ANTIMYCOBACTERIAL DRUGS.

 These include:
 Mycobacterium tuberculosis (tuberculosis)
1. Mycobacterium leprae (leprosy)
2. Atypical mycobacteria (with various clinical
presentations)
 TUBERCULOSIS

 what is TB???
 Causative agent???
 ANTI _TB DRUGS

FIRST LINE DRUGS

Isoniazid (INH)
Rifampin
Ethambutol
Pyrazinamide
Streptomycin
SECOND LINE DRUGS OR ALTERNATIVE DRUGS.
1. Para-amino Salicylic Acid(PAS) 2. Ethionamide
3. Cycloserine 4.Capreomycin
5.Amikacin
6.Ciprofloxacin 7.Ofloxacin
 PHASES OF TREATMENT

INITIAL PHASE
At least 3 drugs for at least 8 weeks.
CONTINUATION PHASE
After initial phase only 2 drugs for rest of
period
 ISONIAZID OR INH
CHEMISTRY: Structural congener of pyridoxine

Acts on both extra and intracellular

mycobacteria because it can penetrate into
phagocytic cells.
 Mechanism of action of INH
Inhibits synthesis of mycolic acids which are
essential components of mycobacterial cell walls.

• catalase peroxidase (katG)

• NAD
• enoyl reductase (inhA)

RESISTANCE??
 INH PHARMACOKINETICS

Absorption:- rapid from GIT & inj site

DISTRIBUTION:-
 Readily in all body fluids
 Very well penetration into caseous material

 METABOLISM:
 Liver
 acetylation (slow/fast)
 Half life (3-4h / 60-90m)
Metabolism (acetylation) in liver

Slow inactivators or Rapid or fast inactivators or

slow acetylators acetylators.
T ½ 3-4 hrs T ½ 60 minutes to 90 min.
 ADVERSE EFFECTS OF INH

Allergic reactions
 Fever. Skin rashes
 Drug induced SLE
Direct toxicity
1. Liver
2. Neurotoxicity
a.peripheral neuropathy (B6 supplementation)
b.seizures
3. Haematological system
1. Liver:- most frequent & major toxic ef-
fect
INH induced hepatitis

• s/s in 1 % can be fatal if drug not discon-

tinued promptly
2. Neurological
a. peripheral nervous system
b. central nervous system
PERIPHERAL NEUROPATHY
More in alcoholic, diabetics and mal
nutrition

(impaired memory, insomnia, restlessness, muscle

twitching, convulsions)

3. HAEMATOLOGICAL in glucose 6 PO4 dehydroge-

nase deficiency ( haemolysis & anaemia)
 Drug interactions

INH increases toxicity of these by decreasing their

metabolism
•phenytoin
•warfarin
•carbamazepine

RESISTANCE??
 CLINICAL USE & DOSAGE ORAL OR
BY INJ.
A) In active disease combine with ethambutol, rifampin
or streptomycin.
Max adult dose 300 mg daily (5 mg/kg/day)
Pyridoxine 10 mg/100 mg of INH given along
with to prevent ? …….
B) Prophylactic use (latent TB)

C)Also for house hold and close contacts esp children

and for nursing homes
 Rifampin
•derivative of Rifamycin
Antibacterial spectrum
 Inhibit growth of many bacteria ie some G +VE
and G –Ve Cocci
 Enteric bacteria
 Mycobacteria
 MECHANISM OF ACTION
 Binds with RNA polymerase enzyme
 Human RNA polymerase is not affected
 RIFAMPIN
Pharmacokinetics
 Absorbed well after oral route.
 Wide distribution in body tissues
 orange red colour metabolites
 Mainly metabolised through liver
 Undergoes enterohepatic circulation
 Bulk excreted in faeces, little in urine
 (Clinical Uses) RIFAMPIN
► In tuberculosis 600 mg/daily orally with INH,
Ethambutol or another anti TB drug. Sometime
short course therapy 600 mg given twice weekly.
As an alternative in INH prophylaxis … If they cannot
take INH or if strain is resistnat to INH & sensitive to rifampin.
► In Leprosy
► In pneumococcal or STAPHYLOCOCCAL infections resis-
tant to penicillin (with vanco)

► other meningococcal and staphylococcal carrier states

 Adverse reactions (Rifampin)
 Imparts harmless orange colour to all secretions and excretion
(urine, sweat, tears contact lenses) Soft lenses stained perma-
nently
 Occasional adverse effects
 Rashes
 Thrombocytopenia,Anemia
 Interstitial Nephritis (light chain proteinurea)
 Impaired LFT if liver dysfunction
 Flue like syndrome (uncertain nature)

Drug interactions due to enzyme induction in liver (cy-

tochrome P450)
Hence decrease in t ½ of many drugs
• anticoagulants, anticonvulsants, & contraceptives,
steroids,methadone. Thus enhancing their elimination
HIV????
 ETHAMBUTOL
Mechanism of action: inhibit
arabinogalactan syntesis an essential cell
wall compound
•arabinosyl transferase
•arabinose + galactose

