Pharm-Fluroquinolones & PCNs & Ceph
Terms
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- Mechanism of Fluoquinoles?
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G-: Inhibit DNA Gyrases (topoisomerase II in mammals). It cuts & reanneals DNA to get rid of supercoils.
G+: Inhibits Topoisomerase IV – involved in separation of daughter cells - Cipro HC Otic
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Class: Fluroquinolones
Ciprofloxacin plus hydrocortisone, used for Otis Media - Which 3 Fluoroquinolones has an ophtlamic use?
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Ciprofloxacin
Gatifloxacin
Moxifloxacin - Which Fluoroquinolone is used for community-acquired pneumonia & chronic bronchitis?
- Gemifloxacin
- Which fluorquinolone is used only for UTIs?
- Norfloxacin
- Which fluroquinoline is used for both UTIs and Lower RTIs?
- Lomefloxacin
- What are 3 fluorquinolones with no special characteristics?
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Levofloxacin
Ofloxacin
Sparfloxacin - Which fluoroquinolone has the best G- activity?
- Ciprofloxacin
- Which Fluoroquinolon is a good choice against anaerobes?
- Moxifloxacin
- Which bacteria is a common cause of peritonitis in a perforated colon? What is used to treat it?
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Bacteroides fagilis (G- rod)
Use ampicillin + Sulbactam or Piperacillin + Taxobactam
Another common peritonitis pathogen: P. aeruginosa - What does Sulbactam do?
- It's a beta-lactamase inhibitor, can used in association with penicillin n increase G- spectrum
- What was Piperacillin designed for?
- For Tx of "stubborn" pseudomonas infections
- Side effects of Fluoquinolones
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NVD are always SE with antibiotics, but esp. with this class.
Phototoxicity
Cardiotoxicity/Increased QT interval - not for cardiac conduction pts
Arthopathy - damage to growing cartilage in kids
Tendon rupture (shoulder, hands)
CNS stimulation - convulsions/pyschoses - Major "Side effect" infection caused by fluoroquinoles?
- C. difficile diarrhea & pseudomembanous colitis due to killing normal flora that keeps it in check in the gut. 2 toxins produced. Plaques on mucosa form "pseudomembrane."
- Treatment for pseudomembranous colitis?
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1st choice: Metronidazole (usually for protozoa). Mech: forms reactive anion that damages DNA of C. difficile
2nd choice: Vancomycin - What's the general structure of Penicillin and what determines the different properties of Rx in the class?
- Made of a thiazolidine ring + a beta-lactam ring with side chains that give the different drugs their properties.
- What's the mechanism of Penicillins?
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Treat mostly G+, but some G- too.
Penicilin permanently inhibits transpeptidase, inhibiting synthesis of cell wall (can't x link because can't remove terminal D-alanine), making it easily lysed. Therefore penicillin is cidal. - What is the main mechanism of bacterial resistance to PCNs?
- Beta-lactamases break the b-lactam ring of PCM, making the molecule non-functional
- PCN-G
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aka benzyl PCM
Given IV or IM, not acid stable for PO use
Three forms:
Aqueous - IM/IV with Na or K salt (Na an issue with CHF)
Procaine - IM, depot slows absorption, numbs site - can cause allergy (ester)
Benzathine - IM, longest acting - Dosing for PCN G?
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Expressed in "units" where 1 unit - 0.6 ug. 1 million units=600 mg.
Example: for Syphillis, tx 2.4 mil units IM single dose - PCN V?
- Acid stable PCN for oral use, dosed in mg. Given 1 hr a.c. or p.c.
- Alternative treatment for Syphillis with PCN allergy?
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doxycycline or tetracycline PO
ceftriazone IV/IM (3rd gen cephlosporin) -
a.c. stands for?
p.c.? -
antes cibos - before meal
post cibos - after meal
(think AM and PM) - The 3 penicillinase-resistant PCNs?
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DON
Dicloxacillin - PO
Oxacillin - PO or injectable
Nafcillin - injectable
Cleared by both biliary & renal excretion, good in liver or kidney disease - MRSA - what does it stand for?
- Methicillin Resistant Staph Aureus. Refers to bacteria that are resistant to the 3 Penicillinase-resistant PCNs (also called Beta-lactamase resistant PCNs). Methicillin discontinued, name stuck
- Aminopenicillins
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Also known as extended spectrum PCNs
Similiar spectrum as PCN but with greater G- coverage. Susceptible to PCNases. - Describe the 2 Aminiopenicillins
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Ampicillin - PO or IV
Amoxicillin - PO
With Clavulanate (b-lactase inhibitor)= Augmentin
Not used for peritonitis - no IV use - Organisms causing most Otitis media? Tx?
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Strep. pneumonia (G+) = 50%
H. influenzae (G-) = 25%
If antibiotics used in last month, use Augmentin rather than Amoxicillin
In kids, use pediazole (sulfsozizole + erythomycin) - Use for Aminopenicillins?
