Mechanisms of Drug Action Unit 3

Antibiotic

Substance produced by microorganism that suppresses growth of other microorganisms and may destroy them

Bacteriostatic

Halts further growth

Used when host immune defenses are working

Bactericidal

Kills present bacteria

Used when host defenses are impaired

Susceptible

Drug can inhibit/kill invading organism without harming host

Resistant

Drug dose needed to inhibit/kill invading organisms is toxic to host

Transduction

Transfer of genetic info from phage

Transformation

Take in genetic material from environment — free DNA

Conjugation

Giving plasmid — transfer of genetic material between 2 bacteria

Mechanisms of resistance

Altered target site

Enzymatic degradation

Bypass pathway

Efflux pump + decreased entry

Causes of resistance

Drug fails to reach target

Drug is inactivate

Target is altered

B-Lactams

Penicillins, monobactam, cephalosporins, carbapenem

4 membered ring

Amoxicillin/clavulanate

B-lactam/b-lactamase inhibitor combo

Inhibit pcb + inhibit b lactamase

Ticarcillin/clavulanate

B-lactam/b-lactamase inhibitor combo

Inhibit pcb + inhibit b lactamase

Ampicillin/sulbactam

B-lactam/b-lactamase inhibitor combo

Inhibit pcb + inhibit b lactamase

Piperacillin/tazobactam

B-lactam/b-lactamase inhibitor combo

Inhibit pcb + inhibit b lactamase

Penicillin

B-lactam

PBP antagonist

(Amoxicillin, Ticarcillin, Ampicillin, Piperacillin)

Monobactam

B-lactam

PBP antagonist

Aztreonam

Monobactam

B lactam

PBP antagonist

Cephalosporin

B-lactam

PBP antagonist

Cephalexin

Cephalosporin

B lactam

PBP antagonist

Carbapenem

B-lactam

PBP antagonist

Resistant to B-lactamase degradation

Imipenem

Carbapenem

B lactam

PBP antagonist

Resistant to b-lactamase

Clavulanate

B lactamase inhibitor

Sulbactam

B lactamase inhibitor

Tazobactam

B lactamase inhibitor

Vancomycin + Bactrain bind

D-Alanyl-D-alanine terminus of wall precursor

Block PBP binding

No crossing

Dec cell wall

Not susceptible to b lactamase

Effective for resistant strains

Vancomycin

Bind AA terminus

Glycopeptide

Telavancin

Bind AA terminus

Antibacterial

Glycopeptide

Dalbavancin

Bind aa terminus

Antibacterial

Glycopeptide drug

Oritavancin

Bind aa terminus

Glycopeptide drug

Antibacterial

Are cell wall metabolism inhibitors bactericidal or bacteriostatic?

Bactericidal

Aminoglycosides

bind to 30S subunit

• block 70s complex formation

• misread mRNA. (make improper proteins)

  • block complex movement

bactericidal

Gentamicin

aminoglycoside

binds 30s subunit

Kanamycin

aminoglycoside

binds 30s subunit

Tobramycin

aminoglycoside

binds 30s subunit

Neomycin C

aminoglycoside

binds 30s subunit

Streptomycin

aminoglycoside

binds 30s subunit

Amikacin

aminoglycoside

binds 30s subunit

Tetracyclines

bind 30s subunit

block tRNA to A acceptor site

premature chain termination

bateriostatic

doxycycline

tetracycline

bind 30s

Chloramphenicol

binds 50s ribosomal subunit

prevents chain addition

no peptidyl transferase reaction bc no access to binding pocket

bacteriostatic

only for serious diseases

Macrolides

bind 50s ribosomal subunit

inhibit ribosome movement along mRNA

no racheting

bacteriostatic

Ertythromycin

Macrolide

bind 50s subunit

Clarithromycin

Macrolide

bind 50s subunit

Azithromycin

Macrolide

bind 50s subunit

Sulfonamides

derivative of PABA

work as competitive antagonist of 1st rxn of THF synthesis

INHIBIT Dyhydropteroate synthase

sulfanilamide

sulfonamide

inhibit Dyhydropteroate synthase

Sulfadiazine

sulfonamide

inhibit Dyhydropteroate synthase

sulfisoxazole

sulfonamide

inhibit Dyhydropteroate synthase

sulfamethoxazole

sulfonamide

inhibit Dyhydropteroate synthase

component of bactrim

sulfathalidine

sulfonamide

inhibit Dyhydropteroate synthase

Trimethoprim

inhibits another step in THF synthesis

INHIBITS dihydrofolate reductase

competitive inhibition antagonist

Bactrim

Synergy between sulfonamides and trimethoprim

Sulfamethoxazole + trimethoprim

sulfonamides are bacteriostatic vs bactericidal

bacteriostatic

Fluroquinolones

inhibit bacterial DNA replication via inhibition of gyrase

no supercoil release, break, no rep

ciprofloxacin

Fluroquinolone

inhibit gyrase and bacterial DNA rep

nalidixic acid

Fluroquinolone

inhibit gyrase and bacterial DNA rep

norfloxacin

Fluroquinolone

inhibit gyrase and bacterial DNA rep

levofloxacin

Fluroquinolone

inhibit gyrase and bacterial DNA rep

gatifloxacin

Fluroquinolone

inhibit gyrase and bacterial DNA rep

moxifloxacin

Fluroquinolone

inhibit gyrase and bacterial DNA rep

gemifloxacin

Fluroquinolone

inhibit gyrase and bacterial DNA rep