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121 Cards in this Set
- Front
- Back
This drug works by inhibiting transcription in bacteria (i.e DNA --XXX--> RNA)
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Rifampin
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Sulfonamides & other anti-metabolites are often ______
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bacteriostatic (slow growth only)
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Sulfonamides are ____ and sulfanylmides are used to mimic ___ in _____ acid metabolism
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antimetabolites
PABA folic |
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Tetracyclines, chloramphenicol, and erythromycin are _____ while aminoglycosides are ____. They all work by ____.
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bacteriostatic
bactericidal inhibiting protein synthesis. |
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Factors that influence drug choice.
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1.)Sensitivity of the infecting organism to the drug
2.)Distribution of the drug within the body (will it get to the site of infection?) 3.)Relative toxicity of the drug 4.)Severity of the infection |
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For most sites what is the major route of drug uptake?
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passive diffusion
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Active transport of anionic and cationic drugs leads to their accumulation in the ____, and their export from the _____.
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kidney
brain |
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Factors which determine outcome of treatment?
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Condition of tissue,
status of the patient immune system, development of microbial resistance |
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When are you most likely to see suprainfection?
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1.)Prolonged treatment
2.)Use of broad spectrum antibiotics 3.)Immunocompromised patient |
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When should you use drug combinations?
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Emergency treatment
Prevention of resistance Synergism Mixed infections |
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What are the 3 types of beta-lactams?
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Penicillins
Cephalosporins Other beta-lactams |
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Most commonly prescribed beta-lactam?
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amoxicillin
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Bacteria resistant to penicillin G?
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Staph aureus (mostly resistant now)
Enterococcus faecalis Gram Neg Bacilli Bacteroides fragilis (other bacteroides are susceptible) Chlamydia |
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The beta-lactam ring is responsible for what properties of beta-lactams?
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a. essential for antimic. activity
b. responsible for drug allergy c. responsible for neurotoxicity |
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The weak acid group in beta-lactams is responsible for what properties of beta-lactams?
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a. renal tubular secretion
b. potential cation toxicity |
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Combination with ____ decreases rate of renal secretion of _____
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probenicid
Penicillin G |
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Phenoxymethylpenicillin also known as _____, is ____, and has good ______
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Pen V
acid stable oral availability |
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The two repoistory pencillins are?
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Procaine Penicillin G
Benzathine Penicillin G |
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How should repository pencillins be administered?
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Intramusculary, because they are poorly soluble
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Which one, Pen G or Pen V should be used against Neisseria?
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Pen G
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The beta-lactamase resistant penicillins are?
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Methicillin (no longer used)
Oxacillin Cloxacillin Dicloxacillin Nafcillin |
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The beta-lactamase resistant penicillins should be used to treat ___?
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Penicillin G-resistant Staph. aureus
Methicillin (no longer used) Oxacillin Cloxacillin Dicloxacillin Nafcillin |
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Methicillin is no longer marketed because of ______.
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renal toxicity (interstitial nephritis
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Nafcillin is eliminated by ______ – thus there is less chance of ___ in patients with compromised ______
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biliary excretion
CNS toxicity renal function |
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Aminopenicillin, Carboxypenicillins
Ureidopenicillins are examples of ___ |
BROAD SPECTRUM PENICILLINS
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Better oral absorption? amoxicillin or ampicillin?
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Amoxicillin
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Available for both oral & parenteral use? amoxicillin or ampicillin?
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Ampicillin
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Effective against shigella and listeria? amoxicillin or ampicillin?
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Ampicillin
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This broad spectrum penicillin is useful against UTI's because it's concentrated in the urine.
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Carbenicillin indanyl
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None of the broad-spectrum penicillins are resistant to _____
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b-lactamases.
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B-lactamase inhibitors affect ____ class A b-lactamases but not _____ b-lactamase.
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plasmid
chromosomal |
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Hypersensitivity, Neurotoxicity
Cation toxicity are all side effects seen with _____ |
penicillins
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What is the Herxheimer reaction, what drug class associated with it, and what disease is usually being treated?