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Ampicillin + sulbactam for peritonitis due to b. fragilis
Amoxicillin for Otitis media and dental procedure prophylaxis
Either: URTIs from Strep pyogenes/pneumonias (G+) or H. flu (G-), Sinusitis from Strep peumonia, H. flu or Moraxella catarrhalis
Either Amol - Antipseudomonas PCNs?
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Still susceptible to b-lactamases
Good against some psudomonas (modest vs P. aerugiosa) and some resistant Proteus
Ticarcillia - IV
Piperacillin - IV - Side effects of PCNs?
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-Hypersensitivity (allergy). Rashes, fever, bronchospasms, serum sicknes, Stevens-Johnson syndrome, anaphylaxis
-Diarrhea
-Superinfection - normal flora can't keep pathogen in check
-Increase seizure risk if penetrates BBB (such as with low renal fcn) - Penicilin metabolite is:
- Penicilloic acid
- Another name for PCNases?
- B-lactamase
- How do B-lactam antibiotics work and what are examples?
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Inhibit transpeptidase
PCNs, Cephalosporins, Carbapenems - Structure & Mech of Cephalosporins?
- Similar to PCN but instead of Thiazolanine ring, has a dihydrothiazine ring. Again the side chain determines character. Same mechanism – inhibit transpeptidase.
- What is the advantage of Cephalosporins over PCNs?
- Resist many b-lactamases but not all
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How many 1st generation Cephlosporins? What are they?
What bacteria are covered? -
Just two:
Cephalexin
Cefadroxil
G+ plus these G-: Proteus mirabilis, E.coli, Klebsiella pneumonia (PEcK) - What can 2nd generation Cephlosporins cover?
- Les G+ than 1st gen & more G-: HNPEcK - adds H. flu & Neisseria (meningitidis & gonorrhoeae)
- What's the Cephlosporin that doesn't start with Cef? Brand name? Route? What generation of Cephlosporin?
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Leorcarfef - Lorabid
Oral BID (thus the "bid" in name)
2nd generation - List 2nd gen Cephlosporins
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Cefaclor
Cefuroxxime
Loracargef
Cephamycins (ie Cefoxitin for B. fragilis) - Coverage of 3rd Generation of Cepholosproins compared to early generations?
- Much less G+ but much more G-
- List some 3rd generation cephlosporins
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Ceftriaxone
Cefotaxime
Cefpodoxime
Cefdinir - Ceftriaxone - use, route, CI
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USE: Meningitis from Strp pneum & N mening & for Gonorrhoeae
IV/IM - easily displaces bilirubin from albumin
Don't use in infants ,3mon (risk of kernicterus) unless as single dose for gonorrhea conjuct. - Cefotaxime - use, route
- Also good for meningitis (like ceftriaxone). Coveres Bacteroides. IV/IM
- Special characteristic of Cefdinir?
- A 3rd gen cephlosporin that binds Fe - reddens feces, esp in infants on high Fe formula
- Name 2 4th generation Cephalosporins
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Cefepime
Cefditoren - Characteristeics of Cefepime
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Route: IV/IM
Use: G- rods resistant to 3rd gen, good CNS penetration
SE: myclonus, disorientation, EEG changes and higher risk in epileptics - Side effects of Cephalosporins?
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For all of them: Hypersensitivity (allergic rxn)
Coagulation abnormalities with Cemetazole, cefoperazone, cefotetan & ceftriaxone - Carbapenems: coverage? Mech?
- Broadest spectrum B-lacm, G+ and G-, includes anaerobes & some MRSA. Reserved for resistant infrections
- Name 3 Carbapenems
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Imipenem - always with Cilastatin, IV/IM
Meropenem - IV
Ertapenem - qd - Use of Carbapenems?
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For resistant infections of
-UTI
-Lower Resp tract
-Intra-abdom, gyn, bacterial septicemia
-Bone, joint, skin infections - Vancomycin - use, route
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For MRSA or MSSA + PCN allergy, or food poisoning for B. cereus
IV
Esp. used for pseudomembranous colitis - Mechanism for Vancomycin
- Binds to d-alanine terminus so can’t X-link peptidoglycan (PCN can’t x-link because the enzyme is knocked out)
- Side Effect of Vancomycin
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Red man/ Red neck syndrom after rapid IV --> flushing of upper body/neck, hypotension, tachycardia & shock.
Cause: Histamine release from mast cells & basophils - Fosomycin - mechanism?
- Inhibits enolpyruvate transferase – which catalyzes PEP to UDP-N-aceytlglucosamine (which goes to form the Park Peptide) for making peptidoglycan. So: no cell wall synthesis
- Use of Fosomycin?
- UTIs from E. coli and Enterococcus faecalis in women
- Use, route & SE of Daptomycin?
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IV, lipopeptide, for skin infections from G+ & MRSA
SE: Increase creatin kinase - Bacitracin characteristics & use?
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Cidal vs. various G+ cocci & bacilli
USE: topical for minor cuts/scrapes, opthalmic ointment (DOC is bacitracin + polymyxin B, an OTC) - Bacitracin mechanism? SE?
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Binds to pyrolphosphate so lipid carrier can’t carry NAG/NAM outside for cell wall synthesis
Nephrotoxic