HCP 9: Regal Domalagang Tuberculosis

Question 1

What is the MOA of Robitussin DM?

When is it used?

Answer 1

Dextramethorphan: Non-competitively antagonizes NMDA receptor in brain/spinal cord
Decrease activation of cough center (NTS)
Cough suppression (anti-tussive effect)
Guafenesin: Decrease adhesiveness/surface tension of mucous secretions
Promot ciliary action
Increase secretion clearance (expectorant)
ONLY USED TO TREAT COUGH DUE TO THROAT IRRITATION, NOT smoking/COPD

Question 2

Who gets screened for PPD?

Answer 2

Those at increased risk (close contact, immigrant from TB-endemic regions), HIV, immunosuppressed, smokers, drug abusers, recent transplant

Question 3

What is a PPD?

Answer 3

Purified protein derivative intradermal injection that measures delayed-type hypersensitivity & read induration (not erythema)
+ means that PAST infection, NOT necessarily ACTIVE TB
Expose to protein-antigen
APC phagocytose and present to memory T cells
CD4 activated
Differentiated into TH1 & TH17 effects cells that secrete cytokines -> inflamm.

Question 4

Why do we use a 2 step PPD?

Answer 4

Used for those re-tested periodically

Reduces likelihood that misinterpreted for false negative

Question 5

What can cause false positives in PPD?

Answer 5

Infection of non-TB mycobacterium
Prior BCG vaccination (not used in US)
Improper administration/interpretation/antigen

Question 6

What can cause false negatives in PPD?

Answer 6

Recent infection
Very old TB
Young (<6 months)
Anergy

Question 7

What is anergy?

Answer 7

Inability of lymphocytes to respond to antigen due to weakened immune system, so PPD may result in false negative
If inhibitory receptor engaged during co-stimulation or co-stimulatory signals not delivered
+ anergy panel = immune system in tact, so PPD is true negative

Question 8

What is the Xpert MTB/RIF?

Answer 8

Simultaneously detects presence of MTB & RIF resistance in <2 hr. by collecting sputum, mixing w/ reagent - the rest is automated
Advantages: Fast, more specific/sensitive, can simultaneously id Abx resistance, less training for personnel
Disadvantage: expensive
*SHOULD STILL perform acid fast stain/culture

Question 9

What is the Acid fast stain/culture?

Answer 9

Bacteria testing for are mycobacterium, some Actinomyces, Nocardia
Stain/Smear= red to bright pink against blue
Traditionally used Ziehl-Neelson dye
Disadvantages: Time, Low sensitivity, trained eye to identify
Culture takes even longer to grow (4-8 weeks) but is the “Gold standard”

Question 10

What is the MOA of imipenem/cilistatin?

When is it used?

Answer 10

Cilistatin prevents degradation of imipenem by competitively inhibiting dihydropeptidase I on renal tubule brush border
Imipenem binds to PBP to inhibits final step of cell wall synthesis (transpeptidation), inhibit cross-linking of cell wall, bacterial cell death
EMPIRICAL THERAPY: “Atomic bomb”

Question 11

What are some identifying factors of Mycobacterium tuberculosis?

Answer 11

Neither Gram + or -
Acid-fast
Rod-shaped
Non-motile
Obligate anaerobe
Catalase +
Non-spore forming
Grows at 37C but not body temp
Slow growing

Question 12

What are some virulence factors for MTB?

Answer 12

Mycolic acid: unique large FA, inhibit complement activity
LAM: inactivates macrophages
Cord factor: only in VIRULENT strains, allows for serpentine-like growth (stimulate TNF release, inhibit neutrophil migration)
Sulfatides-inhibit phagosome fusion w/ lysosome (contains bacteriocidal enzymes)
Wax D-enhance Ab formation to antigen
Phthiocerol Dimycocerosate - necessary for pathogen in lungs

Question 13

How is MTB transmitted?

Pathogenesis?

Answer 13

Respiratory aerosols ( Healed lesion -> +PPD

• Reactivation -> 2* TB
• Liquefaction & release bacilli-> cough/into blood (military TB)

Question 14

What are the first line drugs for treating TB?

