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Pharmacology > Antibiotics 4 > Flashcards

Antibiotics 4 Flashcards

1
Q

What are the 4 medications used to treat tuberculosis?

A
  • isoniazid
  • rifampin
  • pyrazinamide
  • ethambutol
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2
Q

What constitutes a tuberculosis infection?

A
  • presence of organisms which may or may not cause clinically significant disease
  • only evidence of a tuberculosis infection on an X-ray would be a tiny fibrocalcific nodule at the site of infection
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3
Q

How is tuberculosis spread?

A
  • acquired by person-person transmission of airborne droplets or organisms from an active case to a susceptible host
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4
Q

What constitutes a latent tuberculosis infection?

A
  • positive tuberculin skin test - no disease
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5
Q

What constitutes an active tuberculosis infection?

A
  • pulmonary cavitation
  • mycobacteria dissemination
  • presence of bacteria in sputum
  • malaise, anorexia, weight loss, fever
  • increased sputum, at first mucoid and later purulent
  • extra pulmonary effects (liver, bone marrow, spleen, adrenals, meninges, kidneys, fallopian tubes, epididymis)
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6
Q

Describe mycrobacterium tuberculosis

A
  • acid fast bacteria
  • high lipid content of cell wall causes it to stain gram negative
  • slow growing (divides every 16h -20 h)
  • resistant to drying
  • resistant to most antibiotics
  • resistant to host killing
  • intracellular survival
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7
Q

How does a person become infected with tuberculosis?

A
  • TB is spread by inhaled droplet nuclei
  • approximately 10% of the inhaled droplet nuclei reach the terminal airways where they can cause infection
  • once a droplet lands on something it is no longer infectious
  • droplets produced in both coughing and sneezing
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8
Q

Describe the primary infection stage of tuberculosis?

A
  • most often the patient is asymptomatic
  • there is a regional lymph node spread and bacteraemia
  • with the development of cellular immunity the infection is controlled
  • TST becomes positive
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9
Q

Immune defences in tuberculosis are _____ and reinfection is common when the latent infection becomes reactivated

A

lowered

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10
Q

What has to happen in order for reactivation to occur?

A
  • loss of balance between the immune system and bacilli
  • reactivation most often occurs in the lungs but can occur in lymph nodes, pleural space, kidneys, guts and CNS
  • the patient is now symptomatic (cough, weight loss, fever and night sweats are all common- if the patient has pulmonary TB they will now be infectious)
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11
Q

What are the first line antibiotics used in tuberculosis therapy?

A
  • isoniazid
  • rifampin
  • pyrazinamide
  • ethambutol
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12
Q

What are mycolic acids?

A
  • mycelia acids are unique/essential mycobacteria cell wall components
  • B-hydroxy fatty acids with a long alkyl side chain
  • each molecule contains between 60 and 90 carbon atoms
  • this is a multi-step synthesis
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13
Q

How does isoniazid work?

A
  • bactericidal to actively growing bacilli
  • a prodrug that is converted to active form by bacterial catalase peroxidase
  • inhibits mycolic acid synthetase
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14
Q

What are the adverse effects of isoniazid?

A

peripheral neuropathy
rash
hepatic toxicity

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15
Q

How does rifampin work?

A
  • rifampin is a semi-syntheitic macrocyclic antibiotic
  • – rifabutin and rifapentine belong to the same class
  • effective against several gram positive and gram negative microorganisms in addition to M. tuberculosis
  • inhibits DNA dependent RNA polymerase
    • inhibits RNA synthesis
    • mycobacterial cell death
  • does not bind mammalian RNA polymerase
  • froms stable drug enzyme complex
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16
Q

How does pyrazinamide work?

A
  • pyrazine analogue of nicotinamide
  • converted by pyrazinamidase to active pyrazinoic acid
  • inhibits mycolic acid synthesis, leading to mycobacterial cell death
  • active against dormant and semi-dormant mycobacteria in acidic environments
17
Q

Describe the action of ethambutol?

A
  • synthetic
  • causes inhibition of arabinosyl transferase
  • inhibits arabinogalactan chain elongation
  • inhibits bacterial cell wall synthesis
  • reduced mycobacterial cell wall growth (bacteriostatic)
18
Q

What is the overall “task” of isoniazid?