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chills, fever, headache, muscle & joint pain shortly after first penicillin injection in patients with syphilis. Rash develops at syphilitic lesions – disappears in a few weeks. Does not recur with subsequent penicillin injections. Usually not necessary to withhold treatment.
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High doses of penicillin can result in ___ and ___ loss
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Fluid and electrolyte loss – high doses of any penicillin: penicillin anion is concentrated in renal tubules and produces an osmotic diuresis: increases Na+ uptake by principal cells of collecting tubules & secretion of K+ and H+ into the luminal fluid. Thereby producing hypokalemic alkalosis.
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Doses of penicillin > 6 g/day can cause ___ anemia.
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Coombs-positive hemolytic anemia
Penicillin dose > 6 grams/day About 10% of patients will show a positive Coombs test. A few patients will become anemic |
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____ was a side-effect that caused methicillin to be withdrawn from the market and often seen with other penicillins (>10g/day) as well.
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Interstitial nephritis
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Diarrhea, pseudomembranous colitis, maculopapular rash caused by which two drugs?
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Ampicillin, amoxicillin
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Prolonged bleeding caused by platelet inhibition are associated w/ these two drugs?
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Carbenicillin, ticarcillin
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Cephalosporins are b-lactams. What ring position substitution is associated with beta-lactamase resistance and spectrum?
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7
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Cephalosporins are b-lactams. What ring position substitution is associated with pharmokinetic profile and toxicity?
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3
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Which has a broader antimicrobial spectrum? Cephalosporins or penicillin G?
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Cephalosporins
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Should cephalosporins be prescribed to people with hypersensitivity reactions to penicillins?
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Hell no. There is an approximately 10% incidence of cross-hypersensitivity between penicillins and cephalosporins: cephalosporins are generally too risky for use in patients who have had an anaphylactic episode with a penicillin.
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Second generation cephalosporins are more active versus ____ or ____than 1st gen.
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Haemophilus
B. fragilis |
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Of the 1st and 2nd generation cephalosporins, only _____ reaches CNS at therapeutic levels. Is it the drug of choice for treatment of meningitis?
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cefuroxime
no |
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Unique property of 4th generation cephalosporins?
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Resistant to most beta-lactamases and doesn't induce their expression.
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Name the only 4th generation cephalosporin we talked about in class.
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Cefepime
(NOT stable to some extended spectrum b-lactamases ) |
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CEPHALOSPORIN used to treat gonorrhea? How is excreted? What generation?
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Ceftriaxone
biliary excretion (just like Nafcillin) 3rd generation |
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CEPHALOSPORIN used to treat pseudomonas? What generation?
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Ceftazidime
3rd generation (plus aminoglycoside for pseudomonal meningitis) |
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Cephalosporins that can be administered orally have an _______
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alpha-amino group on the substituent attached to carbon 7. This structure allows uptake by a dipeptide transport system in the gut
CEPHALEXIN is an example. |
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Group A 2nd generation cephalosporins used for
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H. influenzae
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Group B 2nd generation cephalosporins used for
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B. fragilis
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3rd generation cephalosporins use a ____ group to confer stability to b-lactamases of ____
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Oxime ether group
enterobacteriaceae |
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3rd generation cephalosporins use a ____ group that affects binding to PBPs and entry into the periplasm
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Aminothiazole ring
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Cephalosporins are known to cause ___ damage EXCEPT for ____ (looking for a drug name here)
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Kidney damage (direct tubular necrosis).
