Term
| what can be used with PCN-sensitive pts? |
|
Definition
|
|
Term
| what is the mechanism of action for PCN/cephalosporin? |
|
Definition
| these drugs bind and inhibit PBPs (PCN-binding-proteins), which are bacterial transpeptidase enzymes required for new bacterial cell wall synthesis |
|
|
Term
| what happens if PBPs are successfully blocked? is this a bactericidal rxn? |
|
Definition
| defective cells walls cause osmotic swelling/release of autolytic enzymes and bacterial lysis. this is a bactericidal rxn. |
|
|
Term
| what does PCN/cephalosporin compete with in binding PBPs? |
|
Definition
|
|
Term
| what is the primary method of bacterial antibiotic resistance? what does it do? |
|
Definition
| beta-lactamase which breaks open and inactivates the B-lactam ring |
|
|
Term
| what is the result of breaking the beta lactam ring? what is this the source of in some pts? |
|
Definition
| penicilloic acids, this can be the source of a lot of allergies associated with the drug; can be a rash all the way up to anaphylaxis. |
|
|
Term
| is beta lactamase effective on both PCN/cephalosporin? |
|
Definition
|
|
Term
| how do PCN/cephalosporins interact with gram positive bacteria? what about gram negative? |
|
Definition
| they can just diffuse and bind to the PBPs easily. gram negative bacteria are harder for PCN/cephalosporin to enter, but 3rd/4th generation drugs are more efficacious. |
|
|
Term
| are 1st gen PCNs soluble? how are they administered? do they have much CNS penetration? are they biotransformed? acid labile? |
|
Definition
| they are water soluble and most are administered paraentrally, (IV/IM). they have low CNS penetration at normal doses. they are unchanged in the urine. they are acid labile. |
|
|
Term
|
Definition
| slows/blocks tubular secretion of B-lactam antibiotics, otherwise they only act for about an hour. |
|
|
Term
|
Definition
| the oral version of the original PCN G, used only for minor infections |
|
|
Term
| what spectrum drug is PCN-G considered? what is it paired with for more serious infections? is it resistant to B lactamases? can it penetrate gram – rods? |
|
Definition
| PCN-G is considered a narrow spectrum drug, and is paired with aminoglycosides. it is not resistant to B lactamases and it has difficulty penetrating gram – rods. |
|
|
Term
|
Definition
| a penicillinase –R drug that is resistant to beta-lactamase produces as some staphylococcal infections are. |
|
|
Term
| what are the 2nd generation PCNs? what is their advantage? |
|
Definition
| 2nd generation PCNs or aminoPCNs have the advantage of reliable oral bioavailability vs PCN G. amoxicillin/ampcillin are examples. |
|
|
Term
| are 2nd generation PCNs effective against gram - proteus vulgaris, pseudomonas aeruginosa, serratia? are they resistant to B-lactamases? |
|
Definition
|
|
Term
| what are gram – rods that are sensitive to 2nd generation PCNs/aminoPCNs? |
|
Definition
| e. coli, p. mirabilis, h. influenzae, salmonella\shigella, anaerobes |
|
|
Term
| what is the gram + spectrum of 2nd generation PCNs? |
|
Definition
| their gram + spectrum is the same as Pen G |
|
|
Term
| what is an example of a 3rd gen PCN? |
|
Definition
|
|
Term
| what is the 3rd generation PCN? are they indicated for gram +? what are the indicated for? are they co-prescribed with any other drugs? |
|
Definition
| antipseudomonal PCN (3rd generation) have less gram + activity than 1st,2nd generations and are mainly indicated for gram – P. aeruginosa, P, vulgaris. they are often prescribed in combination with an aminogylcoside such as gentamicin. |
|
|
Term
| are 3rd gen PCNs/antipseudomonals resistant to B-lactamases? are they used orally? |
|
Definition
| no and they have poor oral bioavailability. |
|
|
Term
| what is an example of the 4th gen PCNs/antipseudomonals? what spectrum are they? how are they administered? |
|
Definition
| piperacillin, and they are broad spectrum drugs, similar to 3rd gen PCNs, but with more gram - strains and less gram + strains, (similar to ampicillin). they require paraenteral administration. ** they are the most efficacious against pseudomonas** |
