Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
188 Cards in this Set
- Front
- Back
|
Antimicrobial Tx -- Mechanism of Action
|
|
|
|
The penicillin type drugs work by blocking ------ synthesis, specifically by inhibiting this molecule from cross-linking?
|
blocks bacterial cell wall synthesis by inhibition of peptidoglycan synthesis.
|
|
|
Which other drugs (aside from penicillin) have this same mechanism of action? 3
|
Imipenem, aztreonam and cephalosporins
|
|
|
Block the synthesis of peptidoglycan, preventing cell wall synthesis 3
|
Bacitracin, cycloserine, vancomycin
|
|
|
These drugs block the 50s ribosomal subunit 6
|
chloramphenicol, clindamycin, erythromycin, lincomycin, linezolid, streptogramins
|
|
|
These drugs block the 30s ribosomal subunit 2
|
Aminoglycosides and tetracyclines
|
|
|
These drugs block nucleotide synthesis by interfering with the folate pathway 2
|
Sulfonamides (e.g. Bactrim), trimethoprim
|
|
|
These drugs block DNA topoisomerases 1
|
Quinolones (e.g. Cipro)
|
|
|
Which drug blocks mRNA synthesis 1
|
rifampin
|
|
|
Which are the bacteriacidal Abx 6
|
aminoglycosides, cephalosporin, fluoroquinolones, metronidazole, Penicillin, vancomycin
|
|
|
These drugs disrupt the bacterial/fungal cell membranes 1
|
polymyxins
|
|
|
What is the mechanism of action of Pentamidine
|
Unknown
|
|
|
Rx THAT MESS WITH CELL WALL
|
|
|
|
Penicillin
|
360
|
|
|
Which is the IV form and which is the oral form
|
G = IV, V=oral
|
|
|
Mechanism of action? 3
|
Bind PBP; Inh transpeptidase rxn; activate autolytic enzymes
|
|
|
T or F: penicillin is effective against gram pos and gram neg rods 4
|
False: pcn used for common streptococci (not staph), meningococci, gram pos bacilli and treponema. Not used for GNR
|
|
|
What give with PCN for inhibiting tubular secretion in kidney?
|
Probenecid
|
|
|
What should you watch out for when giving penicillin? 2
|
Hypersensitivity rxn (urticaria,severe pruritus) and hemolytic anemia
|
|
|
Methicillin, nafcillin, dicloxacillin
|
362
|
|
|
These drugs are used mainly for what type of infection
|
Staphlococcal infection (hence very narrow spectrum) NOT MRSA
|
|
|
T or F: these drugs have the same mechanism of action as penicillin
|
TRUE
|
|
|
Are these drugs penicillinase resistant? If so why?
|
Bulkier R group makes these drugs resistant to penicillinase
|
|
|
What should you watch out for when giving these drugs? 3
|
Hypersensitivity rxn (urticaria,severe pruritus); methicillin can cause interstitial nephritis; naficillin can cause neutropenia
|
|
|
Ampicillin and amoxicillin
|
362
|
|
|
T or F: these drugs have the same mechanism of action as penicillin
|
TRUE
|
|
|
Which has greater oral bioavailability?
|
amOxicillin (O for Oral)
|
|
|
What do you use these for?
|
Ampicillin/amoxicillin HELPS to kill enterococci, H. influenzae, E. coli, Listeria monocytogenes, Proteus mirabilis, Morazella catarrhalis
|
|
|
Can penicillinase effect these drugs efficacy?
|
Yes, they are penicillinase sensitive
|
|
|
Why not give these drugs with a penicillinase inhibitor. Name one.
|
clavulanic acid
|
|
|
Ampillicin + aminoglycosides synergistic for? 2
|
Enterococcal & listerial inf
|
|
|
What should you watch out for when giving these drugs?
|
Hypersensitivity rxn (ampicillin rash is not HSR), pseudomembranous colitis
|
|
|
Carbenicillin, piperacillin, ticarcillin
|
362
|
|
|
Why are these considered to have an extended spectrum? 3
|
Because they are effective against GNR like pseudomonas, enterobacter, klebsiella
|
|
|
What should you watch out for when giving these drugs? 1
|
Hypersensitivity rxn
|
|
|
Why does concomitant administration with clavulanic acid increase the efficacy of these drugs?
