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TB
Exam 2 study guide
75
Pharmacology
Graduate
02/26/2012

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Cards

Term
What bacteria causes TB?
Definition
Mycobacterium Tuberculosis
Term
What stain are used to identify TB pathogen?
Definition

Ziehl Neelsen and fluorochrome stain

Acid-fast for bacilli

Grow slowly when cultured 

Term
What is the most common agar method?
Definition
Proportional method 
Term
What are other tests for TB?
Definition

BACTEC: takes 9-14 days and give a quantitative measure (MIC)

Rapid identification tests: use technique like PCR, high performance liquid chromatography(HLPC)

Genetic changes associated w/ resistance to particular drugs 

Term
What is the name of the particles from an infected person?
Definition
Droplet nuclei 
Term
What are the 3 factors that the progression of disease depends on?
Definition

1) number of organism inhaled

2) virulence of the organism

3) host's immune response

Term
T/F: At alveolar surface the bacteria are consumed by the pulmonary macrophages?
Definition
True, an eating, releasing, and multiplying process continues until the body can form a more coordinated response 
Term
Where can the bacteria be found other then the alveolar?
Definition

Some macrophages carry replicating bacteria to the lymph nodes

Some bacteria travel to the bloodstream: from here they can travel and infect any area of the body 

Term
In what region is the M. tuberculosis most happy?
Definition
In the posterior apical region of the lungs, where most oxygen is and immune system can't get in. 
Term
What happens after 3 weeks of invasion?
Definition

Cell mediated immunity begins

Macrophages from granulomas to contain organism 

Replication begins to slow 

Term
What happen after 1-3 months?
Definition

Most bacteria are now within the granulomas 

Tissue hypersensitivity occurs: this is characterized by a + TB skin test 

Term
What percentage have no further progression?
Definition
90%
Term
What percentage have progression to active disease?
Definition

10%

1/2 occurs in the first 2 yrs of infection

Term
When does reactivation of the disease occur?
Definition
Reactivation occurs in the apices of the lungs. The organisms are in the granulomas surface and begin to replicate, the immune response is reactivated and causes the existing granulomas to liquefy and create a hole in the lungs via necrosis. Bacteria can be transmitted to others during this time 
Term
What are rare forms of TB?
Definition

1) Miliary TB: when a large amount of bacteria enter the bloodstream at once (rapidly progresses to death)

2) Extrapulmonary TB: when liquefied granulomas occur at locations other than the lungs (difficult to diagnose), most common locations  lymphatic and pleural locations 

Term
What is MDR?
Definition

Multi drug resistant TB
Term
T/F: key to a succesful treatment is to use one drug and add one drug at a time to regimen?
Definition
False, Never do that 
Term
What is XDR?
Definition

Extensively drug resistant TB

Resistant to : rifampin, isoniazid, A FQ, one 2nd line injectable drug such as amikacin, capreomycin or kanamycin

Term
What are S & S of TB?
Definition
Weight loss, productive cough, frank hemoptysis (3 most common), fatigue, fever, night sweats 
Term
Which WBC predominate in TB?
Definition
Lymphocyte 
Term
How does an extrapulmonary TB presents?
Definition
As slow, progressive loss of organ function
Term
What do we call an infection of the spine?
Definition
Potts disease 
Term
TB in children?
Definition

Involves lower and middle lobes

Extrapulmonary TB in the lymph nodes, GI tract, genitourinary tract, bone marrow, and meninges is common. (rapidly fatal)

Term
What is the most common sign of Elderly TB?
Definition
Mental confusion
Term
What is the preffered skin test for TB?
Definition

Mantoux test 

It uses tuberculin purified protein derivative (PPD), 5 unit inserted intercutaneously on the volar aspect of the forearm

