Rifampicin (Rifampin)•Refamycins are a group of macrocyclic antibiotics which areProduced by Streptomyces mediterranei.Refamycins inhibit the enzyme RNA polymerase and preventRNA synthesis.Than in turn prevent protein synthesis.•So they are useful in treating tuberculosis, leprosy,Mycobacterium avium complex (MAC) infection, andStaphylococcus infections.•Eventually 7, rifamycins were developed they areRifamycin A,B,C,D,E,S,SV.•Refampicin is a semi-synthetic rifamycin made fromRifamycin-B isolated from streptomyces mediterranei in 1957•Among the various rifamycins, rifamycin-B was the firstCommercial product.
Mechanism/mode of action:Refampin is bactericidal at 0.005-0.2micrograms/ml vsMicobacterium tuberculosis.Rifampicin inhibits Grampositive bacteria and works byBinding non-covalently to DNA-dependent RNA polymeraseand inhibiting the start of RNA synthesisThe DNA-dependent RNA polymerases in eukaryotic cellsare unaffected, since the drug binds to a peptide chain notPresent in the mamalian RNA polymerase. Therefore it ishighlyselective..It acts by inhibiting DNA-dependent RNA polymerase(DDRP)of mycobacteria and other microorganismsby binding strongly to their β-subunits viz ( α, α1, β, β1And sigma) and there by supression of inhibiting the m-RNA synthesis
•Intact macrocyclic molecule is required for antimycobacterial activity.•Double bonds in macrocyclic ring should not be redcuced ,or opening of the macro ringresults in compounds have decreased activity.• Free hydroxyl groups should be present at c-1,c-8,c-21,c-23 all lie in a plane and play arole in acting as binding groups for attachment to DDRP.• When –OH groups at c-21 and c-23 were completely removed or substituted theformation of derivatives are devoid of anti-mycrobial activity were obtained.•Activity of the compounds get diminished when the –OH groups at c21 and c23 areacetylated.• The maintenance of drug activity relies on the presence of either –OH or carbonylgroupboth of which should be unsubstituted.•Refampicin compound is formed by substitution of [(4-methyl-1piperazinyl)imino)methyl]at 3rdposition in rifamycin-B. It is a bactericidal antibiotic of Refamycin group and itFlat naphthalene ring andSeveral of the –OH groupsAre essential for activity.It is a zwitterion, and has goodSolubility both lipids and aqueous acid.
CH3Refampicin Refapentine.(more potent than Refampicin)[(4-methyl-1piperazinyl)imino)methyl]
Uses:-• Refampicin is used as a first line drug in the treatment of tuberculosis. Asmost of the tubercle bacilli develop resistance to rifampicin. It is used incombination with other anti-tubercular drugs in the multiple drug therapy tominimize the problum.• It is also used the treatment of leprosy.• Infection like endocarditis(inflammation of membrane lining the heart.)• For prophylaxis in people exposed to meningococcemia or H. influenzae typeB meningitis.Oesteomyelitis(inflammation of bone)It is used in the first-line therapy of brucellosis in combination with doxycline.It is also an excellent drug for Pneumonia.• It is an active inducer of hepatic cytochrome P450 oxygenases.• It is also used in combination with dapsone in Treating leprosy.• It is a very useful antibiotic, showing a high degre of selectivityagainst bacterial cells over mammalian cells.• Unfortunately, it is so expensive, which discourages its use against awide range of infections.
How is TB treated?How is TB treated?Optimal treatment of TB utilizes a combination of 2 to 3 antibiotics taken over aperiod of 6 to 9 months. Drug resistant strains of TB are not uncommon, whichis why multiple antibiotics are used together during treatment. Drugs used mostcommonly to treat TB include isoniazid, rifampin, ethambutol, andpyrazinamide7.
Multidrug therapyMultidrug therapyMost species of bacteria develop resistance to Rifampicin. Use of single drugRefampicin for tuberculosis will not be effective. That’s why it is used inCombination with other antitubercular drugs in multidrug therapy.Each tablet containsGenarally the following dosage regimen is givenRifampicin----120mg.Isoniazid ------50mg.Pyrimethamine-300mg.4 tablets/day for patients ≤ 44kg.6 tablets /day for patients ≥ 55kg.child dose:- 100mg/kg of body weight as a single dose.2 phases of drug therapy are genarally usedInitial phase: In this phase 3 drugs namely Refampicin,isoniazid,Pyrazinamide areused.some times ethambutol drug is used . All these drugs used for 2 months.Continuation phase:-Two drugs i.e. Rifampicin and isoniazid are to be used for a time period of the next4months. (2 times/week)Isoniazid---15mg/kg(orally),Rifampicin—10mg/kg (upto60mg/dose).
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