Antibiotic drugs Flashcards
drugs that block peptidoglycan synthesis
bacitracin, vancomycin
drugs that work by damaging DNA
metronidazole
Drugs that block 50S
Chloramphenicol, clindamycin, Linezolid
Erythromycin
Also streptogramins (-pristin)
cephalosporin, aztreonam, imipenem mechanism
block cell wall synthesis by inhibiting peptidoglycan cross linking
penicillin toxicity
allergy
hemolytic anemia
clinical use of penicillin
S pneumo S pyogenes actinomyces (STREP is susceptible!) Also neisseria meningitidis and syphilis
toxicity of oxacillin
hypersensitivity
interstitial nephritis
Ampicillin vs amoxicillin
amoxicillin has greater oral availability
amp/amoxicillin coverage
Hemophilus E Coli Listeria Proteus Salmonella Shigella
HELPSS
Toxicity of ampicillin/amoxicillin
pseudomembranous colitis
Which bugs not covered by cephalosporins?
Listeria
Atypicals
MRSA
Enterococci
Ceftazidime
pseudomonas (3rd generation)
Cefazolin coverage
PEcK Proteus E coli Klebsiella Cefazolin
Ceftriaxone use
meningitis and gonorrhea
Additional coverage of 2nd generation cephalosporin (Cefoxitin)
H flu
Enterobacter
neisseria
Serratia
Toxicity of cephalosporins
Vitamin K deficiency
Increases toxicity of aminoglycosides on kidneys
aztreonam coverage
gram negatives
when do you use aztreonam?
For pts allergic to penicillin
For pts with renal insufficiency and can’t take aminoglycosides
Mechanism aztreonam
Prevents peptidoglycan cross linking by binding to PBP3.
Resistant to beta lactamases
Imipenem mechanism
beta-lactamase resistant carbapenem
what do you administer with imipenem/meropenem?
ciastatin, an inhibitor of renal dehydropeptidase I which extends activation
coverage of imipenem/meropenem?
gram positive cocci
gram negative rods
Side effects of imipenem/meropenem
Seizure (but meropenem does NOT cause seizure)
GI, skin rash, CNS toxicity
Mechanism vanco
Inhibits peptidoglycan formation by binding D-Ala D Ala
resistance to vanco arises from
Changing Dala D ala to D Ala D lac
Toxicity of vanco
nephrotoxicity
ototoxicity
thrombophlebitis
RED MAN syndrome
How do you prevent red man syndrome
slow infusion rate
–Can also pre-treat with antihistamines
Indications for VANCO
enterococci
C Difficile
mech: AGs
inhibit formation of initiation complex and cause misreading of mRNA at 30S. Requires O2 for uptake
Tox of Ags
nephrotox
ototox
teratogen
neuromuscular blockade
AG resistance
transferase enzymes inactivate the drug by acetylation, phosphorylation, adenylation
Demeclocycline use
ADH antagonist. Used in SIADH
Doxy is okay to use in patients with
Renal failure
don’t take tetracyclines with
milkd, antacids, iron preparation. Any divalent ions inhibit absorption
Tx for mycoplasma pneumoniae
azithromycin/levofloxacin
Tetracycline uses
lyme rickettsia chlamydia mycoplasma pneumoniae ---DRUG ACCUMULATES INTRACELLULARLY
Tox: tetra
grey teeth
inhibition of bone growth
photosensitivity
DON”T use in pregnant women
Mech: erythromycin, azithromycin, clarithromycin
Bind to 23S rRNA of 50S subunit
Use: macrolides
Atypical pneumonias: mycoplasma, chlamydia, legionella
STDS (chlamydia)
gram positive cocci
side effect of macrolides
motility Prolonged QT acute cholestatic hepatitis Rash Eosinophilia
Resistance to macrolides
methylation of 23S rRNA binding site
Most protein synthesis inhibitor drugs are bacteriostatic EXCEPT for
aminoglycosides
Mechanism of chloramphenicol
Block of 50S ribosomal subunit peptidyltransferase
Tox of chloramphenicol
anemia
aplastic anemia
gray baby syndrome
Chloramphenicol use
meningitis from encapsulated organism (Strep, HiB, N men)
clinamycin mechanism
Blocks PEPTIDE TRANSFER
use: clinamycin
