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Pharmacology - Block 3 - Part 3

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davidwurbel7's version from 2016-08-14 07:01

Antimicrobial Drugs

Question Answer
Molecule in the cell wall of bacteria that is the target of beta-lactam drugsPeptidoglycan
This enzyme cross links the D-Alanine in the cell wallTranspeptidase
Beta-lactams act on this enzyme in the cell wallTranspeptidase
Vancomycin acts on this enzyme in the cell wall Transglycosylase
Bacteria that absorbs Gram stainGram Positive
Bacteria that do not absorbs Gram stainGram Negative
Bacteria that has a thick cell wall containing large amounts of peptidoglycan along with Teichoic acid and Lipoteichoic acidGram Positive
Bacteria that has a thin cell wall containing peptidoglycan and an outer membrane composed of Lipopolysaccharide (LPS)Gram Negative
Outer membrane of Gram negativeLipopolysaccharide (LPS)
Holes in the Lipopolysaccharide that allow substances to reach the bacteria cell wallsPorins
Lipopolysaccharide (LPS) is also known asEndotoxin
The toxic component of Lipopolysaccharide (LPS)Lipid A
This antibiotic is a cell wall inhibitor but is not a beta-lactam drugVancomycin
This antibiotic cannot pass through the porins of Gram negative bacteria to target the peptidoglycan and is therefore not a viable treatment antibiotic for Gram negative bacteriaVancomycin
Bacteria that are Gram positiveThick Cell Wall
Bacteria that are Gram negativeThin Cell Wall
The structure of peptidoglycan is composed of these glycan subunitsn-Acetylmuramic Acid (NAM) and n-Acetylglucosamine (NAG)
The peptide sequence that is targeted by vancomycinD-Alanine - D-Alanine
Transpeptidase-carboxypeptidase enzymes are also known asPenicillin-Binding Proteins
Long acting penicillin GRepository Penicillin
Repository penicillins areProcaine Penicillin G and Benzathine Penicillin G
Penicillins are excreted by this routeTubular Secretion
This drug competitively inhibits the renal tubular secretion of penicillinProbenecid
DOC for syphilisBenzathine/Procaine Penicillin G
DOC for actinomycosisPenicillin G
DOC for Staph aureusMethacillin Group
DOC for ListeriaAmpicillin
DOC for infective endocarditis and H. pylori infectionAmoxicillin
Amoxicillin, Metronidazole, Tetracycline and Clarithromycin are the antibiotics that can be used against this bacteriaH. pylori
The treatment regime for this bacteria is a proton pump inhibitor (Omeprazole) with two antibioticsH pylori
Methicillin is no longer used clinically due thisNephrotoxicity
Penicillin G and Penicillin V only work on these types of bacteriaGram (+) and Spirochetes
Amoxicillin and Ampicillin work on these types of bacteriaGram (+) and a few Gram (-)
DOC for Pseudomonas infectionPiperacillin
DOC for Rheumatic feverBenzathine Penicillin G
DOC for Listeria meningitis and Enterococcal infectionsAminopenicillins (Amoxicillin and Ampicillin)
DOC for prophylactic gonorrhea and syphilisBenzathine/Procaine Penicillin G
DOC for prophylactic bacterial endocarditisAmoxicillin
Ureidopenicillins and Carboxypenicillins are type ofExtended Spectrum Penicillins
Piperacillin and MezlocillinUreidopenicillins
Carboxycillin and TicarcillinCarboxypenicillins
Piperacillin and Ticarcillin have a synergistic action when combined with this class of antibioticsAminoglycosides
Methicillin, Nafcillin, Oxacillin, Cloxacillin and DicloxacillinPenicillinase-Resistant Penicillins
Clavulanate, Sulbactam, TazobactamBeta-Lactumase Inhibitors
Amoxicillin + Clavulanate, Ampicillin + Sulbactam, Piperacillin + Tazobactam, Ticarcillin + TazobactamPenicillin + Beta-Lactamase Inhibitor
Amoxicillin + ClavulanateAugmentin
DOC for C. difficileMetronidazole or Vancomycin
DOC for Staph aureus skin infections and abcessesCloxacillin
DOC for MRSAVancomycin
