Chapter 18. Anti-Tb And Anti-Leprosy Antibiotics

Front 1

Treatment of Tuberculosis (1st-line, and side effects)

Back 1

1st line drugs in order of use:

Isoniazid (INH) "I SAW A... Rifampin "RED" Pyrazinamide "PYRE BURNING THE LIVER."

ES (Ethambutol and Streptomycin)

RIP | ES "RIPES" works too.

Since I saw a red Pyre burning the liver, these first-line agents can cause liver damage.

Front 2

2 types of TB populations that you will treat

Back 2

1. Those with active tuberculosis
2. Those with a reactive PPD skin test, representing a latent infection

Front 3

Tx.of active Tuberculosis

Back 3

6 month regimin-->2 months of isoniazid, rifampin, and pyrazinamide + 4 mos. isoniazid and rifampin

9-monh regimin-->9 months of isoniazid and rifampin.

Pyrazinamide is in the shorter treatment regimin, and is rapidly bacteriocidal to M. TB, but if used longer than 2 months, then risk of liver toxicity too high! "LIVER ON PYRE!"

Front 4

Tx. of those witha positive PPD skin test

Back 4

Preventative tx. is initiated in case they are in latency.

Isoniazid is used alone 6-12 months (prophylaxis), but rifampin +pyrazinamide for 2 months may be just as effective.

Balance risk of developing isoniazid-induced liver injury with the with the risk of reactivation TB.

Front 5

Factors that increase the risk of reactivation TB include:

Back 5

1. recent PPD conversion
2. having fibrotic scars on chest x-ray
3. exposure to household members with active TB
4. Being immunosuppressed.

Front 6

Differences in treatment between high/low TB-activation risk groups?

Back 6

Greatest risk of activation (PPD>5mm)
1. HIV infxn
2. Fibrotic changes on CXR
3. Close contacts with newly diagnosed active TB. in case # 3 tx for 3 mos. is needed even if PPD is negative.

MODERATE RISK (any age if PPD is >10mm

1. persons with med conditions (diabetes, prolonged steroid tx., renal failure) that lower the immune system.
2. Persons with recent skin test conversion within the last 2 years
3. Persons who inject drugs

LESS RISK: Patients if age <35 and PD >10mm:

High-risk populations such as homeless, residents of long-term care facilities, prisons/nursing homes, foreign born etc)

LOWEST RISK:

Tx. at physician's discretion if age <35. A person with no known risk factors and a PPD >15 mm.

Front 7

Resistance to Isoniazid (INH)

Back 7

Suspected of asians/africans/south americans, homeless person's, and patients who have sputum cultures that remain positive after 2 months of tx.

1. Culture susceptibility testing should follow the tx. initiation
2.If resistance is suspected, 4 or more 1st-line drugs should be used (INH, rifampin, pyrazinamide, ethambutol, or streptomycin-->RIPES)
3. If resistance develops, never add a single new antibiotic, always add two.

Front 8

What is a common strategy that is used to prevent multiply resistant M. tuberculosis strains from developing?

Back 8

DOT (Directly observed therapy)

Front 9

Anti-TB antibiotics: (Isoniazid, Rifampin, and Pyrazinamide)= RIP

side effects, absorption, distribution

Back 9

1. all cause hepatotoxicity--> patients must understand the symptoms of hepatitis and rpeort to physician immediately if they develop.

Mild elevations of liver enzymes can be expected to occur in 15-20% of patients on isoniazid, but should these levels exceed 3-5x the upper limit of normal, the drugs should be discontinued.

2. All are absorbed early: this is important since they must be adminsitered for 6-9 months. They must be orally absorbed!!!!!

3. All penetrate into most tissues-->and into the center of caseous granulomas.

Front 10

Isoniazid (INH)

Mechanism of action.

Back 10

Great drug! It's inexpensive, absorbed orally, and bacteriocidal. Were it not for the toxicity it would be perfect.

INH interferes with the biosynthesis of the mycolic acid component of the cell wall of the mycobacteria.

Front 11

Adverse effects of Isoniazid (INH)

Back 11

1. Hepatotoxicity

2. INH increases urinary excretion and depletion of pyridoxine (B6) which is needed for proper nerve function.

INH-->decreased B6 levels -->pellagra (peripheral neuropathy, rash anemia.)

B6 vitamins often coadministered with INH.

Front 12

Rifampin

Back 12

("Red") Think Rifampin:

1. Red: Body fluids such as urine, feces, salive, sweat, and tears are colored bright red-orange by rifampin. Not harmful, inform patient.
2. "R"NA: Rifampin inhibits the DNA-dependent RNA polymerase of the M. tuberculosis bugs.

Front 13

Adverse effects of Rifampin

Back 13

1. Hepatitis (must less than INH)
2. Rifampin induces cytochrome P450 enzyme system (microsomal oxidase system, or MOS). Overactive P450 gobbles up other drugs the patient is taking faster (increased half lives)

This can affect:
a. coumadin (anticoagulant)
b. oral contraceptives
c. oral hypoglycemics and corticosteroids
d. anticonvulsants such as phenytoin

Front 14

Rifabutin

Back 14

Similar to rifampin in structure, antibacterial activity, metabolism, and adverse reactions. Commonly used to treat mycobacterium avium intracellulare (MAI)-->MAI > sensitive to rifabutin than rifampin.

Front 15

Pyrazinamide

Mechanism and adverse effects

Back 15

The "P" or Ripe. The mechanism is not known, but there are adverse effects:

1. hepatotoxic (no kidding!?)

This medicine is usually given for no more than 2 months to avoid liver toxicity. Avoid in prenancy

Front 16

Ethambutol

Back 16

"Ethane-Butane Torch"

Adverse effects:
Main side effect is dose-dependent, reversible ocular toxicity.
1. Decreased visual acuity (central scotomata)
2. Color vision loss.


Ethambutol is not used in young children because they are not able to report vision deterioration.