Answer 14

Isoniazid, rifampin, ethambutol, streptomycin, & pyrazinamide. Used in combo bc high resistance to drugs.

Question 15

What should you have supplemental pyridine (vitamin B6) on isoniazid?

Answer 15

One of the main side effects is peripheral neuropathy, which is caused by drug stimulating pyroxidine excretion -> deficiency.
Isoniazid also known for hepatotoxicity.

Question 16

Why would someone need higher doses of opioid analgesics while on rifampin?

Answer 16

RIF induces hepatic P450 enzymes, including those that metabolize opioids

Question 17

What causes orange urine?

Answer 17

Rifampin

Question 18

What causes vision problems?

Answer 18

Ethambutol (decreased visual acuity & green/red color blindness)

Question 19

What is the standard treatment regimen so long?

Answer 19

1. Intracellular location (difficult to get to)
2. Bacillus often in large cavities w/ avascular centers (don’t penetrate well)
3. Slow generation time

Question 20

Is cell-mediated or humoral immunity more important for fighting TB?

Answer 20

Cell-mediated bc bacillus resides intracellularly & cell-mediated targets intracellular pathogens

Question 21

Why is reactivation TB more likely to occur in apical lungs rather than lower lobes?

Answer 21

Obligate aerobes & higher O2 tension in apex of lung facilities growth (but primary infection more likely to occur in lower segments where bacteria initially deposited)

Question 22

What is the MOA of Rifampin?

Side effects?

Answer 22

Binds to B-subunit of DNA-dependent RNA polymerase (w/o binding to eukaryotic)
Inhibit RNA transcription
Bacteriostatic
SIDE EFFECT: orange urine, LFTs, rash, nausea, vomiting

Question 23

What is the MOA of Isoniazid?

Side effects?

Answer 23

Activated by mycobacterial catalase peroxidase (KatG)
Inhibit long-chain enoyl reductase (Inh)
Inhibit mycolic acid synthesis
Inhibit cell wall synthesis
Apoptosis
SIDE EFFECTS: hepatotoxicity, peripheral neuropathy

Question 24

What is the MOA of Ethambutol?

Side effects?

Answer 24

Inhibit arabinosyl transferase
Decrease synthesis of arabinogalactan
Decrease covalent linking of mycolic acid to cell wall
Increase cell permeability
Increase susceptibility to other drugs
SIDE EFFECTS: optic neuropathy (decrease visual acuity, red/green color blindness)

Question 25

What is the MOA of pyrazinamide?

Side effects?

Answer 25

Only works in acidic conditions (granuloma)
Prodrug that’s activated by pyrazinamidase secreted by Mtb
Converted to pyrazanoic acid
Diffuses out of Mtb & protonated (more lipid-soluble)
Re-enters Mtb
Inhibits mycobacterial FA synthase I
Decrease mycolic acid synthesis
Decrease cell wall synthesis
Disrupt membrane transport

Question 26

What is the immunopathology of TB?

Answer 26

Majority of TB expelled by cilia, but MTB killing
Activated macrophages release TNF
Recruit monocytes
Differentiate into epithelioid histiocytes
Fusion -> giant Langhans cells (granuloma)
Localized caseation

Question 27

What is the proper protocol of reporting TB to DOH?

Answer 27

HI has one of highest annual TB cases in US due to immigration
Report when:
-+AFB smear (& suspicion)
-+ result from rapid diagnosis test (Xpert)
-+ culture
-Pathology/autopsy consistent
-Clinical suspicion such that airborne isolation initiated

Needs to be done w/in 24 hr of diagnosis

Question 28

What is a surveillance program?

Answer 28

After TB case confirmed, screen patient’s contacts with risk assessment
-Lanakila Health Center

Question 29

What are the 4 major types of isolation?

Answer 29

4 types:

1. Standard (universal) - PPE, hand hygiene, soiled patient-care equipment, environmental control, textiles/laundry, needles/sharps
2. Airborne: patient has separate entrance, isolation room (negative pressure), respirator mask (workers), PPE, hand hygiene - MTB, rubeola, varicella
3. Droplet: individual room w/ closed door
4. Contact: Individual room/bathroom