Block 9 Drugs - Antimicrobials Flashcards

Question

**Tetracyclines**

Answer 1

**Inhibitors of Protein Synthesis** **Interference with tRNA binding**

Answer 2

MOA: Bind to the 30S ribosoomal subunit and prevent assocation of the [AA-tRNA] complex with tthe A site on 70S ribosome USE: Rickettsia (Rocky Mountain spotted fever) Cholera Chlamydia * Mycoplasma pneumonia* * B. burgdorferi* (Lyme disease) brucellosis anthrax S/E: Photosensitivity (sunburn) GI distress Hepatotoxicity Deposition in bones and teeth (dicoloration); limited use in pediatric patients Hypersensitivity CI: Cross resistance common across each tetracycline (excpet tigecycline) Risk to fetus during pregnancy Unique: Resistance due to: 1. decreased accumulation of the drug-efflux 2. enzymatic inactivation 3. decreased access of the drug to the ribosome Each drug in the class has similar resistance mechanisms

Answer 3

MOA: Bind to the 30S ribosoomal subunit and prevent assocation of the [AA-tRNA] complex with tthe A site on 70S ribosome USE: Rickettsia (Rocky Mountain spotted fever) Cholera Chlamydia Mycoplasma pneumonia B. burgdorferi (Lyme disease) brucellosis anthrax S/E: Photosensitivity (sunburn) GI distress Hepatotoxicity Deposition in bones and teeth (dicoloration); limited use in pediatric patients Hypersensitivity CI: Cross resistance common across each tetracycline (except tigecycline) Risk to fetus during pregnancy Unique: \*\*Most commonly used tetracycline class drug\*\* Resistance due to: decreased accumulation of the drug-efflux enzymatic inactivation decreased access of the drug to the ribosome Each drug in the class has similar resistance mechanisms

Answer 4

MOA: Bind to the 30S ribosoomal subunit and prevent assocation of the [AA-tRNA] complex with tthe A site on 70S ribosome USE: Rickettsia (Rocky Mountain spotted fever) Cholera Chlamydia Mycoplasma pneumonia B. burgdorferi (Lyme disease) brucellosis anthrax S/E: Photosensitivity (sunburn) GI distress Hepatotoxicity Deposition in bones and teeth (dicoloration); limited use in pediatric patients Hypersensitivity Concentrates in the endolymph of the ear: dizziness, vertigo, tinnitus CI: Cross resistance common across each tetracycline (except tigecycline) Risk to fetus during pregnancy Unique: \*\*Effective in getting into cerebrospinal fluid (CSF)\*\* Resistance due to: decreased accumulation of the drug-efflux enzymatic inactivation decreased access of the drug to the ribosome Each drug in the class has similar resistance mechanisms

Answer 5

MOA: Bind to the 30S ribosoomal subunit and prevent assocation of the [AA-tRNA] complex with tthe A site on 70S ribosome USE: Vancomycin resistant MRSA S/E: Significant nausea & vomiting Acute pancreatis other SE similar to tetracycline (Photosensitivity, Gi distress, hepatotoxicity, etc.) CI: Not cross-resistant with other tetracyclines Risk to fetus during pregnancy Unique: Glycyl cyclic derivative of monocycline

Answer 6

MOA: Inhibits bacterial protein synthesis by binding specifically to isoleucyl-tRNA synthetase *Inhibitors of protein synthesis, inhibitor of tRNA synthetases* USE: Topical (nasal) MRSA infections **ONLY used topically** - rapidly inactivated upon absorption

Answer 7

Inhibitors of Protein Synthesis Alteration of mRNA translation and chain initiation

Answer 8

MOA: Interacts specifically with 30s subunit of ribosome, blocks the initiation process Bactericidal USE: Enterococci (+ ß-lactam) *Y. pestis* (+ ß-lactam) S/E: Ototoxicity\* Nephrotoxicity\* \*Elderly particularly sensitive to both Neuromuscular paralysis if pushed rapidly IV CI: Plasma levels of drug should be monitored Unique: Usually used in combination with other antibiotics Resistance due to: 1. Acetly-, nucleotidyl and phospho- transferase modifcations to drug 2. Decreased uptake 3. Mutation of S12 protein

Answer 9

MOA: Interacts specifically with 30s subunit of ribosome, blocks the initiation process Bactericidal USE: *P. aeruginosa* (+ ß-lactam) S/E: Ototoxicity\* Nephrotoxicity\* \*Elderly particularly sensitive to both Neuromuscular paralysis if pushed rapidly IV CI: Plasma levels of drug should be monitored Unique: Usually used in combination with other antibiotics Resistance due to: Acetly-, nucleotidyl and phospho- transferase modifcations to drug Decreased uptake Mutation of S12 protein

Answer 10

MOA: Interacts specifically with 30s subunit of ribosome, blocks the initiation process Bactericidal USE: Francisella tularemia * Brucella sp* (+ doxycycline) * Klebsiella sp* (+ ß-lactam) S/E: Ototoxicity\* Nephrotoxicity\* \*Elderly particularly sensitive to both Neuromuscular paralysis if pushed rapidly IV CI: Plasma levels of drug should be monitored Unique: Usually used in combination with other antibiotics Resistance due to: Acetly-, nucleotidyl and phospho- transferase modifcations to drug Decreased uptake Mutation of S12 protein

