A FIGHT AGAINST

DEADLY DISEASE
PRESENTED TO:
Presented by:

 Ayesha Mumtaz  DP 305-901

 Fatima Shabab  DP 305-902
 Adeela Atiq  DP305-903
 Rizwana Raheel  DP305-904
 Parameters to be discussed
 Name of drug
 Chemical data
 Administration data
 Pharmacokinetics
 Pharmacodynamics
 Indications
 Contraindications
 Precautions
 Contd……
 Interactions
 Adverse effects Company data
 Research data
 Marketing information
 TUBERCULOSIS
 History:
Tuberculosis was first formally
described by Greek physician
Hippocrates around 460 B.C.E.
 Introduction.
TB, or tuberculosis, is a disease caused by
bacteria called Mycobacterium
tuberculosis. The bacteria can attack any
part of your body, but they usually attack
the lungs.
Site of infection of TB
 Types of tuberculosis
 Asymptomatic TB
Also known as LATENT TB
 Symptomatic TB
Known as TB DISEASE
Symptoms:

Pain in the chest

Coughing up blood or sputum (phlegm
from deep inside the lungs)
A bad cough that lasts longer than 2
weeks
Other symptoms of TB disease are
Weight loss
Contd……….

no appetite
chills
fever
sweating at night
weakness or fatigue
 Tests for identification of
TB:
 Chest x-ray
 Mantoux test
Treatment strategies
 ANTITUBERCULAR DRUGS
 Isoniazid (INH)
Rifampin
Ethambutol
Pyrazinamide
 Recommended Drugs for the Initial Treatment of Tuberculosis in Children and Adults

Maximal
  Daily Dose\ * Twice Weekly Dose
Daily
Drug Children Adults Dose in Childre Adults
Childre n
n
and
Adults
Isoniazid 10 to 20 5 mg/kg 300 mg 20 to 40 15 mg/kg
mg/kg PO or IM mg/kg Max. 900 mg
PO or IM Max.
900 mg

Rifampin 10 to 20 10 mg/kg 600 mg 10 to 20 10 mg/kg

mg/kg PO mg/kg Max. 600 mg
PO Max.
600 mg

Pyrazinamide 15 to 30 15 to 30 2g 50 to 70 50 to 70 mg/kg
mg/kg mg/kg mg/kg
PO PO

Ethambutol 15 to 25 15 to 25 2.5 g 50 50 mg/kg

mg/kg mg/kg mg/kg
 Chemical structures of
antitubercular drugs

Rifampin isoniazid
ethambutol pyrazinamide
Dosage form available

Capsule
Tablet
injections
Syrup
Powder for
injections
 Administration Data
 Isoniazid  Oral, IM, IV
 Rifampin  Oral, IV
 Pyrazinamide  Oral
 Ethambutol  Oral
 Origin of antitubercular drugs

 All the four drugs are synthesized

chemically
Pharmacodynamics

Mechanism of action
 INH
MOA of Isoniazid
Isonicot
-inic NADH isonicotinic
catalase-
peroxidase acyl radical or acyl-NADH
enzyme anion anion complex
katG
ketoenoylreductase

Cell mycolic enoyl-

lysis acid AcpM
substrat
e
 MOA of Rifampin
Rifampin

translation

prokaryotic DNA- Cell

transcription death
Bacteri dependent RNA
a polymerase

PROTEIN
RNA
 MOA of Pyrazinamide
Pyrazinoic acid
pyrazinamid Pyrazinamidas
e e

fatty acid
synthetase I

Short chain
fatty acid
precursors
 MOA of Ethambutol
Arabinosyl
Ethambutol transferase

ETB

Mycobacterial
Arabinogalactan
Cell Wall

Mycolic acid

Bacteri
a
Indications
Indications of Isoniazid
Rifampicin

Ethambutol
INH OR
Pulmonary
extrapulmon
ary
Pyrazinami
tuberculosis
de
T.b
prophylaxis
 Indications of Rifampin
isoniazid
Pulmonary
rifampin
Tuberculosis
Leprosy Ethambutol
Rifampin Meningitidis rifampin
MRSA
isoniazid,
Gram_,+ve
ethambutol
Bacteria
rifampin
chlamydial
activity
Viruses
brucellosis.
 Indications of Pyrazinamide
2
isoniazid,
Mont
rifampin
h
pyrazinami
regim 6
Active de
en Month
Pyrazina tuberculosi
mide s 4 regim
isoniazid
Mont en
and
h rifampin
regim
en
Indications of Ethambutol
continuati Ethambuto
on phase l
of Isoniazid
Ethambutol tuberculos
is

Category category Tablet

I
III
Contraindications of Antitubercular
drugs
 Contd….

pregnancy
Pharmacokinetics
 Pharmacokinetic
NAME OF BIOAVAILABILI HAL METABOLI PROTEI VOL D EXCR
DRUG TY F SM N ETIO
LIFE BINDIN N
G

