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MICABI - Exam 1
Lecture 4
| Question | Answer |
|---|---|
| these proteins are important for gram-negative susceptibility to b-lactam drugs | porin proteins |
| general mechanism of action of beta-lactam drugs | inhibition of cell wall synthesis (bactericidal) |
| three mechanisms of resistance to beta-lactam drugs | 1) beta-lactamases2) altered PBP structure3) failure to penetrate the cell (gram-negatives, can be due to porin changes) |
| beta-lactamase inhibitors (3) | Clavulanate; Sulbactam; Tazobactam |
| an example of altered PBP structure resistance to beta-lactams | MRSA: PBP2’ in Staphylococci – resistant to ALL Beta-lactams |
| absolute contraindications to beta-lactams (3) | Steven's johnsons; exfolative dermatitis; toxic epidermatitis necrolysis (TEN) |
| cross-reactivity between penicillins and cephalosporins | Small risk (5-10%), and highest with 1st generation. If patient is skin test +, should probably not receive cephalosporins unless the benefit > risk. |
| cross-reactivity between penicillins and carbapenems | Appreciable cross-reactivity |
| cross-reactivity between penicillins and monobactams | Negligible cross-reactivity (acceptible to prescribe if penicllin hypersensitivity) |
| indications where you would use desensitization | Syphilis in pregnancy, Neurosyphilis, Listeria, Enterococcal Endocaditis (cases where penicillin is the gold standard and ptn is allergic) |
| beta-lactam drug toxicities | Hypersensitivity, GI upset, Neurotoxicity |
| characteristics of beta-lactam neurotoxicity | associated with high-dose, esp. high-dose penicillin IV to treat serious infections; common sign is seizure (esp in young children) |
| these patients require dose monitoring and adjustment with beta-lactams | patiens with renal or hepatic insufficiencies |
| most staph and neisseria produce this | beta-lactamases |
| members of class I penicillin; narrow-spectrum, penicillinase-sensitive (4) | penicillin G, procaine PG, benzathine PG, penicillin V |
| class I penicillin spectrum | narrow-spectrum, penicillinase sensitive; Gram-positive (most of streptococci) plus Neisseria, many anaerobes, and spirochetes; Good CNS penetration |
| class I pencillin typically administered | IV (Pen V can be oral; the PGs have parenteral) |
| class I penicillins - metabolism | renally excreted |
| class I penicillins - common uses | meningitis, Strep, and syphillis (Jarisch-Herxheimer Reaction) |
| class I penicillins - primary SE | allergy |
| class II penicillins spectrum | Narrow spectrum, penicillinase-resistant (Same spectrum but not as potent as penicillin G to nonpenicillinase-producing strains of staphylcocci); Gram-positive (most of streptococci) plus Neisseria, many anaerobes, and spirochetes |
| class II penicillins - common uses | Staphylococcus aureus infection |
| class II penicillins (5) | Methicillin, Oxacillin, Cloxacillin, Dicloxacillin, Nafcillin |
| isoxazolyl penicillins [class II], (3) | Oxacillin, Cloxacillin, Dicloxacillin |
| class II penicillins - administration | isoxazolyl penicillins - oral or IV; methicillin and Nafcillin - IV only |
| methicillin toxicity | nephrotoxicity (not used that much anymore, class II) |
| nafcillin metabolism | Excreted in bile - eliminated mostly thru the liver (no need to adjust dose in renal impairment). |
| class III penicillins (aminopenicillins) spectrum | broader spectrum - Gram positive, plus some gram negative bacilli (H. influenzae, E. coli, Proteus mirabilis) and gram negative cocci (Neisseria) and entercocci |
| class III penicillins - administration | oral and IV |
| gram-positive cocci that are resistant to many antibiotics | enterococcus |
| class III penicillins - primary SEs | GI upset and rash |
| class III penicillins - uses | UTI, URI, pneumonia, STDs, meningitis |
| class III penicillins; Gram positive, plus some gram negative bacilli (2) | Ampicillin, Amoxicillin |
| class III penicillin combined with clavulante | amoxicillin (better absorbed than ampicillin) |
| class IV penicillins spectrum | broader spectrum - Gram positive, expanded gram-negative bacilli activity including anti-pseudomonas (which is notoriously resistant) |
| class IV penicillins (5) | Carbenicillin, Mezlocillin, Piperacillin, Ticarcillin, Carbenicillin indanyl |
| Carbenicillin | Beta-lactamase sensitive; Di-sodium, (conjugated with 2 sodiums, used for severe infections); Class IV |
| Carbenicillin indanyl | indanyl ester, oral for UTIs; Bleeding side effect (alpha-carboxy); Class IV |
