WK 5- Tuberculosis and HIV Flashcards
What causes tissue destruction in TB
results from “excessive” cellular immune response (macrophage-derived proteases)→ degrade collagens, elastin, proteoglycans, fibronectin, laminin
How can immunosuppression cause reactivation of TB
Primary infection is usually by inhalation of micro-droplets containing M. tuberculosis→ when inhaled will move to the lungs and be engulfed by pulmonary macrophages→ resistant to macrophage killing so will create a granuloma→ this is what allows for latency (shields off infection) → granulomas can sit in lungs for decades, and when you are exposed to immunosuppressive factors the granulomas can change structure into necrotic granuloma→ granuloma breaks down and releases the MTB
What are the symptoms of TB
weight loss, fatigue, night sweats, cachexia, chest pain, fever, cough with sputum/blood stained sputum
What are the 4 drugs used for the initial HRZE TB regimen
- Isoniazid (INH)
- Rifampin (RIF)
- Pyrazinamide (PZA)
- Ethambutol (EMB)
How often are the HRZE drugs given for
- all four drugs are given for an extended period of time→ multiple agents are given daily for 2 months
- continue to give isoniazid and rifampin for another 4 months to ensure TB is cleared
What drug of the 4 produces peripheral neurotoxicity and what medication is given along with HRZE to reduce this
Isoniazid-> give vitamin B6 to reduce toxicity
What are the specific adverse reactions of Ethambutol (EMB)
Eye damage causes blurred/changed vision, including colour vision
What drugs cause hepatitis as a side effect (what symptoms appear as a result)
- Isoniazid (INH)
- Rifampin (RIF)
- Pyrazinamide (PZA)
- -> cause abdo pain, dark urine, fatigue, lack of appetite, nausea, vomiting, jaundice
What specific drug causes peripheral neuropathy as a side effect
Isoniazid (INH)
What 2 side effects are specific to only Pyrazinamide (PZA)
Stomach upset (vomiting, abdo pain) and increased uric acid (gout, joint aches)
What is Multi-drug resistant TB
-strains of TB are resistant to at least isoniazid and rifampin, the two most potent TB drugs.
What is XDR= extensively drug resistant tuberculosis
rare type of MDR TB that is resistant to isoniazid and rifampin, plus any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin). Because XDR TB is resistant to the most potent TB drugs, patients are left with treatment options that are much less effective.
What can contribute to/cause drug resistant TB
can occur when these drugs are misused or mismanaged. Examples include when patients do not complete their full course of treatment; when health-care providers prescribe the wrong treatment, the wrong dose, or length of time for taking the drugs; when the supply of drugs is not always available; or when the drugs are of poor quality.
How can MDR/XDR be prevented
take all medications as prescribed and for the prescribed time, don’t miss doses, quickly diagnosing cases, avoid contact with known MDR or XDR patients.
Who is the BCG vaccine not recommended for and why
not recommended for infants due to it being a live vaccine→ increased risk of complications
-not shown to be affective
What is the interaction between HIV and TB
ability for co-infection due to diminished immune system, co-infection makes tx more complicated due to resistance and multiple drug use (isoniazide prevention therapy)
What are the 3 pillars of the global TB strategy and what do they involve
→ Integrated, patient-centred TB care and prevention: involves preventative treatment for high risk pt, treatment for all infected people including MDR, early diagnosis, systematic screening of contacts and at risk
→ Bold policies and supportive systems: political commitment with adequate resources for TB care and prevention, engagement of communities, social protection, poverty alleviation
→ Intensified research and innovation: research to optimise implementation and impact and promote innovations, discovery, development and rapid uptake of new tools
What is PMTCT and how can it apply to HIV transmission
-prevention of mother to child transmission
→ can be prevented by giving the mother ART- if viral load is too high, mothers are advised not to breastfeed
-primary prevention of HIV is a key component of preventing HIV transmission→ prevent the mother getting HIV through regular screening, safe sex practice, not sharing needles etc
What are the 3 methods by which HIV can be transmitted from mother to child
- Pregnancy - The chance of HIV being passed from mother-to-child is 15% to 45%
without treatment. With treatment, the risk falls below 5%. - Labor & Delivery – medically assisted delivery can help prevent vertical transmission during labour and delivery
- Breastfeeding – HIV +ve pregnant/ breastfeeding women should be treated with TDF, 3TC or FTC, EFV
What are the 5 classes of drugs used to treat HIV
- nucleoside/tide reverse transcriptase inhibitors
- non-nucleoside reverse transcriptase inhibitors
- HIV-protease inhibitors
- integrase inhibitors
- entry / fusion inhibitors
What is selective toxicity
-effective antimicrobial therapy relies on targeting pathogen-specific processes that do not occur in the host (ie. Targeting bacterial cell wall)
Why is treatment for viral infections delayed slightly
most available antiviral drugs are effective only while the virus is replicating→ treatment is often delayed until the infection is well established
How do nucleotide reverse transcriptase inhibitors (NRTI) work
-once inside cell, is phosphorylated by host cell enzymes to 5’-trisphosphate derivatives and will act as a false substrate→ competes with the natural deoxynucleotides, and will get made into a non-functional nucleoside that will then get taken up into the DNA chain→ don’t have 3-hydroxyl group, meaning next nucleotide group cannot bind, resulting in chain termination
What are the adverse effects of NRTI’s
DNA polymerase (makes DNA from RNA) is also inhibited→ cells naturally use this enzyme but at a lower affinity→ toxic to mitochondrial DNA polymerase gamma→ cells are not able to repair self as well→ can cause redistribution of fat (lipoatrophy) and lactic acidosis