|
|
Term
| what are 4th gen PCNs such as piperacillin used with for enterococci such as those causing endocarditis? are they resistant to B-lactamases? |
|
Definition
| they are often paired with aminogylcosides and are not resistant to B-lactamases |
|
|
Term
| what are some examples of B-lactamase inhibitors? how do they bind? does it inhibit the chromosomal B-lactamase? |
|
Definition
| clavulanic acid, sulbactam, tazobactum are all suicide molecules that bind/inhibit the lactamase enzyme. different inhibitors combined with extended spectrum penicillins e.g., piperacillin-tazobactam. they doesn’t inhibit the chromosomal B-lactamase, just the plasmid version. |
|
|
Term
| what are the carbapenems? what are they similar to? what kind of spectrum do they have? are they effective against MRSA? if pts are allergic to PCN, will they be allergic to carbapenems? are they resisitant to B-lactamase? |
|
Definition
| carbapenems such as imipenem-cliastatin are other B-lactam antibiotics that have a similar M/A to PCN, they are broad spectrum for both gram+/- and anaerobes. they used for enterobacter infections, but not MRSA. they have cross-reactivity with PCN allergic rxn however. imipenem-cliastatin and other carbapenems are relatively resistant to B-lactamase. |
|
|
Term
| what does vancomycin bind to? what bacteria are sensitive to it? can PCN-allergic pts use this? |
|
Definition
| vancomycin is another B-lactam antibiotic that inhibits transglycosylase, (cell wall synth), and is bactericidal for only gram + bacteria including MRSA. PCN-allergic pts can used vancomycin. |
|
|
Term
| what are monobactams such as aztreonam used for? what is their M/A? what gram stain are they effective against? anaerobes? PCN allergy cross-reactivity? |
|
Definition
| aztreonam and other monobactams have a similar M/A to PCN, but only high affinity to gram – PBPs, and not much efficacy against gram+/anaerobes. monobactams have no cross-reactivity with PCN-allergic pts. |
|
|
Term
| what are clinical indications for B-lactam drugs? |
|
Definition
| otitis media, sinusitis, pharyngitis, lower respiratory infections, UTIs, and systemic infections. |
|
|
Term
| where do cephalosporins get their name from? |
|
Definition
| cephalosporin-isolated from cephalosporium acremonium in 1948 |
|
|
Term
| are cephalosporins B-lactam antibiotics? |
|
Definition
| yes, though the ring is larger and thus more inherently resistant to B-lactamases, often effective in penicillin-R (lactamase +) infections. |
|
|
Term
| do cephalosporins have cross-reactivity with PCN allergies? |
|
Definition
|
|
Term
| how are cephalosporins divided? |
|
Definition
| they are divided into 4 gens based on spectrum of activity against gram – rods. |
|
|
Term
| are cephalosporins effective against staph and typhoid fever? |
|
Definition
|
|
Term
| what do you see with increase in generation of cephalosporins? |
|
Definition
| gradual decrease with gram +, increase in gram – coverage, increase in resistance to inactivation by B-lactamases. |
|
|
Term
| what do you see with the 3-4th gen cephalosporins? |
|
Definition
| increase in CNS penetration, (lipid soluble) |
|
|
Term
| in terms of cephalosporin pharmacokinetics, how is cephalosporin absorption, distribution, metabolism, and excretion? |
|
Definition
| cephalosporins are mostly acid-labile, most administered via IM/IV, but each gen has some oral options. 1-2nd gen are water soluble. cephalosporins are metabolized very little, (sometimes deacetylated to active metabolites). they are mostly unchanged in urine, except cefeperazone & ceftriaxone with increased amounts via liver/biliary/GI. |
|
|
Term
| what does pairing cephalosporin with probenecid do? |
|
Definition
| slows/blocks tubular secretion |
|
|
Term
| what gram+/gram- efficacy do 1st gen cephalosporins have? |
|
Definition
| all 1st gen cephalosporins have a similar spectrum. their gram + is similar to PCN G, but often effective against lactamase and staphylococci. their gram – efficacy is similar to 2nd gen PCN. |
