Pharm- antimicrobials

Question 1

Penicillin G, V

Answer 1

CLASS: Penicillinase-sensitive penicillins - G (IV + IM) V (oral)
MECHANISM: Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptioglycan in cell wall. Transpeptidase recognize D-ALA- D-ALA sequence on peptioglycan. Activate autolytic enzymes
CLINICAL USE: Bactericidal. Gram+ (S.pneumo, S. pyogense, actinomyces) Gram(neg) cocci (N.meningitidis) and spirochetes (T. pallidum)
TOXICITY: Hypersensitivity reactions, hemolytic anemia
RESISTANCE: Penicillinase in bacteria

Question 2

Amoxicillin,amplicillin

Answer 2

CLASS: Same as penicillin- Wider spectrum. AmOxicillin has better Oral bioabailability.
MECHANISM:Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptioglycan in cell wall. Transpeptidase recognize D-ALA- D-ALA sequence on peptioglycan. Activate autolytic enzymes
CLINICAL USE: “HHELPSS kill enterocci) - H.influenza, H. pylori, E. coli, Listeria monocytogenes, Proteus mirabilis, Salmonella, Shigella, and enterocci
TOXICITY: Hypersensitivity reactions, rash, pseudomembranous colitis
RESISTANCE: Penicillinase

Question 3

Dicloxacillin, nafcillin, oxacilling

Answer 3

CLASS: Penicillnase- resistant penicillins
MECHANISM:Bind penicillin-binding proteins (transpeptidases). Block transpeptidase cross-linking of peptioglycan in cell wall. Transpeptidase recognize D-ALA- D-ALA sequence on peptioglycan. Activate autolytic enzymes. Narrow specturm. Penicillinase resistant because bulky R group blocks access of B-lactamase to B-lactam ring
CLINICAL USE: S. Aureus ( except MRSA) - “use naf for staph”
TOXICITY: Hypersensitivty reactions
RESISTANCE: MRSA- altered penicillin-binding protein target site

Question 4

Clavulanic Acid

Answer 4

B-lactamase inhibitor. Often added to penicillin antibiotics to protect the antibiotic from destruction by B-lactamase (penicillinase)

Question 5

Sulbactam

Answer 5

B-lactamase inhibitor. Often added to penicillin antibiotics to protect the antibiotic from destruction by B-lactamase (penicillinase)

Question 6

Tazobactam

Answer 6

B-lactamase inhibitor. Often added to penicillin antibiotics to protect the antibiotic from destruction by B-lactamase (penicillinase)

Question 7

Cefazolin, cephalexin

Answer 7

CLASS: 1st generation cephalosporins
MECHANISM: B-lactam that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.
CLINICAL USE: gram+ cocci (strep and staph), Proteus mirabilis, E.coli, Klebsiela. Cefazolin used prior to surgery to prevent S. aureus wound infections
TOXICITY: Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency. Exhibit cross-reactivity with penicillins. ^ nephrotoxicity of aminglycosides
MECHANISM OF RESISTANCE: Structural change in penicillin binding proteins (transpeptidases)

Question 8

Cefoxitin, cefaclor, cefuroxime

Answer 8

CLASS: 2nd generation cephalosporin
MECHANISM:B-lactam that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.
CLINICAL USE: gram- positive cocci ( strep and staph) Haemphilus influenzae, Enterobacter, Neisseria, Proteus mirabilis, E. coli, Klebsiela pneumonia, Serratia marcescens
TOXICITY:Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency. Exhibit cross-reactivity with penicillins. ^ nephrotoxicity of aminglycosides
MECHANISM OF RESISTANCE:Structural change in penicillin binding proteins (transpeptidases)

