Step 1 First Aid – Antibiotics – Flashcards

MOA: 1. Bind penicillin binding proteins 2. Block transpeptidase cross-linking of cell wall 3. Activate autolytic enzymes (Bactericidal) Side Effects: Hypersensitivity reaction (with cross alergenicity) Hemolytic anemia

Class - 1st generation PCNs Target Orgs/Use: Gram+ orgs (Grp A Strep, S. pneumoniae, Actinomyces) Treponema pallidum (syphilis) Bactericidal for Gram+ cocci, gram+ rods, gram- cocci and spirochetes Administration: PCN G - IV or IM (with anesthetic to increase t1/2) PCN V - oral

Class - 2nd generation PCNs (narrow spectrum, b-lactamase resistant due to bulkier R-group) Target Orgs/Use - S. aureus (excep MRSA-altered penicillin binding protein) Side Effects: Methicillin - allergic interstitial nephritis Nafcillin/Oxacillin - hepatitis (some hepatic excretion) Administration - Dicloxacillin oral

Class - Aminopenicillins - 3rd generation PCNs (wider spectrum than 1st gen, b-lactamase sensitive) Target Orgs/Use: Gram- rods (H. flu, E. coli, Listeria, Proteus, Salmonella) and enterococcus "HELPS kill enteroccus" H. pylori triple therapy Side Effects - hypersensitivity reactions, ampicillin rash, pseudomembranous colitis Administration: Amoxicillin oral with food Can be given with b-lactam inhibitor to enhance spectrum

Class - 4th generation PCN (Ureidopenicillins) - Extended sprectrum, susceptible to b-lactamase (use w/b-lactamase inhibitor) Target Orgs/Use - Pseudomonas and gram- rods

Class - 4th generation PCN (Carboxypenicillins) - Extended spectrum, b-lactamase sensitive (use w/b-lactamase inhibitor) Target Orgs/Use - Pseudomonas, gram- rods Side Effects - Disodium salts that can produce large salt load

Class - b-lactamase inhibitors (given in combination with b-lactam abx) MOA - (No antimicrobial activity) covalent inhibitors of b-lactamase Target Orgs/Use: Effective in conjunction with 3-4 gen PCN against Gram- b-lactamases and S. aureus NOT effective for chromosomal b-lactamase of Pseudomonas, Enterobacter, Citrobacter, Serratia,

3 Strategies: 1. Decrease penetration - Gram- orgs let b-lactam in via porin - change porin to restrict entry (ex Pseudomonas) 2. Alter PCN binding protein (ex MRSA via mec locus, S. pneumoniae via transformation) 3. B-lactamase

MOA - Bactericidal b-lactam drugs that inhibit cell wall synthesis but less susceptible to penicillinases Side Effects: Hypersensitivity reaction (5-10% cross hypersensitivity with PCN) Vitamin K deficiency (Cefotetan, Cefonicid, Cefoperazone) Disulfuram-like reaction w/ethanol (Cefotetan, Cefonicid, Cefoperazone) Increase nephrotoxicity of Aminoglycosides

Class - 1st gen Cephalosporins Target Orgs/Use - Gram+ cocci (MSSA, Streptococci), Enterobacteriaceae (PEcK - Proteus, E. coli, Klebsiella) Metabolism: Cephalothin - deacylated by liver (not good for meningitis b/c deacylated form competes with active form for transport to CSF) Cephapirin - deacylated by liver but w/active metabolites

Class - 2nd Generatoin Cephalosporins Target Orgs/Use: More stable vs. gram- orgs (HEN PEcKS - H. flu, Enterobacter, Neisseria, Proteus, E. coli, Klebsiella, Serratia) Less active vs. Gram+ cocci/S.aureus Side Effects: (Cefotetan/Cefonicid - MTT side chain ) 1. Inhibits Vitamin K mediated gamma carboxylation 2. Associated with Disulfuram-like reaction with alcohol (throbbing of neck, headache, nausea, etc)

Class - 3rd generation Cephalosporins Target Orgs/Uses: Broader activity vs. Gram- Ceftriaxone - meningitis and gonorrhea Ceftazidime - Pseudomonas Side Effects: (Cefoperazone - MTT side chain) 1. Inhibits Vitamin K mediated gamma carboxylation 2. Associated with Disulfuram-like reaction with alcohol (throbbing of neck, headache, nausea, etc)

Class - 4th generation Cephalosporin Target Orgs/Uses: More resistant to destruction by chormosomal b-lactamase Increased activity (over 3rd gen) vs. Pseudomonas and gram+

Class - Monobactam MOA - b-lactam antibiotic (but only binds gram- transpeptidase PBP3) resistant to b-lactamases (synergistic w/aminoglycosides) Target Orgs/Use - Facultative Gram- bacteria (resistant to b-lactamase) - Use for PCN-allergic pts and those w/renal insufficiency who cannot tolerate aminoglycosides Side Effects - Rare (diarrhea/rash), NO cross alergenicity with PCN