|
|
Term
| what is a common example of 1st gen cephalosporin use? Why? |
|
Definition
| cefazolin is used for pre-sx prophylaxis. it has a longer half life than others. |
|
|
Term
| what is the main feature of 2nd gen cephalosporins? what is an example of a 2nd gen cephalosporin? are they active against P aeruginosa? |
|
Definition
| their main feature is increased gram – activity, including against P. vulgaris/H. influenza. cefoxtin is an example of a cephalosporin . they are effective against lactamase-producing neisseria gonorrhea, bacteroides fragile and most anaerobes – but 3rd gen ceftriaxone is the DOC, (drug of choice). they are not active against P. aeruginosa. |
|
|
Term
| what is an example of a 3rd-gen cephalosporin? what is their gram + activity? gram -? are they active against P aeruginosa? are they active against lactamase? |
|
Definition
| 3rd gen cephalosporins usually have less gram + activity than 1-2nd gen, however they are used in gram + meningitis b/c of good lipid solubility for CNS penetration. ceftriaxone is a 3rd gen used for resistant gonorrhea, meningitis and pneumonia. they have increased gram – activity, covering most enterobacteriaceae and anaerobes, (cefotaxime). they have some activity against P. aeruginosa, but only via ceftazidime and cefoperazone. they have increased stability against lactamases. |
|
|
Term
| the mechanism of antibacterial action of cephalosporins involves: |
|
Definition
| inhibition of transpeptidation reactions |
|
|
Term
| what is the M/A for quinolones/fluoroquinolones? |
|
Definition
| bactericidal, bacterial DNA gyrase is inhibited, (bacterial enzyme is more susceptible than the human counterpart - topoisomerase) |
|
|
Term
| how do bacteria develop resistance for quinolones/fluoroquinolones? |
|
Definition
| bacterial resistance involves decreased bacterial uptake/binding to gyrase and increased efflux of the drug, (w/a pump) |
|
|
Term
| what are 3 drugs from the chicona tree in peru? |
|
Definition
| quinolones, quinidine, chloroquinolone |
|
|
Term
| are 1st gen quinolones used much anymore? what are some examples? |
|
Definition
| no. nalidixic acid and cinoxacin |
|
|
Term
| what are 1st gen quinolones used for? what is a caveat for their usage? what is their ADR? what characterized their pharmacokinetics? |
|
Definition
| they are used infrequently for UTIs, (common with gram + organisms like E. coli. resistance to these drugs can develop fairly rapidly to these drugs w/in a few days. ADRs include rash/GI disturbances. 1st gen quinolones are rapidly absorbed/rapidly excreted |
|
|
Term
| what are some examples of the fluoroquinilones/2nd gen quinolones |
|
Definition
| ciproflaxin, ofloxacin, and lomefloxacin |
|
|
Term
| what characterizes the fluoroquinilones/2nd gen quinolones? |
|
Definition
| the addition of fluoride and side rings significantly extents the gram – spectrum and unreliably adds some gram + activity. ciproflaxin, PO/IV is used as well as ofloxacin, PO/IV, and lomefloxacin, PO which are isomers |
|
|
Term
| would fluoroqunilones be effective for bacterial meningitis? what is their half life like? |
|
Definition
| no, they have low CNS penetrance. their half life ranges from 3-8 hrs |
|
|
Term
| is there anything that can interfere with fluroquinolone absorption? how is their excretion? |
|
Definition
| antacids with Al, Mg, Zn, FE, Ca may result in 50% decrease. they have mixed excretion: urine/GI unchanged: all reach effective concentration in urine/GI and accumulate in renal failure. |
|
|
Term
| can ciprofloxacin affect the half-life of other drugs? |
|
Definition
| yes, ciprofloxacin inhibits CYP-450 (drug metabolizing enzyme) and can increase the half life of other drugs |
|
|
Term
| how do 2nd generation quinolones affect pseudomonas? other gram -? |
|
Definition
| 2nd generation quinolones are broadly effective with gram – including most klebsiella, enterobacteriaceaa, pseudomonas (cipro is most active), hemophilius, mycobacteria, legionella, N. gonorrhoeae. |