Mechanism of resistance to methicillinModified PBPs
DOC for VRSALinzoid
Drug of last resort (DOLR) for VRSAStrepogramins
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Adverse Effects of Penicillins
Hypersensitivity
Question Answer
Interstitial nephritisMethicillin and Nafcillin
Maculopapular rashAmpicillin
Diarrhea - pseudomembranous entercolitisAmpicillin
A patient can have a cross sensitivity reaction with this antibiotic class if already sensitive to penicillinCephalosporins
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Mechanism of Drug Resistance
Question Answer
Bacteria modify porin channel frequency, or size of porins and selectivity prohibiting entry of drugsInhibition of drug uptake
Enzyme that break the beta-lactam ringPenicillinase
VRSA (vancomycin resistant Staph aureus) have thicker cell walls trapping vancomycin Inhibition of drug uptake
Membrane proteins that pump out the drug. Results in low intracellular concentrations of drug that are insufficient to elicit an effectEfflux pumps
Destroying the active component of the drug. Usually by producing enzymes that modify the drugDrug Inactivation
Alteration in PBPs , Altered peptidoglycan, Alterations in subunits of DNA gyrase, Alteration in subunits of topoisomerase IV and Changes in RNA polymeraseModify the drug targets
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Cephalosporins
Question Answer
Cephalexin and cefazolin1st Generation Cephalosporins
Uses for skin & soft tissue infections caused by S.pyogenes/Staph.aureus1st Generation Cephalosporins
DOC for surgical prophylaxisCefazolin
1st Generation Cephalosporins are effective againstPEcK
Proteus, E. coli, KlebsiellaPEcK
Cefuroxime and cefoxitin2nd Generation Cephalosporins
2nd Generation Cephalosporins are effective againstHEN PEcKS
Haemophilus influenzae, Enterobacter, Neisseria, Proteus, E.coli, Klebsiella, SerratiaHEN PEcKS
Cefoxitin and cefotetan can be used to treat thisBacteroids fragilis
Cefotaxime, Ceftriaxone and Ceftazidime3rd Generation Cephalosporins
Cephalosporin DOC for PseudomonasCeftazidime or Cefoperazone
Penetrate blood-brain barrier and concentrate in CSF3rd Generation Cephalosporins
DOC for empiric treatment in adults against bacteria meningitisCeftriaxone
DOC for empiric treatment in pediatrics against bacteria meningitisCefotaxime
DOC for gonorrhoeaeCeftriaxone
DOC for S. typhiCeftriaxone or Cefotaxime, or Cefaperazone
Cefepime4th generation Cephalosporins
Cephalosporin that has good activity against PseudomonasCefoperazone and Ceftazidime
DOC for empirical treatment of nosocomial infections by suspected beta-lactamase-producing bacteriaCefepime
Ceftaroline5th generation Cephalosporins
Can be used against MRSA/MRSE infections but vancomycin is still drug of choiceCeftaroline
Cross-allergenicity in patients with penicillin allergiesCephalosporins
Organisms not covered by cephalosporinsListeria monocytogenes, Atypical bacteria (Chlamydia, Mycoplasma), MRSA (exception; ceftaroline coveres MRSA) and Enterococci
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Other Beta-Lactams and Non-Beta-Lactam
Question Answer
DOC for a patient with history of sensitivity to pencillins and/or cephalosporinsAztreonam
Cefamandole, Cefoperazone & Cefotetan may cause this adverse effectDisulfiram-like Reaction
The reason for Dusulfiram-like Reaction with Cefamandole, Cefoperazone & Cefotetan is due to thisMethylthiotetrazole Group (MTT Group)
The drug is only effective against Gram negative rod bacteriaAztreonam
Broad spectrum: gram positive & negative bacteria, anaerobes- Bact.fragilis, clostridiaCarbapenems
Imipenem is rapidly inactivated by thisRenal Dehydropeptidase I
Imipenem is combined with this to prevent hydrolysis by enzymes in the renal brush borderCilastatin
An inhibitor of renal dehydropeptidaseCilastatin