| Ticarcillin | Like carbenicillin but more active; lower doses; Combined with clavulanate(Timentin); Class IV |
| Mezlocillin & Piperacillin | Uriedo penicillins. Expanded gram negative spectra, including Psuedomonas; Beta-lactamase sensitive; i.v. only; renally excreted; Class IV/V |
| Class IV penicillin uses | serious gram-negative infections; IN COMBINATION with aminoglycosides |
| First generation Cephalosporins - spectrum | Most gram-positive aerobes, limited gram-negative aerobes, including Staph; E. coli, Klebsiella, Proteus mirabilis; NOT active against Strep. Faecalis (enterococcus), Neisseria, H. influenza; Penicillinase resistant but destroyed by gram-negative beta-la |
| First generation Cephalosporins - excretion, penetration, and cross-reactivity | Renally excreted; Little CSF penetration; 10% cross-sensitivity with penicillins (rashes mostly) |
| First generation Cephalosporins - uses | gram positive infections (Pneumococci, strep, staph), some UTIs |
| First generation Cephalosporins (5) | Cephalothin, Cefazolin, Cephalexin, Cefadroxil, Cephradine |
| Cephalothin - admin & major SEs (1st gen ceph) | i.v. only; pain and thrombophlebitis |
| Cefazolin - admin & major SEs (1st gen ceph) | i.v. only; no pain/Thrombophlebitis; longer half-life (t.i.d.) |
| Cephalexin - admin (1st gen ceph) | Orally absorbed, q.i.d. |
| Cefadroxil - admin (1st gen ceph) | Orally absorbed, long T1/2 |
| Cephradine - admin (1st gen ceph) | IV & oral |
| only first generation cephalosporin available both IV and oral | Cephradine |
| 2nd generation cephalosporins - spectrum | Spectrum is expanded with activity against a greater number of gram-negative organisms, including resistance to some beta-lactamase hydrolysis; somewhat higher MICs for gram-positives; no CSF penetration |
| two groups of 2nd generation cephalosporins (based on spectrum) | Cefamandole-like & Cefoxitin-like |
| spectrum of Cefoxitin-like cephalosporins (2nd gen) | Excellent activity against Bacteroides (gram neg-anaerobes); use for pelvic infection |
| spectrum of Cefamandole-like cephalosporins (2nd gen) | Good activity against Hemophilus influenzae, including beta-lactamase-producing strains; also expanded activity against E. coli, etc |
| Cefamandole-like 2nd gen cephalosporins (3) | Cefamandole, Cefuroxime, Cefaclor |
| Cefamandole specifics (2nd gen ceph) | i.v. only; no CSF penetration; Renally excreted; Methythiotetrazole (MTT) side chain is related to bleeding, disulfiram reaction |
| Cefaclor specifics (2nd gen ceph) | orally absorbed, widely used for URI in children |
| Cefuroxime specifics (2nd gen ceph) | like cephamandole, longer T1/2 ; some CNS penetration (but not good enough for therapuetic use) |
| Cefuroxime axetil | Cefuroxime prodrug (2nd gen ceph) |
| Cefoxitin specifics (2nd gen ceph) | i.v. only, no CSF penetration |
| Cefotetan specifics (2nd gen ceph) | like cefoxitin, has MTT side chain |
| Cefmetazole specifics (2nd gen ceph) | like cefoxitin |
| 3rd generation cephalosporins spectrum | gram positive, Expanded gram-negative spectrum, increased beta-lactamase stability; Less activity against gram-positive organisms; NO activity against Strep faecalis (enterococcus); Most are not active against Pseudomonas; most have CSF penetration so the |
| 3rd generation ceph uses | mostly reserved for gram-negative infections |
| cefotaxime specifics (3rd gen ceph) | CSF penetration. Some gm + activity, iv., renally excreted |
| ceftizoxime specifics (3rd gen ceph) | Deacetylated Cefotaxime |
| ceftriaxone specifics (3rd gen ceph) | Important addition, im. iv. long half-life, good CSF levels; good for gonorrhea in 3rd world countries where ptns may only get one dose |
| Ceftazidime specifics (3rd gen ceph) | Antipseudomonal, iv. (v. important because most cephs don't have anti-pseudomonas activity) |
| Cefoperazone specifics (3rd gen ceph) | Some biliary excretion; Bleeding side effect |
| Cefixime specifics (3rd gen ceph) | Oral absorption; long T1/2; Used for H. influenzae URIs |
| Cefpodoxime proxetil specifics (3rd gen ceph) | Prodrug; like cefixime |
| 3rd generation cephalosporins (7) | cefotaxime, ceftizoxime, ceftriaxone, Ceftazidime, Cefoperazone, Cefixime, Cefpodoxime proxetil |
| 4th generation cephalosporin (1) | Cefepime |
| Cefepime (4th gen ceph) - spectrum | spectrum is more extensive than 3rd gen cephs, has cefotaxime's gram-pos spec and ceftazidime's in gram neg spec; Cefepime has better resistance to beta-lactamases; NOT good for MRSA or enterococcus |
