Id Therapeutics Exam 2 Set 6

Front 1

Factors which contributed to the resurgence of tuberculosis include (5)

Back 1

1) increased immigration from areas of the world where tuberculosis is endemic;
2) shift in health care focus;
3) increasing numbers of individuals in the lower socioeconomic classes;
4) multi-drug resistant strains of M. tuberculosis;
5) increasing number of immunocompromised individuals, especially HIV-infected

Front 2

Risk factors for infection and development of the disease (7)

Back 2

1. Close contact with individuals with active disease (>40 hours/week)
2. Low socioeconomic class (Crowded living conditions, Homeless shelters,Prisons)
3. Race (Most likely a function of socioeconomic class and immigration history--Caucasian dec. 11.1%; Hispanic inc 4.7%; Asian-Pacific inc. 12%; non-Hispanic black inc. 38%
4. Crowded living conditions (Incidence of tuberculosis in rural areas has remained relatively unchanged while the incidence in urban areas has increased 29% since 1985)
5. Extremes of age
6. Gender (Males are twice as likely to contract tuberculosis than females)
7. HIV/AIDS (Individuals infected with HIV are 113-170 times more likely to develop active disease than HIV negative individuals)

Front 3

sx of TB (9)

Back 3

• Generalized malaise
• Shortness of breath
• Anorexia
• Hemoptysis
• Weight loss
• Productive cough
• Fatigue
• Night sweats
• Fever/chills

Front 4

reading TB skin test

____is considered positive for HIV-infected individuals, patients with a documented recent exposure, or patients with fibrotic lesions on chest x-ray.

Back 4

5 mm or greater

Front 5

reading TB skin test

____ is considered positive for individuals with a recent negative test, infants and children < 4 years of age, or patients with a history of diabetes, gastrectomy, cancer, immunosuppressive therapy, or renal failure.

Back 5

10 mm or greater

Front 6

reading TB skin test

_____ is considered positive for individuals with no other risk factors.

Back 6

15 mm or greater

Front 7

to rule out tuberculosis, ____ sputum collections over _____ days are recommneded

Back 7

3 sputum cultures over 3 days

Front 8

where in the body is this m. tuberculosis?

• Most numerous
• Rapidly growing
• Environment is favorable for growth (high oxygen tension, neutral pH)
• Killed by isoniazid, streptomycin, quinolones, β-lactam/β-lactamase inhibitor combinations, and ethambutol

Back 8

extracellular

Front 9

where in the body is this m. tuberculosis?

• Dormant metabolic state with short periods of growth
• Hypoxic environment with a pH of approximately 5.5
• Pyrazinamide, isoniazid, and rifampin are active in this environment

Back 9

Contained within caseating granulomas

Front 10

where in the body is this m. tuberculosis?

• Generally dormant state
• Acidic environment
• Pyrazinamide, isoniazid, and rifampin are active in this environment

Back 10

Intracellular organisms within macrophages

Front 11

• Bactericidal
• Active against all three subpopulations
• Mechanism of action: inhibits mycolic acid synthesis resulting in loss of acid fastness and disruption of the bacterial cell wall. Active only against actively dividing bacteria.
• Metabolized via hepatic acetylation. Half-life may be prolonged in slow acetylators.
• Toxicity: elevation of liver transaminases within 8-12 weeks (do not d/c until 5x ULN); hepatitis; peripheral neuropathy--supplement with vit B6 10-15 mg QD

Back 11

isoniazid (INH)

Front 12

dose for INH

1. adults
2. children

Back 12

Adult: 5 mg/kg (300 mg ) daily or 15 mg/kg (900 mg) 2-3 times weekly.
Child: 10-20 mg/kg (300 mg) daily or 20-40 mg/kg (900 mg) 2-3 times weekly.

Front 13

• Bactericidal
• Active against all three subpopulations
• Mechanism of action: Suppresses initiation of chain formation for RNA synthesis by inhibiting DNA-dependent RNA polymerase.
• Hepatically metabolized. Inducer of CYP3A and CYP2D6 (DDI!!!!). Metabolite is excreted via bile.
• Toxicity:-Elevation of liver transaminases. ____acts synergistically with INH to produce transaminase elevations (4 times greater risk of elevation when INH and ____are used together); Hepatitis in <1% of patients; Flu-like symptoms; Body fluid discoloration.