ISONIAZID 0.5- liver 0-10% 0.57-0.76 Urine

_ 1.6 L/kg &Fec
hour es
s

RIFAMPIN 90-95% 6-7 Hepatic and _ 1.6 L/kg Renal

hour Intestinal &
s wall Faeca
l

ETHAMBUTO Absorbed from 3-4 Liver 20-30% 1.6 L/kg Renal

L GIT hour
s

PYRAZINAMI >90% 9-10 Hepatic _ 0.57-0.74 Renal

DE hour L/kg
s
Drug Interactions
Interactions of Isoniazid

Phenytoin

Enflurane Rifampin

ISONIAZID

Benzodia
Warfarin
zipine

Antacids
Interactions of Pyrazinamide

Probenecid
Probenecid
Urinary
Urinary ketone
ketone Acetest
Acetest
Deamination
Deamination Ketostix
Ketostix
test
test PYRAZINAMIDE
PYRAZINAMIDE test
test

Ofloxacin
Ofloxacin Allopurinol
Allopurinol
levofloxacin
levofloxacin
Interactions of Rifampin
Digoxin

RIFAMPIN

warfarin steroids
Interactions of Ethambutol
Antacids

ETHAMBUTOL

Uricosuric
Rifampin agents
 ADVERSE EFFECTS

Blurred vision hepatotoxic seizures

decreased apetite
 Precautions
 Protect from light
and moisture.
 Concurrent use of
any chronically
administered
medication is
prohibited.
 Injection drug
should be carefully
used
Marketing information
 Marketing information
 Tb is distributed throughout the world
 But is more frequent in underdeveloped
countries due to lack of awareness.
 In Pakistan it was abolished in mid 19s, but due
to development of multidrug resistant bacterias
it has reoccured in Pakistan.
 So, these drugs are used worldwide.
 It is INTERNATIONALLY RECOMMENDED TO
USE THESE DRUGS IN COMBINTIONS.
 Contd….
 In Pakistan these drugs are produced by:

 SANDOZ PHARMACEUTICAL COMPANY

 Wilsons pharmaceutical company

 Worldwide, these drugs are distributed by

 LARK LABORTARIES INDIA.
Company Data
Brand Names
DRUGS BRAND DOSE DOSAGE COMPANY
NAME FORM

ISONIAZI I.N.H 100mg TABLET IRZA

D SONOREX 5mg/5 SYRUP REX
ml

RIFAMPI RIFAMP 150mg CAPS. LISKO

N
PYRAZIN PYRAZINA 500mg TABLET WYETH
AMIDE MIDE LISKO
ETHAMU U-BUTOL 400mg TABLET UNEXO
TOL
Combination of ATT-Drugs
DRUGS BRAND DOSE DOSAGE COMPANY
NAME FORM

INH&RIFA RIFAMATE- 450mg TABLET WILSHIRE

MPIN INH

RIAMPIN, PYRATAR - TABLET UNEXO

INH&PYR
AZINMID
E
ETB.INH- CYREX - TABLET REX
RIFAMYCI MYRIN - TABLET WYETH
N
Research Data
Clinical trials
 CLINICAL TRIALS
• Objective:
To assess the severity and frequency of
hepatotoxicity caused by different
antituberculosis (ATT) drugs and to
evaluate whether concurrence of risk
factors influence the antituberculosis drug
induced hepatotoxicity.
 Hepatotoxicity:
Normalization of liver function after
withdrawal of all anti-tuberculosis
drugs, and the presence of at least one
of the following criteria:
appearance of jaundice
 a rise in the level of serum total
bilirubin > 1.5mg/dl.
 Reported risk factors for
hepatotoxicity include:
 older age,
 female sex,
 poor nutritional status,
 high alcohol intake,
 advanced tuberculosis,
 inappropriate use of drugs and
 acetylator status
 Patient Selection
This prospective cohort study was
conducted in:
 Medical Unit-V and
 Out Patient Department of Civil Hospital,
Karachi,
 from 15 July 2004 to 14 July 2005
 Total 393 patients selected
 males were 183 (53.98%) and
female 156 (46.02%) included
 who were prescribed to receive anti
tuberculosis drugs for pulmonary or extra
pulmonary tuberculosis.
 393 PTS. Experiment
With
Active TB
Infection and
with:

Normal liver
clinical
And
Biochemical
tests
 ISONIAZID
5mg/kg/day

RIFAMPIN
10mg/kg/day

PYRAZINMIDE
20-25mg/kg/day
 67 Pts.
Developed
hepatitis

TT - I NDUCED
A
Concomitant use of LIVER
Alcohol INJURY
Paracetamol
 Conclusion:
 ATT-induced hepatitis is significantly more
frequent and more severe in patients with
hepatotoxicity risk factors.
 References
 http://www.doctorslounge.com/infections/d
rugs/antibiotics/antitubercular/
 http://www.thesynapticleap.org/node/118
 http://gateway.nlm.nih.gov/MeetingAbstrac
ts/ma?f=102265766.html
 http://www.liebertonline.com/doi/abs/10.10
89/10966200260398206
 http://www.freepatentsonline.com/7001893
.html