Answer 11

MOA: Interacts specifically with 30s subunit of ribosome, blocks the initiation process Bactericidal USE: *P. aeruginosa* * Acinetobacter sp.* * Enterobacter* * S. marcescens* 2^nd line mycobacteria TB S/E: Ototoxicity\* Nephrotoxicity\* \*Elderly particularly sensitive to both Neuromuscular paralysis if pushed rapidly IV CI: Plasma levels of drug should be monitored Unique: Uniquely resistant to drug modifying enzymes Usually used in combination with other antibiotics Resistance due to: Acetly-, nucleotidyl and phospho- transferase modifcations to drug Decreased uptake Mutation of S12 protein

Answer 12

MOA: Binds to the 23S rRNA in the 50s ribosomal subunit and interferes with the formation of the initiation complex Bacteriostatic (Oxazolidinones - alteration of mRNA translation and chain initiation) USE: treatement of vancomycin-resistant *S. aureus* (VRSA) and vancomycin-resistant Enterococcus (VRE) S/E: GI; nausea, diarrhea Thrombocytopenia, anemia, neutropenia CI: Weak MAOI activity; careful with other serotonergic meds (e.g. SSRIs) Unique: Primarily used for drug resistant gram (+) microbes

Answer 13

MOA: Inhibit bacterial DNA gyrase (topoisomerase II) and DNA topoisomerase IV Forms a complex with DNA and gyrase, results in DNA cleavage USE: Urinary tract infections Anthrax Enterobacter sp. *P. aeruginosa* in cystic fibrosis patients Effective for intracellular microbes S/E: nausea, vomiting, diarrhea May damage growing cartilage - arthropathy; avoid in patients \< 18 y/o **Tendonitis, tendon rupture** **Can prolong QT interval** CI: Not effective for MRSA, enterococci and pneumococci Avoid in pregnancy or during lactation due to arthropathy concers Unique: Enter bacteria via porins in the outer membrane Resistance due to mutations in gyrase and topoisomerase Increased efflux and decreased porins

Answer 14

MOA: Cyclic lipopeptide binds to bacterial cytoplasmic membrane causing rapid deploarization Disrupts all membrane and functional activities Bactericidal USE: Gram(+) cocci, including VRE, MRSA, and MSSA Gram (+) bacilli S/E: Nausea, Dizziness, Headache CI: Should not be used for pneumonias due to inactivation by pulmonary surfactants Unique: Different mechanism of action than other antibiotics \*Alternative to Vancomycin Increased MIC can occur with prolonged use

Answer 15

MOA: Reduction of the drug by enzymes that perform the phosphoroclastic reaction produce a reactive drug product that interferes with DNA replication Bactericidal USE: anaerobic microorganisms which carryout the **phosphoroclastic reaction** S/E: GI upset; nausea, diarrhea Rash CI: Avoid in pregnancy Avoid alcohol; disulfram reaction w/ alcohol Unique: Selectivity based on mammalian cells not performing the phosphoroclastic reaction

Answer 16

MOA: reduced to toxic, hihgly reactive intermediates by bacterial enzymes; binds covalently to DNA USE: UTI S/E: Nausea Pulmonary fibrosis risk in long-term use Unique: Selectivity; drug reduced more rapidly by bacterial enzymes than mammalian

Answer 17

MOA: Antitubercular agent Prodrug activated by mycobacterial catalase-peroxidase that inhibits synthesis of long chain mycolic acids unique to mycobacterial cell walls USE: *M. tuberculosis* S/E: Peripheral neuritis Hepatitis and idiosyncratic hepatotoxicity CI: MAOI activity; avoid serotonergic meds (e.g. SSRIs) Unique: Bacteriostatic for non-dividing mycobacteria; bactericidal for dividing cells Resistance due to chromosomal mutations in the catalase-peroxidase gene

Answer 18

MOA: Antitubercular agents Blocks transcription by inhibiting the beta subunit of mycobacterial DNA dependent RNA polymerase Bactericidal USE: Active for both intracellular and extracellular mycobacteria S/E: Mild, nausea, vomiting, rash Hepatotoxicity, jaundice; check LFTs (liver enzyme tests) CI: Never given as a single agent due to rapid drug resistance **Inducer of P450s;** may affect other drugs Unique: Most active anti-leprosy drug Not active agaianst the beta subunit of the human enzyme

Answer 19

MOA: Antitubercular Agent Similar to Rifampin - blocks transcription by inhibiting the beta subunit of mycobacterial DNA dependent RNA polymerase Bactericidal USE: TB in HIV patients Also from Mycobacteria avium complex S/E: Similar to Rifampin - Mild, nausea, vomiting, rash Hepatotoxicity, jaundice, check LFTs Unique: Used for treating TB in HIV patients; ***_not_*** potent inducer of P450s

Answer 20

MOA: Antitubercular Agent Mechanism unknown 🤷🏻‍♀️ mycolic acid synthese affected Bactericidal USE: Active against tubercle bacilli in lysosomes and macrophages S/E: Possible liver dysfunction in combination treatments Hyperuricemia/Gout Unique: Used only in combination with isoniazid, rifampin, & ethambutol

Answer 21

MOA: Antitubercular Agents Inhibits arabinosyl-transferase involved in arabinogalactan cell wall biosynthesis USE: *M. tuberculosis* and M. kansasii S/E: Optic neuritis with blurred vision Unique: Unique drug target; Drug resistance is low when used in drug combinations