Class - Carbapenem MOA - b-lactam antibiotic resistant to all b-lactamases Target Orgs/Use: Broadest spectrum abx (but side effects limit use) Imipenem - More active vs. Gram+ cocci Meropenem - More activity vs. Gram- rods Side Effects: Cross reactivity with PCN Imipenem must be infused slowly or causes Gi distress Imipenem causes seizures (pts at increase risk - renal insufficiency) Metabolism: Imipenem - hydrolyzed by peptidase on renal tubular cells (coadmin with cilastatin - dipeptidase inhibitor) Resistance: Pseudomonas - porin mutation Carbapenemase may arise

MOA - Inhibits cell wall mucopeptide formation by binding to D-ala-D-ala portion of the cell wall precursors. Bactericidal. Target Orgs/Use: Gram+ bacteria including MRSA and Enterococcus Used for all gram+ infections in PCN allergic pt Used oral to treat C. difficile Side Effects: (NOT many) Nephrotoxicity (especially with aminoglycosides) Ototoxic Thrombophlebitis "Red man syndrome" (HM release) - diffuse flushing (prevent w/antiHM and slow infusion) Administration - Given IV (except for to tx C. diff) Resistance: Block penetration (Gram- bacteria mode of resistance) Plasmid genes altering structure of cell wall to D-ala-D-lac (some Gram+ strains)

MOA - Bacteriostatic, binds 50S ribosome and inhibits peptide translocation from A-<P site Target Orgs/Use - Broad spectrum used in developing world (not used in US) for Meningitis (covers H. flu, N. meningiditis, S. pneumoniae) Side Effects: Dose-dependent irreversible aplastic anemia and reversible BM suppression "Gray baby syndrome" due to failure of glucuronidation in liver of neonates (can lead to circulatory collapse and death) Hemolysis in pts with G6PD deficiency Resistance - plasmid-encoded acetyl transferase that inactivates drug

MOA - Bacteriostatic, binds 23S rRNA on 50S ribosomal subunit and blocks chain elongation (peptide bond formation) Target Orgs/Use - Anaerobes (above diaphragm - aspiration pneumonia/lung abscess) Side Effects - Pseudomembranous colitis due to overgrowth of C. diff Resistance - Plasmid encoded resistance due to methylation of 23S rRNA -< decreased binding

MOA - Binds 23S portion of 50S ribosomal subunit and blocks formation of initiation complex Target Orgs/Use - Gram+ cocci (including MRSA, VRE and b-lactam resistant pneumococcal disease) Side Effects - BM suppression, MAO inhibitor (toxicity with tyramine or other related drugs)

Class - Macrolide (Inhibitor of protein synthesis), Azithromycin/Clarithromycin are long-acting MOA - Bacteriostatic, binds 23S rRNA on 50S ribosomal subunit and blocks chain elongation (blocks translocation) Target Orgs/Use: Atypical pneumonias (mycoplasma, chlamydia, legionella) URIs, STDs Gram+ cocci (strep infections in pts allergic to PCN) Neisseria Azithromycin - MAC (M. avium intracellulare) prophylaxis and treatment Side Effects: Nausea/Diarrhea (motilin agonist) - worse w/Erythromycin Cholestatic hepatitis Inhibits P-450 enzymes - increases concentration of warfarin and theophylline Eosinophilia, skin rash QT prolongation (mostly Erythromycin) Terratogen (Clarithromycin) Resistance: Plasmid encoded resistance due to methylation of 23S rRNA -< decreased binding

Class - Tetracycline (Inhibitor of protein synthesis) MOA - Bacteriostatic, binds 30S ribosome and inhibits tRNA binding Target Orgs/Use: Atypical orgs (Chlamydia, Mycoplasma pneumoniae, Rickettsia, Brucella, Leptospira, B. burgdorferi) H. pylori triple therapy Demeclocycline - ADH antagonist (diuretic in SIADH) Side Effects: Bind newly synthesized bone and discolors teeth (don't give pregnant women/kids) Photosensitivity skin rash (esp Doxycycline) GI distress Administration: Given Oral (only doxycycline can be given IV - others cause thrombophlebitis) Antacids, milk/dairy products inhibit absorption (divalent cations inhibit absorption) Metabolism: Renal + hepatic excretion Doxycycline hepatic excretion (can be used in pts w/renal failure) Resistance - Decrease uptake into cells of increase efflux out of cell by plasmid-encoded transport pump

