anti tubercular drugs (1)
TRANSCRIPT
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A FIGHT AGAINST DEADLY DISEASE
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PRESENTED TO:PRESENTED TO:
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Presented by:Presented by:
Ayesha MumtazAyesha Mumtaz Fatima ShababFatima Shabab Adeela AtiqAdeela Atiq Rizwana RaheelRizwana Raheel
DP 305-901DP 305-901 DP 305-902DP 305-902 DP305-903DP305-903 DP305-904DP305-904
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Parameters to be discussedParameters to be discussed
Name of drugName of drug Chemical dataChemical data Administration dataAdministration data PharmacokineticsPharmacokinetics PharmacodynamicsPharmacodynamics IndicationsIndications ContraindicationsContraindications PrecautionsPrecautions
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Contd……Contd……
InteractionsInteractions Adverse effects Company dataAdverse effects Company data Research dataResearch data Marketing informationMarketing information
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TUBERCULOSISTUBERCULOSIS
History:
Tuberculosis was first formally described by Greek physician Hippocrates around 460 B.C.E.
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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.
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Site of infection of TBSite of infection of TB
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Types of tuberculosis
Asymptomatic TBAlso known as LATENT TB
Symptomatic TBKnown as TB DISEASE
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Symptoms:Symptoms:
Pain in the chest Pain in the chest Coughing up blood or sputum Coughing up blood or sputum
(phlegm from deep inside the lungs) (phlegm from deep inside the lungs) A bad cough that lasts longer than 2 A bad cough that lasts longer than 2
weeksweeksOther symptoms of TB disease are Other symptoms of TB disease are Weight loss Weight loss
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Contd……….Contd……….
no appetite no appetite chills chills fever fever sweating at night sweating at night weakness or fatigueweakness or fatigue
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Tests for identification of Tests for identification of TB:TB:
Chest x-rayChest x-ray Mantoux testMantoux test
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Treatment strategies
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ANTITUBERCULAR DRUGS
Isoniazid (INH)RifampinEthambutolPyrazinamide
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Recommended Drugs for the Initial Treatment of Tuberculosis in Children and Adults
Daily Dose\ *
Maximal
Daily Dose in Childre
n and
Adults
Twice Weekly Dose
Drug Children Adults Children
Adults
Isoniazid 10 to 20 mg/kg
PO or IM
5 mg/kg PO or IM
300 mg 20 to 40 mg/kg Max.
900 mg
15 mg/kg Max. 900 mg
Rifampin 10 to 20 mg/kg
PO
10 mg/kg PO
600 mg 10 to 20 mg/kg Max.
600 mg
10 mg/kg Max. 600 mg
Pyrazinamide 15 to 30 mg/kg
PO
15 to 30 mg/kg
PO
2 g 50 to 70 mg/kg
50 to 70 mg/kg
Ethambutol 15 to 25 mg/kg
PO
15 to 25 mg/kg
PO
2.5 g 50 mg/kg
50 mg/kg
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Chemical structures of antitubercular drugs
Rifampin isoniazid
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ethambutol pyrazinamide
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Dosage form available
Capsule
Tablet
injections
Syrup
Powder for injections
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Administration DataAdministration Data
IsoniazidIsoniazid RifampinRifampin PyrazinamidePyrazinamide EthambutolEthambutol
Oral, IM, IVOral, IM, IV Oral, IVOral, IV OralOral OralOral
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Origin of antitubercular drugsOrigin of antitubercular drugs
All the four drugs are synthesized All the four drugs are synthesized chemicallychemically
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Pharmacodynamics
Mechanism of action
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catalase-peroxidase enzyme katG
INH
Isonicot-inic acyl anion
NADH radical or anion
isonicotinic acyl-NADH complex
ketoenoylreductase
enoyl-AcpM substrate
mycolic acid
Cell lysis
MOA of Isoniazid
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Bacteria
Rifampin
translation
Cell deathtranscripti
on
prokaryotic DNA-dependent RNA polymerase
RNAPROTEIN
MOA of Rifampin
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pyrazinamide
Pyrazinamidase
Pyrazinoic acid
fatty acid synthetase I
Short chain fatty acid precursors
MOA of Pyrazinamide
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Arabinosyl transferase
Mycobacterial Arabinogalactan Cell Wall
ETB
Bacteria
Mycolic acid
Ethambutol
MOA of Ethambutol
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IndicationsIndications
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INH
Rifampicin
Ethambutol OR
Pulmonary extrapulmonarytuberculosis T.b prophylaxis
Pyrazinamide
Indications of IsoniazidIndications of Isoniazid
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Pulmonary Tuberculosis LeprosyMeningitidisMRSAGram_,+veBacteriachlamydial activity Virusesbrucellosis.