ANTI BACTERIAL SPECTRUM:- Many strains of

mycobact tuberculosis & other mycobact are
inhibited.
RESISTANCE:mutations in emb gene
 Pharmacokinetics
 well absorbed orally
 distributed to most tissues
 eliminated in urine
 DOSE:- 15-25 mg/kg/d in comb with INH or Ri-
fampin
Resistance rapidly if given alone so give in combination
 Ethambutol
Commonest Adverse Effects are visual
disturbances (i) reduced visual acuity,
opitc neuritis and retinal damage in pts
taking drug for several months in larger
doses.
red green color blindness
•precaution: periodic visual acuity exami-
nation required if 25 mg/kg per day is
used.
 PYRAZINAMIDE PZA

MOA: unknown (mycolic acid)(FA SYNTHASE inh)

Resistance: mutations in genesencoding enzymes

involved in its bioactivation
Pharmacokinetics:-
Well absorbed from G.I.T.
Widely distributed in body including inflamed
meninges
 PYRAZINAMIDE
RESISTANCE:-
 Develops rapidly
 No cross resistance with INH or other Antimycobacte-
rial drug.
ADVERSE EFFECTS:-
 Major effect is Hepatotoxicity
 Nausea, vomiting, drug fever, rash,
photosensitivity,hyper uricemia (polyarthralgia)

USE:- for prevention of active disease in comb with

others.pregnancy××
 STREPTOMYCIN
 15 mg/kg/d I m I/V
 It is an aminoglycoside.(MOA??)
Tuberculosis cases:-
- (Severe Cases, Tuber Meningitis and disseminated
disease ie miliary TB)
 Anti Bacterial Activity
 Primary resistance in 2-3%
 IResistance is due to a point mutation that al-
ters the ribosomal binding site.
 T/M for severe life threatening T.B ie Meningi-
tis, Milliary Dissemination, Organ T.B
Untoward Effect:-
 Nephrotoxicity, Ototoxic (VC Nerve)
 Teratogenic
 NM blockade(MG××)
 Second Line Drugs
When to use:-
1- If resistance to 1st line drugs.
2- Failure of clinical response.
 Paraaminosalicylic Acid (PAS)

It is a folate synthesis antagonist

Chemical Structure:- closely resemble to PABA
P. Aminobenzoic acid
Antibacterial spectrum:- Highly specific drug, only tuber-
cle bacill are inhibited ie bactstatic

MECHANISM OF ACTION:- PAS & PABA complete for the

active center of an enzyme which is involved in con-
verting PABA to dihydrofolate.
 PHARMACOKINETICS OF PAS
1. ABSORBED
2. DISTRIBUTION
3. EXCRETION IN
ABSORBED:- Readily from GIT, average daily dose in
adult 8-12 G orally/day .Child 30 mg/kg/d.
DISTRIBUTION:- Throughout B.W high conc. in pleu-
ral fluid & caseous material
t ½ is 1 hour.
EXCRETION IN:- Urine
 UNTOWARD EFFECTS

GIT symptom of drug intolerance i.e anorexia, nausea

diarrhea. Epigost pain. Peptic ulcer haemorrhage can
occur. Give drug with meals or give antacids.
SENSITIVITY REACTIONS
Rarely liver & kidney damage skin rashes, high
fever.
 ETHIONAMIDE
Closely related to INH
Mechanism of action also blocks synthesis of mycolic acid.
Antibacterial spectrum most of Mycobacterial tuberculosis
are inhibited.
Doses 0.5 – 1 G daily
Pharmacokinetics
Absorbed after oral administration But intense gastric irritation.
other untoward effects are neurological i.e
postural hypotension drowsiness, depression, olfactory
and visual disturbances.
Many hormonal disturbances
Resistance develops rapidly.
Use if primary drug ineffective or contraindicated
 OTHER SECOND LINE DRUGS
1. Kanamycin
2. Amikacin
3. Capreomycin
4. Viomycin
Similar in following ways
 All given by inj.
 Similar pharmacokinetics
 All have similar toxicity
(potentially nephrotoxic ototoxic
 Important:- two drugs of this group should not be
given together.
 Should not be given with streptomycin.
 Fluoroquinolones
ciprofloxacin and ofloxacin
Important recent addition in treatment of tuberculosis
Especially useful in treatment of those strains which are resistant
to first line agent. They are effective at conc of less than 2
µg/ml in blood.
Drug should be used in combination with two or more other ac-
tive agents because otherwise resistance may develop rapidly.
This drug may be used along with pyrazinamide for prevention of
disease in those contacts who come across active cases of
multi drug resistant tuberculosis .
Ofloxacin is slighly more effective than ciprofloxacin
Dosage:- ofloxacin —› 600 – 800 mg as a single daily dose
ciprofloxacin —› 750 mg orally twice a day.
 General Principles of Treatment
I. Rest
II. Chemotherapy
III. follow up
General principles for various schemes of
treatment
 Initial treatment with several drugs
 Then followed by continuation T/M with reduced number of
drugs
 ANTI-TB DRUG REGIMENS

STANDARD REGIMEN:
RIP (2M)
RI (4M)

ALTERNATIVE REGIMEN:
RI (9M)
IE (18M)