Drug of reserve for life-threatening systemic infectionsCarbapenems
This is a side effect seen in patients with renal dysfunction when given carbapenemsSeizures
The primary mechanism of action is by binding to D-Ala-D-Ala terminal of the resulting in inhibition of the transpeptidase, which prevents further elongation and cross-linking of the peptidoglycan. The secondary mechanism of action inhibits transglycosylase(Glycosyl transferase-GT), a second enzyme responsible for cross-linking sugar residuesVancomycin
Bacterial replacement of the terminal D-Ala by D-LactateVancomycin Resistance
Vancomycin Resistance in bacteria is due to thisD-Ala to D-Lactate Replacement
Adverse effect of vancomycin because of release of histamine (flushing, redness of face, hypotension)Red Man Syndrome
This adverse effect of vancomycin can be prevented by slow IV infusion and pretreatment with antihistaminesRed Man Syndrome
Adverse effects include pretreatment with antihistamines Nephrotoxicity, Ototoxicity and neuromuscular blockageVancomycin
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Protein Synthesis Inhibitors

Question Answer
Binds to the 30S ribosomal subunit. Blocks the binding of aminoacyl-tRNA to the acceptor site on the mRNA-ribosome complex Tetracycline
Binds to the 30S ribosomal subunit. Blocks the formation of initiation complex, prevent polysome formation, misreading of mRNAAminoglycosides
Binds to the 50S ribosomal subunit. Inhibits peptidyl transferase and transfer of peptide chain from site P to acceptor siteChloramphenicol
Binds to the 50S ribosomal subunit. Protein synthesis is inhibited because aminoacyl translocation reactions and the formation of initiation complexes are blockedMacrolides
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Question Answer
Bacteriostatic, broad spectrum Bind to 50S ribosomal subunit Inhibits transpeptidation and transfer of peptide chain from site P to acceptor site. Highly toxic. Less used systemicallyChloramphenicol
Bind to the 30S ribosome and inhibit bacterial protein synthesis. They interfere with the initiation complex of peptide formation- by blocking the association of 50s subunit with mRNA-30s. They induce misreading of mRNA, which causes incorporation of wrong amino acid into the peptide, resulting in a nonfunctional or toxic protein. They cause a breakup of polysomes into nonfunctional monosomes. Requires oxygen dependent active transport meaning that anaerobic bacteria are resistantAminoglycosides
Not effective against anaerobic bacteria or Gram positive bacteriaAminoglycosides
Production of transferase enzyme by the bacteria that inactivate the aminoglycoside by phosphorylation, acetylation and adenylation. Impaired penetration of aminoglycoside into the cell. The receptor protein on the 30S ribosomal subunit may be deleted or altered as a result of a mutationMechanism of Aminoglycoside Resistance
All aminoglycosides are parenterally administered except for this drugNeomycin
The primary route of aminoglycoside clearance is at this siteKidneys
Aminoglycosides accumulate here resulting in nephrotoxicityRenal Cortical Tissue
Aminoglycosides accumulate here resulting in ototoxicityOtic Perilymph
Increasing concentrations kill an increasing proportion of bacteria and at a more rapid rate so single large dose is more effective than multiple small dosesConcentration-dependent killing
Antibacterial activity persists beyond the time during which measurable drug is present.Postantibiotic Effect
Ototoxicity of aminoglycoside can be enhanced by these drugsLoop Diuretics
Neuromuscular blockage is only see at very high doses with this drugAminoglycoside
Neuromuscular blockage seen with aminoglycoside is treated with thisCalcium and Neostigmine
