FF

1. A presentationon-

2. Clinical Pharmacist
Dept. Of Nephrology
M. N. G. Hospital
TUBERCULOSIS TREATMENT

3. Definition
 Tuberculosis (TB) is a potentially fatal
contagious disease that can affect almost any part
of the body but is mainly an infection of the
lungs.
Neo-latin word :
- Round nodule/Swelling
- Condition
“Tubercle”
“Osis”

4. Causative Organisms
Mycobacterium tuberculosis
Human
Mycobacterium Bovis
Animals

5. Other causative organisms
 Mycobacterium africanum
 Mycobacterium microti
Non-Mycobacterium Genus
 Mycobacterium leprae
 Mycobacterium avium
 Mycobacteriumasiaticum
M.
africanum
M. Bovis
M. Canetti
M. microti
M. tuberculosis complex

6.  Discovered in 1882 by RobertKoch.

8. Classification
Pulmonary TB
- Primary Disease
- Secondary Disease
Extra pulmonary
i. Lymph node TB
ii. Pleural TB
iii. TB of upper airways
iv. Skeletal TB
v. Genitourinary TB
vi. Miliary TB
vii. Pericardial TB
viii. Gastrointestinal TB
ix. Tuberculous Meningitis
x. Less common forms

9. Based on types of TB

10. Severe Symptoms
Persistentcough
Chest pain
Coughing with bloodysputum
Shortness of breath
Urine discoloration
Cloudy & reddish urine
Fever with chills.
Fatigue

11. Spread of Tuberculosis

12. TB Transmission
• Probability that TB will be
transmitted depends on:
– Infectiousness of
person with TB disease
– Environment in which
exposure occurred
– Length of exposure
– Virulence (strength) of the
tubercle bacilli
• The best way to stop
transmission is to:
– Isolate infectious
persons
– Provide effective
treatment to infectious
persons as soon as
possible

13. Preventive measures
1) Mask
2) BCG vaccine
3) Regular medical follow up
4) Isolation of Patient
5) Ventilation
6) Natural sunlight
7) UV germicidal irradiation

15. Diagnosis
1.Bacteriological test:
a. Zeihl-Neelsen stain
b. Auramine stain(fluorescence microscopy)
2. Sputum culturetest:
a. Lowenstein –Jensen(LJ) solid medium: 4-18 weeks
b. Liquid medium : 8-14 days
c. Agar medium : 7 to 14days

16. 3.Radiography:
Chest X-Ray(CXR)
4.Nucleic acid amplification:
 Species identification ; several hours
 Low sensitivity, high cost
 Most useful for the rapid confirmation of
tuberculosis in persons with AFB-positive sputa

17. 5.Tuberculin skin test (PPD)
 Injection of fluid into
the skin of the lower
arm.
 48-72 hours later –
checked for a reaction.
 Diagnosis is based on
the size of the wheal.
1 dose = 0.1 ml contains0.04µg
Tuberculin PPD.

18. Tuberculin test interpretation

19. BCG vaccine
 Bacille Calmette Guerin(BCG).
 First used in 1921.
 Onlyvaccine available today forprotectionagainst tuberculosis.
 It is mosteffective in protecting children from thedisease.
 Given 0.1 ml intradermally.
 Duration of Protection 15 to 20years
 Efficacy 0 to80%.
 Should begiven toall healthy infantsas soonas possibleafterbirth
unless thechild presented with symptomatic HIV infection.

20. LTBI vs. TB Disease
Latent TB Infection (LTBI) TB Disease (in the lungs)
Inactive, contained tubercle bacilli
in the body
TST or blood test results usually
positive
Chest x-ray usually normal
Sputum smears and cultures
negative
No symptoms
Not infectious
Not a case of TB
Active, multiplying tubercle bacilli
in the body
TST or blood test results usually
positive
Chest x-ray usually abnormal
Sputum smears and cultures may
be positive
Symptoms such as cough, fever,
weight loss
Often infectious before treatment
A case of TB

