-
Inhibition of peptidoglycan cross-linking in cell wall
the -cillins plus -penems, aztreonam, cephalosporins
-
Block peptidoglycan synthesis
-
Disrupt bacterial cell membranes
Polymyxins
-
Block nucleotide synthesis
-
Block topoisomerase II (gyrase)
Fluoroquinolones (-floxacin, like cipro)
-
Block mRNA synthesis
Rifampin
-
Block 50s ribosomal subunit
- Chloramphenicol
- Macrolides
- Clindamycin
- Streptogramins
- Linezolid
-
Block 30S subunit
- aminoglycosides (gent, neomycin, amikacin, tobramycin, streptomycin)
- tetracyclines
-
Bacteriostatic antibiotics
- Erythromycin
- Clindamycin
- Sulfamethoxazole
- Trimethoprim
- Tetracyclines
- Chloramphenicol
-
Bactericidal
- vanc
- fluroquinolones
- penicillin
- aminoglycosides
- cephalosporins
- metronidazole
-
Nafcillin, methicillin, dicloxacillin
- Penicillinase-resistant penicillins
- Use for s. aureas but not MRSA
- Methicillin causes AIN
-
Ampicillin, amoxicillin (aminopenicillins) use and toxicity
- Combine with clavulanic acid to enhance spectrum
- Amoxicillin has greater oral bioavailability than ampicillin
- HELPS cover gram-neg rods: H. flu, E. coli, Listeria, Proteus, Salmonella, enterococci
-
Ticarcillin, carbenicillin, piperacillin
- anti-pseudomonals
- use with clavulanic acid
-
Anti-pseudomonals
- ticarcillin, carbenicillin, piperacillin
- aztreonam
- fluoroquinolones - oral
- (carbapenems
- polymyxins
- 3rd and 4th generation cephalosporins
- aminoglycosides)
-
1st generation cephalosporins
- cefazolin and cephalexin
- cover: gram + cocci, proteus, e. coli, Kleb (PEcK)
-
2nd generation cephalosporins
- cefoxitin, cefaclor, cefuroxime
- gram + cocci, H. flu, Enterobacter, Neisseria, Proteus, E. coli, Kleb, Serratia
- From 1st gen, added haemophilus, enterobacter, neisseria, and serratia
-
3rd generation cephalosporins
- ceftriaxone, cefotaxime, ceftazidime
- coverE: serious gram-neg infxn, meningitis
- e.g. pseudomonas, gonorrhea
-
4th generation cephalosporin
- cefepime
- has increased activity against pseudomonas
-
aztreonam
- For penicillin allergic patients or renal insuff
- Gram-neg rods: Kleb, pseudomonas, serratia
- No activity against gram+ or anerobes
-
Carbapenems
- Administer imipenem with cilastatin to decrease inactivation in kidney
- DOC for enterobacter
- Gram+ cocci, gram- rods, anaerobes
- Tox: seizures, GI, rash
-
vancomycin
- Binds D-ala-D-ala portion of cell wall precursors
- Resistance: d-ala-d-lac
- For s. aureus, c. diff
- Tox: nephro, oto, thrombophlebitis, redman
-
Aminoglycosides
- Inhibit formation of initiation complex
- Require O2 (use for aerobic organisms only)
- For gram- rods
- Tox: nephro, oto, teratogen
-
Tetracycline
- Prevents aminoacyl-tRNA attachment at 30S
- Use doxy in renal failure
- Use democlocycline as an ADH antagonist in SIADH
- Use: vibrio, acne, chlamydia, ureaplasma, mycoplasma, tularemia, h. pylori, borrelia, rickettsia
- Tox: teeth and photosensitivity
-
Macrolides
- e.g. erythromycin, azithromycin, clarithromycin
- Block translocation at 50S
- Use: strep, mycoplasma, legionella, chlamydia, neisseria
- Tox: QT, GI, cholestatic hepatitis, eosinophilia
- Increases theophylline & oral anticoagulants
-
Chloramphenicol
- Inhibits 50S peptidyltransferase activity
- Tox: aplastic anemia, gray baby syndrome (infants lack UDP-glucuronyl transferase)
-
Clindamycin
- Blocks peptide bond at 50S
- For aerobes above the diaphragm
- Tox: pseudomembranous colitis, fever
-
Sulfonamides
- PABA antimetabolites inhibit dihydropteroate synthetase
- gram+ and - and nocardia, chlamydia
- UTI
- Tox: hypersensitivity, G6PDD hemolysis, AIN, photosensitivity, kernicterus in infants
- Displaces warfarin from albumin
- Allergic pts also cannot take sulfonylureas, sulfasalazine, thiazide diuretics, acetazolamide, furosemide
-
Trimethoprim
- Inhibits bacterial DHF reductase
- For UTI, shigella, salmonella, pneumocystis jiroveci
- Tox: marrow toxicity; supplement folinic acid
-
Fluoroquinolones
- Inhibit DNA gyrase (topo II). avoid antacids.
- Gram- rods including pseudomonas, neisseria
- Tox: GI, superinfections, rash, HA, dizziness. Cartilage/tendon damage esp in fetus
-
Metronidazole
- Forms toxic metabolites that damage DNA
- For anaerobes below the diaphragm and protozoans, h. pylori
- Tox: metallic taste, doesn't mix with alcohol
-
Polymyxins
- Disrupt cell membrane osmotic properties (detergent)
- For resistant gram- infxns
- Tox: neuro, ATN
-
How to prophylax and treat TB
- Px: INH
- Tx: RIF, INH, pyrazinamide, ethambutol
- Cycloserine is 2nd line
- All are bad for liver; Ethambutol tox: optic neuropathy
-
How to prophylax and treat M. avium intracellulare
- Px: azithromycin
- Tx: azithro, RIF, ethambutol, streptomycin
-
How to treat leprosy (M. leprae)
Dapson, RIF, clofazimine
-
INH
- Decreases synthesis of mycolic acid
- Tox: neuro, hepato. Give B6 to prevent neurotox.
