Puteri Shamillah Wan Hidayu Farhana Azmira Shazeenah Nadeeja

May be associated with night sweats

 TB is major cause of illness & death worldwide Highest in ASIA & AFRICA In 2011, almost 1.4 million people died from TB (WHO, 2012)

Physical examination
Unusual breath sounds Swollen lymph nodes

Clubbing of fingers/toes

LABORATORY AND PHYSICAL TESTING

1) PPD (Purified protein derivative) 2) Thoracentesis 3) Sputum Examination

4) Chest Radiography
cavity

4) Chest Radiography
Acute miliary tuberculosis

5) Bronchoscopy 6) Tuberculosis antibody testing

 Isoniazid (INH, H)
Ethambutol (RIF, R) Pyrazinamide (PZA,Z) Rifampicin (EMB,E)

The First line Supplementary Drugs

Streptomycin (SM, S)

Second line Essential Drugs

Category Inhibit cell wall synthesis Aminoglycosides Thioamide Ethionamide Action Inhibit Protein synthesis Amikacin Inhibit DNA gyrase

Polypeptide Fluoroquinolones
PAS

capreomycin Ofloxacin, ciprofloxacin

 Drugs which interfere with mycolic acid synthesis Drugs which inhibit nucleic acid synthesis

Drugs inhibiting protein synthesis

Table 1: The drugs and duration of the doses used to treat latent tuberculosis

Drugs

Duration

Interval

Minimum doses

Isoniazid
Isoniazid Isoniazid and Rifapentine Rifampin

9 months
6 months 3 months 4 months

Daily
Twice weekly* Daily Twice weekly* Once weekly* Daily

270
76 180 52 12 120

*used directly observed therapy (DOT) (http://www.cdc.gov/tb/topic/treatment/ltbi.htm)

Highest ++++

High +++

Intermediate ++

Low +

First Line Drugs

High efficacy, low toxicity. Always used in combination.

Bactericidal for rapid multipliers Bacteriostatic for dormant bacteria Effective against intracellular & extracellular M.

tuberculosis Combination with other drugs can combat bacterial drug resistance

Mycolate depleted cell walls structurally weak

 Used specifically as a TB treatment Used during first two months of antibiotic therapy to enhance the efficiency of the antibiotic therapy Always used with isoniazid and rifampicin Bacteriostatic & bactericidal effect Well absorbed from GI tract and can penetrate into cerebrospinal fluid Partially metabolised in liver

Converted into pyrazinoic acid by bacterial pyrazinamidase Acid accumulates inside the bacteria (acidic pH) Inhibits the fatty acid synthesis in bacteria Disturbs bacteria cell membrane &energy production Approximately 70% of an oral dose is excreted in the urine

 Used for drug resistance Affects for growing bacteria Disturbs for the formation of bacteria cell

wall
Well absorbed from GI tract Excreted in urine and faeces

Inhibit mycobacterial Arabinosyl transferases Inhibit polymerizasion of arabinoglucans Inhibit cell wall formation Inhibit bacterial growth

 Resistance

Results from an alteration in the polymerase enzyme (mutation in the rpoB gene). Semi-synthetic derivative of one of the rifamycins, a group of complex macrocyclic antibiotics. agent

It is also considered the most important and potent antituberculosis Like isoniazid it is bactericidal and highly effective.

Category Absorption Distribution

Explanation Well absorbed from the GI tract -80% bound to plasma protein. -half life: 2-5 hour -Widely distributed throughout the body including the CNS. In the liver

Metabolism

Excretion

About 1/3 of the drug is excreted in urine, and 2/3 in the intestine. Adjust dose with decreased liver function.

Antiarrhythmic ( i.e quinidine) Anticoagulants (i.e warfarin) Oral hypoglycemic Antiepileptics Antifungals (i.e ketoconazole) Antivirals Oral contraceptive- alternative method

necessary Thyroxine

 Aminoglycoside antibiotic Source: Streptomyces griseus Bactericidal against the extracellular tuberculosis bacilli.

Overall only suppressive

Resistance: Combination therapy will delay or prevent resistance.

Category Absorption

Explanation Well absorbed by Intramuscular and intravenous.

Distribution

Metabolism

-extracellular fluid -34% bound to plasma protein. -half life: 4 -10 hour (Infant), 2-4 (adults) -cross placenta- enter milk Does not well metabolise.

Excretion

-90% in urine - <1%: faeces, saliva, sweat and tears.

Drugs Isoniazid Rifampin Pyrazinamide Streptomycin Ethambutol

Significant side effects Hepatotoxicity, peripheral neuropathy Gastrointestinal upset, hepatitis hepatotoxicity Ototoxity, Renal toxicity Retrobulbar optic neuritis

1. Skin tests (Tuberculin) detect whether body

had been exposed to TB

Used in high risk populations or in people who

may have been exposed to TB such as health care workers Vital for prevention of mycobacterium tuberculosis

2. BCG (Bacillus Calmete Guerin) vaccination

Live attenuated vaccine- derived from the bovine strain of tuberculosis

bacteria (mycobacterium bovis)

inducing an artificial primary infection leads to stimulation of acquired

resistance to possible successive infections with virulent bacilli Recommended for:

a) b) c)

Babies Older children and adults ( <35 years) High-risk occupation

Disadvantages:
Effectiveness of the vaccine is LIMITED especially in adults

3. Ventilation of the room to reduce concentration of aerosolized droplet nuclei 4. Prevent spread from those infected with pulmonary tuberculosis -Isolation from crowded areas 5. Usage of protective measures-masks, gloves 6. Implementation of education programs to educate people about transmission and methods of prevention

5. Practice of several measure to eliminate the conditions that can increase the risk of infection Wearing mask Avoid spending long time in stuffy area with infected patients 6. Implementation of education programs Educate people about the transmission and methods of prevention

REFERENCES

Carroll, N. M., Uys, P., Hesseling, A., Lawrence, K., Pheiffer, C.,

Salker, F., .Helden, P. D. (2008). Prediction of delayed treatment response in pulmonary tuberculosis: Use of time to positivity values of Bactec cultures. Tuberculosis, 88(6), 624-630.
Parsyan, A. E., Saukkonen, J., Barry, M. A., Sharnprapai, S., &

Horsburgh Jr, C. R. (2007). Predictors of failure to complete treatment for latent tuberculosis infection. Journal of Infection, 54(3), 262-266.
Robertson, B. D., Altmann, D., Barry, C., Bishai, B., Cole, S.,

Thomas, D., Young, D. (2012). Detection and treatment of subclinical tuberculosis. Tuberculosis, 92(6), 447-452.