Cephalexin and a few other cephalosporins. |
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Adverse effects associated with the methythiotetrazole cephalosporins (e.g., Cefoperazone)
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Delayed blood clotting because of low prothrombin levels in blood
Alcohol intolerance |
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These two other beta-lactams are Broad spectrum - useful in emergency treatment
No cross-resistance with other b-lactams: they are not recognized well by bacterial b-lactamases |
meropenem & imipenem - cilastatin
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This other beta-lactam is Only effective against aerobic Gram neg. bacteria, Not hydrolyzed by b-lactamases
Little cross-allergenicity with other b-lactams |
Aztreonam
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Cilastatin inhibits renal ______, an enzyme that inactivates ________
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dehydropeptidase-1
imipenem |
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____ helps prevent kidney toxicity of imipenem by blocking its active uptake and accumulation by renal tubule cells
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Cilastatin
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Most serious side-effect of cilastatin and imipenem?
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CNS toxicity is the most serious adverse effect: decreased consciousness and myoclonic jerking. In part, this may result from cilastatin inhibition of imipenem transport out of the CSF.
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Not hydrolyzed by dehydropeptidase-1.
Decreased incidence of CNS toxicity compared with imipenem/cilastatin |
Meropenem ( an "other" beta-lactam)
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Binds to PBP-3 of aerobic Gram negative bacteria ONLY. Little cross-allergenicity w/ other beta-lactams
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Aztreonam
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Not hydrolyzed by plasmid or chromosomal b-lactamases, and does not induce expression of the latter.
If chromosomal b-lactamases have been induced by other b-lactams, they will bind _______ and prevent it from binding to PBP-3. |
aztreonam
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Single i.m. injection for urethral gonorrhea
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beta-lactam substitute
Spectinomycin (Trobicin®) |
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Treatment of meth.-resistant Staph. aureus (MRSA)
Backup drug for C. difficile pseudomembranous colitis. Little activity vs Gm- bacilli |
beta-lactam substitute
Vancomycin |
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Side effects of vancomycin?? (there's a whole bunch)
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Ototoxic: deafness, sometimes irreversible
Nephrotoxic: Blood & protein in urine Thrombophlebitis: (clots in bloodstream) occur in over 10% of patients Hypotension & “red man” syndrome because the drug releases histamine. Administer antihistamines 2 hrs before infusing the drug slowly (over 1 hr) i.v.. |
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NEW AGENTS PRIMARILY FOR RESISTANT Gm+ ORGANISMS
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Quinupristin/dalfopristin (Synercid®)
Linezolid (Zyvox®) Daptomycin(Cubicin®) |
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A combination of two streptogramins: inhibitors of protein synthesis
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Quinupristin/Dalfopristin (Synercid IV®)
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Active against vancomycin-resistant and multidrug-resistant Enterococcus faecium.
NOT active against Enterococcus faecalis |
Quinupristin/Dalfopristin (Synercid IV®)
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Main adverse reaction is muscle and joint pain
Inhibits Cyp3A4. |
Quinupristin/Dalfopristin (Synercid IV®)
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Parenteral and oral formulations for treatment of vancomycin-resistant enterococci.
Binds to 23S ribosomal RNA – no cross-resistance with other protein synthesis inhibitors |
Linezolid (Zyvox®)
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Thrombocytopenia is possible. Platelet counts should be monitored if treatment exceeds two weeks.
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Linezolid (Zyvox®)
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_________inhibits MAO – patients should avoid foods rich in tyramine, or drugs metabolized by MAO.
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Linezolid (Zyvox®)
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A cyclic lipopeptide antibiotic.
Inserts in cell membrane and causes rapid depolarization |
Daptomycin(Cubicin®)
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Indicated for skin and skin structure infections caused by:
Staph. aureus (including MRSA) Strep. pyogenes Strep. agalactiae Strep. dysgalactiae subsp. Equisimilis E. faecalis (Vanco sensitive) Toxicities: Rhabdomyolysis: Monitor patients for muscle pain/weakness. Discontinue if blood CPK>1000 units/L. Consider temporary discontinuation of HMG-CoA reductase inhibitors (“statins”). Paresthesias (at high doses). |
Daptomycin(Cubicin®)
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Bacterial Protein Synthesis Inhibitors
BROAD SPECTRUM? (name 2 classes) |
Chloramphenicol
Tetracyclines |
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Bacterial Protein Synthesis Inhibitors
Intermediate SPECTRUM? (name 2 classes) |
Macrolides
Ketolides |
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Bacterial Protein Synthesis Inhibitors
Narrow SPECTRUM? (name 3 classes) |
Lincosamides
Streptogramins Linezolid |
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Bacterial Protein Synthesis Inhibitors
All act on bacterial ___S ribosome except ____ which act on ____S |
50S
tetracyclines; 30S |
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Describe tetracycline mode of action.