Class - Aminoglycosides (Inhibitor of protein synthesis) MOA - Bactericidal; Binds 30S ribosomal subunit blocking formation of initiation complex (Low conc - mRNA misread, High conc - translation inhibited) Target Orgs/Use: Active vs. orgs with ETC (use ETC to get in cell) Severe gram- rod infection, synergistic w/b-lactam antibiotics (b-lactam facilitates entry) Neomycin for bowel surgery Side Effects: Reversible nephrotoxicity (especially w/cephs) Irreversible ototoxicity (kill cochlear hair cells) - especially w/loop diuretics Teratogen Resistance: 1. Block penetration (Anaerobes, streptococci - no ETC so resistant) 2. Alter binding target (more common with Streptomycin) 3. Inactivate Abx by acetylation, phosphorylation or adenylation with enzyme (typically plasmid/transposon mediated)

Class - First generation Quinolone MOA - Bactericidal, Inhibits DNA Gyrase

Class - Fluoroquinolone MOA - Bactericidal, Inhibits DNA Gyrase Target Orgs/Use - Gram- rods of urinary/gi tracts (UTIs/Gastroenteritis) including Pseudomonas, Neisseria, Some Gram+ orgs Side Effects: Tendonitis and tendon rupture (adults) Leg cramps, myalgias (kids) Potential for cartilage damage (contraindicated in pregnancy and children) GI upset, superinfections, skin rash, headache, dizziness Administration: Oral or IV Antacids, iron, calcium, food, HM blockers delay absorption Resistance - Chromosomal-encoded mutation in DNA gyrase

Class - DNA Synthesis inhibitors MOA - Bactericidal/antiprotozoal, Forms free radical toxic metabolites in the bacterial cell that damage DNA Target Orgs/Use: "GET GAP" G iardia E ntamoeba T richomonas vaginalis G ardnerella vaginalis A naerobes (except Actinomyces) H. p ylori (triple therapy w/ amoxicillin or tetracycline and bismuth) Side Effects: Associated with Disulfuram-like reaction with alcohol (throbbing of neck, headache, nausea, etc) Metallic taste in the mouth Resistance - Actinomyces intrinsically resistant

MOA - Bactericidal, Inhibit DNA-dependent RNA polymerase (inhibit txn initiation) Target Orgs/Use: M. tb combo agent (rapid resistance if used alone) Delays resistance to dapsone when used for leprosy Meningococcal and H. flu B prophylaxis Side Effects: Turns urine, tears, sweat redish/orange Induces Cyp-450 -< reduce blood levels of many drugs 4 R's of Rifampin - RNA pol inhibitor, Revs up P450s, Red body fluid, Rapid resistance

MOA - Bactericidal together (bacteriostatic alone), Competitively inhibit folate metabolism in different steps: Trimethoprim inhibits DHFR Sulfonamides inhibit folate synthesis (block dihydropteroate synthetase) Target Orgs/Use - UTIs, Prophylaxis and tx of PCP in AIDS pts, Gram+ (including MRSA), Gram-, Salmonella, Shigella, Nocardia, Chlamydia Side Effects: Rash/skin reaction (as severe as SJS) Hemolysis if G6PD deficient Nephrotoxicity (interstitial nephritis) Megaloblastic anemia Displace other drugs from albumin (eg., warfarin) Sulfa drugs - kernicterus in new borns (contraindicated) Leukopenia, Granulocytopenia (alleviated w/leucovorin rescue) Resistance - Plasmid/transposon mediated altered target, decreased uptake, increased PABA precursor (outcompetes sulfonamide)

MOA - Bind cell membranes of bacteria and disrupt their osmotic properties (cationic, basic proteins that act like detergents) Target Orgs/Use - Resistant gram- infection Toxicity - Neurotoxicity, acute renal tubular necrosis

MOA - Decrease synthesis of mycolic acids (use bacterial catalase peroxidase to convert INH to active metabolite) Target Orgs/Use - M. tb prophylaxis and treatment (diff t1/2 in fast vs. slow acetylators) Side Effects: (INH - I njures N eurons and H epatocytes) Hepatotoxicity Neurotoxicity, Lupus (Pyridoxine (B6) can prevent)

MOA - bactericidal in acidic pH of phagolysosome (where TB engulfed by macrophages is found) Target Orgs/Use - TB

MOA - Decrease carbohydrate polymerization of mycobacterium cell wall by blocking arabinsyltransferase Target Orgs/Use - TB Side Effect - Optic neuropathy (red-green color blindness)

M. tb: Prophylaxis - INH Treatment - Rifampin, INH, Pyrazinamide, Ethambutol (RIPE for treatment) M. avium-intracellulare: Prophylaxis - Azithromycin Treatment - Azithromycin, rifampin, ethambutol, streptomycin M. leprae: Prophylaxis - N/A Treatment - Dapsone, rifampin, clofazimine

Rifampin

Ceftriaxone

Benzathine penicillin G

TMP-SMX

TMP-SMX

PCNs

Intrapartum PCN

2 Triple Therapy options: 1. Metronidazole, Bismuth, Tetracycline or Amoxicillin 2. Metronidazole, Omeprazole, Clarithromycin (more expensive)

Aminoglycoside + 4th gen PCN (Piperacillin, Ticarcillin)