Antibiotics 2

Question 1

Tetracycline

Answer 1

• Tetra-; doxy-; mino-;tige-;
• Broad spectrum
• Bacteriostatic
• reversibly binds to 30S
• Widespread resistance
• impaired influx and increased efflux
• ribosome protection
• enzymatic inactivation

Question 2

Pharmacokinetics of Tetracycline

Answer 2

• bioavailability varies
• cross placenta
• chelation with Ca2+ , Fe2+

Question 3

Tetracycline Side Effects

Answer 3

• GI disturbance (alter GI flora)
• deposit in bones and teeth (tetra-)
• hepatotoxicity
• vestibular disturbance
• photosensitivity

Question 4

Macrolides

Answer 4

• Erythromycin; Azithro-; Clazithro-
• Broad spectrum (Erythro- G+)
• Binding to 50S, blocking transpetidation
• Bacterio-static or -cidal
• Widespread resistance
• plasmid-encoded
• impaired influx and increased efflux
• enzymatic inactivation (esterase)
• ribosome protection

Question 5

pharmacokinetics macrolides

Answer 5

• oral (erythro- coated)
• GI intolerance (increase GI motility)
• P450 CYP3A4 inhibitor
• azithromycin t1/2 ~ 3days

Question 6

Aminoglycosides

Answer 6

• Streptomycin; neo-; tobra-; gentamicin-; amikacin
• Bactericidal
• irreversibly binds to 30S subunit
• G –>G+
• CDK & PAE
• synergistic effect w. β-lactams
• Resistance mediated by
• enzymatic inactivation
• impaired penetration by porin modification
• ribosome protection

Question 7

pharmacokinetics aminoglycosides

Answer 7

• water soluble, poor GI absorption
• nephro- & oto-toxicity (duration & concentration dependent)

Question 8

Inhibiting Nucleic Acid Synthesis

Answer 8

• Inhibiting synthesis of nucleotide
• DNA gyrase inhibition: prevent
  relaxation of + supercoiled DNA
• Topoisomerase IV inhibition: prevent separation of replicated DNA

Question 9

Fluoroquinolones

Answer 9

• eg. cipro-floxacin; levo-; gati-; moxi-; etc.
• broad spectrum
• bactericidal
• Increasing resistance
• enzyme modification
• decreased influx
• pharmacokinetics
• good GI absorption,
• chelating with di-(tri-)valent cations
• well tolerated
• alternation of BG level; phototoxicity; tendonitis, tendon rupture
• CYP1A2 inhibitors

Question 10

Folate Inhibitors

Answer 10

• bacteriostatic
• synergistic effects
• TMP-SMX (sulfamethoxazole)
• urinary tract, respiratory infection, malaria, toxoplasmosis
• common resistance
• plasmid-mediated
• sulfa insensitive enzyme
• side effects
• upset GI
• skin rashes
• light sensitivity
• high risk for hypersensitivity
• risk of blood disorder in chronic use

Question 11

common mechanism for drug resistance

Answer 11

enzymatic inactivation
decreased entry & accumulation
reduced affinity
increasing efflux

Question 12

Genetic Basis of Resistance

Answer 12

• Chromosome-mediated
• genetic mutation, lower frequency (10-7 to 10-9)
• Plasmid-mediated (R plasmid, R factor)
• occurs in many species, esp. G-rods
• mediate resistance to multiple drugs
• horizontal transfer of resistance
• higher frequency
• Transposons
• fragments of DNA w. mobility

Question 13

Mechanism for Transferable Resistance

Answer 13

• Conjugation
• mutational resistance
• plasmid transfer
• Transduction
• mediated by bacteriophages
• Transformation
• scavenging “naked” resistance DNA

Question 14

Non-genetic Basis of Resistance

Answer 14

• Poor penetrance to abscess cavity
• Bacteria staying dormant
• Bacteria survive as protoplasts
• Presence of foreign body
• Antibiotic overuse
• unnecessarily long course of TM
• overuse in self-limited conditions
• overuse in prophylaxis
• OTC antibiotics
• animal feed
• Patient compliance