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Reversible binding to 30S ribosome subunit blocks aminoacyl-tRNA access to acceptor site (A site)
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What organisms are tetracyclines active against?
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Active against many Gram + and Gram – bacteria including anaerobes, rickettsiae, chlamydiae(intracellular things), mycoplasmae (no wall).
Some drugs act against protozoa (e.g. doxycyline: Entamoeba and Plasmodium falciparum |
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2 ways tetracycline gets taken in by cells?
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Both passive diffusion and active uptake by bacteria with intracellular concentration.
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3 modes of resistance developed to tetracyclines?
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1.)Upregulation of efflux pump
2.)Production of proteins interfering with ribosomal binding 3.)Can sometimes find Impaired uptake via the active process Enzymatic inactivation of the drug |
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Tetracyclines are usually administered ___ except ___ which is administered by ___
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orally
tigecycline; IV |
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What interferes with absorption of tetracyclines?
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Interference of uptake by food, divalent cations (Ca++, Mg++, Fe++ ) and antacids, dairy products.
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Tetracyclines Enter all body fluids well except ____
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CSF
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Tetracyclines are excreted in the ___ and ____ except these two drugs (__ and ___) which are only excreted in the _____
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bile and urine
doxycycline and tigecycline are exclusively in bile |
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true or false? tetracyclines enter breast milk and cross placenta?
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true
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Side-effect of tetracycline discussed extensively in class
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Chelation with calcium causes binding to growing bones/teeth - damage.
Stained teeth |
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Huge list of Tetracycline side effects
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Irritation of GI tract (diarrhea, vomiting, nausea)
Gastrointestinal effects due to microbial flora change Effects on bones and teeth Some minor liver toxicity but can be pronounced during pregnancy, in persons with liver dysfunction or with high I.V. drug doses High does may cause dizziness etc (vestibular toxicity) Significant urinary excretion of most drugs means accumulation to high dose and more toxicity can be found in persons with impaired kidney function (not for tigecycline/doxycyline which are excreted only via bile Hypersensitivity (drug fever and skin rashes) is uncommon. Occasional cases of photosensitivity reported after i.v. tetracyclines |
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____ has very broad spectrum of activity but NOT effective against ____ or ____ where the efflux pump is effective thereby causing intrinsic resistance.
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Tigecycline
Pseudomonas or Proteus |
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Approx 30% patients develop nausea
IV admin Excreted in bile. Name the drug |
Tigecycline
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Class of drug w/ Macrocyclic lactone ring
with deoxy sugars attached |
Macrolides
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Macrolides include:
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Erythromycin
Clarithromycin Azithromycin Kelotides (telithromycin) |
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Macrolides mode of action
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block transpeptidylation; bind to 50S ribosomal subunit
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Macrolides: susceptible organisms
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Many Gram positive and negative organisms including Neisseria
Some mycobacteria Intracellular bacteria, spirochetes (Treponema), Mycoplasmae, Legionella, Listeria, Helicobacter. |
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Methylation of the binding site in the 50S ribosome
blocks all ___ plus ___ and _____ |
macrolides
clindamycin (lincosamide) streptogramin B MLSb resistance |
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Erythromycin Resistance is usually plasmid or chromonsomally encoded? What are some ways resistance is conferred?
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plasmid
Reduced intracellular concentration Reduced cell permeability Increase active efflux Hydrolysis by esterases Methylation of the binding site in the 50S ribosome |
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Erythromycin is excreted in what?
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bile
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Erythromycin base is destroyed by ______
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stomach acid (enteric coating needed).