Term
A reaction of ≥ 10mm of induration occur in what patient population?
Definition
Pts w/ silicosis, DM, chronic renal failure, some hematologic disorders, maligancies, weight loss ≥10% of IBW, gastrectomy, jejunoileal bypass. Residents or employees of prisons, LTC facilities, hospitals, homeless shelters. Recent immigrants from high prevalence contries. Mycobateriology lab personnel. Injection drug users. All children < 4 yrs, children <4 &<18 who were exposed to adults at high risk
Term
T/F: Persons w/ no risk factors for TB get a reaction ≥ 15 mm of induration?
Definition
True 
Term
T/F: A diabetic patient w/ no risk factors w/ a PPD induration of 11 mm is considered a positive result?
Definition
True 
Term
T/F: COPD but no other risk factors w/ a PPD induration?
Definition
False, because COPD is not a risk factor 
Term
Other TB tests?
Definition
—Interferon gamma release assays (IGRA): Measures release of INF-γ in whole blood in response to TB antigens
—QuantiFERON-TB Gold test (GFT-G): ELISA test approved in 2005
—T-SPOT.TB: Enzyme linked immunospot (ELISPOT) assay approved in 2008
—GFT-G & T-SPOT.TB: Results available in <24 hr. Unable to differentiate between active and latent TB
Term
What is a radiodense area on a chest X-Ray called?
Definition
Ghon complex 
Term
What are primary goals of TB TX?
Definition

Quick identification

Start specific TB therapy

Resolve signs and symptoms

REach non-infectious state

Adherence to drug regimen

Cure patient, Minimize transmission

Term
What are First line treatment of TB?
Definition

RIPE:

Rifampin (RIF)or rifabutin or rifapentine

Isoniazid (INH)

Pyrazinamide (PZA)

Ethambutol (EMB)

Term
What are 2nd line agents?
Definition
Ethionamide, Levofloxacin, Cycloserine, Streptomycin, Amikacin, Kanamycin, Capreomycin, p-aminosalicylic acid (PAS), Moxifloxacin, Gatifloxacin 
Term
ADE of isoniazid?
Definition
Hepatotoxicity, neurotoxicity
Term
Which Vitamin should be used with isoniazid to decrease chance of CNS effects and peripheral neuropathy?
Definition

Pyridoxine (B6) 10-50 mg 

Pts who are pregnant, alcoholics, or have a poor diet need to supplement with B6 

Term
What are DDI with isoniazid?
Definition

Inhibits metabolism of phenytoin, carbamazapine, primidone, warfarin 

Seprate dose from antacids for 2 hrs 

(take isoniazid on empty stomach)

Term
Isoniazid resistance results from mutations in which genes?
Definition
KatG or inhA genes 
Term
What are SE of rifampin (PO, 30 min IV infusion)?
Definition

Common SE: rash, fever, GI upset

Rare SE: Rash associated with flu-like syndrome, hemolytic anemia or acute renal failure 

May change urine and other secretions orange-red Hepatoxicity

 

 

 

 

 

Term
DDI with rifampin?
Definition

Strong inducer of CYP3A4

Caution w/ protease inhibitors, oral contraceptives 

Term
What is the common site for mutation in rifampin?
Definition
rpoB gene 
Term
Most common side effects of pyrazinamide?
Definition

GI upset, arthralgias, elevations in serum uric acid concentrations (measurement not required)

- Hepatotoxicity (liver test shoud be done)

Occasional SE: Rash and photosensitivity

Term
T/F: Ethambutol can be used with antacids?
Definition
False, avoid use 
Term
What is a major SE of ethambutol?
Definition

Retrobulbar neuritis, characterized by changes in visual acuity and inability to see the color green. Monitor monthly via Snellen wall chart and Ishihara red-green color discrimination card 

Rare SE: peripheral neuritis and rash

Term
What are 1st line combination products?
Definition

Rifater: 120 mg rifampin, 50 mg isoniazid, 300 mg pyrazinamide

Rifamate: 150 mg isoniazid, 300 mg rifampin

Term
What are AMG ADE?
Definition
Nephrotoxicity (caution in renal dysfunction), and ototoxicity 
Term
If resistant to streptomycin what other AMG can be used?
Definition

amikacin and kanamycin 

However, if resistant to amikacin likely resistant to kanamycin

Term
When can we use cycloserine?
Definition

when MDR-TB, take on empty stomack, can cause dose-related CNS toxicity 

Add pyridoxine 50-200 mg QD may help w/ tolerance 

Term
What is a major toxicity with ethionamide?
Definition
GI toxicity, can give at bedtime or w a light snack
Term
What other ADE w/ ethionamide?
Definition

May cause Goiter (more common when combined w/ p-aminosalicylic acid( (w or w/o hypothyroidism)

SE: gynecomastia, alopecia, acne, impotence, menorrhagia, photodermatitis, hypothyroidism. 

