Pulmonary Infections- Pharm Flashcards
Are macrolides bacteriocidal or bacteriostatic?
Bacteriostatic
Targeting the 23s rRNA on the 50s subunit does what from macrolides?
block translation and prevents exit
Why are macrolides really good for lung infections?
They can penetrate lung tissue really well.
Which bug do macrolids have intracellular activity against?
Legionella
Which subunit again do macrolides act upon?
23s rRNA of the 50s subunit
Which enzyme is produced by gram + organisms to cause resistance against macrolides?
Methylase
What does methylase do to bacteria to cause the resistance to macrolides?
it modifies the ribosomal target of macrolides, leading to ↓ drug binding
What is the #1 reason to discontinue erythromycin?
think side effects
GI intolerance
cuz it stimualtes gut motility –> N/V, diarrhea, anorexia
What are the 2 mechanisms for quinolones as an antibiotic?
- inhibits topoisomerases
2. coverts these enzymes into DNA-damaging agents
Which type of isomerases do quinolones act upon?
Type II topoisomerases (topoisomerase II and IV)
What are the 3 types of infections do u use fluoroquinolones?
- Urogenital
- Respiratory
- GI
Which gram stain bacteria do u use fluoroquinolones for?
Gram -
like E. coli, Neisseria gonorrhoeae, Enterobacter, Salmonella, and Shigella
What are the 3 mechanisms to cause resistance to quinolones?
- chromosomal mutations in the genes that encode type II topoisomerases
- alterations in the expression of membrane porins
- alterations in the expression of efflux pumps
What is the mechanism of topisomerase II, which is inhibited by quinolones?
DNA gyrase
Which gram stain bacteria use topisomerase IV, which is inhibited by quinolones?
Gram +
like S. aureus
What are the 2 main species of mycobacteria?
M. TB
M. leprae
What are the 2 targets for antimycobacterials?
- synthesis of NAG-arabinogalactan
2. early reactions of mycolic acid synthesis
What is it about the mycobacterial cell envelope that makes it hard to have antimycobacterials treat the infection?
It’s thick, asymmetric, and highly impermeable to hydrophobinand hydrophilic substances.
Why are antimyobacterials that target cell growth ineffective?
Myobacteria are very slow growers
What are the 5 drugs that are first-line agents for TB?
Ethambutol, pyrazinamide, isoniazid, rifampin, and streptomycin
SPIRE
What are the indications for the 4-drug regimen for TB (isonazid, refampin, pyrazinamide, and either Ethambutol or Streptomycin)?
4-RIP(E/S)
pt with active TB and w/o a Hx of prior therapy
What are teh indications for the 3-drug regimen for TB (isonazid, refampin, pyrazinamide)?
3-RIP
if isonazid resistance is rare
Is ethambutol bacteriocidal or bacteriostatic?
bacteriostatic
What enzyme does ethambutol target to decrease arabinogalactan synthesis?
Arabinosyl transferase
Is isonazid a bacteriocidal or bacteriostatic?
bacteriocidal
Which enzyme does isonazid target to inhibit mycolic acid synthesis?
FAS2
What do u use a lotta drugs for TB?
TB has a high frequency of mutations –> resistances.
What can isonazid do to cytochrome P450?
inhibit or induce it
What 5 drugs can be affected by isonazid action on cytochrome P450?
Rifampin, Carbamazepine, Phenytoin, Azole-type antifungals, and alcohol
Why is selectivity harder for antifungals than antibacterials?
fungi cell structure is similiar to animal cells.
In humans, we have cholesterol in our cell membranes, but what is it in fungi that does the same thing?
Ergosterol
Imidazole and triazole inhibits which enzyme?
14a sterol demethylase
14a sterol demethylase is used by fungi to do what?
converts Lanosterol –> ergosterol
Which enzyme do echinocandins act on to inhibit cell wall biosynthesis in fungi?
beta-(1,3)-D-glucan synthase
What is the fxn of beta-(1,3)-D-glucan synthase for the cell wall?
It adds glucose residues from UDP-glucose to the growing polysaccharide chain
So are echinocandins fungicidal or fungistatic?