Esters and salts can provide acid resistance. Food interferes with uptake i.v. preparations also used |
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What drug for
Corynebacterium sp infections including erythrasma & diphtheria (to eradicate the organism) Chlamydial infections Community acquired pneumonia (because it covers both Strep pneumoniae and Legionella) Used for susceptible Staph and Strep infections with penicillin-allergic persons |
erythromycin
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_______metabolites inhibit cytochrome P450 enzymes (increased theophylline, oral anticoagulants, cyclosporine, methylprednisone)
Increases bioavailability of oral digoxin |
erythromycin
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Similar to erythromycin but also works on
Mycobacterium avium and M. leprae, Toxoplasma gondii |
Clarithromycin
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Similar to clarithromycin but does not interact with cytochrome P450 enzymes (smaller macrocyclic ring)
Very active against Chlamydia Penetrates tissues to high concn with in slow release, 3 day half life. Once a week dosing – very useful for STDs |
Azithromycin
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For macrolide-resistant strains where efflux pumps give resistance. Doesn’t work with resistance due to methylated target in ribosome.
Useful for community acquired pneumonias (Mycoplasma, Chlamydia, Legionella, Strep pneumoniae). Interacts with cytochrome P450 3A4 |
Ketolides (Telithromycin) small macrocyclic ring
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High risk of inducing Clostridium difficile pseudomembranous colitis
Mainly used for acne (as lotion) and in antibiotic combinations for treating and preventing mixed anaerobe infections (penetrating abdominal wounds, endocarditis prophylaxis in dental procedures pelvic abscess & septic abortion) |
Clindamycin
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Chloramphenicol mode of action?
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Chloramphenicol Binds 50S subunit and blocks transpeptidation
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Active against rickettsiae
Not active against chlamydiae |
Chloramphenicol
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Clinical resistance mainly associated with plasmid encoded acetyltransferase which inactivates the drug
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Chloramphenicol
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May be taken orally – absorbed very well
Provided as a succinate salt for i.v. use as base is insoluble - hydrolyzed in vivo. Distributes into all body fluids and tissues including CNS Inactivated in liver Metabolites and free drug mainly excreted in urine |
Chloramphenicol
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Inactivation is via conjugation with glucuronic acid
Conjugate excreted mainly in urine If liver dysfunction present, dosage must be reduced greatly since drug metabolism is mainly in the liver. |
Chloramphenicol
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Dose-related suppression of red cell production – can lead to aplastic anemia (rare)
Is bacteriostatic so may antagonize b-lactams where killing of bacteria depends on bacterial growth Inhibits liver metabolism of several drugs (including warfarin, phenytoin) |
Chloramphenicol
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Name the drug:
Newborn infants have poor glucuronic acid conjugation activity - develop gray baby syndrome gray color, flaccidity, hypothermia, shock |
Chloramphenicol
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Toxicity limits routine use of ______ in spite of extremely good bioavailability and range of microbes inhibited.
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Chloramphenicol
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Largely restricted to serious rickettsial infections and for bacterial meningitis when beta-lactams cannot be used.
Topical use in eye infections (but not effective for Chlamydia) |
Chloramphenicol
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Drug combination of a streptogramin A with a streptogramin B
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Quinupristin-dalfopristin
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Treatment of staphylococcal infections including VRSA and MRSA
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Quinupristin-dalfopristin
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Treatment of vancomycin-resistant Enterococcus faecium (but not E. faecalis)
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Quinupristin-dalfopristin
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Active against Gram-positives (including anaerobes) – including MRSA, VRSA, enterococci (both E. faecium & E. faecalis)
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Linezolid (an oxazolidone)
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Binds at a unique site on the 50S ribosome subunit causing protein synthesis inhibition. No cross-reactivity of resistance with other antibiotics
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Linezolid (an oxazolidone)
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Adverse effects include mild thrombocytopenia and bone marrow suppression
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Linezolid (an oxazolidone)
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