Development of efflux pumps and decreased activity of the uptake systems for tetracyclinesResistance Mechanism
Has chelating property. Binds Ca2+, Mg2+, Fe2+ - which decreases their absorption, Should not be given with milk products, antacids. Bind to tissues like teeth, bones which are undergoing calcification. Can cross placenta and concentrate in fetal bones and teethTetracyline
Tetracycline eliminated through liver…safe in renal dysfunctionDoxycline
Tetracycline best CSF penetration..hence used for meningococcal carrier state. Concentrates in saliva and tearsMinocycline
Adverse effects include teeth: permanent brown discoloration & illformed teeth. Stunted bone growth. Phototoxicity on exposure to UV light. Super infections: Diarrhea, Candida. Epigastric pain, abdominal distention, nausea, vomiting, Hepatic injury. Nephrotoxicity. Fanconi’s syndrome: A form of renal tubular acidosis is attributed to use of outdated drug in this classTetracycline
Contraindications include Pregnancy, Children - 8years or younger and Renal insufficiencyTetracyclines
Tetracycline drug of last resort for systemic infectionsTigecycline
Drug rarely used in the US due toxicity causing aplastic anemia Chloramphenicol
Occurs in neonates- due to deficient hepatic glucuronosyltransferase- lack of effective glucuronic acid conjugation degradation of chloramphenicol. C/F: vomiting,abdominal distension, cyanosis, refusal to feed, CV collapse, deathGray Baby Syndrome
MOA Bind reversibly to the 50S subunit. Protein synthesis is inhibited because aminoacyl translocation reactions and the formation of initiation complexes are blockedMacrolides
Mechanism of Resistance to macrolides is the production of this by bacteriaMethylase Enzyme
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(Insert 27)
Question Answer
Uses for this drug for atypical pneumonia- caused by Mycoplasma pneumoniae and in streptococcal infections in patients who are allergic to penicillinErythromycin
Adverse effect of this drug causes diarrhea as it stimulates motillin receptorsErythromycin
Macrolide that is an CYP450 Enzyme inhibitor and can cause prolongation of QT interval, ventricular arrhythmiaErythromycin
Twice a day dosing; acid stable with better GI absorption than erythromycinClarithromycin
Macrolide that can be used to treat H.pylori treatment in recurrent peptic ulcer, MAC infection in AIDS patients and LeprosyClarithromycin
Macrolide that is acid stable. Long t1/2 2-4 days. High concentration inside macrophages and fibroblasts. Does not interact with hepatic CYP enzymes- No drug interactionAzithromycin
Uses for this drug Legionnaire’s pneumonia. Chlamydia infection of urogenital tract, pneumonia, trachoma. MAC infection in AIDS patientsAzithromycin
Uses for this drug second choice anaerobic infections- Bacteroides fragilis. Prophylaxis of endocarditis in valvular disease patients who are allergic to Penicillin. Second choice for Pneumocystis jiroveci pneumoniaClindamycin
A toxicity of this drug is can cause psuedomembranous enterocolitis caused by Clostridium difficileClindamycin
Mechanism of action bind to 23S ribosomal RNA of the 50S ribosomes. No cross resistance to other protein synthesis inhibitorsLinezolid
Uses for this drug VRSA, VRE, Drug resistant pneumococciLinezolid
Adverse effect of this drug is thrombocytopeniaLinezolid
The drug binds to 50S ribosomes, they prevent the interaction of aminoacyl t-RNA with acceptor site and stimulates its dissociation from ternery complex. Also decreases the release of completed polypeptide by blocking its extrusion. Also inhibits t RNA synthetase activityQuinupristin- Dalfopristine
Drug of last resort for MRSA, VRSA and VREQuinupristin- Dalfopristine
Adverse effect includes arthralgia- myalgia syndromeQuinupristin- Dalfopristine
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