Rifamycin pharmacology

1. RIFAMYCINS
A PRESENTAION ON
PRESENTING BY
BIBEK GC
(O5)

2. INTRODUCTION
Complex macrocyclic antibiotics.
Naturally produce by Streptomyces mediterranei.
Bactericidal drug (intracellular and extracellular).
Particulary effective against Mycobacteria.
Used to treat TB, Leprosy and mycobacterium avium
complex.

3. CLASSSIFICATION
Based on production
a) Natural rifamycins
e.g. rifamycins B,O,SV and x.
b) Semi-synthetic rifamycins derivatives
e.g. rifampicin, rifabutin, rifaximin and
rifapentine

4. MECHANISM OF ACTION
• Inhibits bacterial DNA-dependent RNA
synthesis by inhibiting bacterial DNA-
dependent RNA polymerase.
• Halts initiation of mRNA transcription
• Prevention of translation of polypeptides

5. SELECTIVITY
• Inhibits only prokaryotic DNA-primed RNA
polymerase
• In normal concentration-does not inhibit
mammalian enzyme.

6. ANTIMICROBIAL SPECTRUM
• High activity against gram +ve and
mycobacteria.
• Suceptible organisms:
Stayphylococcus, Nesseria, Chlamydia, Mycob
acterium sps etc.
• Some activity against a few gram –ve;
Brucella and vaccinia virus

7. BACTERIAL RESISTANCE
• Natural resistance in gram –ve(due to failure
to penetrate organism)
• Resistance quickly when use sole.
• Alteration in DNA dependent RNA
polymerase.

8. PHARMACOKINETICS
ABSORBTION
• Well absorbed (40-70%) from GI tract in oral
administration
• I/m injection site – rapid absorption.

9. PHARMACOKINETICS
DISTRIBUTION
• Rapidly distributed to body tissues & fluids.
• Enters into the cell.
• Effective concentration reaches to many
organs and body fluid including CSF.
• Also penetrate abscess and caseous material.

10. PHARMACOKINETICS
METABOLISM
• In liver by deacetylated.
EXCRETION
• Mainly in bile(60-65%) and to a lesser extent
to urine(30%)

11. ADVERSE EFFECT
• Hepatitis
• GI disturbances-
nausea,
vomiting,
abdominal cramps with or without diarrhoea
• CNS effects-
headache,
drowsiness,
ataxia, and confusion

12. ADVERSE EFFECT
• Myelosuppression
• Respiratory – breathlessness
• Cutaneous - flushing, pruritus, rash, redness
and watering of eyes
• Hypersensitivity reactions

13. CONTRAINDIACATION/PRECAUTION
• Patient with Hypersensitivity to rifamycins.
• Cautiously use in patient with pre-existing
hepatic dysfunction.
• Use carefully in pregnant animal, although
significant teratogenicity has not been
reported

14. Drug interaction
Help in the metabolism/elimination of DRUGS
• digitalis, coticosteriods,
• quinidine, barbiturates,
• ketoconazole, propranolol,
• verapamil and oral anticoagulant
(Effective liver enzyme inducer-hepatic cytochrome P450)

15. Drug interaction
• Synergism with amphotericin B
• Drugs Increasing toxicity of rifamycins
azoles protease inhibitors
The macrolide Clarithromycin
Nonnucleoside reverse transcriptase inhibitors
(increase levels of rifamycins by inhibiting CYP450 enzymes )

16. CLINICAL USES
• TB
• LEPROSY
• MYCOBACTERIUM AVIUM COMPLEX

17. THANK YOU