21. •
•
• Substance abuse
• Recent TB infection
• Prolonged therapy with
corticosteroids and other
immunosuppressive
therapy, such as prednisone
and tumor necrosis factor-
alpha [TNF-α] antagonists
• Diabetes mellitus
• Severe kidney disease
• Certain types of cancer
• Certain intestinal conditions
• Low body weight
Some conditions increase probability of LTBI
progressing to TB disease
Infection with HIV • Organ transplant
Chest x-ray findings • Silicosis
suggestive of previous TB
Progression to TB Disease

22. Tuberculosis Treatment
• refers to the medical treatment of the infectious disease tuberculosis(TB).
Active tuberculosis will kill about 2 of every 3 people affected if left
untreated. Treated tuberculosis has a mortality rate of less than 5%.
• The standard "short" course treatment for TB is isoniazid,
rifampicin, pyrazinamideand
ethambutol for 2 months, then isoniazid and
rifampicin alone for a further 4 months. The patient is considered cured
at six months (although there is still a relapse rate of 2 to 3%).

23. • For latent tuberculosis,
• the standard treatment is six to
• nine months of isoniazid alone.

24. • Ethambutol
• isoniazid
• pyrazinamide
• rifampicin
First line Drugs

25. Drug regimens:
• 2HREZ/4HR3
• means isoniazid, rifampicin, ethambutol,
pyrazinamide daily for two months, followed
by four months of isoniazid and rifampicin
given three times a week.

26. Dosage regimen
 Intensive phase + continuationphase
 HREZ (2 months) + HRE (4 months)

27. Second line
• There are six classes of second-line drugs (SLDs)
used for the treatment of TB. A drug may be
classed as second-line instead of first-line for one
of three possible reasons:
• *it may be less effective than the first-line drugs
• (e.g., p-aminosalicylic acid)
• or
•*it may have toxic side-effects (e.g., cycloserine)
or
• *it may be unavailable in many developing countries
(e.g., fluoroquinolones)

28. Third line
• Other drugs that may be useful, but are not on the WHO
list of SLDs:
• rifabutin
• macrolides e.g.clarithromycin
• linezolid
• thioacetazone
• thioridazine
• arginine
• These drugs may be considered "third-line drugs" and are
listed here either because they are not very effective (e.g.,
clarithromycin) or because their efficacy has not been
proven (e.g., linezolid). Rifabutin is effective, but is not
included on the WHO list because for most developing
countries, it is impractically expensive

29. Drugs MOA Diagram
Isoniazid Inhibits mycolic acidsynthesis.
RIFAMPICIN Blocks RNA synthesis by blocking
DNA dependent RNA polymerase
PYRAZINAMIDE •Bactericidal-slowly metabolizing
organism within acidic
environment of Phagocyte or
caseous granuloma.

30. Drugs MOA Diagram
ETHAMBUTOL •Bacteriostatic
•Inhibition of Arabinosyl
Transferase
STREPTOMYCIN •Inhibition of Protein
synthesis by disruption of
ribosomal function

31. Mode of action & Recommended dose
mg/kg
Essential anti-
tuberculosis
drug
Mode of
action
Daily
dose mg/
kg
3times/
week
Twice/
week
NH
bactericidal 5 10 15
Rifampicin bactericidal 10 10 10
pyrazinamide bactericidal 25 35 50
streptomyicin bactericidal 15 15 15
Ethambutol bacteriostatic 15 30 45

32. Pharmacokinetic
Drugs name Half-life Metabolism Excretion
rifampicin 6 to 7 hours Hepatic and
intestinal wall
renal 15to 030%
Faecal 60%
INH 0.5-1.6h (fast
acetylators), 2-5h
(slow acetylators)
liver urine (primarily),
feces
Ethambutol 3-4 hr (increased
in impaired renal
function)
liver renal
pyrazinamide 9-10hr liver renal
streptomycin 5-6hr Without hepatic
metabolism
renal

33. •
•
•

34. Drug
name
Adverse
effects
cautions contrai
ndicati
ons
Interaction Results
INH *Nausea
*vomiting
*peripheral
neuritis
*hepatic
impairmet
*renal
drug-
induced
liver
disease
*Carbamazepine
& phynetoin
↑toxicity
of these
drugs
↑INH
hepatoto
xicity
INH
effects↓
*Convulsion
impairment *Carbamazepine
*psychotic *epilepsy
episodes
*alcohol
*allergic dependence
reactions
*Antacids
*blood
dyscrasias
*breast-
feeding

35. Drugs
names
Adverse effects cautions contrai
ndicati
ons
interaction Result
s
Rifampici n GI
disturbance,
liver damage
,
influenza-like
syndrome some
times with
thrombocytopen
ia, haemolytic
anaemia, shock
and renal failure
(particularly
with
intermittent
therapy)
*hepatic
impairme
nt
*pregnancy &
breast-
feeding,
advise
patients on
hormonal
contraceptive
to use
additional
means,
jaundice Phenytoin
Digoxin
Theophylline
Oral
anticoagulant
Contraceptive
b-blockers
↓
Effects
of
these
drugs
may coloure
skin, urine,
*discolours
soft contact
Sulphonylureas

36. Drugs
names
Adverse
effects
cautions contrain
dication
s
interactio
n
Results
Ethambut
ol
optic neuritis,
red/green
colour
blindness,
peripheral
neuritis,
rarely rash,
pruritus,
urticaria,
thrombocytope
nia
reduce dose in
renal
impairment
and if
creatinine
clearance less
than
30 mL/minut
*children
under 6 years
optic
neuritis,
poor
vision
Almunium
hydroxide
↓effect of
Ethambutol

37. Drugs
names
Adverse
effects
cautions contra
indicat
ions
interaction result
pyrazinami
de
Liver damage,
hyperuricemia,
*diabetes
*gout
Liver
damage
Probenecid antagonize
effects of
these drugs
*GI disturbance,
arthralgia, rash
*renal
dysfunctio
n
Sulfinpyrazone
and
occasionally
photosensitivity

38. Drugs
names
Adverse
effects
cautions contrain
dications
interaction Results
streptomyci
n
*ototoxicity
•reversible
nephrotoxicty
neuromascular
blockade with
apnea
↑dose
interval in
renal
dysfunction
*pregnancy
*Cephalosprins
,cycloserine,
vancomycin,
↑nephrotox
icty
↑
ototoxicity
↑skletal
muscle
paralysis
amphotericin,
myasthenia
gravis
furosemide
*Loop diuretic
,vancomycin,
neuromascular
blockers

39. Kidney disease
• *Isoniazid ,rifampicin and pyrazinamide are
either eliminated almost entierly by biliary
excretion or metabolized into non toxic substance .
• *these drugs may be given in normal dosage to
patients with renal dysfunction.
• *In sever renal failure patients should recived
pyridoxine with isoniazid in order to prevent
peripheral neuropathy.

40. • *Streptomycin & Ethambutol can given
in reduced dose under close monitoring of
renal function (since these drugs are
excreted by the kidney).
• *Thiocetazone, which is partially in urine,
but has a narrow margin of safety , should be
avoided in patients with renal failure

41. • *When using 2HRZ/4HR in patients on
dialysis, the drugs should be given daily
during the initial high-intensity phase.
• *In the continuation phase, the drugs should be
given at the end of each haemodialysis session
and no dose should be taken on non-dialysis
days.

42. DOTS
DOTS - Directly observed treatment,short-course
 DOT means that a trained health care worker or other designated
individual provides the prescribed TB drugsand watches the patient
swallow everydose.

43. • Lewis, S. Heitkemper, M.,
Dirksen, S., O’Brien, P.,& Bucher,
L. (2011). Medical –Surgical
Nursing Assessment and
Management of Clinical Problems
(8th ed.), volume 1, Philadelphia,
PA,: Mosby Elsevier
• CDC - Tuberculosis (TB)
• www.cdc.gov/tb/ Jun 30, 2018
- Centers for Disease Control and
Prevention, Division of
Tuberculosis Elimination.
• Lippincott’s Mannual
• Saunder’s Theory 4th edition
• www.seha-elibrary.com
REFERENCE