|
Because they are penicillinase sensitive. (only piperacillin and ticarcillin)
|
|
|
Have a synergistic fx w/? 1
|
Aminoglycosides
|
|
|
Cephalosporins
|
363
|
|
|
What is the mechanism of action of Cephalosporins?
|
bind PBP
|
|
|
How are they similar/different from penicillin?
|
both have a beta-lactam ring structure but cephalosporins are less susceptible to penicillinases; both bactericidal
|
|
|
What are the main similarities/difference between 1st and 2nd generation cephalosporins?
|
2nd gen has extensive gram neg coverage but weaker gram pos coverage
|
|
|
1st gen covers what bugs? Cefazolin, cephalexin 5
|
gram positives (staph and strep), Proteus mirabilis, E. coli, Klebsiella (PEcK)
|
|
|
2nd gen covers what bugs? Cefotetan, cefoxitin, cefamandole, cefuroxime, cefaclor 8
|
Less gram positives (staph and strep), H. influenzae, Enterobacter aerogenes, Neisseria, Proteus mirabilis, E. coli, Klebsiella (HEN PEcK)
|
|
|
What can 3rd generation drugs do that 1st and 2nd generation can't?
|
Cross the blood brain barrier
|
|
|
What are some other benefits of 3rd gen? Ceftazidime, cefoperazone, cefotaxime, cefoperazone, ceftriaxone, cefixime 3
|
better activity against gram neg bugs resistant to beta-lactam drugs. Ceftazidime for Pseudomonas and ceftriaxone for N. gonorrhea
|
|
|
What are the benefits of 4th gen (e.g. Cefipime)? 3
|
increased activity against Pseudomonas, gram pos organisms and more beta-lactamase resistant (i.e. 4th gen combines 1st gen and 3rd gen characteristics into super drug)
|
|
|
What drugs should you avoid taking with cephalosporins? 2
|
Aminoglycosides (increases nephrotoxicity) and ethanol (causes a disulfiram-like rxn -- headache, nausea, flushing, hypotension)
|
|
|
Aztreonam
|
364
|
|
|
When would you use aztreonam? 3
|
Only to treat Klebsiella, Pseudomonas and Serratia spp.
|
|
|
Is it beta-lactamase resistant?
|
Yes, this is one of the huge benefits of the drug, and it is not cross-reactive with PCN!
|
|
|
Which population of pt. is this drug good for?
|
The PCN-allergic patient that can't take aminoglycosides b/c of renal insufficiency
|
|
|
Are there any toxicity issues with this drug?
|
Not really. Generally well tolerated with occasional GI upset. Vertigo, Headache and rare hepatotoxicity have been reported.
|
|
|
Imipenem/cilastatin
|
364
|
|
|
What is imipenem?
|
broad spectrum beta-lactamase-resistant abx
|
|
|
What do you always administer it with and why?
|
cilastatin -- it decreases inactivation of imipenem in renal tubules
|
|
|
What do you use it for? 3
|
Gram pos cocci, gram neg rods and anaerobes (broad spectrum)
|
|
|
What bug is it the drug of choice for?
|
Enterobacter
|
|
|
What are its side-effects 3
|
GI distress, skin rash, seizures at high conc.
|
|
|
Vancomycin
|
364
|
|
|
Is it bactericidal or bacteriastatic and why?
|
Bactericidal because it blocks cross linkage and elongation of peptidoglycan by binding D-ala D-ala protion of cell wall.
|
|
|
How does resistance to Vanco occur?
|
D-ala D-ala is replaced with D-ala D-lactate which vanco does not block
|
|
|
What is it used for? 2
|
Used for serious infection that is resistant to other drugs (e.g. gram pos multi-drug resistant organisms like S. aureus and C. difficile, methicillin resistant staph (MRSA))
|
|
|
What are the important toxicities of vanco? 3
|
generally NOT many problems except: Nephrotoxicity, Ototoxicity and Thrombophlebitis
|
|
|
What can happen with rapid infusion of vanco?
|
Red man's syndrome. Diffuse flushing which can be controlled by pretreatment with anti-histamines and with slow infusion rate
|
|
|
Fosfomycin
|
364
|
|
|
Mech of action?
|
Inh formation of N-acetylmuranic acid for peptidoglycan synth
|
|
|
Resistance from?
