Pharm Test 5 Antimycobacterial Agents

Front 1

How you getTuberculosis

Back 1

A person may contact pulmonary tuberculosis from inhaling droplets from a cough or sneeze by an infected person.

Front 2

Droplet/Contact Precaustion

Back 2

Wear N95 respiratory protection, gown, gloves, wash hand before entering and before exiting, and eye protection.

Front 3

Micobacteria

Back 3

Slow growing microbes

Infections require prolonged treatment

Prolonged therapy leads to drug toxicity, poor patient compliance with treatment, and the emergence of drug-resistant mycobacteria

Drug therapy 6 months: first 2 months- 4 drugs

last 4 months- 2 drugs

Front 4

Tuberculosis

Back 4

2 billion infected worldwide

About 2 million die each year from TB (more than any other infectious disease)

US cases have declined but new cases are on the rise everywhere else.

US: 9-14 million have latent TB

9 million new cases each year, most in developing countries.

Reasons for AIDs with compromised immune system, increased incidence of crowded living conditions in urban areas, and multidrug-resistant mycobacteria

Front 5

Those susceptible to TB

Back 5

Alcohol addiction, debilitative condition, and AIDs

Front 6

Tuberculosis

Back 6

Caused by acid-fast bacillus Mycobacgterium tuberculosis or tubercle bacillus

Transmitted from one person to another by droplets dispersed in air through coughing and sneezing.

The tubercle bacilli are inhaled into the alveoli and can migrate to other organs via the blood and lymphatic system

If body's immune system is strong, phagocytes will stop the multiplication of the tubercle bacilli and the spread.

Front 7

Systems of active TB

Back 7

Anorexia and weight loss, cough and sputum production, increased fever, night sweats, positive acid-fast bacilli in the sputum, and in most cases, the bacteria lie dormant and the infected person has no symptoms

Front 8

Diagnosis of TB

Back 8

Sputum evaluation: microscopic smear and culture

Chest X-Ray

Front 9

Testing for Latent TB

Back 9

Tubercle bacilli that are present, lying dormant, but giving no evidence of signs and symptoms. Those who have had contact with TB patients: Residents and staff of high-risk populations like prisons, nursing homes, hospitals, homeless shelter, residental facillities for AIDs patients should all get tested for TB

Front 10

Who should be tested for Latent TB

Back 10

Persons that have immigrated within the last 5 years from a country where TB is prevalent, staff of mycobacteriology labs, children and adolescents exposed to high-risk adults, and children under the age of 4.

Those at high risk of progression from latent to active TB, HIV infected persons, IV drug abusers, patients on immunosuppressive drugs for 1 month or more, patients with high-risk medical conditions like diabetes, chronic renal failure, leukemia, lymphoma, clinical conditions associated with weight loss, intestinal bypass surgery, chronic peptic ulcer disease, malabsorption syndromes, cancer of oropharynx & upper GI tract, any disorder that inhibits nutritional intake.

Front 11

How to test for latent TB

Back 11

Tubercullin skin test purified protein derivative (PPD)- an antigen derived from M. Tuberculosis. If individual has an intact immune system and has been exposed to M. tuberculosis, the PPD will elicit a local immune response: a region of induration (hardness) around injection site within 48-72 hours. Before starting treatment for latent TB, you must rule out active TB with sputum and chest X-ray. Active TB requires multi-drug treatment to prevent resistance; latent TB can be treated with one or two medications.

Front 12

Treating TB

Back 12

Drug resistance: some bacilli are resistant to just one drug; others to multiple drugs. Infection with a resistant organism may be acquired through: contact with person who harbors a resistant bacillus and repeated ineffectual course of therapy

Front 13

The problem of multi-drug resistance

Back 13

Increases risk of death from TB (especially among AIDs patients). Cost of treating multi-drug resistant TB is $180,000 compared to $12,000 for nonresistant TB.