anaerobic infections and aspiration pneumonia. treats anerobes ABOVE the diaphragm
Sulfonamide mechanism
PABA antimetabolites inhibit dihydropteroate synthase in bacteria. Bacteriostatic
Clinical use of sulfonamides
Gram positive, gram negative, nocardia, chlamydia Good for UTI
Tox of sulfonamides
Hypersensitivity rxn, Hemolysis in G6PD individuals nephrotoxicity photosensitivity kernicterus displaces warfarin from albumin
Sulfonamide resistance comes from
altered enzyme decreased uptake or increased PABA synthesis
Bactrim is good for
UTIs, shigella, salmonella, PCP
Side effects of trimethoprim
megaloblastic anemia
leukopenia
granulocytopenia
May be helped by leucovorin rescue
Fluoroquinolones cannot be taken with
antacids
Toxicity of fluoroquinolones
GI upset
prolong QT interval
tendon rupture, myalgias especially in peeps takin prednisone
fluoroquinolones are contraindicated in
pregnant women and children. may damage cartilage
resistance to fluoroquinolones
efflux pumps
or mutation in DNA gyrase
Side effect of metro
disulfiram reaction with alcohol
Metro treats
giardia entamoeba trichomonas gardnerella anaerobes H pylori
Tx; MAC
azithromycin
rifampin
ethambutol
streptomycin
Treat for 12 months with 2-3 of these
isoniazid mechanism
decreased synthesis of mycolic acids. Needs bacterial catalase peroxidase to convert INH to an active metabolite
why might you need to adjust the INH dosing?
Different INH half lives in fast vs slow acetylators
Tox of isoniazid
neurotoxicity
hepatotoxicity
how do you prevent isoniazid toxicity?
vitamin B6 (pyridoxine)
Rifampin mechanism
inhibits DNA-dependent RNA polymerase
The 4 R’s of rifampin
RNA polymerase inhibitor
Revs up microsomal P450
Red body fluids
Rapid resistance if used alone
USe of rifampin prophylactically
Meningitis in kids
HiB
Tox of pyrazinamide
Unknown mechanism
- -hyperuricemia
- -hepatotoxicity
Etham butol mechanism
decreased carbohydrate polymerization of mycobacterium cell wall. Blocks arabinosyltransferase.
Ethambutol toxicity
optic neuropathy
prophylaxis of meningitis
ceftriaxone
prevention of gonococcal or chlamydial conjunctivits in a newborn
erythromycin
Prevention of postsurgical infection from S aureus
Cefazolin
Pregnant woman with GBS
ampicillin
Prevention of rheumatic fever
oral penicillin
Prevention of PCP and toxoplasma
Sulfa-TMP
Prevention of MAC
azithromycin
Treatment of VRE
Linezolid and streptogramins
streptogramins
quinupristin/dalfopristin
amphotericin binds
ergosterol
what do you need to supplement ampho B with?
K and Mg
Side effect of ampho
fever hypotension nephrotox arrhythmias anemia IV phlebitis
Nystatin for
oral candidiasis or diaperrash/vaginal candida
Mech: azoles
inhibit ergosterol synthesis
–inhibits P-450 enzyme that converts lanosterol to ergosterol
Toxicity of zoles
gynecomastia
Inhibits P450
Itraconazole for
blastomyces, coccidioides, histoplasma
fluconazole for
chronic suppression of cryptococcal meningitis
clotrimazole and miconazole for
topical fungal infections
flucytosine mechanism
Inhibits DNA/RNA biosynthesis by conversion to 5 FU by cytosine deaminase
toxicity of flucytosine
bone marrow suppression
use: flucytosine
combo with ampho B for systemic fungal infections like cryptococcus
Caspofungin mechanism
inhibits cell wall synthesis of B glucan
Indications of caspofungin
invasive aspergillosis
candida
Side effect of caspofungin
GI upset and flushing
terbinafine used for
dermatophytoses like onychomycosis
Terbinafine tox
Abnormal LFTs and visual disturbances
Griseofulvin mechanism
Interferes with microtubule function, mitosis
Where does griseofulvin deposit
In nails and kertin tissues. used for dermatophytes like ring worm or tinea
