HCP 9: Regal Domalagang Tuberculosis Flashcards
What is the MOA of Robitussin DM?
When is it used?
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
Who gets screened for PPD?
Those at increased risk (close contact, immigrant from TB-endemic regions), HIV, immunosuppressed, smokers, drug abusers, recent transplant
What is a PPD?
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.
Why do we use a 2 step PPD?
Used for those re-tested periodically
Reduces likelihood that misinterpreted for false negative
What can cause false positives in PPD?
Infection of non-TB mycobacterium
Prior BCG vaccination (not used in US)
Improper administration/interpretation/antigen
What can cause false negatives in PPD?
Recent infection
Very old TB
Young (<6 months)
Anergy
What is anergy?
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
What is the Xpert MTB/RIF?
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
What is the Acid fast stain/culture?
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”
What is the MOA of imipenem/cilistatin?
When is it used?
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”
What are some identifying factors of Mycobacterium tuberculosis?
Neither Gram + or - Acid-fast Rod-shaped Non-motile Obligate anaerobe Catalase + Non-spore forming Grows at 37C but not body temp Slow growing
What are some virulence factors for MTB?
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
How is MTB transmitted?
Pathogenesis?
Respiratory aerosols ( Healed lesion -> +PPD
- Reactivation -> 2* TB
- Liquefaction & release bacilli-> cough/into blood (military TB)
What are the first line drugs for treating TB?
Isoniazid, rifampin, ethambutol, streptomycin, & pyrazinamide. Used in combo bc high resistance to drugs.
What should you have supplemental pyridine (vitamin B6) on isoniazid?
One of the main side effects is peripheral neuropathy, which is caused by drug stimulating pyroxidine excretion -> deficiency.
Isoniazid also known for hepatotoxicity.
Why would someone need higher doses of opioid analgesics while on rifampin?
RIF induces hepatic P450 enzymes, including those that metabolize opioids
What causes orange urine?
Rifampin
What causes vision problems?
Ethambutol (decreased visual acuity & green/red color blindness)
What is the standard treatment regimen so long?
- Intracellular location (difficult to get to)
- Bacillus often in large cavities w/ avascular centers (don’t penetrate well)
- Slow generation time
Is cell-mediated or humoral immunity more important for fighting TB?
Cell-mediated bc bacillus resides intracellularly & cell-mediated targets intracellular pathogens
Why is reactivation TB more likely to occur in apical lungs rather than lower lobes?
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)
What is the MOA of Rifampin?
Side effects?
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
What is the MOA of Isoniazid?
Side effects?
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
What is the MOA of Ethambutol?
Side effects?
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)
