Rifampin

IT is the most active anti lepromatous drug available

To avoid resistance ,it is given in combination

Mechanism of Action

Rifamycins / Rifampicin are protein synthesis inhibitors that work by inhibiting RNA polymerase, preventing transcription by blocking the production of messenger RNA. This separates them from other protein synthesis inhibitors, which inhibit translation

Pharmacokinetics:

It is well absorbed after oral administration. Rifampin is widely distributed in tissue and body fluids. It can reach TB cavities, sputum and penetrate macrophage killing TB bacilli. Rifampin is excreted mainly through liver and small amount is excreted in urine, saliva and tears. It give red orange color to urine, saliva and tears. Rifampin can result in induction (increase synthesis or activity ) of liver microsomal enzymes.

Antibacterial spectrum:

• is active against mycobacteria tuberculosis and mycobacteria lepra.
• has a broad activity against gram-positive especially resistant Staphylococci and gram- negative bacteria.
• effective on chlamydia and poxviruses

Mechanism of action:

It is bactericidal. Rifampin bind strongly to DNA- dependent RNA polymarse enzyme inhibiting RNA synthesis (human enzyme is not affected). In poxviruses, rifampin interferes with envelope formation. • It enters phagocytic cells and can therefore kill intracellular micro-organisms including the tubercle bacillus

Therapeutic uses:

1. one of first line anti-TB drugs. in combination with one or more of other anti-TB drugs. Z
2. treatment of pharyngeal carrier of Niesseria meningitides.
3. prophylaxis against Haemophilis influenza meningitides.Z
4. It is used in combination with other antimicrobials in treatment of resistant Staphylococcus aureus.
5. effective in leprosyZ.
6. It can be used for treatment of gram-negative infections. In combination with ceftriaxone or vancomycin intreatment of meningitis caused by highly penicillin- resistant strains of pneumococci.

Adverse effects:

1. Hepatotoxicity in the form of: abnormal liver enzyme, jaundice or hepatitis. This side effect occurs if there is chronic liver disease, alcoholism or old age.

2. Rifampin is an enzyme inducer, thus, it increases the metabolism of anticoagulants, contraceptives and other drugs leading to a decrease in its therapeutic effect.

3. Intermittent therapy causes flue like syndrome or influenza-like syndrome as fever, chills, malaise, vomiting, diarrhea.

4. CNS: headache and dizziness fatigue.

5. GIT disturbance.

6. Hypersensitivity reactions.

7. Red urine and tears.

   In viruses INHIBITION OF ASSEMBLY OR RELEASE OF VIRAL PARTICLES: phase 4

   It inhibits poxviruses by preventing the assembly of enveloped mature particles. It is not used in treatment of human poxvirus infection but topical application can inhibit human vaccinia lesions (Rifampin has antibacterial action).