Tox griseofulvin
Increase P450 and warfarin metabolism
Teratogen, carcinogen
headaches
Tx: leishmaniasis
sodium gluconate
Chloroquine mechanism
Blocks detoxification of heme into hemozoin. Then, the hem accumulates and becomes toxic to plasmodia
toxicity of chloroquine
retinopathy
use: chloroquine
Treatment of plasmodial species OTHER than P falciprum. Because resistance is really high in falciprum
In general, use praziquantel against
flukes
zanamivir, oseltamivir mechanism
inhibits influenza neuraminidase, decreasing release of progeny virus
Ribavirin mechanism
Inhibits synthesis of guanine nucleotides by inhibiting IMP dehydrogenase
Toxicity of ribavirin
Hemolytic anemia TERATOGEN
Acyclovir mechanism
activated by the HSV thymidine kinase. Works as guanosine analog=CHAIN TERMINATION
Rivavirin use:
RSV, chronic Hep C
Resistance to acyclovir
mutated viral thymidine kinase
Use: acyclovir
HSV and VZV
Tx of herpes zoster
famciclovir (shingles) Because acyclovir has NO effect on latent forms
Valacyclovir
like acyclovir but better oral availability
Ganciclovir used to treat
CMV
Mechanism ganciclovir
CMV viral kinase forms guanosine triphosphate from monophosphate.
Inhibits DNA polymerase
Valganciclovir
ganciclovir with better oral bioavailability
Tox: gangiclovir
leukopenia, neutropenia, thrombocytopenia, renal toxicity
Resistance of ganciclovir
Mutated CMV DNA polymerase or NO viral kinase
Foscarnet mechanism
Inhibits DNA polymerase
- -binds pyrophosphate site of enzyme
- -no activation by viral kinase NEEDED!!
Use: foscarnet
CMV retinitis in immunocompromised pts when ganciclovir fails
OR acyclovir resistant HSV
Tox of foscarnet
Nephrotoxicity
resistance foscarnet
mutated DNA poly
Cidofovir mechanism
like foscarnet. Inhibits DNA polymerase. No phosphorylation needed by viral kinase
Cidofovir indications
CMV retinitis in immunocompromised pts or acyclovir HSV
Cidofovir toxicity
Nephrotoxicity
how to reduce toxicity of cidofovir
give with probenecid and IV saline
Toxicity of protease inhibitors
hyperglycemia GI intolerance lipodystrophy
-inavir
protease inhibitor
Ritonavir uses
protease booster; inhibits P45-
tox of indinavir
nephropathy and hematuria
Mechanism NRTIs
lack a 3’ OH group, inhibiting nucleotide binding to RT and terminates DNA
Name the NRTIs
-tenofovir emtricitabine -abacavir -lamivudine -zidovudine (AZT) didanosine stavudine
benefit of tenofovir
No need to be activated. a nucleotide, not a nucleoside
Zidovudine use
prophylaxis during pregnancy
toxicity of NRTIs
bone marrow suppression
peripheral neuropathy
lactic acidosis
anemia
Name the NNRTIs
nevirapine
efavirenz
delavirdine
what’s different about NNRTIs
Do NOT require phosphorylation to be active or compete with nucleotides. They bind to the reverse transcriptase itself
Raltegravir
integrase inhibitor
Mechanism of raltegravir
blocks integrase
toxicity of raltegravir
hypercholesterolemia
Interferon drugs: mechanism?
Blocks replication of both RNA and DNA viruses
IFN a
chronic Hep B and C
IFN b
MS
IFN y
NADPH oxidase deficiency
toxicity of interferons
neutorpenia and myopathy
Drugs to avoid in pregnancy
SAFe Children Take Really Good Care -sulfonamide aminoglycoside fluoroquinolone clarithromycin tetracycline ribavirin griseofulvin chloramphenicol
sulfonamide in pregnancy
kernicterus
aminoglycoside in pregnancy
ototoxicity
fluoroquinolone in pregnancy
cartilage damage
clarithromycin in pregnancy
embryotoxin
tetracycline in pregnancy
discolored teeth, bone growth problem
griseofulvin in pregnancy
teratogen
ribavirin in pregnancy
teratogen
chloramphenicol in pregnancy
gray baby syndrome