Refampicin structure, SAR, Mechanism of action, Uses.

1. Rifampicin [Rifampin]
Medicinal chemistry
Prof.P.Ravisankar
Vignan Pharmacy College
Vadlamudi
Guntur (Dist)
Andhra Pradesh, India.
banuman35@gmail.com
Phone: 09059994000
09000199106

2. Rifampicin (Rifampin)
•Refamycins are a group of macrocyclic antibiotics which are
Produced by Streptomyces mediterranei.
Refamycins inhibit the enzyme RNA polymerase and prevent
RNA synthesis.Than in turn prevent protein synthesis.
•So they are useful in treating tuberculosis, leprosy,
Mycobacterium avium complex (MAC) infection, and
Staphylococcus infections.
•Eventually 7, rifamycins were developed they are
Rifamycin A,B,C,D,E,S,SV.
•Refampicin is a semi-synthetic rifamycin made from
Rifamycin-B isolated from streptomyces mediterranei in 1957
•Among the various rifamycins, rifamycin-B was the first
Commercial product.

3. Mechanism/mode of action:
Refampin is bactericidal at 0.005-0.2micrograms/ml vs
Micobacterium tuberculosis.
Rifampicin inhibits Grampositive bacteria and works by
Binding non-covalently to DNA-dependent RNA polymerase
and inhibiting the start of RNA synthesis
The DNA-dependent RNA polymerases in eukaryotic cells
are unaffected, since the drug binds to a peptide chain not
Present in the mamalian RNA polymerase. Therefore it is
highlyselective..
It acts by inhibiting DNA-dependent RNA polymerase
(DDRP)of mycobacteria and other microorganisms
by binding strongly to their β-subunits viz ( α, α1
, β, β1
And sigma) and there by supression of inhibiting the m-RNA synthesis

4. •Intact macrocyclic molecule is required for antimycobacterial activity.
•Double bonds in macrocyclic ring should not be redcuced ,or opening of the macro ring
results 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 a
role in acting as binding groups for attachment to DDRP.
• When –OH groups at c-21 and c-23 were completely removed or substituted the
formation of derivatives are devoid of anti-mycrobial activity were obtained.
•Activity of the compounds get diminished when the –OH groups at c21 and c23 are
acetylated.
• The maintenance of drug activity relies on the presence of either –OH or carbonyl
group
both of which should be unsubstituted.
•Refampicin compound is formed by substitution of [(4-methyl-1piperazinyl)imino)methyl]
at 3rd
position in rifamycin-B. It is a bactericidal antibiotic of Refamycin group and it
Flat naphthalene ring and
Several of the –OH groups
Are essential for activity.
It is a zwitterion, and has good
Solubility both lipids and aqueous acid.

5. O-CH2-COOH
Refamycin-B

6. CH3
Refampicin Refapentine.(more potent than Refampicin)
[(4-methyl-1piperazinyl)imino)methyl]

7. Uses:-
• Refampicin is used as a first line drug in the treatment of tuberculosis. As
most of the tubercle bacilli develop resistance to rifampicin. It is used in
combination with other anti-tubercular drugs in the multiple drug therapy to
minimize 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 type
B 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 selectivity
against bacterial cells over mammalian cells.
• Unfortunately, it is so expensive, which discourages its use against a
wide range of infections.

8. How is TB treated?How is TB treated?
Optimal treatment of TB utilizes a combination of 2 to 3 antibiotics taken over a
period of 6 to 9 months. Drug resistant strains of TB are not uncommon, which
is why multiple antibiotics are used together during treatment. Drugs used most
commonly to treat TB include isoniazid, rifampin, ethambutol, and
pyrazinamide7
.

9. Multidrug therapyMultidrug therapy
Most species of bacteria develop resistance to Rifampicin. Use of single drug
Refampicin for tuberculosis will not be effective. That’s why it is used in
Combination with other antitubercular drugs in multidrug therapy.
Each tablet contains
Genarally the following dosage regimen is given
Rifampicin----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 used
Initial phase: In this phase 3 drugs namely Refampicin,isoniazid,Pyrazinamide are
used.
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 next
4months. (2 times/week)
Isoniazid---15mg/kg(orally),Rifampicin—10mg/kg (upto60mg/dose).

10. Multidrug therapyMultidrug therapy
Most species of bacteria develop resistance to Rifampicin. Use of single drug
Refampicin for tuberculosis will not be effective. That’s why it is used in
Combination with other antitubercular drugs in multidrug therapy.
Each tablet contains
Genarally the following dosage regimen is given
Rifampicin----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 used
Initial phase: In this phase 3 drugs namely Refampicin,isoniazid,Pyrazinamide are
used.
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 next
4months. (2 times/week)
Isoniazid---15mg/kg(orally),Rifampicin—10mg/kg (upto60mg/dose).