Front 14

Treatment of Latent TB

Back 14

Drug combinations decrease risk of resistance. Drug combinations decrease incidence of relapse. Isoniazid and Rifampin are very effective against actively dividing bacilli. Pyrazinamide most active against intracellular, quiescent bacilli. By using combinations of these drugs, we increase chances of killing all bacilli, whether they increase chances of killing all bacilli, whether they are actively multiplying or dormant.

Front 15

Treatment for active TB

Back 15

Usually initiated with a Four-drug regimen:

Isoniazid and rifampin with pyrazinamide and ethambutol. Treatment includes an initial phase (induction) to eliminate actively dividing bacilli (2 months long) and then a second phase to eliminate "persisters" (4 months) with the 2 drugs isoniazid and rifampin.

Front 16

Treatment for multi-drug resistant TB

Back 16

Treatment requires at least 3 drugs (maybe 5, 6, or 7) and should continue for 12 to 24 months after sputum converts to normal.

Front 17

Isoniazid (INH) Laniazid, Nydrazid

Back 17

Primary agent for treatment and prophylaxis of TB. Inhibits mycolic acid which necessary for building the mycobacterial cell wall. Bactericidal to mycobacteria that are actively dividing. Given PO or IM.

Front 18

Adverse Effects of Isoniazid (INH) Laniazid, Nydrazid

Back 18

Peripheral neuropathy: paresthesis (tingling, numbness, burning, pain in hands and feet) clumsiness, unsteadiness and muscle aches also occur (happens because INH induces a deficiency in pyridoxine, vitamin B12). May need to supplement with Vitamin B6 (50-200 mg daily).

Hepatotoxicity due to production of a toxic metabolite; see in older population.

Optic neuritis: blurred vision, constriction of visual field, disturbance of color discrimination "report any visual changes". Anemia.

Front 19

INH: Drug interactions

Back 19

Phenytoin (Dilantin): INH can interfere with metabolism of phenytoin causing phenytoid to accumulate to toxic levels. Concurrent use of alcohol, rifampin, & pyrazinamide increase risk of hepatotoxicity.

Front 20

INH: Teach patients to . . .

Back 20

Be seen by MD if s/s of hepatitis: anorexia, fatigue, nausea, yellowing of skin or eyes- jaundice. Have serum aspartate aminotransferase (AST) levels drawn monthly. Take Vitamin B6.

Front 21

Rifampin (Rifadin)

Back 21

Broad spectrum antibiotic; inhibits protein synthesis of bacilli-bacteriocidal. Best absorbed on empty stomach; given PO. Eliminated by hepatic metabolism; is a powerful inducer of P450 enzymes and can decrease levels of many other drugs. Uses: Tuberculosis, Leprosy, Haemophilus influenzae, Legionella.

Front 22

Adverse Effects of Rifampin (Rifadin)

Back 22

Hepatotoxicity & Hepatitis (see MD if symptoms: check liver enzymes, avoid alcoho & hepatoxic drugs. Discoloration of body fluids: red-orange color to urine, sweat, saliva, tears, staining of soft contact lens.

Front 23

Rifampin Interactions

Back 23

Through enzyme induction, may reduce effects of oral contraceptives, warfarin portease inhibitors and non-nucleoside reverse transcriptase inhibitors. Coumadin dose may need to be increased. Women should use a non-hormonal form of birth control.

Front 24

Ethambutol (Myambutol)

Back 24

Bacteriostatic.

Uses: TB (active against bacilli that are resistant to INH & rifampin; must use with other anti-tubercullar drugs.

Front 25

Ethambutol Adverse Effects

Back 25

Optic neuritis: blurred vision, constriction of visual field, disturbance of color discrimination "report any visual changes"

Allergy, hyperuricemia; gout, Make take with food if GI upset occurs.

Front 26

Pyrazinamide

Back 26

Used in combination therapy.

Adverse Effects: Hepatotoxicity- monitor Aspartate aminotransferase (ALT) levels and alanine aminotransferase (ALT) levels; s/s of hepatitis; use with caution in patients taking other hepatotoxic drugs or alcohol.