Health centre

1. Antimycobacterial drugs
 First line of drugs:
 Isoniazid (INH)
 Rifampicin
 Ethambutol
 Streptomycin
 Pyrazinamide

2. Never use a single drug therapy
 Isoniazid –rifampicin combination administered
for 9 months will cure 95-98% of cases .
 Addition of pyrazinamide for this combination for
the first 2 months allows total duration to be
reduced to 6 months.

3. Isoniazid
 Bacteriostatic at low conc. & bacteriocidal at high
conc. Especially against actively growing bacteria.
 Inhibits synthesis of mycolic acid is an essential
components of mycobacterial cell wall.

4. Pharmacokinetics
 Readily absorbed from GIT.
 Diffuse into all body fluids and tissues
 Penetrates caseous material and macrophages so it
is effective against intra and extracellular
organisms.
 Metabolized in liver by acetylation
 Excreted mainly in urine

5. Clinical uses
 Mycobacterial infections (it is recommended to be
given with pyridoxine to avoid neuropathy).
 Latent tuberculosis in patients with positive
tuberculin skin test
 Prophylaxis against active TB in individuals who
are in great risk as very young or
immunocompromised individuals.

6. Adverse effects
 Peripheral neuritis
 Optic neuritis.
 Allergic reactions ( fever,skin rash,systemic lupus
erythematosus )
 Hepatitis
 Gastric upset
 Haemolytic anaemia
 Enzyme inhibitor
 CNS toxicity.

7. Rifampicin
 Bactericidal ,binds strongly to β subunit of
bacterial DNA-dependent RNA polymerase
leading to inhibition of RNA synthesis .

8. Pharmacokinetics
 Well absorbed orall.
 Excreted mainly through liver into bile.
 Highly protein bind .
 Penetrates macrophages so affect extra and
intracellular organisms.
 Adequate CSF conc. Only in meningeal
inflammation.

9. Clinical uses
 Mycobacterial infections
 Prophylaxis in contacts of children with
Haemophilus influenzae type b disease.
 Treatment of serious staphylococcal infections as
osteomyelitis and endocarditis.
 Meningitis by highly resistant penicillin
pneumococci

10. Adverse effects
 Harmless red-orange colour to urine,sweat,tears,contact
lenses.
 Rashes
 Thrombocytopenia
 Nephritis
 Cholestatic jaundice,hepatitis
 Flu-like syndrome
 Induce cytochrome p-450

11. Ethambutol
 Inhibits mycobacterial cell wall synthesis by inhibiting
arabinosyl transferase .
 Bacteriostatic
 Active against intra&extracellular bacilli .
 Well absorbed from gut.
 20% excreted in feces and 50% in urine in unchanged
form.
 Crosses BBB in meningitis
 Used only in mycobacterial infections.

12. Adverse effects
 Retrobulbar (optic) neuritis causing loss of visual
acuity and red-green colour blindness.
 It is relatively contraindicated in children.
 GIT .upset .
 Hyperuricemia

13. Pyrazinamide
 It is converted to pyrazinoic acid ,the active form
(prodrug)
 Mechanism is unknown.
 Bactericidal
 Acting on intracellular organisms.
 Well absorbed orally ,metabolized in liver
,excreted mainly through kidney .

14. Clinical uses
 Mycobacterial infections (TB) mainly in multidrug
resistance cases.
 It is important in short –course (6 months)
regimens with isoniazid and rifampicin.
 Prophylaxis of TB in combination with
ciprofloxacin.

15. Adverse effects
 Hepatotoxic
 Hyperuricemia( provoke acute gouty arthritis )
 Nausea & vomiting
 Drug fever & skin rash

16. Streptomycin
 Life threating forms of TB ( meningitis,
dissiminated disease).
 Resistant cases (Multidrug resistance tuberculosis
at least to INH & rifampicin ) .
 Amikacin can be used as alternative to
streptomycin.
 Both active mainly against extracellular bacilli.

