. Rifampin, due to its ability to induce CYP3A4, will reduce the plasma levels of ritonavir, and their coadministration is not recommended. Since ritonavir is also an inhibitor of CYP2D6, its coadministration with most antidepressants, certain antiarrhythmics and narcotic analgesics should be carefully monitored. 

Cholestyramine, calcium carbonate, sucralfate, aluminum hydroxide, ferrous sulfate, soybean formula, and dietary fiber supplements may impair the absorption of levothyroxine from the G1 tract. Drugs that increase nondeiodinative T4 clearance include rifampin, carbamazepine, and possibly phenytoin. Amiodarone may block the conversion of T4 to T3. Thyroid, USP (or desiccated thyroid) is derived from hog, beef, or sheep thyroid gland. It may he antigenic in allergic or sensitive patients. Inexpensive generic brands may not be bioequivalent. 

Systemically taken drugs that can induce photosensitivity are many. Of the drug groups given below, those most commonly reported are antimitotics dacarbazine, vinblastine antimicrobials demeclocycline, doxycycline, nalidixic acid, sulphonamides antipsychotics chlorpromazine, prochlorperazine cardiac arrhythmic amiodarone diuretics frusemide (furosemide), chlorothiazide, hydrochlorothiazide fibric acid derivatives, e.g. fenofibrate hypoglycaemic tolbutamide... 

Benzbromarone is a benzofuran derivative chemically related to amiodarone. It increases uric acid excretion by non-specifically inhibiting its tubular reabsorption. 

IAsu ].p-ANP(7-28). aminosuccinic acid aspartic acid, aminosultopride amisulpnde. amiodarone [ban, inn, usan) (Cordarone ) is a benzofuran derivative, a (Class III) antiarrhythmic used mainly to treat ventricular arrhythmias, amiphenazole [ban, inn] (DHA 245 amifenazole) is a phenylthiazole and has similar properties as doxapram as a CNS STIMULANT and RESPIRATORY STIMULANT. It was previously used intramuscularly to treat barbiturate and other CNS DEPRESSANT overdose. 

Dronedarone is a derivative of amiodarone and has similar properties. However, it has less organ toxicity. 

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