Fungicidal
What are in the fungal membranes that takes up Flucytosin?
Cytosine-specific permeases
Once inside the fungal cells, which enzyme converts flucytosin –> 5-FU?
Cytosine deaminase
5-FU then is converted to 5dUMP, which inhibits which enzyme?
Thymidylate synthase
Inhibition of thymidylate synthase causes inhibition of what cellular process, thus resulting in inhbiition of cell division?
DNA synthesis
What are the 3 fungi that flucytosine works upon?
Candidiasis
Cryptococcosis
Chromomycosis
CCC
Griseofulvin inhibits fungal mitosis by binding to what cellular structure?
Tubulin
Binding of tubulin by griseofulvin causes what to be inhibited in the fungal cell?
assembly of the mitotic spindle
Griseofulvin accumulated in which cells?
Keratin precursor cells
Accumulation of griseofulvin in keratin precursor cells causes growth of which structures to be free of dermatophyte infection?
skin, hair, and nails
Is griseofulvin fungistatic or fungicidal?
Fungistatic
Squalene epoxidase converts squalene into what?
Lanosterol
What are the 3 drugs that inhibit squalene epoxidase to be fungicidal from the prevention of ergosterol formation?
Terbinafine (allyamines)
Naftifine (allylamines)
Butenafine (benzylamines)
“squalene are -fine”
Which 3 pts are condraindications for terbinafine?
Renal failure
Hepatic failure
Pregnant women
Again, which enzyme is inhibited by azoles?
14a steroid demethylase
Why is ketoconazole limited by oral intake if the pt has low stomach acid?
It has to be converted to a salt by stomach acid.
What has replaced ketoconazole?
Itraconazole
What 2 conditions do u use topical ketoconazole?
Common dermatophyte infection
Seborrheic dermatitis
Why is fluconazole used for cryptococcal meningitis?
free diffusion into CSF
What does polyenes bind directly to inhibit the fungal membrane?
Ergosterol
Binding and inhibition of ergosterol by polyenes causes pores, which does what to the cell?
Cause leaking of essential cellular contents, leading to cell death.
Why are polyenes selective for fungi than animal cells?
it has a 500x stronger affinity for ergosterol than cholesterol
What are the 2 polyenes?
Amphotericin B
Nystatins
IV administration of amphotericin B causes a cytokine storm by the relase of what 2 factors from cells of the host immune system?
TNFa and IL-1
What are the 5 Sx to amphoteticin B after administration?
fever, chills, hypoTN, renal toxicity and anemia
What are the 3 echnocandins?
Capsofungin
Anidulafungin
Micofungin
“Fungin CAM!”
What is the mechanism of adamantane?
inhibits viral uncoating
Adamantane works only against which 1 specific virus?
Influenza A
What is the channel on the viral envelope to move H+ protons into the viral envelope?
M2 proton channel
Movement of protons into the viral envelope, which is inside the acidic endosome, causes what to happen?
Viral uncoating and release of viral RNP into the hsot cell cytosol
Which drug has largely replaced the adamantanes?
Neuraminidase inhibitors
What action do neuraminidase inhbitors block for viral infetions?
they block viral relase from the host cell
Neruaminidase inhibitors are analogues of which host protein?
sialic acid
Neuraminidase usually does what to sialic acid in the host cell to cause it’s release?
it cleaves sialic acid
This is a neuraminidase inhibitor and is active against influenza A and B.
Zanamavir
Since zanamavir has poor oral availability, what is the route of administration?
Inhaler
Which neuraminidase inhibitor has a better oral bioavailability than zanamavir?
Oseltamavir
Oseltamavir is used as a prophylactic for what 2 serious viral infections?
H5N1 (bird flu)
H1N1 (swine flu)
What is the route of administration for ribavirin?
Aerosol
Ribavarin is used as a Tx for what condition?
RSV
Ribavirin can also be used in combination with an interferon (like INFa) for what condition?
chronic hep C infection
Palivizumab is used to prevent what illness in high-risk children?
RSV
this was an LDP test question