A
  • bactericidal in extracellular areas with a high oxygen concentration
  • important at preventing resistance by killing off rapidly growing bacilli
  • high early bactericidal activity
19
Q

What is the overall “task” of rifampin?

A
  • bactericidal in extracellular areas
  • the only drug that is bactericidal in fibrotic areas
  • has many drug-drug interactions
  • without rifampin- 18 mo of treatment would be required
20
Q

What is the overall “task” of pyrazinamide?

A
  • important in sterilizing semi-dormant bacteria
  • active in an acidic environment
  • loses activity as inflammation resolves
  • no benefit in using beyond 2 months
  • when used with rifampin, the course of therapy is completed in 6 months
21
Q

What is the overall “task” of ethambutol?

A
  • primarily used to prevent resistance to rifampin when primary resistance to isoniazid may be present
  • drug of choice if the organism is sensitive to isoniazid
  • not used in renal failure and in children
22
Q

What is the goal of antibiotic action in the intensive phase? (0-8 weeks)

A
  • goal is to quickly kill the rapidly dividing organism to control disease and render the patient non-infectious and prevent the emergence of drug resistance
  • use 4 drugs for the first 8 weeks daily
23
Q

What is the goal of antibiotic treatment in the continuation phase? (2-6 months)

A
  • sterile the lungs by killing dormant and semi-dormant organisms and prevent relapse
  • twice weekly use isoniazid and rifampin DOT
24
Q

What is the treatment regimen for latent tuberculosis infection?

A
  • isoniazid daily for 9 months
    OR
  • rifampin daily for 4 months
25
Q

What is the definition of multi-drug resistant tuberculosis?

A
  • resistance to rifampin and isoniazid as well as one other drug
  • estimated 4% of patients are multi-drug resistant
26
Q

What grouping of patients does multi-drug resistant tuberculosis occur most often in?

A
  • in those with weakened immune systems (HIV drugs or immunosuppressants)
  • for economic reasons (poverty, lack of healthcare, high rates in the third world)
27
Q

What is extensively drug resistant tuberculosis?

A
  • tuberculosis that is resistant to rifampin and isoniazid
  • resistant to any quinolone
  • resistant to any injectable 2nd line agent
  • possible as high as 25% of patients with multi-drug resistance are extensively drug resistant
  • makes tuberculosis untreatable
28
Q

What is the mechanism of rifampin resistance?

A
  • rapid resistance due to alteration in DNA dependent RNA polymerase structure
  • decreased drug binding
  • mycobacterial cell survival
29
Q

What is the mechanism of isoniazid resistance?

A
  • resistance is due to decreased drug uptake
30
Q

What is the alternative therapy when there is isoniazid resistance?

A
  • rifampin + pyrazinamide + ethambutol for 6-9 months
  • rifampin + pyrazinamide + streptokinase for 6-9 months
  • rifampin + ethambutol for 12 months
31
Q

What is the mechanism of pyrazinamide resistance?

A
  • resistance due to loss of pyrazinamidase
  • decreased conversion to pyrazinoic acid
  • mycolic acid synthesis occurs
  • mycobacterial cell survives
32
Q

What is the mechanism of ethambutol resistance?

A
  • resistance due to mutations in bacterial arabinosyltransferase gene
  • arabinogalactan elongation continues
  • mycolic acid synthesis occurs
  • mycobacterial cell survives
33
Q

Tuberculosis infections are generally treated with a combination of 5-7 different drugs. Other than the first line therapies, which drugs can be added?

A
  • protein synthesis inhibitors (cycloserine, capreomycin, kanamycin)
  • DNA synthesis inhibitors (fluorowuinolones, amino salicylic acid)
  • metabolite synthesis inhibitor (ethionamide)
34
Q

Situro (bedaquiline) is a new drug used to treat multi-drug resistant tuberculosis. How does it work?

A
  • inhibits mycobacterium ATP synthase
  • potent against MDR tuberculosis
  • used in combination with rifampicin and pyrazinamide
  • approved for use when other drugs are ineffective
  • unknown use against latent infections
35
Q

What are the safety issues associated with sirturo?

A
  • liver toxicity
  • prolonged QT
  • chest pain
  • hemoptysis
  • nausea/headache

Pharmacology (23 decks)

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