Rifampin
isoniazid rifampin
Ethambutol rifampin
isoniazid, ethambutol rifampin
Indications of RifampinIndications of Rifampin
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Pyrazinamide
Active tuberculosis
isoniazid, rifampin pyrazinamide
2 Month regimen
4 Month regimen
isoniazid and rifampin
6 Month regimen
Indications of PyrazinamideIndications of Pyrazinamide
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Ethambutol
continuation phase of tuberculosis
Ethambutol
Isoniazid
TabletCategory I
category III
Indications of EthambutolIndications of Ethambutol
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Contraindications of Antitubercular Contraindications of Antitubercular drugsdrugs
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pregnancy
Contd….Contd….
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PharmacokineticsPharmacokinetics
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PharmacokineticPharmacokineticNAME OF DRUG
BIOAVAILABILITY
HALF LIFE
METABOLISM
PROTEIN BINDING
VOL D EXCRETION
ISONIAZID _
0.5-1.6 hours
liver 0-10% 0.57-0.76 L/kg
Urine &Feces
RIFAMPIN 90-95% 6-7 hours
Hepatic and Intestinal wall
_ 1.6 L/kg Renal & Faecal
ETHAMBUTOL
Absorbed from GIT
3-4 hours
Liver 20-30% 1.6 L/kg Renal
PYRAZINAMIDE
>90% 9-10 hours
Hepatic _ 0.57-0.74 L/kg
Renal
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Drug InteractionsDrug Interactions
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Interactions of Isoniazid
Enflurane
Warfarin
Antacids
Benzodiazipine
Rifampin
Phenytoin
ISONIAZID
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Interactions of Pyrazinamide
ProbenecidProbenecid
AcetestKetostix
test
AcetestKetostix
test
AllopurinolAllopurinolOfloxacinlevofloxacinOfloxacin
levofloxacin
Urinary ketone Deamination
test
Urinary ketone Deamination
test PYRAZINAMIDEPYRAZINAMIDE
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warfarin steroids
Digoxin
RIFAMPIN
Interactions of Rifampin
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RifampinUricosuric
agents
Antacids
ETHAMBUTOL
Interactions of Ethambutol
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ADVERSE EFFECTSADVERSE EFFECTS
Blurred vision hepatotoxic seizuresBlurred vision hepatotoxic seizures
decreased apetitedecreased apetite
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PrecautionsPrecautions
Protect from light Protect from light and moisture. and moisture.
Concurrent use of Concurrent use of any chronically any chronically administered administered medication is medication is prohibited. prohibited.
Injection drug Injection drug should be carefully should be carefully usedused
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Marketing informationMarketing information
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Marketing informationMarketing information
Tb is distributed throughout the worldTb is distributed throughout the world But is more frequent in underdeveloped But is more frequent in underdeveloped
countries due to lack of awareness.countries due to lack of awareness. In Pakistan it was abolished in mid 19s, but due In Pakistan it was abolished in mid 19s, but due
to development of multidrug resistant bacterias to development of multidrug resistant bacterias it has reoccured in Pakistan.it has reoccured in Pakistan.
