2 - Antimicrobials III Flashcards
Intensive TB therapy is always initiated with:
FOUR DRUGS for at least 8 weeks
Isoniazid and Rifampin are ALWAYS included
- Isoniazid
- Rifampin
- Pyrazinamide
- Ethambutol
TB continuation therapy consists of:
Isoniazid and Rifampin for at least 18 weeks
Why is TB so hard to treat in patients with HIV
Obviously their host immune system is weaker
BUT ALSO Rifampin accelerate the metabolism of reverse transcriptase inhibitors, so the most beneficial drug is unavailable to them
What causes TB to transition from latent to active?
Anything that severely taxes the immune system
What percentage of people with latent TB will develop active TB?
5-10%
When is isoniazid bactericidal? When is it bacteriostatic?
Bactericidal to mycobacteria that are actively dividing
bacteriostatic to dormant organisms
Isoniazid carries a black box warning for:
hepatotoxicity
What is the most common adverse effect of isoniazid?
Peripheral neuropathy
Does Isoniazid cross the BBB?
Yes
It causes several CNS effects
What is the MOA of Rifampin?
Inhibits bacterial protein synthesis by inhibiting RNA polymerase
Mammalian RNA polymerases are not effected
What are two main adverse effects of Rifampin?
Hepatotoxicity
Discoloration of body fluids
What is the MOA of pyrazinamide?
Inhibits growth by lowering pH and inhibiting fatty acid synthesis
What is the main adverse effect of pyrazinimide?
It is THE MOST Hepatotoxic of all the first line drugs!!!
What is the MOA of ethambutol?
Bactericidal
Inhibits mycobacterial cell wall synthesis
What should you say to a woman taking pyrazinamide who is having joint pain?
May be causing gouty arthritis
recommend NSAIDs for pain and reassure it will resolve after therapy ends
When you prescribe fluroquinolones, what is the one adverse effect that should be first in your mind?
The possibility of tendon rupture
Especially in patients over 60
Name four fluoroquinolones
- Ciprofloxacin
- Levaquin
- Ofloxacin
- Metronidazole
What is the MOA of ciprofloxacin?
Inhibits two bacterial enzymes required for DNA replication and cell division
RAPIDLY bactericidal
Which ABX is used to treat anthrax?
Cipro
Why do fluoroquinolones damage tendons?
They disrupt the extracellular matrix of cartilage in immature animals
It’s reversible if diagnosed early
What are the first signs of tendon rupture?
tendon pain, swelling, or inflammation
How should patients on fluoroquinolones be advised?
Don’t exercise if you’re having an tendon pain whatsoever until a rupture has been ruled out
Cipro carries a black box warning for two AEs:
Tendon Rupture
Myasthenia Gravis (exacerbates muscle weakness)
What is the MOA of metronidazole?
prodrug that’s converted in the cell and causes DNA destruction
ONLY WORKS IN ANAEROBES, because aerobes don’t have the enzyme to convert it
When you think Metronidazole, think:
GI:
H Pylori and C. Diff
Which mycoses are opportunistic?
Candidiasis
Aspergillosis
Cryptococcosis
mucormycosis
Which mycoses are non-opportunistic?
Histoplasmosis
Coccidioidomycosis
Sporotrichosis
Blastomycosis
Amphotericin B belongs to which drug class?
Polyene antibiotics
What is the MOA of Amphotericin B?
Binds to sterol components of the fungal cell membrane and causes leakage of cations (K)
Why are bacteria not effected by Amphotericin B?
They don’t have any sterols in their cytoplasmic membrane
Why is Amphotericin B so toxic to humans?
Because mammalian cell membranes have sterol
Ampho binds more strongly to ergosterol in fungi than it does to cholesterol in mammals, so fungi are more effected, but it’s not totally selective
Why does Amphotericin B cause infusion reactions?
causes monocytes and macrophages to release TNF, IL-1 and IL-6
Begins 11-3 hours after administration
Pretreat with benadryl and tylenol
Which organ is most effected by Amphotericin B?
Kidneys
Renal impairment occurs in practically all patients
May be reversible, but if the total dose is greater than 4g, residual impairment will probably be present
How can you minimize kidney impairment in patients receiving Amphotericin B IV?
Infuse 1L saline on days ampho will be given
Which drug formulation of Amphotericin B is least likely to cause nephrotoxicity?
The lipid based formulas are less toxic, but much more expensive
Which class of drugs is used to get rid of parasitic worms?
Anthelmintics