Back 13

rifampin** synergy with INH for inc in liver transaminases
rifabutin

Front 14

dose for

rifampin and rifabutin (child and adult)

Back 14

Rifampin
Adult: 10 mg/kg (600 mg) daily or 2-3 times weekly.
Child: 10-20 mg/kg (600 mg) daily or 2-3 times weekly.


Rifabutin
Adult: 5 mg/kg (300 mg) daily or 2-3 times weekly.
Child: 10-20 mg/kg (300 mg) daily or 2-3 times weekly.

Front 15

• Bactericidal
• Most active against bacteria within granulomas and macrophages.
• Mechanism of action is unknown.
• Hydrolyzed in the liver to pyrazinoic acid (active metabolite) and eventually excreted in the urine.
• Toxicity: Hepatotoxicity (not synergistic with INH or RFM); Pyrazinoic acid may compete with uric acid for elimination, resulting in exacerbation of gout; GI disturbances

Back 15

pyrazinimide

Front 16

dose for pyrazinimide for children and adults

Back 16

Adult: 15-30 mg/kg (2 g) daily, 50-70 mg/kg (4 g) 2 times weekly, or 50-70 mg/kg (3 g) 3 times weekly.

Child: 15-30 mg/kg (2 g) daily, 50-70 mg/kg (4 g) 2 times weekly, or 50-70 mg/kg (3 g) 3 times weekly.

Front 17

• Bacteriostatic (bactericidal activity noted with concentrations > 5-10 μg/ml)
• Active against extracellular bacteria.
• Mechanism of action: interferes with bacterial RNA synthesis.
• Metabolized in the liver (50%) and excreted unchanged in the urine (50%).
• Toxicity: Dose-related retrobulbar neuritis. Incidence is ~5% with daily doses of 25 mg/kg and <1% with daily doses of 15 mg/kg. Patients are unable to discriminate between red and green. Avoid use in young children.

Back 17

ethambutol

Front 18

dose for ethambutol

adult and children

Back 18

Adult:15-25 mg/kg (2.5 g) daily, 50 mg/kg (2.5 g) 2 times weekly, or 25-30 mg/kg (2.5 g) 3 times weekly.

Child: 15-25 mg/kg (2.5 g) daily, 50 mg/kg (2.5 g) 2 times weekly, or 25-30 mg/kg (2.5 g) 3 times weekly. Avoid use in children less than 6 years old.

Front 19

second line agents (10)

Back 19

1. amikacin
2. capreomycin
3. ciprofloxacin
4. cycloserine
5. ethionamide
6. kanamycin
7. ofloxacin
8. para-aminosalicylic acid
9. streptomycin
10. moxifloxacin

Front 20

Individuals who should receive prophylaxis
• Persons with a positive PPD who do not have active disease that should be considered candidates for INH preventive therapy regardless of age include:(7)

Back 20

1. Suspected or documented HIV infection
2. Close contacts of persons with newly diagnosed disease. Additionally, children who have been in close contact to an active case should receive prophylaxis regardless of PPD status.

Recent PPD converters.
3. greater 10 mm increase for those less than 35 years.
4. greater than 15 mm increase for those greater 35 years.

Individuals with a PPD less than 10 mm who are:
5. Foreign-born persons from high-prevalence countries (i.e., Latin America, Asia, and Africa)
6. Medically underserved low-income populations including blacks, Hispanics, and Native Americans.
7. Residents and staff of institutions (i.e., correctional facilities, nursing homes, mental institutions)

Front 21

regimen for prophylaxis for TB

dose and duration

Back 21

INH
adults: 300 mg QD
children: 10-15 mg/kg/day

unreliable patients
15 mg/kg twice weekly under DOT

duration:
6 months for individuals with no risk factors
9 months for children
9 months for HIV infected individuals