|
|
Term
| what gram + are 2nd generation quinolones effective against? anaerobic? |
|
Definition
| 2nd generation quinolones are effective against selected gram +, some staph aureus, active against PCNase producers, but minimal activity against streptococci. they also have minimal anaerobic activity |
|
|
Term
| what is the main thing you want to think about in terms of 2nd gen quinolones? |
|
Definition
|
|
Term
| what are common clinical uses for 2nd gen quinolones? any advantages? |
|
Definition
| wide: skin/soft tissue, bone/joint, UTI/GI, respiratory. advantage: PO in serious gram – infections such as pseudomonas, which it is used prophylactically as in neutropenic pts. also, sexually transmitted disease such as C. trachomatis, (treated with ofloxacin) |
|
|
Term
| are 2nd generation quinolones indicated for use in CNS/meningitis? |
|
Definition
| no, due to low penetrance of CSF/CNS |
|
|
Term
| what are some examples of 3rd gen fluoroqunilones? |
|
Definition
| levofloxacin and gatifloxacin |
|
|
Term
| what characterizes 3rd gen fluoroqunilones? |
|
Definition
| increased PO absorbtion. high intracellular concentration in neutrophils/macrophages. they have a higher half life allowing one/day dosing such as levofloxacin w/a half life of 2-7 hrs and gatifloxacin at 2-8 hrs |
|
|
Term
| what characterizes 3rd gen fluoroqunilones against gram +/-? |
|
Definition
| they have increased gram + (esp w/streptococci). their gram – is similar to cipro, but cipro is still generally considered more gram – active. |
|
|
Term
| what are some ADRs for fluoroquinolone? |
|
Definition
| GI: nausea, vomiting, diarrhea, anorexia, taste disturbance. CNS: headache, dizziness, insomina. skin: rash, allergy, either photoallergy or phototoxicity, (highest w/lomefloxacin) nephrotoxicity: crystalluria may occur in alkaline urine |
|
|
Term
| how do qunilones and sulfonamides compare w/respect to nephrotoxicity? |
|
Definition
| opposites. with quinolones: crystalluria may occur in alkaline urine. with sulfonamides: crystalluria may occur in acid urine |
|
|
Term
| how do quinolones affect cartilage? |
|
Definition
| they can produce cartilage erosion/inhibition of juvenile cartilage development; leading to joint swelling, tendonitis, and tendon rupture, esp involving weight-bearing joints. |
|
|
Term
| who are quinolones contraindicated for? |
|
Definition
| pregnant/nursing women, children |
|
|
Term
| how do quinolones and PCNs/cephalosporins compare in terms of ADRs? |
|
Definition
| PCN/cephalosporins are generally more safe |
|
|
Term
| what is the mechanism of action for sulfonamides? |
|
Definition
| sulfonamides are bacteriostatic, synthetic analogs of PABA, which is essential for bacterial synthesis of folate. they inhibit dihydropteroate synthase, (enzyme that converts PABA to folic acid needed for DNA synth) |
|
|
Term
| what are sulfonamides commonly used for? |
|
Definition
|
|
Term
| what are sulfonamides used for systemically? |
|
Definition
|
|
Term
| what does bacterial resistance to sulfonamides usually consist of? |
|
Definition
| resistance usually consists of increased or altered production of dihydropteroate synthase, mutation of the PABA binding site, or decreased permeability of the bacterial membrane |
|
|
Term
| what do sulfonamides compete with (as anti-metabolites)? what are two important sulfonamide molecules? are they complexed with anything? |
|
Definition
| para-aminobenzoic acid. sulfamethoxazole (complexed with trimethoprim) and sulfisoxazole are 2 important sulfonamides. |
|
|
Term
| what do sulfonamides inhibit? what does trimetheprin inhibit? what is the action of these individually? what is the action of these together? |
|
Definition
| sulfonamides inhibit dihydropteroate sythase and trimetheprin inhibits dihydrofolate reductase. individually, these are bacteriostatic, together they are bactericidal |
|
|
Term
| what is the gram + spectrum for sulfonamides? |
|
Definition
| gram +: strepto-, gono-, meningococci, but generally not used alone due to increased resistance and preference for bactericidal drugs |
