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Flashcards in Microbio - antimicrobials Deck (19):
1

How do B-lactams work?

Blocks transpeptidase cross-linking of peptidoglycan in cell wall (weakened cell wall --> osmotic lysis)

Note: these are D-ala-D-ala analogs, thus blocking transpeptidase

2

Which drugs are B-lactams?

Penicillin, amox/ampicillin, cephalosporins, carbapenems, monobactams

3

How do bacitracin and vancomycin work?

Similar to B-lactams, but they block peptidoglycan synthesis (as opposed to blocking the cross-linking)

Mechanism: bind D-ala D-ala portion of cell wall precursors (pay back 2 D-alas for van-dalizing)

4

Protein synthesis inhibitors (buy AT 30, CCEL at 50)

30S inhibitors: Aminoglycosides = irreversible (genta, neomycin, amikacin, tobra, strepto) and Tetracyclines = static (tetra, doxy, mino

)50S inhibitors: Chloramphenicol, Clindamycin, Erythromycin (macrolides, azithro, clarithro), Linezolid

5

Aminoglycosides special things to know (side effects, uptake)

Side effects: nephro, ototoxicity, teratogen

Requires O2 for uptake, therefore can't use for anaerobes (Nocardia, Pseudomonas, myco TB)

6

Tetracyclines things to know

Doxy is used in renal failure pts

Don't give with divalent cations (Fe, Ca, Mg), they decrease absorption of the drug

7

Anaerobic infection tx

Above diaphragm: clindamycin (aspiration pneumo, lung abscesses, oral infxns)

Below diaphragm: metronidazole

8

Macrolides special factsside effects (MACRO)

Bind 23S subunit of 50S, block translocation

Motility issues
Arrythymias
Cholestatic hepatitis
Rashe
Osinophilia

9

Folate synthesis inhibitors (Bactrim)

Trimethoprim - inhibit DHF reductase, TMP - treats marrow poorly (lots of -penias)

Sulfonamide - metabolites inhibit dihydropteroate synthase, watch out in G6PDH, can displace warfarin

10

Fluoroquinolones (levofloxacin, cipro, xacin)

inhibit DNA gyrase and topoisomerase IV

- hurt attachments to your bones! tendon problems in elderly and steroid pts

11

Metronidazole

forms toxic free radicals in the bacterial cell wall

disulfiram-like with alcohol

metallic taste

12

Anti-mycobacterial (red body fluids, B6, optic neuropathy)

R: rifampin (4 R's = RNA pol inhibitor, Ramps up p-450, Red/orange urine, Rapid resistance alone

)I: isoniazid = decreased mycolic acid (cell wall), requires bacterial activation, used as solo ppx, give with B6 (INH hurt Neuron and Hepatos)

P: pyrazinamide

E: decreased cell wall polymerization, optic neuropathy (color blindness)!

13

Antifungals

Amphotericin B/Nystatin - forms pores by binding ergosterol

Flucytosine - used with Ampho, inhibit DNA/RNA synth

Azoles - inhibit p450, which makes ergosterol

Terbanifine - inhibit squalene epoxidase

14

Chloroquine resistance mech

Blocks detox of heme in hemozoin (heme is toxic to malaria)

resistance arises due to membrane pump that decreases [drug]i

15

Antiviral therapy

release of progeny virus
nucleic acid synthesis
protein synthesis

release of progeny - oseltamivir (inhibit influenza neuraminidase)

nucleic acid synthesis - guanosine analogs, inhibit viral DNA polymerase by chain termination (acyclovir: HSV, VZV) (ganciclovir: CMV) (last line: foscarnet: binds to polymerase)

protein synthesis - IFN-a, -B (MS), -y (CGD)

16

HIV medsProtease inhibitorsNRTIs (nucleoside reverse transcriptase inhibitor)NNRTIsintegrase inhibitorfusion inhibitor

HAART (3 drugs total)
2 NRTIs + NNRTI/protease inhib/integrase inhib

Navir = protease inhib (prevents HIV-1 protease from cleaving mRNA), don't give with rifampin (induces accel p450 metab!)

Vudine = nucleosides (cause bone marrow suppression, give G-CSF or EPO)

17

Hep C therapy

ribavirin - inhibit synthesis of guanine nucleotides (also used in RSV)

simeprevir - HCV protease inhibitor

sofosbuvir - inhibit HCV RNA-depndent RNA pol

18

M. tuberculosis virulence

Cord factor - in virulent strains, inhibit macrophage maturation, induces release of TNF-a (forms serpentine cords)

Sulfatides - inhibit phagolysosomal fusion

19

Resistance mechanisms

Decreased uptake - fluoroquinolones, aminoglycosides

Altered binding proteins/target - penicillins, sulfonamides, rifampin