Term
T/F: Ethionamide can be used in patients with diabetes?
Definition
False, use cautiously 
Term
What to know about p-aminosalicylic acid?
Definition

Empty granules will appear in the stool 

GI SE common 

Rare effects: hypersensitivity rx, hepatotoxicity, malabsorption syndrome, increased clotting time

may cause goiter 

Term
What are some monitoring parameter done w/ capreomycin (for MDR-TB IV)?
Definition

audiogram, vestibular testing, romberg testing, and SCr done at baseline and every month while on therapy, also K+ and Mg2+

Can cause: nephrotoxicity and ototoxicity

 

Term
Clofazimine?
Definition

Used for MDR-TB

SE: GI upset ans skin discoloration

Rarely may cause severe GI pain due to formation of crystals in the intestines

Term
Quinolone?
Definition

Levo, Cipro, and moxif (PO, IV)

used for MDR-TB 

Term
Cefoxitin?
Definition
used as last line 
Term
Macrolides/azalide?
Definition
Clarith, and azithr have limited activity against M. tuberculosis (rare use)
Term
Extracellular bacteria found within cavities respond to what drugs?
Definition
Isoniazid, rifampin, streptomycin
Term
Bacteria in caseating granulomas responds to?
Definition
Pyrazinamide, rifampin, isoniazid
Term
Bacteria within macrophages responds to?
Definition
Rifampin, isoniazid, quinolones
Term
What is the 1st line therapy for latent TB?
Definition

Isoniazid 300 mg QD or 5-10 mg/kg (children) for 9 months (min 6 months)

Can be dosed 900 mg twice weekly if DOT (directly observed therapyused)

Term
What is 2nd line tx for latent TB?
Definition

Rifampin 600 mg QD for 4 month can be used in case of resistance or person can't tolerate isoniazid 

Rifabutin can be substituted in pts at high risk for drug interactions

Term
What are new latent TB tx options?
Definition
Isoniazid + rifapentine once weekly for 12 weeks has less hepatotoxicity, must use DOT, Expensive 
Term
What is the Standard active TB treatment?
Definition

Isoniazid + rifampin + pyrazinamide + ethambutol (RIPE) for 2 months, Then isoniazid + rifampin for 4 more months

If TB susceptible to "RIP," E can be stopped early 

Term
T/F: Patients who still have positive cultures after 2 months of Tx, pts w/ HIV, and those w/ cavitary lesions on X-ray, must be treated for 9 months and at least 6 months from time they become smear and culture negative?
Definition
True 
Term
T/F: patients who are not susceptible to isoniazid and riampin treatment lasts for a maximum of 2 years?
Definition
False, minimum of 2 years 
Term
What is the treamtent for TB meningitis and extrapulmonary disease?
Definition

Treat for 9-12 months minimum 

Isoniazid, pyrazinamide, ethionamide, cycloserine (best CNS penetration)

Variable CNS penetration: rifampin, ethambutol, streptomycin.

Levo is preferred quinolone 

Soft tissue tx with RIPE

Site is pericarditis or CNS adjunct corticosteroids recommended 

Term
Tx children?
Definition
Isoniazid and rifampin based in weight tx for 9 months
Term
TX Pregnancy?
Definition

Rifampin, isoniazid and ethambutol for 9 month 

B vitamins (B6, folic acid)

Term
TX obesisty?
Definition
Isoniazid, pyrazinamide, AMG, capreomycin, ethanbutol, p-aminosalicylic acid, and cycloserine based in IBW 
Term
T/F: patient with HIV should receive intermittent therapy options?
Definition

False, should not always use daily dose 

Tx for 9 months 

Term
Hepatic failure TX?
Definition

Streptomycin + levo +ethambutol

Tx minimum of 18 months 

typically switched to an isoniazid &/or rifampin when liver gets better 

Term
Renal failure adjustment?
Definition

Pyrazinamide and ethambutol require a frequency reduction 

Dosing interval must be increased w/ amikacin, kanamycin, streptomycin, capreomycin, ethambutol, cycloserine, and levofloxacin 

 

Term
T/F: patients who are acid-fast bacilli smear positive should have sputum samples sent Q 1-2 weeks until 2 consecutive smears are negative?
Definition
True 
Term
Birth defect with some TB meds?
Definition

Rifampin has been associated w/ causing limb reduction and CNS lesions

Streptomycin may lead to hearing loss in child

Ethionamide can cause premature delivery and congenital deformities 

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