So, these drugs are used worldwide. So, these drugs are used worldwide. It is It is INTERNATIONALLY RECOMMENDED TO INTERNATIONALLY RECOMMENDED TO
USE THESE DRUGS IN COMBINTIONS.USE THESE DRUGS IN COMBINTIONS.
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Contd….Contd….
In Pakistan these drugs are produced by:In Pakistan these drugs are produced by:
SANDOZ PHARMACEUTICAL COMPANYSANDOZ PHARMACEUTICAL COMPANY Wilsons pharmaceutical companyWilsons pharmaceutical company
Worldwide, these drugs are distributed byWorldwide, these drugs are distributed by LARK LABORTARIES INDIA.LARK LABORTARIES INDIA.
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Company DataCompany Data
Brand NamesBrand Names
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DRUGSDRUGS BRAND BRAND NAMENAME
DOSEDOSE DOSAGEDOSAGE
FORMFORMCOMPANYCOMPANY
ISONIAZISONIAZIDID
I.N.HI.N.H
SONOREXSONOREX100m100mgg
5mg/5mg/5ml5ml
TABLETTABLET
SYRUPSYRUPIRZAIRZA
REXREX
RIFAMPIRIFAMPINN
RIFAMPRIFAMP 150m150mgg
CAPS.CAPS. LISKOLISKO
PYRAZINPYRAZINAMIDEAMIDE
PYRAZINAPYRAZINAMIDEMIDE
500m500mgg
TABLETTABLET WYETHWYETH
LISKOLISKO
ETHAMUETHAMUTOLTOL
U-BUTOLU-BUTOL 400m400mgg
TABLETTABLET UNEXOUNEXO
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Combination of ATT-DrugsCombination of ATT-DrugsDRUGSDRUGS BRAND BRAND
NAMENAMEDOSEDOSE DOSAGE DOSAGE
FORMFORMCOMPANYCOMPANY
INH&RIFINH&RIFAMPINAMPIN
RIFAMATERIFAMATE-INH-INH
450m450mgg
TABLETTABLET WILSHIREWILSHIRE
RIAMPIN, RIAMPIN, INH&PYRINH&PYRAZINMIDAZINMIDEE
PYRATARPYRATAR -- TABLETTABLET UNEXOUNEXO
ETB.INH-ETB.INH-RIFAMYCRIFAMYCININ
CYREXCYREX
MYRINMYRIN - -
--TABLETTABLET
TABLETTABLETREXREX
WYETHWYETH
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Research DataResearch Data
Clinical trialsClinical trials
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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.
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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.
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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
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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
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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.
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393 PTS.With
Active TBInfection and
with:
Normal liver clinical
And Biochemical
tests
ExperimentExperiment
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ISONIAZID5mg/kg/day
RIFAMPIN10mg/kg/day
PYRAZINMIDE20-25mg/kg/day
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67 Pts. Developed hepatitis
Concomitant use ofAlcohol
Paracetamol
ATT-INDUCED
LIVER
INJURY
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Conclusion:Conclusion:
ATT-induced hepatitis is significantly more ATT-induced hepatitis is significantly more frequent and more severe in patients with frequent and more severe in patients with hepatotoxicity risk factors.hepatotoxicity risk factors.
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ReferencesReferences
http://www.doctorslounge.com/infections/http://www.doctorslounge.com/infections/drugs/antibiotics/antitubercular/drugs/antibiotics/antitubercular/
http://www.thesynapticleap.org/node/118http://www.thesynapticleap.org/node/118http://gateway.nlm.nih.gov/http://gateway.nlm.nih.gov/
MeetingAbstracts/ma?f=102265766.htmlMeetingAbstracts/ma?f=102265766.htmlhttp://www.liebertonline.com/doi/abs/http://www.liebertonline.com/doi/abs/
10.1089/1096620026039820610.1089/10966200260398206http://www.freepatentsonline.com/http://www.freepatentsonline.com/
7001893.html7001893.html
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