Tuberculosis

dr. Yora Nindita

2009

2nd Line Drugs:

Not as effective and have more toxicity

Streptomycin

The first drug used clinically for treatment

of TB 1947-1952;
was the only drug available at that time.
An aminoglycoside antibiotic
Acts by protein synthesis inhibitor and
decreases the fidelity mRNA and garbles the
message, leads to nonsense proteins.
Streptomycin only binds to the 30s subunit.

Streptomycin

Adverse Effects :

affects C. Nerve VIII :

auditory and vestibular functions.
- this drug is now 2nd 'line
because of its toxicity.

para- Aminosalicylic Acid

a structural analog of PABA ( para

amino benzoic acid) is bacteriostatic
inhibits de novo folate synthesis
half life = 1 hour after 4 g. dose
you can give this drug up to 12 grams/day.
80% of the drug is excreted in the urine and
50% of that is as an acetylated metabolite
which is insoluble.
You must make sure the patient's urine is
normal or alkaline.

para- Aminosalicylic Acid

Adverse effects

GI irritation due to the amount of drug given

(high doses) nausea, vomiting, bleeding,
occurs in 30-40% of the patients. Be careful
with those who have peptic ulcers
Hypersensitivity reactions
Rash, Fever some hepatotoxicity
All will disappear when the drug is stopped
This drug has poor patient acceptability
and compliance

Third Line Drugs

lest effective and most toxic

Third line drugs are used when resistance

is developed to 1st and 2nd line drugs;
these drugs are also used in combination.
Aminoglycosides
Capreomycin - Viomycin - Kanamycin

Third Line Drugs Adverse

effects

These drugs are: Nephrotoxic

- will cause :
Proteinuria, Hematuria,
Nitrogen metabolism,
and Electrolyte disturbances
However effect is reversible when drug
is stopped.

Third Line Drugs

Adverse effects

Ototoxic
will result in deafness and some loss
of vestibular function, leads to
cranial nerve VIII damage.
The nerve damage is permanent.
Capreomycin has replaced viomycin
because of less toxic effects, but all
three drugs have the same effects.

Cycloserine

can cause CNS disturbances

Therapeutic States
Cycloserine should be used when re -treatment
is necessary or when the micro-organism is
resistant to the other drugs.
It must be given in combination with other
anti-tuberculosis drugs.

Mechanism of Action :
An analog of D-alanine synthetase, will block
bacterial cell wall synthesis.

Cycloserine

Toxicity:
Most common in the CNS :
Headache, tremor, vertigo, confusion,
nervousness, psychotic states with
suicidal tendencies, paranoid reactions,
catatonic and depressed reactions

Cycloserine

Pharmacokinetics :

Rapidly absorbed
Peak [plasma] occurs in 3-4 hours
Distributed throughout all body fluids,
including CSF

Cycloserine

Pharmacokinetics :

About 50 % is excreted in unchanged form

in the urine during the first 12 hours
Only about 35 % of the drug metabolized
This drug can accumulate to toxic
concentration in patients with renal
insufficiency

Chemoprophylaxis of TB
Used only in high risk groups

Household members and other close

contacts of a patient with active TB.
A positive skin test in persons less than
35 years.
A positive skin test reactive in the
immunosuppressed, persons with leukemia,
and Hodgkin's Disease
HIV+ patients with a positive TB test

Chemoprophylaxis of TB
Used only in high risk groups

The drug of choice for chemoprophylaxis is

isoniazid. Prophylaxis uses only one drug.
In patients who are HIV+ and TB+ and have
the disease; they are treated for a minimum of
9 months,

The first two months using isoniazid and rifampin

and for the next seven months or longer,
use only two or three of the 2nd /3rd line drugs and
Isoniazid / Rifampin.

Chemotherapy of TB

Most patients are treated in an ambulatory

setting - admitted to the hospital diagnosis is established - initiate and
stabilize therapy - send patient home ,
usually after 2 or 3 weeks
First and second line agents are usually
given orally.
Third line drugs are given parenterally.

Treatment

Isoniazid, ethambutol, & rifampin are given

for 2 months.
Isoniazid & rifampin are given for 4 months.
If you suspect resistance to isoniazid use
isoniazid, ethambutol, rifampin & pirazinamide.
Incidence of drug resistance is 2-5% in the
U.S.

Treatment

Isoniazid, Ethambutol, & Rifampin are given for 2

months.
Isoniazid & Rifampin are given for 4 months.
If you suspect resistance to isoniazid use Isoniazid,
Ethambutol, Rifampin & Parazinamide. Incidence of
drug resistance is 2-5% in the U.S.
Prolonged bed rest is not necessary or helpful in
obtaining a speedy recovery. The patient must be seen at
regular and frequent intervals to follow the course of the
disease and treatment. Look for toxic effects

Other Resources

Tuberculosis Resources (Columbia Medical School)

http://www.cpmc.columbia.edu/tbcpp
Tuberculosis, NIAID Fact Sheet http://www.niaid.nih.gov/factsheets/tb.htm
Positive Skin Tests for Tuberculosis (American Family Physician)
http://www.aafp.org/afp/961101ap/pat_1991.html
National Tuberculosis Center http://www.umdnj.edu/~ntbcweb/ntbchome.htm
CDC; Division of Tuberculosis Elimination
http://www.cdc.gov/nchstp/tb/structure.htm
Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children
American Thoracic Society Medical Section of the American Lung Association
American Journal of Respiratory and Critical Care Medicine Vol 149 1994
http://aepo-xdv-www.epo.cdc.gov/wonder/PrevGuid/p0000413/p0000413.htm
Brief History of Tuberculosis http://www.umdnj.edu/~ntbcweb/history.htm