Question 9

ceftriaxone, ceftriaxime, ceftadizdime

Answer 9

CLASS: 3rd generation cephalosporin
MECHANISM:B-lactam that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.
CLINICAL USE: serious gram (neg) infections resistant to other b-lactams. CEFTRIAXONE FOR Meningitis, gonorrhea disseminated lyme disease. CEFTADIZDIME FOR PSEUDOMONAS
TOXICITY: CEFTRIAXONE CAN CAUSE KERNICTERUS USE CEFUROXIME Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency. Exhibit cross-reactivity with penicillins. ^ nephrotoxicity of aminglycosides
MECHANISM OF RESISTANCE: Structural change in penicillin binding proteins (transpeptidases)

Question 10

cefepime

Answer 10

CLASS: 4th generation cephalosporin
MECHANISM:B-lactam that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.
CLINICAL USE: gram-negative organisim, with ^ activity against Pseudomonas and gram + organism.
TOXICITY:Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency. Exhibit cross-reactivity with penicillins. ^ nephrotoxicity of aminglycosides
MECHANISM OF RESISTANCE: Structural change in penicillin binding proteins (transpeptidases)

Question 11

ceftaroline

Answer 11

CLASS: 5th generation cephalosporin
MECHANISM:B-lactam that inhibit cell wall synthesis but are less susceptible to penicillinases. Bactericidal.
CLINICAL USE: broad gram-positive and gram-negative, including MRSA; does not cover Pseudomonas
TOXICITY:Hypersensitivity reactions, autoimmune hemolytic anemia, disulfiram-like reaction, vitamin K deficiency. Exhibit cross-reactivity with penicillins. ^ nephrotoxicity of aminglycosides
MECHANISM OF RESISTANCE: Structural change in penicillin binding proteins (transpeptidases)

Question 12

What organism are typical not covered by cephalosporins

Answer 12

‘LAME’ - Listeria, Atypicals (chlamydia, mycoplasma, MRSA and Enterocci. (ceftarolin covers MRSA)

Question 13

Imipenem, meropenem, ertapenem, doripenem

Answer 13

CLASS: Carbapenems
MECHANISM: Broad-spectrum, B-lactamase resistant. Imipenem always administered with CILASTATIN (inhibitor of renal dehydropeptidase I) to decrease inactivation of drug in renal tubules
CLINICAL USE: Gram+ cocci, Grame-neg rods. Wide spectrum but significant side efects, only use to life-threatening infections or after drugs failed.
TOXICITY: GI distress, skin rash, and CNS toxicity (seizures) (DECREASEDRISK WITH MEROPENEM)

Question 14

Aztreonam

Answer 14

CLASS: Monobactams
MECHANISM: Less susceptible to B-lactamases. Prevents peptidoglycan cross-linking by binding to penicillin-binding protein 3. Synergistic with aminoglycosides. No cross allergenicty with penicillins.
CLINICAL USE: For penicillin-allergic patients and those with renal insufficiency who cannot take aminoglycosides Gram-neg rods only ( klebsiela, e. coli, enterobacter, citrobacter, salmonella, prteus, yerisnia, shigella, pseudomonas)
TOXICITY: Usually nontoxic, occasional GI upset

Question 15

Vancomycin

Answer 15

MECHANISM: Inhibits cell wall peptidoglycan formation by binding D-ala D -ala portion of cell wall precursors. Bactericidal. Not susceptible to B-lactamases
CLINICAL USE: Gram+ bugs only- multipdrug-resistant organism, including MRSA, S. epi, sensitive enteroccocus, and Clostridium difficile ( oral dose for pseudomembranous colitis)
TOXICITY: Nephrotoxicity, Ototoxicty, Thrombophlebitis. diffuse flushing - redman syndrome ( prevent with pretreatment with antihistamines)
MECHANISM OF RESISTANCE: Occurs in bacteria via amino acid modificatino of D-ala D ala to D-ala D-lac

Question 16

30s inhibitors

Answer 16

Aminoglycosides (bactericidal)

Tetracyclines (bacteriostatic)

Question 17

50s inhibitors

Answer 17

“buy AT 30, CCEL at 50)
C= Chloramphenical, Clindamycin (bacteriostatic
E= Erythromycin (macrolides) (bacteriostatic)
L= Linezolid