|
Dec intracellular accumulation
|
|
|
Synergistic with? 2
|
Beta-lactam, quinolone
|
|
|
Bacitracin
|
365
|
|
|
Mechanism of action
|
Interfere with late stage of cell wall synth
|
|
|
Limited use to? Why?
|
Nephrotoxicity makes it only topical
|
|
|
Cycloserine
|
365
|
|
|
Mechanism of axn?
|
Antimetabolit that blocks D-ala incorporation
|
|
|
Only used for?
|
2nd line TB
|
|
|
Significant tox?
|
Neurotox: tremors, seizures, psychosis
|
|
|
Daptomycin
|
365
|
|
|
Mechanism of action?
|
Vanco-like
|
|
|
Extended spectrum to?
|
VRE, staph
|
|
|
Significant tox?
|
Myopathy -> monitor Cr
|
|
|
Protein Synthesis Inhibitors
|
|
|
|
Which drugs target bacterial protein synthesis by blocking the 30S unit vs 50S unit?
|
Buy AT 30, CCELLS at 50
|
|
|
What does AT stand for?
|
A = Aminoglycosides (streptomycin, gentamicin, tobramycin an damikacin. And T = Tetracyclines
|
|
|
What does CCELLS stand for?
|
C = Chloramphenicol, clindamycin, E= Erythromycin, L= Lincomycin and L= Linelizod; Streptogramin
|
|
|
Which of the above are bactericidal?
|
Only the aminoglycosides are, the rest are bacteriostatic
|
|
|
Aminoglycosides
|
377
|
|
|
Name some aminoglycosides? 5
|
Gentamicin, neomycin, amikacin, tobramycin and streptomycin
|
|
|
How do these drugs work? 3
|
Block initiation complex formation; cause misreading of mRNA code; inh translocation
|
|
|
Why are they ineffective against anaerobes?
|
They require oxygen for uptake into bacteria
|
|
|
When would you use aminoglycosides? 1
|
against severe gram-negative rod infections
|
|
|
What drugs can you use aminoglycosides with for synergy?
|
the drugs that inhibit cell wall synthesis (e.g. penicillin and cephalosporins -- the beta-lactam antibiotics). Presumably this allows the drug to get in with out reliance on oxygen transport
|
|
|
What drug in this class is commonly used for bowel surgery?
|
Neomycin
|
|
|
For systemic fx, must be given? 2
|
IM, IV
|
|
|
What are the 2 major toxicities? Other 2?
|
Nephrotoxicity (esp. when used with cephalosporins) and Ototoxicity (esp. when used with loop diuretics) -amiNOglycosides - NM blockade, skin rxn
|
|
|
Tetracyclines
|
371
|
|
|
Name some tetracylcines 4
|
Tetracycline, doxycycline, demeclocycline, minocycline
|
|
|
How does it work?
|
Blocks t-RNA attachment to 30S subunit
|
|
|
Which tetracycline can you use in patients with renal failure and why?
|
Can use doxycycline because its elimination is fecal
|
|
|
Should you take these drugs with a glass of milk?
|
NO, because it intereferes with absorption in the gut as does antacids and iron-containing preparations
|
|
|
What are tetracyclines used for?
|
VACUUM your RUG -- Vibrio cholerae, Acne, Chlamydia, Ureaplasma, Urealyticum, Mycoplasma pneumoniae, Rickettsia, tUlaremia, b. burGdorferi
|
|
|
What are the common toxicities 6
|
GI distress, bone & teeth deposition, Fanconi's, photosensitivity, hepatotox, vestibular tox (dose-dependent, reversible)
|
|
|
Macrolides
|
372
|
|
|
Name some macrolides? 3
|
Erythromycin, azithromycin, clarithromycin
|
|
|
How do these drugs work?
|
inhibit 50S transpeptidation
|
|
|
What are they used for? 4
|
M pneumoniae, u. urealytic, legionella, chlamydia trachomatis, chyl pneumoniae, c. jejuni, diph, pertussis, HIB, moraxella, neisseria, MAC, h. pylori
|
|
|
Mnemonic for macrolide use?
|
Eryc's Nipple is at his Mid Clavicular Line (Eryc is brand name for erythromycin). Mycoplasm, Legionella, Chlamydia, Neisseria.
