Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
36 Cards in this Set
- Front
- Back
|
Characteristics of mycobacteria |
Strictly aerobic, acid-fast, bacilli, very slow growing
|
|
|
Virulence factors of M. tuberculosis
|
Cord factor correlates with virulence - inhibits macrophage maturation and induces TNF-alpha release.
Lipids in cell wall required for pathogenesis in lung - mycolic acids, glycolipids, arabinogalactans, free lipids. Resistant to acids and alkalis. Resistant to dehydration - survives in dried sputum. Lives in macrophages' phagosomes. Prevents fusion via PknG |
|
|
Resistance of M. tuberculosis
|
Some strains resistant to Isoniazid and multiple antibiotics. Mutations in mycolic acid synthesis and catalase-peroxidase.
|
|
|
Disease of M. tuberculosis
|
TB - human only. Usually low SES, elderly men.
|
|
|
Ghon complex
|
Parenchymal exudative lesion and draining lymph nodes
|
|
|
Areas of TB lesions
|
Primary = lower lobes.
Reactivation = apices, kidneys, brain, and bone. |
|
|
Immunity to TB
|
Cellular - Th1 helper T-cells and macrophages activated by IFN-gamma. Nramp gene plays role in natural defense.
|
|
|
Clinical features of TB
|
Fever, fatigue, night sweats, weightloss. Cough and hemoptysis.
Scrofula - nontender, unilateral cervical lymphadenitis. Erythema nodosum 90% asymptomatic. |
|
|
Diagnosis of M. tuberculosis
|
*Acid-fast stain*.
Culture on Lowenstein-Jensen agar for up to 8 weeks or in liquid media. Niacin and catalase positive. PCR on sputum. Sensitivity testing by luciferase assay. PPD skin test and IFN-gamma release assay (no false positives with vaccine or other mycobacteria infections) for latent infections. |
|
|
Treatment of TB
|
Isoniazid, rifampin, pyrazinamide
|
|
|
BCG vaccine
|
Partial resistance. Contains live, attenuated M. bovis - bacillus Calmette-Guerin.
|
|
|
First-line therapy for M. tuberculosis
|
Isoniazid + rifampin + pyrazinamide + ethambutol/streptomycin = RIPE
|
|
|
First-line therapy for M. avium complex
|
Clarithromycin + ethambutol/clofazimine/ciprofloxacin/amikacin
|
|
|
Treatment for latent TB infections
|
Isoniazid 9 months
Isoniazid 6 months Isoniazid and rifapentine 3 months Rifampin 4 months |
|
|
MoA of Isoniazid
|
Alters mycolic acid synthesis to prevent cell wall formation
Penetrates host cells. Rapid resistance development. |
|
|
Metabolism of isoniazid
|
Acetylated via N-acetyl transferase. Slow and fast acetylators. Decreased in chronic liver disease.
|
|
|
Adverse effects of isoniazid
|
Peripheral neuropathy - corrected with B6 supplement
Dose-related hepatotoxicity |
|
|
Drug interactions with isoniazid
|
Antacids: decreased absorption.
Corticosteroids: decreased efficacy. Inhibitor of P450. |
|
|
MoA of Rifampin
|
Inhibits DNA-dependent RNA-polymerase by binding beta-subunit.
Rapid resistance development. Works intracellularly |
|
|
Adverse effects of rifampin
|
Orange-red body fluids. Hepatotoxicity & jaundice in susceptible.
GI & nervous system complaints. Fevers, chills, aches. |
|
|
Drug interactions with rifampin
|
Induces cytochrome P450 - HIV PIs and NNRTIs, anticoagulants, oral contraceptives.
Serum level increased by probenecid. |
|
|
MoA of ethambutol
|
Inhibits arabinosyl transferase to disrupt cell wall synthesis
|
|
|
Adverse effects of ethambutol |
Reduce dose with renal dysfunction.
Optic neuritis, reversible and dose-dependent. Hyperuricemia. |
|
|
MoA of pyrazinamide
|
Converted to pyrazinoic acid by bacteria. Drops pH below level needed for growth. Works intracellularly.
|
|
|
Adverse effects of pyrazinamide
|
Hepatotoxicity, dose-dependent. Non-gouty athralgias. Hyperuricemia.
|
|
|
MoA of cycloserine
|
Analog of D-alanine that competitively inhibits two enzymes involved in peptidoglycan and cell wall synthesis.
|
|
|
Adverse effects of cycloserine
|
CNS issues, worse with epilepsy or alcohol usage. Appear in first two weeks. Dose adjustment for renal disease.
|
|
|
MoA of ethionamide |
Analog of isoniazid. Inhibits protein synthesis. Resistance develops easily. Activated by mycobacterial system.
|
|
|
Adverse effects of ethionamide
|
GI disturbance, neurologic (depression, asthenia, blurred vision, diplopia, dizziness), hepatotoxicity.
|
|
|
MoA of capreomycin
|
Unknown. Bacteriostatic. Given IM.
|
|
|
Adverse effects of capreomycin
|
Nephrotoxicity (proteinuria, cylindruria, N retention), ototoxicity.
|
|
|
Risk factors for developing TB
|
Outside of US, alcohol consumption, prison, low SES, malnourishment, HIV & immunosuppressment, elderly.
|
|
|
Pathogenesis of TB
|
oiajsdfoiajsfd
|
|
|
MDR TB
|
Resistance to INH and RIF. AIDS patients.
|
|
|
XDR TB
|
Resistance to INH, RIF, fluoroquinolone, and one other drug.
|
|
|
Length of treatment
|
6-9 months |
