ATI TB DmxmmdmdmmnnfjjfjRUGS FOR COG.pdf

How to manage it

1. ZERA INTERNATIONAL COLLEGE OF HEALTHE SCIENCES
CLINICAL OFFICER GENERAL
PHARMACOLOGY
DR M.KATASO MD
ANTI-TB DRUGS

2. TUBERCULOSIS
1.Tuberculosis is a bacterial infection caused by Mycobacterium tuberculosis.
2.Latent Tuberculosis infection (LTBI) is that state in which the bacillus is present in the body but is
asymptomatic.
3.Tuberculosis (disease) exists when the disease becomes evident clinically, radiologically or bacteriologically.
4.The primary site of infection is the lungs-pulmonary Tuberculosis.
5.Most common means of spreading tuberculosis between individuals during respiratory efforts (coughing,
sneezing)
There are two types of TB based on site of infection
1.PULMONARY TUBERCULOSIS ( PTB)
2.EXTRA PULMONARY TUBERCULOSIS (EPTB)
UNIQUE FEATURES OF M TUBERCULOSIS
1.Slow growing orgs
2.Often dormant
3.Lipid rich cell wall (mycolic acid)
4.Facultativelyintracellular orgs
5.Frequently develop drug resistance on monotherapy

3. DRUGS USED IN TUBERCULOSIS
Based on anti-tubercular activity, drugs may be grouped as:
TUBERCULOCIDAL AGENTS
1.Isoniazid
2.Rifampicin,
3.Streptomycin,
4.Pyrazinamide,
5.Capreomycin,
6.Amikacin,
7.Kanamycin,
8.Fluoroquinolones
TUBERCULOSTATIC AGENTS
1.Ethambutol,
2.Ethionamide,
3.Protionamide,
4.Cycloserine,
5.Terizidoneand PAS
TREATMENT
Involves two phases
1.Intensive phase:2 months
2.Continuation phase: depends of the types of Tb.
FIRST LINE DRUGS
1.Isoniazid (INZ)/(H)
2.Rifampicin (RIF)/(R)
3.Pyrazinamide (PZA)/(Z)
4.Ethambutol (EMB)/(E)
5.Streptomycin (SM)*/(S)*
2
ND
LINE DRUGS
ORAL FLUOROQUINOLONES
1.Levofloxacin
2.Moxifloxacin
INJECTABLES
1.Amikacine
2.Capreomycin
3.kanamycin
OTHERS
1.Ethionamide
2.Linzolid
3.Cycloserine
4.Paraminosalicylicacid (PAS)

4. RECOMMENDED REGIMENS

5. ISONIAZID
1.Most active anti-tuberculosis drug
2.Tuberculocidalfor rapidly multiplying bacilli and tuberculostaticfor resting bacilli
3.Structurally similar to pyridoxine
4.For prophylaxis, INH is used alone
5.Effective against both intracellular and extracellular organisms
MOA: inhibits the synthesis of mycolic acids (by inhibiting the enzyme enoyl-acyl carrier protein reductase)
which are important components of the mycobacterial cell wall.
Adverse effects
1.Peripheral neuritis -due to interference with utilisation(inhibits pyridoxal kinase) and increased excretion
of Pyridoxine. More common in slow acetylators. Can be prevented by giving prophylactic pyridoxine.
2.Hepatitis (due to the metabolite acetylisoniazid[acetylhydrazine]). More common in fast acetylators.
3.Other adverse effects: Psychosis, anorexia, GI discomfort, fever, allergic reactions and haemolysisin
patients with G-6-PD deficiency
4.Drug interactions: Inhibits cytochrome P450 thereby reducing metabolism of some drugs (e.g. Phenytoin)
RIFAMPICIN
Derived from Rifamycin
MoA; Binds to DNA-dependent RNA polymerase (mycobacterial not human) –inhibits RNA synthesis
Penetrates macrophages and most tissues
Enzyme inducer

6. RIFAMPICIN
ADVERSE EFFECTS
1.Hepatotoxicity
2.GI disturbances: epigastric distress, nausea, vomiting, abdominal cramps, diarrhoea
3.Flu-like syndrome (more common with intermittent dosing)
4.CNS: Headache, drowsiness, dizziness, ataxia, confusion, peripheral neuropathy
5.Hypersensitivity reactions
6.Stains sweat, tears, saliva and urine an orange red colour
RIFAMPICINE ANALOGUES
Include Rifapentineand Rifabutin
Rifapentine
1.Its pharmacology is similar to Rifampicin
2.Used once weekly in TB treatment after sputum cultures convert to negative (during the continuation phase
of TB therapy)
Rifabutin
1.More active against atypical mycobacteria than rifampicin
2.Less cytochrome P450 induction than rifampicin
3.Can be used in place of Rifampicin in patients receiving ARVs that are substrates for cytochrome P450 (e.g.
protease inhibitors)

7. PYRIZINAMIDE
1.MOA:inhibits mycolic acid synthesis
2.• An analogue of nicotinamide
3.• Drug taken up by macrophages –sterilization
4.• Pro-drug converted to Pyrazinoicacid
5.• Well absorbed orally and distributed in all tissues
6.• Very useful 1st line drug
7.A/E: Hepatotoxicity, nausea, vomiting, hyper-uricaemiawith precipitation of gout and skin rashes
ETHAMBUTOL
1.MOA:inhibits the incorporation of mycolic acids into the mycobacterial cell wall (inhibits arabinosyl
transferases involved in this process)
2.• Also reported to inhibit RNA synthesis
3.• Major excretion by renal route: Reduce dose in kidney failure.
4.• Crosses BBB only in meningitis
5.• A/E: Retro bulbar neuritis –loss of visual acuity and red green colourblindness, headache, fever, allergic
reactions and gout precipitation …Contraindicated in very young children.
STREPTOMYCIN
1.Aminoglycoside antibiotic
2.Inhibits bacterial protein synthesis (Binds to 30s ribosomal subunit)
3.Formerly, Important 1st line drug for TB
4.Useful for life threatening cases (Given IM)
5.A/E: Ototoxicity and nephrotoxicity. CI: Pregnancy

8. CONDITIONS FOR 2
ND
LINE AGENTS
1.Therapeutic failure
2.Resistance to 1st line drugs
3.Adverse reactions limit use of 1st line drugs
DRUG RESISTANCE TUBERCULOSIS
1.Drug resistant TB denotes resistance to one of the first line TB drugs (being Rifampicin or isoniazid)
2.Multidrug resistant (MDR) TB denotes resistance to at least 2 main first line TB drugs i.e. rifampicin and
isoniazide.
3.Extreme drug resistant (XDR) TB denotes MDR-TB + resistance to any fluoroquinolone and at least 1 of the
3 injectable second-line drugs (amikacin, kanamycin or capreomycin)
Treatment failure in TB: This is the presence of continued or recurrently positive cultures during the course of
ant tuberculosis therapy.