|
|
|
What are the major toxicities? 4
|
GI discomfort, acute cholestatic hepatitis, eosinophilia, skin rashes
|
|
|
What is the most common cause for non-compliance to macrolides?
|
GI discomfort
|
|
|
Chloramphenicol
|
370
|
|
|
How does this drug work?
|
inhibits 50S peptidyltransferase
|
|
|
Main use? 3
|
H. influenzae, N. meningitides, bacteriodes. Used conservatively b/c of toxicity
|
|
|
What are the main toxicities? 3
|
Anemia and aplastic anemia (both dose dependent), gray baby syndrome (in premes b/c they lack UDP-glucoronyl transferase), Inh CYP 450
|
|
|
Clindamycin
|
372
|
|
|
How does it work?
|
blocks peptide bond formation at 50S
|
|
|
When do you use it? 2
|
Anaerobic infections (e.g. Bacteroides fragilis and C.perfringens), PCP
|
|
|
Toxicities? 3
|
Pseudomembranous colitis, fever, diarrhea
|
|
|
Streptogramin
|
373
|
|
|
Mechanism of action 2
|
Bind 50S, constricting exit channel; also dec free tRNA
|
|
|
Bacteriostatic or cidal?
|
Bacteriocidal
|
|
|
Fx on CYP324
|
Inh -> incr drugs
|
|
|
Linezolid = oxazolidinones
|
373
|
|
|
Mechanism of action
|
Bind site on 50S; blocking complex
|
|
|
ANTIMETABOLITE
|
|
|
|
Sulfonamides
|
383
|
|
|
Name some sulfonamides 3
|
Sulfamethoxazole (SMX), sulfisoxazole, triple sulfa and sulfadiazine
|
|
|
How does it work?
|
Inhibits bacterial folic acid synthesis from PABA by blocking dihydropteroate synthase.
|
|
|
What are its uses? 4
|
Gram-positive, gram-negative, Nocardia, Chlamydia. Triple sulfas and SMX for simple UTIs
|
|
|
Toxicities? 7
|
hypersensitivity rxn inc exfoliative dermatitis, PAN, Steven-Johnson, hemolysis if G6PD deficient, nephorotoxicity tubulointerstitial nephritis, kernicterus in infants by displacing bilirubin, displace other drugs from albumin (e.g. warfarin)
|
|
|
Trimethoprim
|
384
|
|
|
How does it work?
|
inhibits folic acid pathway by blocking dihydrofolate reductase which humans have as well
|
|
|
What are its uses? 7
|
TMP/SMX for HIB, catarrhalis, cholera, nocardia, Shigella, typhi, and prophylaxis for PCP in AIDS patients
|
|
|
Toxicities? 2
|
Megaloblastic anemia, pancytopenia (may be alleviated with supplemental folinic acid)
|
|
|
Fluoroquinolones
|
385
|
|
|
What the most famous floroquinolone?
|
Ciprofloxacin (treatment for Anthrax)
|
|
|
How does it work?
|
inhibits DNA gyrase (topoisomerase II)
|
|
|
What are its uses? 2
|
GI & GU
|
|
|
What population is contraindicated for use? 2
|
pregnancy and children
|
|
|
What are its toxicities? 6
|
GI upset, superinfection, skin rashes, headache, dizziness and tendonitis and tendon rupture in adults. FluoroquinoLONES hurt attachment to BONES.
|
|
|
Metronidazole
|
|
|
|
How does it work?
|
forms toxic metabolites in the bacteria. Bactericidal.
|
|
|
What are its uses? 5
|
anti-protozoal: Giardia, Entamoeba, Trichomonas, Gardnerella vaginalis, anaerobes (bacteroides, clostridium)
|
|
|
What is the role of Metronidazole in H. pylori infection?
|
Used as part of triple therapy: bismuth, amoxicillin and metronidazole
|
|
|
Main toxicity?
|
disulfiram-like (antabuse) reaction to alcohol and headache
|
|
|
Which drug do you use to treat anaerobic infections above the diaphram and below the diaphram
|
anaerobes above diaphram: Clindamycin, and anaerobes below diaphram: metronidazole
|
|
|
Polymyxins
|
|
|
|
How does it work?
|
disrupts osmotic properties of bacteria, acts like a detergent
|
|
|
What is it used for?