17. Indication of 2nd line treatment
 Resistance to the drugs of 1st line.
 Failure of clinical response
 Increase of risky effects.
 Patient is not tolerating the drugs first line drugs.

18. Ethionamide
 As isoniazid blocks synthesis of mycolic acid .
 Available only in oral form.
 Metabolized by the liver ,excreted by kidney.
 It is poorly tolerated because of :
 -intense gastric irritation
 -neurologic symptoms
 -hepatotoxicity
 Used in TB & leprosy.

19. Capreomycin
 It is an important injectable agent for treatment of
drug-resistant tuberculosis.
 It is nephrotoxic and ototoxic.
 Local pain & sterile abscesses may occur.

20. Cycloserine
 Inhibitor of cell wall synthesis
 Cleared renally
 The most serious side effects are peripheral
neuropathy and CNS dysfunction, including
depression & psychotic reaction.
 Pyridoxine should be given.
 Contraindicated in epileptic patients.

21. Amikacin
 Used as alternative to streptomycin.
 Used in multidrug- resistance tuberculosis.
 No cross resistance between streptomycin and
amikacin.

22. Ciprofloxacin & levofloxacin
 Effective against typical and atypical
mycobacteria.
 Used against resistant strains.
 Used in combination with other drugs.

23. Rifapentine
 As rifampicin , it is RNA polymerase inhibitor.
 Cross resistance with rifampicin.
 Potent inducer of cytochrome p450.
 Effective against typical and atypical
mycobacteria.

24. Aminosalicylic Acid (PAS).
 Similar in structure to sulfonamide and p-aminobenzoic
acid.
 Folate synthesis inhibitor.
 Well absorbed from GIT.
 Widely distributed in tissues except CSF.
 Excreted in urine as active and as metabolic products.
 Causes crystalluria,anorexia,nausea,diarrhea,epigastric
pain.
 Peptic ulcer and haemorrhage can occur.
 Hypersensitivity reactions.

25. Drugs used in leprosy
Dapsone
 Inhibits folate synthesis.
 Well absorbed orally,widely distributed .
 Half-life 1-2 days,tends to be retained in
skin,muscle,liver and kidney.
 Excreted into bile and reabsorbed in the intestine.
 Excreted in urine as acetylated.
 It is well tolerated.

26. Clinical uses
 Tuberculoid leprosy.
 Lepromatous leprosy in combination with rifampin
& clofazimine.
 To prevent & treat Pneumocystis pneumonia in
AIDS caused by Pneumocystis jiroveci (
Pneumocystis carinii).

27. Adverse effects
 Haemolytic anaemia
 Methemoglobinemia
 Gastrointestinal intolerance
 Fever,pruritus,rashes.
 Erythema nodosum leprosum

28. Clofazimine
 It is a phenazine dye.
 Unknown mechanism of action ,may be DNA binding.
 Antiinflammatory effect.
 Absorption from the gut is variable.
 Given orally , once daily.
 Excreted mainly in feces.
 Stored mainly in reticuloendothelial tissues and skin.
 Half-life 2 months.
 Delayed onset of action (6 weeks).

29. Clinical uses
 Multidrug resistance TB.
 Lepromatous leprosy
 Tuberculoid leprosy in :
 patients intolerant to sulfones
 dapsone-resistant bacilli.
 Chronic skin ulcers caused by M.ulcerans.

30. Adverse effects
 Skin discoloration ranging from red-brown to black.
 Gastrointestinal intolerance.
 Red colour urine.
 Eosinophilic enteritis

31. Treatment of TB in pregnant women
 INH ( pyridoxine should be given ),
 Rifampicin , ethambutol
 Pyrazinamide is given only if :
 Resistant to other drugs is documented
 Streptomycin is contraindicated.
 Breast feeding is not contraindication to receive
drugs , but caution should be observed.