Question 18

Gentamicin, Neomycin, Amikacin, Tobramycin, Streptomycin

Answer 18

CLASS: Aminoglycosides
MECHANISM: Bactericidal; irreversible inhibition of initiation complex through binding of the 30S subunit. Can cause misreading of mRNA. Also block translocation. Require O2 for uptake; therefor ineffective against anaerobes
CLINICAL USE: Severe gram-negative rod infections. Synergistic with B-lactam antibiotics. Neomycin for bowel surgery.
TOXICITY: Nephrotoxicity, Neuromuscular blockade, Ototoxicity (especially when used with loop diuretics). Teratogen
MECHANISM OF RESISTANCE: Bacterial transferase enzyme inactivate the drug by acetylation, phosphorylation or adenylation

Question 19

Tetracycline, doxycycline, minocyclin

Answer 19

CLASS: Tetracyclines
MECHANISM: Bacteriostatic; bind to 30S and prevent attachment of aminoacyl-tRNA
CLINICAL USE: Borrelia burgdoferi, M. pneumoniae. Drugs ability to accumulate intracullularly makes them very effective against Rickettsia and Chlamydia.
TOXICITY: GI distress, discoloration of teeth and inhibition of bone growth in children, photosensitivity. Contraindicated in pregnancy
MECHANISM OF RESISTANCE: decreased uptake or increased efflux out of bacterial cells by plasmid-encoded transport pumps

Question 20

Chloramphenicol

Answer 20

MECHANISM: Blocks peptidyltransferase at 50S ribosomal subunit. Bacteriostatic
CLINICAL USE: Meningitis ( H. Influenzae, N. Menigitidis, S. pneumo) and Rocky Mountain spotted fever ( Rickettsia rickesttsii)
TOXICITY: Anemia +aplastic anemia ( dose dependent), gray baby syndrome (in premature infants because they lack liver UDP-glucuronyl transferase)
MECHANISM OF RESISTANCE: Plasmid-encoded acetyltransferase inactivates the drug

Question 21

Clindamycin

Answer 21

MECHANISM: Blocks peptide transfer ( translocation) at 50S ribosomal subunit. Bacteriostatic
CLINICAL USE: Clindamycin for anaerobic infections above the diaphragm vs. metronidazole below the diaphragm
TOXICITY: Psudomembranous colitis ( C. difficile overgrowth), fever, diarrhea

Question 22

Linezolid

Answer 22

CLASS: Oxazolidiones
MECHANISM: Inhibit protein synthesis by binding to 50S subunit and preventing formation of the initiation complex
CLINICAL USE: Gram+ species including MRSA and VRE
TOXICITY: Bone marrow suppression ( especially thrombocytopenia), peripheral neuropathy, serotonin syndrome
MECHANISM OF RESISTANCE: Point mutation of ribosomal RNA

Question 23

Azithromycin, clarithromycin, erythromycin

Answer 23

CLASS: Macrolides
MECHANISM: Inhibit protein synthesis by blocking translocation; bind to the 23S rRNA of the 50S ribosomal subunit. Bacteriostatic
CLINICAL USE: Atypical pneumonias ( Mycoplasma, Chlamydia, Legionella) STIs (chlamydia), gram-positive cocci ( strep infections in patients allergic to penicillin) and B. Pertussis
TOXICITY: “MACRO” gi (M)otility issues, (A)rrhythmia cause by prolong QT, acute (C)holestatic hepaitis, (R)ash, e(O)sinophilia. Increases serum concentration of theophyllines, oral anticoagulants. Clarithromycin and erthro inhibit cytochrome P-450
MECHANISM OF RESISTANCE: Methylation of 23S rRNA-binding site prevents binding of drug

Question 24

Trimethoprim

Answer 24

MECHANISM: Inhibits bacterial dihydrofolate reductase. Used in combination with sulfonamides (trimethoprim-sulfamethoxazole), causing sequential block of folate
CLINICAL USE: UTIs, Shigella, Salmonella, Pneumocystis jirovecii pneumonia ( treatment and prophylaxis), toxoplasomis prophylaxis
TOXICITY: Megaloblastic anemia, leukopenia, granulocytopenia