| Cefepime (4th gen ceph) - penetration and excretion | Excellent penetration to CSF, almost 100% renally excreted |
| Cefepime (4th gen ceph) - use | should be reserved for treatment of serious infections, especially to those in immunocopromised patients and polymicrobial infections |
| Imipenem spectrum (beta-lactam) | Very broad spectrum; active against gram-positives, including Enterococus (maybe); and gram-negatives, including most Pseudomonads and Bacteroides; NO MRSA; some anaerobes; and some pseudomonads; resistant to beta-lactamase |
| Imipenem (b-lac, carbapenem) - admin/penetration | Not orally absorbed; penetrates into CSF (not recc in menigitis b/c of SEs though) |
| Imipenem (b-lac, carbapenem) - metabolism | metabolized by dihydropeptidase in proximal renal tubule; need to combine with cilastatin (dihydropeptidase inhibitor) = Primaxin to get therapeutic levels |
| Imipenem (b-lac, carbapenem) - SEs | cross reactive allergy with penecillins (10%-20% not anaphylactic);seizures |
| Imipenem (b-lac, carbapenem) - uses | Serious gram-negative infections |
| Meropenem (b-lac, carbapenem) - advantages over imipenem | More active against Enterobacteriaciae, Pseudomonas; Less potential to induce seizure; Stable against degradation by renal dehydropeptidase (don't have to give in combo) |
| Aztreonam (monobactam) - spectrum | Gram-negative activity (does not bind to PBPs of gram-positives; binds to PBP3 of Enterobacteriaceae); includes most pseudomonas; Aerobes only; Bactericidal; Good Beta-lactamase stability |
| Aztreonam (monobactam) - admin/excretion | i.v., i.m. only; urinary excretion |
| Aztreonam (monobactam) - penetration | Good CSF levels; good for CNS infections |
| only beta-lactam w/o penicllin cross sensitivity | aztreonam (monobactam) |
| Aztreonam (monobactam) - uses | serious gram-negative infections (doesn't work for gram-positives; also doesn't work against enterobacter or bacteroides b/c they are anaerobes) |
| which of these beta-lactamase inhibitors has the strongest activity - sulbactam, clavulanic acid, tazobactam | tazobactam |
| polypeptide antibiotics (5) | vancomycin, polymixins, mupirocin, spectinomycin, daptomycin |
| vancomycin (polypeptide) mechanism of action | Inhibitor of cell wall synthesis |
| vancomycin (polypeptide) spectrum | Gram-positive bacteria including staphylococci, streptococci, enterococci (anaerobe), and clostridium species; some gram-negative cocci (neisseria); DOES NOT work on gram-negative bacilli and mycobacteria (resistant) |
| vancomycin (polypeptide) PK | NOT orally absorbed; must give i.v. painful for i.m. Administration. Excreted in urine; must adjust dose in renal dysfunction (keep around 30 ug/ml peak). Not concentrated in bile; therapeutic CSF levels achieved in some patients with meningitis, but var |
| vancomycin (polypeptide) major SE if given too fast | "Red neck” or “Red man” syndrome (Flushing and hypotension), including muscle spasms in chest and rarely cardiac arrest, if administered in too fast i.v. infusion; GIVE SLOWLY |
| vancomycin (polypeptide) major SEs if combined with aminoglycosides | nephrotoxicity and ototoxicity (dose dependent, rarer with newer preps) |
| vancomycin (polypeptide) uses | MRSA; Other gram-positive infections including Strep. faecalis in pen-allergic pts.; orally for C. difficile enterocolitis (not absorbed - stays and cleans out GI) |
| Bacitracin (polypeptide) specifics | inhibits cell wall synth (bactericidal) in gram-positives, very little resistance, high nephrotoxicity if administered orally; topical use only |
| Polymixins (polypeptides) specifics | Polymixin B and Polymixin E (mixture); Disrupts cell membranes; Gram-negative bacilli, incl. Pseudomonas; not absorbed orally or through the skin; VERY nephrotoxic and neurotoxic if given systemically; used topically for gram-neg infections |
| Mupirocin (polypeptide) specifics [a.k.a. pseudomonic acid] | binds tRNA screwing up protein synth; covers Staphylococci and streptococci (some resistance w/longterm use); little cross resistance w/other antibiotics; used topically for impetigo (Staph or strep) - RX only |
| Spectinomycin specifics | structurally related to aminoglycosides; single i.m. dose for uncomplicated gonorrhea; (not for other STDs); little toxicity |
| Daptomycin spectrum | Gram-positive organisms only; activity against enterococci (including glycopeptide-resistant Enterococci (GRE)), staphylococci (including methicillin-resistant Staphylococcus aureus), streptococci and corynebacteria |
Created by:
Krafty
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