|
|
Term
| what is the gram - spectrum for sulfonamides? |
|
Definition
| e. coli, P. mirabablis for uncomplicated UTIs -> main indication for systemic sulfonamides |
|
|
Term
| can sulfonamides be used against h. influenzae/h. ducreyi and chlamydia trachomatis? |
|
Definition
| yes, but increased resistance often limits systemic use as single agents |
|
|
Term
| can sulfonamides be used against nocardia asteroides infections (lung/brain infection/abscess)? |
|
Definition
|
|
Term
| can sulfonamides be used PO? what is their distribution? how are they metabolized? how are they excreted? |
|
Definition
| sulfonamides have good PO bioavailabilty. they have wide distrobution, (plural/peritoneal/CNS). they are metabolized by acetylation. they are excreted mainly through urine: both metabolites and unchanged -> acidic urine decreases solubility causes crystalline drug deposits, alkaline urine favors solubility and excretion |
|
|
Term
| what are systemic sulfonamides used primarily for UTIs? |
|
Definition
| sulfisoxazole and sulfamethoxazole |
|
|
Term
| what are local sulfonamides used primarily for ulcerative colitis (bowel lumen)? |
|
Definition
|
|
Term
| what sulfonamide is used topically for opthalmic infections? |
|
Definition
|
|
Term
| what are ADRs for sulfonamides in terms of allergy? |
|
Definition
| rash, fever, hives, photosensitivity and more serious (stevens-johnson syndrome, less than 1%). pts w/ sulfa allergies can be cross-allergic to thiazide diuretics and sulfonylurea hypoglycemics as well |
|
|
Term
| what are ADRs for sulfonamides in terms of blood? |
|
Definition
| hemolytic anemia is possibly especially with G-6-PD deficiency, bone marrow suppression, newborns are at risk of developing kernicterus, (buildup of bilirubin in the brain) |
|
|
Term
| what are ADRs for sulfonamides in terms of the kidneys? |
|
Definition
| nephrotoxicity/crystalluria in acidic urine, esp N-acetylated metabolites |
|
|
Term
| what are ADRs for sulfonamides in terms of GI disturbances? |
|
Definition
| nausea, vomiting, diarrhea, headache |
|
|
Term
| what are ADRs for sulfonamides in terms of affecting blood levels of other things? |
|
Definition
| sulfonamides may decrease absorption/drug levels of oral contraceptives and folic acid |
|
|
Term
| what is the action of sulfamethoxazole and trimethoprim (TMP/SMX)? are they effective against effective for enterococci, pseudomonas aeruginosa, or anaerobes? |
|
Definition
| these have a synergistic inhibitory effect on folic acid synthesis. they have a similar spectrum and half life though trimethoprim is 20x more potent. they are not effective for enterococci, pseudomonas aeruginosa, or anaerobes however. |
|
|
Term
| can sulfonamides be used against gram + bacteria such as MRSA? |
|
Definition
| yes, they have activity against staph (MRSA), and strep, but it usually just increases resistance and variability |
|
|
Term
| can sulfonamides be used against gram - bacteria? |
|
Definition
| yes, gram - is the main indication for sulfonamides, including enterobacteriaceae, BUT not pseudomonas |
|
|
Term
| what are indications for sulfonamides? |
|
Definition
| UTIs, GI, respiratory infections (DOC for pneumoncystis jiroveci), prostatitis/vaginitis, otitis media |
|
|
Term
| are there ADRs for trimethoprin? |
|
Definition
| mostly skin effects/rashes. |
|
|
Term
| what are the bacteria commonly seen with UTIs? what is treatment? |
|
Definition
| e. coli (80%), ssaprophyticus, proteus, enterococci, klebsiella, pseudomonas, and other gram -. PO TMP/SMX for 3 days. (kidney - 14 days IV) |
|
|
Term
| what are males with prostatis treated with if <35? >35? |
|
Definition
| <35 prostatis is usually caused by to N. gonorrhoeae or C. trachomatis and treated by ofloxacin. >35 the infection is usually caused by e coli, pseudomonas or enterococcus and is treated by cipro, ofloxacin, or TMP/SMX for 10 days - 3 months |
|
|
Term
| what would you use to fight and infection by both gonococci and C trachomatis? |
|
Definition
|
|