|
resistant gram negative infections
|
|
|
Toxicities? 2
|
neurotoxicity, ATN
|
|
|
Isoniazid
|
390
|
|
|
How does it work?
|
decreases synthesis of mycolic acid
|
|
|
What is it used for?
|
MTB (mycobacterium tuberculosis). The only agent used as solo prophylaxis against TB
|
|
|
Toxicities? 4
|
Hemolysis if G6PD deficient, neurotoxicity, hepatotoxicitiy, drug induced SLE. INH, Injures Neurons and Hepatocytes
|
|
|
What vitamin prevents neurotoxicity
|
Vitamin B6 (pyridoxine)
|
|
|
Why are toxicities particularly important to monitor in patients taking INH?
|
INH half-lives are different in fast versus slow acetylators!
|
|
|
Rifampin
|
391
|
|
|
How does it work?
|
inhibits DNA-dependent RNA polymerase
|
|
|
What is it used for? 2
|
MTB, meningococcal prophylaxis
|
|
|
Toxicities? 2
|
Minor hepatotoxicity and increases P-450
|
|
|
How can it be used for leprosy?
|
rifampin delays resistance to dapsone when used for leprosy
|
|
|
What would happen if you used rifampin alone?
|
get rapid resistance
|
|
|
What does it do to bodily fluids?
|
makes them red/orange in color
|
|
|
What are the 4 R's of Rifampin
|
RNA polymerase inhibitor, Revs up microsomal p-450, Red/Orange body fluids, Resistance is rapid
|
|
|
Anti-TB Drugs
|
|
|
|
What are the anti-TB drugs? 5
|
Rifampin, Ethambutol, Streptomycin, Pyrazinamide, Isoniazid (INH) -- RESPIre
|
|
|
What do you use for TB prophylaxis?
|
INH
|
|
|
What toxicity is common to all?
|
hepatotoxicity
|
|
|
microtubule
|
|
|
|
what are the shape and dimensions of a microtubule? 3
|
cylindrical, 24 nm in diameter, variable length.
|
|
|
what are the components of a microtubule
|
polymerized dimers of alpha and beta tubulin (+2 GTPs per dimer)
|
|
|
where are microtubules found 4
|
cilia, flagella, mitotic spindles, neuronal axons (slow axoplasmic transport)
|
|
|
antihelminthic drug that acts on microtubules 2
|
mebendazole/thiabendazole
|
|
|
anti breast cancer drug that acts on microtubules (prevent disassembly)
|
taxol
|
|
|
antifungal drug that acts on microtubules
|
griseofluvin
|
|
|
anti cancer drug that acts on microtubules (prevent assembly) 2
|
vincristine/vinblastine
|
|
|
anti gout drug that acts on microtubules
|
cholchicine
|
|
|
Resistance mechanisms for various antibiotics
|
|
|
|
Most common resistance mechanism for penicillins / cephalosporins.
|
Beta-lactamase cleavage of beta-lactam ring.
|
|
|
Most common resistance mechanism for aminoglycosides. 3
|
Modification via acetylation, adenylation, or phosphorylation.
|
|
|
Most common resistance mechanism for vancomycin.
|
Terminal D-ala of cell wall component replaced with D-lac; decrease affinity.
|
|
|
Most common resistance mechanism for Chlorampenicol.
|
Modification via acetylation.
|
|
|
Most common resistance mechanism for macrolides.
|
Methylation of rRNA near erythromycin's ribosome-binding site.
|
|
|
Most common resistance mechanism for tetracycline.
|
Decrease uptake or increase transport out of cell.
|
|
|
Most common resistance mechanism for sulfonamides.
|
Altered enzyme (bacterial dihydropteroate synthetase), decrease uptake, or increase PABA synthesis.
|
|
|
Nonsurgical antimicrobial prophylaxis
|
|
|
|
Drug of choice for meningococcal infection.
|
Rifampin (drug of choice), minocycline.
|
|
|
Drug of choice for gonorrhea.
|
Cefriaxone.
|
|
|
Drug of choice for syphilis.
|
Benzathine penicillin G.
|
|
|
Drug of choice for history of recurrent UTIs.
|
TMP-SMX.
|
|
|
Drug of choice for Pneumocystis carinii pneumonia.
|
TMP-SMX (drug of choice), aerosolized pentamindine.
|
