Antimicrobial Drugs Part 1

dose per kg required to achieve MIC (minimum inhibitory concentration)

(toxic dose/therapeutic dose)
greater the #=safer the drug
lower the #=more toxic drug

*need to maintain minimum effective concentration of the drug

*maximum tolerated dose (dose when you start to see toxic effects)

*TD50/ED50 (toxic dose in 50% of pts/effective dose in 50% of patients)
*space between efficacy and toxicity curve midpoints

*Toxic dose 1/effective dose 99
(toxic dose in 1 % of patients/effective dose in 99% of patients)
used to help determine patient dosages

*use of drugs to treat disease
*cancer tx, antibiotics against bacteria, etc..

interfere with growth of microbes within a host

*drug that kills harmful microbes without damaging the host

concentration range that a drug will work (upto the toxicity point)

*1928 by Fleming

*1940 by HOward Florey and Ernst Chain

*bacteria
*over half originate from Streptomyces

*antibioitic that is effective against a wide range of both gram-positive and/or gram negative bacteria

killing of bacteria

*inhibiting bacterial growth

*antibiotics
*drug
*chemicals (disinfectants)
*other biologicals (pt's serum etc...)

must know the serum antimicrobial concentration, want the amount of antibiotic in serum above the minimum inhibitory concentration

*margin of safety
*metabolism (and rate of metabolism) of drug

*Metabolic inhibitors
*DNA replication inhibitors
*RNA polymerase inhibitors
*protein synthesis inhibitors

*peptidoglycan synthesis

*PCN
*cephalosporins
*vancomycin
*bacitracin
*monobactams

*sulfonamides
*trimethoprim

*quinolones

*rifampin
*pyronins

*chloramphenicol
*macrolides (erythromycin)
*clindamycin
*oxazolidinones (linezolid)
*Streptogramins (synercid)

*Aminoglycosides (gentamicin)
*Tetracyclines (doxycycline)

prevents specific proteins/enzymes from creating peptidotetrad linkages for the NAG and NAM chains within the cell wall
(prevents cell wall synthesis)
*keep in mind, more than one way to accomplish this

*class of antibiotics that contain beta-lactam ring as their common structure
*PCN (natural and semisynthetic)

*destroy the enzyme (produced by bacteria) that would harm the antibiotics

produced by bacteria, destroys beta-lactum ring of antibiotic rendering it useless (ineffective)

*Ampicillin
*Amoxicillin
*Amoxicillin + clavulanic acid = Augmentin
those with betalactamase

*destroy the enzyme that would harm the antibiotic (destory the B-lactum ring)

*Cephalexin (1st gen)
*Cephoxatin (2nd gen)
*Ceftriaxone (3rd gen)

*class of B-lactam antibiotics
*single sulfur in place of carbon (double bond included)

*single ring B-lactam antibiotics

*use penicillinase (break the B-lactam ring)

*Gramicidin
*Polymixin (detergent action)

*B-lactam antibiotic drug that inhibits fatty acid synthesis (damages bacterial membrane)