Question 25

Sulfamethoxazole, sulfisoxazole, sulfadiazine

Answer 25

CLASS: Sulfonamides
MECHANISM: Inhibit folate synthesis. Para-aminobenzoic acid antimetabolits inhibit dihydropteroate synthase. Basteriostatc ( bactericidal with trimethoprim)
CLINICAL USE: Gram +, Gram negs, Nocardia, Chlamydia, SMX for simple UTI
TOXICITY: Hypersensitivity reaction, hemolysis if G6PD deficient, nephrotoxicity, Photosensitivity, kernicterus in infants, displace other drugs from albumin ( warfarin)
MECHANISM OF RESISTANCE: Altered enzyme(bacterial dihydropteroate synthase), decreased uptake, or increase PABA synthesis

Question 26

Ciprofloxacin, norfloxacin, levofloxacin, ofloxacin, moxifloxacin

Answer 26

CLASS: Fluoroguinolones
MECHANISM: Inhibit prokaryotic enzymes topoisomerase II (DNA gyrase) and top IV. Bactericidal. Must not be taken with antacids
CLINICAL USE: Grame-neg rods of urinary and GI tracts ( including Pseudomonas) Neisseria and some gram +
TOXICITY: GI upset, headache leg craps. COntrainicated in pregnant women, nursing mothers and children ( 60 also taking prednison
MECHANISM OF RESISTANCE: Chromosome-encoded mutation in DNA gyrase, plasmid mediate resistance, efflux pumps.

Question 27

Daptomycin

Answer 27

MECHANISM: Lipopeptide that disrupts cell membrane of gram+ cocci
CLINICAL USE: S. aurues skin infections (specialy MRSA), bactermia, endocarditis, VRE. Not used for pneumonia (avidly binds to and is inactivated by surfactant)
TOXICITY: Myopathy, rhabdomyolysis

Question 28

Metronidazole

Answer 28

MECHANISM: Forms toxic free radical metabolites in teh bacterial cell that damage DNA. Bactericidal, antiprotozoal.
CLINICAL USE: “GET GAP on the Metro” (G)iardia, (E)ntameoba, (T)richomonas, (G)ardneralla vaginals, (A)naerobes (bacteroides, C. difficle). and part of “triple therapy: against H. (P)ylori
TOXICITY: Disulfiram-like reaction ( severe flusing, tachycardia, hypotension) with alchohol; headach, metallic taste.

Question 29

Rifampin, rifabutin

Answer 29

CLASS: Rifamycins
MECHANISM: Inhibit DNA-dependent RNA polymerase
CLINICAL USE: TB, delay resitance to dapsone for leprosy, meningococcal prophylaxis and chemoprophlyaxis in contacts of childer with H flu
TOXICITY: ^ cytochrome P-450, orange body fluids
RESISTANCE: Mutations reduce drug binding to RNA polymerase. Monotherapy rapidly leads to resistance

Question 30

Isoniazid

Answer 30

MECHANISM: decrease syntesis of mycolic adcids. Bacterial catalase-peroxidase (encoded by KatG) needed to convert INH to active metabolit
CLINICAL USE: TB- solo prophylaxis
TOXICITY: Neurotoxicity, hepatotoxicty. Pydridoxine ( B6) can prevent neurotox
RESISTANCE: Mutations leading to underexpression of KatG

Question 31

Pyrazinamide

Answer 31

MECHANISM: Mechanism uncertain. prodrug that is converted to active compund pyrazinoic acid
CLINICAL USE: TB
TOXICITY: hyperuricemia, hepatotoxicty

Question 32

Ethambutol

Answer 32

MECHANISM: dcrease carbohydrate polymerization of mycobacterium cell wall by blocking arabinosyltransferase
CLINICAL USE: TB
TOXICITY: Optic neuropathy (red-green color blindness)
RESISTANCE: