tuerculosis- pharmacy practice

1. Samiyathunnisa P
First year m pharm

2.  Tuberculosis (TB) remains a leading infectious
disease caused by Mycobacterium tuberculosis,
which can produce either a silent, latent infection
or a progressive, active disease.
 Transmission usually takes place through the
airborne spread of droplet nuclei produced by
patients with infectious pulmonary tuberculosis

3. ETIOLOGY
 M. tuberculosis preferentially infects
humans, and the closely related
Mycobacterium bovis causes a similar
disease in cattle and other livestock.
humans frequently developed TB by
drinking milk contaminated with M. bovis.
 The complex includes M. africanum, M.
microti and M. canettii

4.  M. tuberculosis is an aerobic ,slender
bacillus with a waxy outer layer.
 under the microscope, it is either straight or
slightly curved in shape.
 It does not stain well with Gram stain, so the
Ziehl-Neelsen stain.
 After Ziehl-Neelsen staining with carbol-
fuchsin, mycobacteria retain the red color
despite acid–alcohol washes. Hence they
are called acid-fast bacilli

5. EPIDEMIOLOGY
 Tuberculosis is the second most common
cause of death from an infectious disease in
the world
 In 2009, there were an estimated 9.4 million
incident cases (range, 8.9 million–9.9 million)
of TB globally
 There were an estimated 14 million prevalent
cases(range 12 million–16 million) of TB in
2009
 There were an estimated 440 000 cases of
multi-drug resistant TB (MDR-TB) in 2008

6. CLASSIFICATION
1)pulmonary TB
2)Extrapulmonary TB:
It occurs in places other than the lungs,
including the larynx, the lymph nodes, the
pleura, the brain, the kidneys, or the bones
and joints. In HIV-infected persons,
extrapulmonary TB disease is often
accompanied by pulmonary TB.
 Lymphadenopathy
 Tubercular meningitis
 Miliary TB
 Bone/joint TB
 Additional sites

7.  lymphadenopathy
 Trials have shown that 6 months of treatment are just as
effective as 9 months for fully susceptible bacilli.
 The standard 6-month treatment regimen is recommended
 Meningeal TB
 Patients with active meningeal TB (tuberculous
meningitis)should be treated with rifampicin and isoniazid
for 12 months together with pyrazinamide, and normally
ethambutol, for the first 2 months.
 Bone and joint TB
 The spine is the most common site for bone TB.
 treated effectively with standard agents such as isoniazid
and rifampicin for 6 months, together with pyrazinamide
and a fourth drug, usually ethambutol in the initial phase
(for 2 months).

8.  Miliary TB
 Miliary TB occurs when tubercle bacilli enter the
bloodstream and disseminate to all parts of the
body, where they grow and cause disease in
multiple sites. This condition is rare but serious.
“
 Miliary” refers to the radiograph appearance of
millet seeds scattered throughout the lung. It is
most common in infants and children younger
than 5 years of age, and in severely
immunocompromised persons.
 The standard 6-month regimen containing both
 isoniazid and rifampicin, with pyrazinamide and
ethambutol in
 the first 2 months, is used.

9. PATHOPHYSIOLOGY
 Primary infection usually results from inhaling
airborne particles that contain M.
tuberculosis.These particles, called droplet
nuclei, contain one to three bacilli and are small
enough (1 to 5 mm)to reach the alveolar
surface.

10.  The progression to clinical disease depends on
three factors:
 (a) the number of M. tuberculosis organisms
inhaled
 (b) the virulence of these organisms
 (c) the host’s cell-mediated immune response.

11.  Droplet nuclei
containing tubercle
bacilli are inhaled,
enter the lungs, and
travel to the alveoli.
 Tubercle bacilli
multiply in the alveoli.
ALVEOLI

12.  Within 2 to 8 weeks, special
immune cells
(macrophages) ingest and
surround the tubercle
bacilli. The cells form a
barrier shell, called a
granuloma, that keeps the
bacilli contained and under
control (LTBI).
 If the immune system
cannot keep the tubercle
bacilli under control, the
bacilli begin to multiply
rapidly (TB disease).

13.  A small number of
tubercle bacilli enter
the bloodstream and
spread throughout
the body. The bacilli
may reach any part
of the body, including
areas where TB
disease is more
likely to develop.

14.  Patients typically
present with weight
loss, fatigue, a
productive cough,
fever, and night sweats
 Frank hemoptysis
SIGNS AND SYMPTOMS

15. DIAGNOSIS
Physical Examination
 Dullness to chest percussion, rales, and
increased vocal fremitus are observed frequently
on auscultation
Laboratory Tests
 Moderate elevations in the WBC count with a
lymphocyte predominance

16. TUBERCULIN /MANTOUX TEST
 The standard 5-
tuberculin-unit PPD dose
is placed intracutaneously
in the forearm.
 Produce wheal 6 mm to
10 mm in diameter
 Represent DTH (delayed
type hypersensitivity)
 read the test in 48 to 72
hours.
 Measure only induration
 Record reaction in mm

17.  AFB Microscopy
 A presumptive diagnosis
is based on the finding of
AFB on microscopic
examination of a
diagnostic specimen such
as a smear of
expectorated sputum or of
tissue.
 three sputum specimens,
preferably collected early
in the morning.
 Strongly consider TB in
patients with smears
containing acid-fast bacilli
(AFB)
Mycobacterium tuberculosis (stained
red) in sputum

18. Chest Radiograph
 Patchy or nodular
infiltrates in the
apical areas of the
upper lobes or the
superior segment of
the lower lobes
 Cavitation that may
show air-fluid levels
as the infection
progresses

20. GENERAL APPROACHES TO TREATMENT
 Drug treatment is the cornerstone of TB management.
 Monotherapy can be used only for infected patients
who do not have active TB.
 Once active disease is present, a minimum of two
drugs, and generally 3 or 4 drugs, must be used
simultaneously.
 The duration of treatment depends on the condition of
the host, extent of disease, presence of drug
resistance, and tolerance of medications.
 The shortest duration of treatment generally is 6
months, and 2 to 3 years of treatment may be
necessary for cases of multidrug-resistant TB (MDR-
TB).

21.  The DOTS strategy has emerged as a
possible solution to the rising number of TB
cases in different parts of the world and has
been incorporated in India’s Revised
National Tuberculosis Control Programme
(RNTCP)as well.
 The strategy assures a compulsory and free
availability of good quality drugs to all TB
cases and necessitates drug administration
under direct supervision, thereby ensuring
the requisite regimen-compliance.

22. Grouping Drugs
Group 1:
First-line oral anti-TB agents
Isoniazid (H); Rifampicin (R);
Ethambutol (E); Pyrazinamide
(Z)
Group 2:
Injectable anti-TB agents
Streptomycin (S); Kanamycin (Km);
Amikacin (Am);
Capreomycin (Cm); Viomycin
(Vm).
Group 3:
Flouroquinolones
Ciprofloxacin (Cfx); Ofloxacin (Ofx);
Levofloxacin (Lvx); Moxifloxacin
(Mfx); Gatifloxacin (Gfx)
Group 4:
Oral second-line anti-TB agents
Ethionamide (Eto); Prothionamide
(Pto); Cycloserine (Cs);
Terizadone (Trd);
para-aminosalycilic acid (PAS);

23. FIRST-LINE DRUGS
DRUG 3 times
per week
dose(ad
ult)
Dose in
mg per kg
(thrice a
week) in
children
SIDE EFFECTS
Isoniazid (H) 900mg
10 – 15mg
clinical hepatitis,peripheral
neuropathy, CNS effects, lupus-
like syndrome, hypersensitivity
Rifampicin(R) 600mg 10mg Pruritis, rash,hepatotoxicity, GI
Symptoms, flu-like
syndrome,thrombocytopenia, renal
failure
Pyrazinamide(Z) 1500mg 35mg Hepatotoxicity,nausea,anorexia,po
lyarthralgia, rash, hyperuricemia,
dermatitis
Ethambutol(E) 1200mg 30mg Optic neuritis, skin rash

24. LATENT TB INFECTION
 Isoniazid preferred drug for treating LTBI.
 Generally, isoniazid alone is given for 9 months.
 The treatment of LTBI reduces a person’s lifetime
risk of active TB.
 adult doses are usually 300mg daily
 Isoniazid should be given on an empty stomach,
and antacids should be avoided within 2 hours of
dosing.
 Pregnant women, alcoholics,and patients with poor
diets who are treated with isoniazid should receive
pyridoxine 10 -50 mg daily to reduce the incidence
of peripheral neuropathy.
 Rifampin 600 mg daily for 4 months can be used
when isoniazid resistance is suspected or when the
patient cannot tolerate isoniazid.

25. Diagnosti
c
category
People with TB
disease
Initial phase 3
times weekly
Continuation
Daily or 3
times weekly
1 New sputum smear
positive
2 HRZE 4 HR
or
6 HE daily
2 Previously treated
sputum smear
positive: relapse
2 HRZES
followed by 1
HRZE
5 HRE
3 Sputum smear-
negative Not
seriously ill, extra-
pulmonary
2 HRZE 4 HR
or 6 HE daily
4 Chronic and multi-
drug-resistant TB
Specially designed standardized
or individualized regimens
ACTIVE TB

26. DRUG-RESISTANT TB DISEASE (CAT 4)
 can develop in two different ways, called
primary and secondary resistance.
 Primary resistance occurs in persons who are
initially exposed to and infected with resistant
organisms.
 Secondary resistance, or acquired resistance,
develops during TB therapy, either because the
patient was treated with an inadequate regimen
or did not take the prescribed regimen
appropriately, or because of other conditions
such as drug malabsorption or drug-drug
interactions that led to low serum levels.

27. 2 TYPE
 1. Multi-drug resistant TB
 2.Extensively resistant TB

28. 1.MDR TB is caused by organisms resistant to
both isoniazid and rifampin, which are the two
most effective anti-TB drugs. These drugs are
considered first-line drugs and are used to treat
most persons with TB disease.
Standardized RNTCP regimen for MDR TB
Intensive phase(6-9
months)
Kanamycin
Ofloxacin Or
levofloxacin
Ethionamide
Cycloserine
Pyrazinamide
Ethambutol
Continuation
phase(18months)
Ofloxacin or levofloxacin
Ethionamide
Cycloserine
ethambutol
+pyridoxine 100mg/day

29.  2.XDR TB is resistant to both isoniazid and
rifampin, plus any fluoroquinolone and at least
one of three injectable second-line drugs (i.e.,
amikacin, kanamycin, or capreomycin). Because
XDR TB disease is resistant to first-line and
second-line drugs, patients are left with
treatment options that are more toxic, more
expensive, and much less effective.

30. SPECIAL POPULATIONS
 Streptomycin should be avoided, while other
drugs can be used safely during pregnancy.
 Lactation:-
 Mother and baby should stay together and the
baby should continue to breastfeed.
 After active TB in the baby is ruled out, the
baby should be given 6 months of isoniazid
preventive therapy, followed by BCG
vaccination
 In the presence of renal disease, H, R and Z are
relatively safe for administration, while S and E
are avoided.

31.  In liver disease, the reverse procedure is
followed i.e. S and E are considered to be
safe, whereas H, R and Z should be
stopped.
 Children under 6 years of age, having a
family member with smear-positive TB,
should be screened for symptoms.

32. BCG VACCINE
 It is a live vaccine bearing an attenuated
bovine strain of M. tuberculosis
 It is supplied as 0.5-1 mg dry powder in
ampules to be suspended in 1 ml of
sterilewater
 DOSE: 0.05 ml (in neonate) 0.1 ml (older
individuals) is injected intracutaneously in
the left deltoid region atbirth.

33. REFERENCE
 Pharmacotherapy - A Pathophysiologic
approach, 7th edition by Joseph. T. Dipiro,
 Applied therapeutics – Marry Anne koda-
kimble
 Medical pharmacology by K.D.Tripathi