Monday, March 13, 2006

Milosevic Took Rifampin (Rifampicin) to Counteract Heart Drugs?

The suggestion that Milosevic took rifampin to inactivate his other medications to me seems bizarre and unlikely.

From BBC NEWS:
Drugs found in the body of former Yugoslav leader Slobodan Milosevic may have neutralised treatment for his heart conditions, a toxicologist says. Full test results are awaited but the comments of Dutch expert Donald Uges raised questions over what caused Mr Milosevic's death from a heart attack...

Mr Uges said he tested Mr Milosevic's blood two weeks ago because the former leader's blood pressure was not falling.

Mr Uges said rifampicin, a powerful antibiotic used to treat leprosy or tuberculosis, was found...

Sources close to the tribunal suggest Mr Milosevic may have deliberately mixed or missed the dosages for his bad heart and high blood pressure.
To review, the following are the drug interactions of rifampin (from Uptodate):
DRUG INTERACTIONS — Substrate (major) of CYP2A6, 2C8/9, 3A4; Induces CYP1A2 (strong), 2A6 (strong), 2B6 (strong), 2C8/9 (strong), 2C19 (strong), 3A4 (strong)

Acetaminophen: Rifampin may increase the metabolism of acetaminophen.

Alfentanil: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of alfentanil.

Amiodarone: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of amiodarone

Angiotensin II receptor blockers (irbesartan, losartan): Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of angiotensin II receptor blockers.

Antiemetics (5-HT3 antagonists): Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of antiemetics (5-HT3 antagonists).

Antifungal Agents (imidazole): Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of antifungal agents (imidazole).

Aprepitant: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of aprepitant.

Barbiturates: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of barbiturates.

Benzodiazepines (metabolized by oxidation): Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of benzodiazepines (metabolized by oxidation).

Beta-blockers: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of beta-blockers.

Buspirone: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of buspirone.

Calcium channel blockers: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of calcium channel blockers.

Chloramphenicol: Rifampin may increase the metabolism, via CYP isoenzymes, of chloramphenicol.

Clopidogrel: Rifamycin derivatives may enhance the therapeutic effect of Clopidogrel.

Corticosteroids (systemic): Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of corticosteroids (systemic).

Cyclosporine: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of cyclosporine.

CYP1A2 substrates: Rifampin may decrease the levels/effects of CYP1A2 substrates. Example substrates include aminophylline, estrogens, fluvoxamine, mirtazapine, ropinirole, and theophylline.

CYP2A6 inducers: May decrease the levels/effects of rifampin. Example inducers include amobarbital, pentobarbital, phenobarbital, and secobarbital.

CYP2A6 substrates: Rifampin may decrease the levels/effects of CYP2A6 substrates (eg, ifosfamide).

CYP2B6 substrates: Rifampin may decrease the levels/effects of CYP2B6 substrates. Example substrates include bupropion, efavirenz, promethazine, selegiline, and sertraline.

CYP2C8/9 inducers: May decrease the levels/effects of rifampin. Example inducers include carbamazepine, phenobarbital, phenytoin, and secobarbital.

CYP2C8/9 substrates: Rifampin may decrease the levels/effects of CYP2C8/9 substrates. Example substrates include amiodarone, fluoxetine, glimepiride, glipizide, losartan, nateglinide, phenytoin, pioglitazone, rosiglitazone, sertraline, sulfonamides, warfarin, and zafirlukast.

CYP2C19 substrates: Rifampin may decrease the levels/effects of CYP2C19 substrates. Example substrates include citalopram, diazepam, methsuximide, phenytoin, propranolol, proton pump inhibitors, sertraline, and voriconazole.

CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of rifampin. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, and phenytoin.

CYP3A4 substrates: Rifampin may decrease the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, clarithromycin, cyclosporine, erythromycin, estrogens, mirtazapine, nateglinide, nefazodone, nevirapine, protease inhibitors, tacrolimus, and venlafaxine.

Dapsone: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of dapsone.

Disopyramide: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of disopyramide.

Estrogens (oral contraceptives): Rifamycin derivatives may decrease the serum concentration of oral contraceptive (estrogens); contraceptive failure is possible.

Fexofenadine: Rifampin may decrease the serum concentration of fexofenadine.

Fluconazole: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of fluconazole.

Fusidic Acid: Rifampin may decrease the excretion of fusidic acid.

Gefitinib: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of gefitinib.

HMG-CoA reductase inhibitors: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of HMG-CoA reductase inhibitors.

Isoniazid: Rifamycin derivatives may enhance the hepatotoxic effect of isoniazid; however, this is a frequently employed combination regimen.

Macrolide antibiotics: Macrolide antibiotics may decrease the metabolism, via CYP isoenzymes, of rifamycin derivatives.

Methadone: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of methadone.

Morphine: Rifamycin derivatives may decrease the serum concentration of morphine sulfate.

Phenytoin: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of phenytoin.

Progestins (contraceptives): Rifamycin derivatives may decrease the serum concentration of contraceptive (progestins); contraceptive failure is possible.

Propafenone: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of propafenone.

Protease inhibitors: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of protease inhibitors. Concurrent use with saquinavir/ritonavir increases risk of hepatotoxicity. Rifampin administration should be avoided.

Pyrazinamide: Pyrazinamide may enhance the hepatotoxic effect of rifampin.

Quinidine: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of quinidine.

Repaglinide: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of repaglinide.

Reverse transcriptase inhibitors (non-nucleoside): Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of reverse transcriptase inhibitors (non-nucleoside).

Sulfonylureas: Rifampin may increase the metabolism, via CYP isoenzymes, of sulfonylureas.

Tacrolimus: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of tacrolimus.

Tamoxifen: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of tamoxifen.

Terbinafine: Rifamycin derivatives may increase the metabolism of terbinafine.

Tocainide: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of tocainide.

Tricyclic antidepressants: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of tricyclic antidepressants.

Warfarin: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of warfarin.

Zaleplon: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of zaleplon.

Zidovudine: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of zidovudine.

Zolpidem: Rifamycin derivatives may increase the metabolism, via CYP isoenzymes, of zolpidem.
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1 comment:

Anonymous said...

IF he was unknowingly given Rifampin, I'm sure he would have become alarmed when his urine turned red. You don't just slip Rifampin to someone, and they never find out about it.

Also, if someone WAS trying to knock him off, I'm sure there are much more efficient ways to do so.