-
RIF
- Inhibits DNA-dependent RNA polymerase
- Revs up P-450
- Red/orange body fluid
- Rapid resistance if used alone
-
How a bug gets resistant to penicillins/cephalosporins
Beta-lactamase cleavage of beta-lactam ring, or aletred PBP (MRSA, s. pneumoniae)
-
How a bug gets resistant to aminoglycosides
Modification via acetylation, adenylation, or phosphorylation
-
How a bug gets resistant to vancomycin
Change terminal D-ala of cell wall to d-lac, which decreases affinity
-
How a bug gets resistant to chloramphenicol
Modifies it via acetylation
-
How a bug gets resistant to macrolides
Methylates the rRNA near erythromycin's ribosome-binding site. Sneaky sneaky!
-
How a bug gets resistant to tetracycline
Decreased uptake or increased export. Pushy pushy!
-
How a bug gets resistant to sulfonamides
Alters its enzyme (dihydropteroate synthetase), or decreases uptake, or increases PABA synth
-
How a bug gets resistant to quinolones
It alters its gyrase or reduces uptake
-
Meningococcal prophylaxis
RIF or minocycline
-
Gonorrhea prophylaxis
Ceftriaxone
-
Syphilis prophylaxis
Benzathine penicillin G
-
Pneumocystis jiroveci pneumonia prophylaxis
TMP-SMX (also px for UTI) or aerosolized pentamidine
-
Endocarditis prophylaxis
penicillin
-
How do you treat VRE?
with linezolid and streptogramins (quinupristin/dalfopristin)
-
Amphotericin B
- Binds ergosterol and tears holes in fungal membrane
- Use for systemic mycoses
- Tox: shake and bake, hypotension, nephrotox, arrhythmias, anemia, phlebitis.
-
Nystatin
- Binds ergosterol to disrupt fungal membrane
- No systemic use; swish and swallow or topical
-
Azoles
- Inhibit ergosterol synthesisUse for systemic mycoses, cryptococcal meningitis (crosses BBB)
- Tox: hormone synth inhibition causing gynecomastia, liver dysfunction (p-450 inhib)
-
Flucytosine
- Converts to 5-FU and inhibits DNA (pyrimidine) synthesis
- Use in combination with amphotericin B
- Tox: nausea, vomiting, bone marrow suppression
-
Capsofungin
- Inhibits cell wall syntehsis by inhibiting synthesis of beta-glucan
- Use for invasive aspergillosis
- Tox: GI, flushing
-
Terbinafine
- Inhibits fungal enzyme squalene epoxidase
- Treat dermatophytoses like onychomycosis
-
Griseofulvin
- Interferes with microtubule function to dirupt mitosis
- Oral tx of superficial infections
- Tox: deposits in nails, teratogen, carinogen, confusion, HA, induces P-450/warfarin metabolism
-
Amantadine
- Blocks influenza A uncoating by buffering endosome. M2 protein (mutated for resistance).
- Can treat Parkinson's because it causes release of DA from intact nerves
- Tox: ataxia, dizziness, slurred speech
-
Zanamivir and oseltamivir
Inhibit influenza neuraminidase for influenza A and B. Baby viruses can't swim free.
-
Ribavirin
- Inhibits IMP dehydrogenase to inhibit synth of guanine nucleotides
- Use for RSV, chronic hep C
- Tox: hemolytic anemia, teratogen
-
Acyclovir
- HSV/VZV thymidine kinase phosphorylates it so it can inhibit viral DNA polymerase and terminate its chain
- Use for herpesviruses except not CMV
-
Ganciclovir
- CMV viral kinase monophosphorylates it, becomes guanosine analog.
- Use for CMV
- Tox: more than acyclovir. marrow and renal.
-
Foscarnet
- PyroFOSphate analogue; viral DNA polymerase inhibitor (can mutate); does not require viral kinase
- Use for CMV retinitis in IC patients when ganciclovir fails or for resistant HSV
- Tox: nephro
-
Protease inhibitors end in:
-navir. ritonavir, indinavir, nelfinavir, saquinavir.
-
Reverse transcriptase inhibitors: name the nucleosides
Zidovudine (AZT), didanosine, zalcitabine, stavudine, lamivudine, abacavir
-
Reverse transcriptase inhibitors: name the non-nucleosides
- Nevirapine, Efavirenze, Delaviridine
- Never Ever Deliver nucleosides
-
Reverse transcriptase inhibitors: mech and tox
- Prevent incorporation of DNA copy of viral genome into host DNA
- Tox: bone marrow, neuropathy, lactic acidosis (nucleosides), rash (non nucleosides), megaloblastic anemia (ZDV)
- Use in pregnancy to reduce transmission
-
Enfuvirtide
- Fusion inhibitor for HIV; binds viral gp41 subunit so it can't enter CD4 cell
- Use when replication continues despite other drugs
- Tox: hypersensitivity, risk of pneumonia
-
How do interferons work as therapy?
- They induce ribonuclease that degrades viral mRNA
- But they can cause neutropenia
-
Use for IFN-alpha
chronic HBV, HCV, Kaposi's sarcoma
-
-
Use for IFN-gamma
NADPH oxidase deficiency
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