Sweatman Antmicrobial Drugs Flashcards
4 MOA’s of antimicrobial agents
- inhibition of cell wall
- inhibition of protein synthesis
- inhibition of folic acid biosynthetic pathways
- Inhibition of DNA/RNA synthesis
Ampicillin: DRUG CLASS
penicillin (beta lactam)
Aztreonam: DRUG CLASS
Penicillin (monobactam)
penicillin G: DRUG CLASS
Penicillin (beta lactam)
Piperacillin
penicillin (beta lactam)
Imipenem
penicillin (Carbapenem) also a beta lactam
Amoxicillin
penicillin
Clavulanic acid
penicillin (beta lactamase inhibitor)
cilastatin
penicillin (renal dihydropeptidase inhibitor)
Sulbactam
penicillin (beta lactamase inhibitor)
Tazobactam
penicillin (beta lactamase inhibitor)
Methicillin
penicillin
Nafcillin
penicillin
oxacillin
penicillin
penicllin V
penicillin
other inhibitors of cell wall synthesis
ceftriaxone (IV; 3rd generation) cephalexin (oral; 1st generation) Vancomycin Cefazolin (IV) Cefepime (IV)
penicillins, carbapenems, and cephalosporins belong to a class of antibiotics known as….
Beta-lactams
4 membered ring where a N is adjacent to carboxy C–> all bind PBP’s
Narrow Spectrum Penicillins and their MOA
Oxacillin, Nafcillin
*larger molecule on penicillin side chain confers steric hindrance–>confers resistance to beta lactamase–> but also restricts their spectrum of activity (cannot conform to as many sterioisomers)
Aminopenicillins and their MOA’s
Ampicillin, Amoxicillin
*added NH2 group makes molecule more hydrophillic–>more able to cross LPS barrier and thus increased efficacy against gram-nagative bacteria
Broad-Spectrum Penicillins
Piperacillin
Prototypical Penicillins
Penicillin G and Penicillin V
MOA for beta lactam antibiotics
- binding to penicillin-binging proteins (transpeptidases)
2. destruction of cell wall
Action of transpeptidases that is disrupted by beta-lactam antibiotics
Cross-linking of peptidoglycan molecules in bacterial cell walls–> lack of cross-links makes them weak and the cell will lyse
Type of bacteria susceptible to beta lactam activity
Gram Positive (relies extensively on a thick, highly cross-linked cell wall)
gram negative bacteria have a LPS layer which protects the thing peptidoglycan from beta-lactam activity
Beta Lactamase inhibitors
- clavulanic acid (added to amoxicillin)
- tazobactam (added to piperacillin)
- Sulbactam
* not inherently toxic to bacteria–>do not contain a beta lactam–>bind to beta lactamase and increase the duration of activity of beta lactam antibiotics
contains a thiazolidine ring
penicillins and cephalosporins
Monobactam with a sulfonic acid attached to beta lactam ring
aztreonam (bactericidal–>binds transpeptidases inside the cell wall)
major difference between carbapenem and other penicillins
carbon atom in 5 membered ring as opposed to sulfer atom
Why does Imipenem need cilastatin
in the kidneys–> cilastin inhibits an enzyme that breaks down the drug, this increases imipenem activity and decreases nephrotoxicity
D.O.C for Staph. Aureus and Staph epi
*Gram-positive cocci
Penicillinase resistant penicllins
methicillin, nafcillin, oxacillin,
DOC for Strep (GROUPS A,B,C,G) and S. bovis
*(Gram-Positive cocci)
Pen G, Pen V, Ampicillin
DOC for Clostridium
(*bacilli)
Pen G
DOC for E. faecalis UTI
* Gram-Positive cocci
ampicillin and amoxicillin
DOC for Strep. pneumonia
*gram-positice cocci
Pen G, Pen V, Ampicillin
DOC for E. coli
*gram-negative bacilli
ampicillin, (*ampicillin+sulbactam), (Amoxicillin + Clavulanate)
DOC for P. Aeurginosa
gram-negative bacilli
piperacilli n/ tazobacta m
Unique features of cephalosporins
- more acid stable than penicillins
- possess 6 membered ring attached to a beta lactam ring
- 4 generations (gram positive activity is lost and gram negative activity is gain with each generation)
List the Cephalosporins
Cefazolin–>1st
Cephalexin–>1st
Ceftriaxone–>3rd
Cefepime–>3rd
Vancomycin MOA
forms H+ bonds with the D-ala D-ala moeities on the NAM/NAG peptides–>prevents long NAM/NAG polymers from forming–>also disrupts cross-linking between those polymers that do form–>cell wall weakens–> bacterium lyses
Vancomycin is a ( ) that interupts ( ) activity during cell wall formation.
- glycopeptide
2. transglycosylase
Solubility of Vanc
VERY POORLY SOLUBLE
- if infection is limited to GI tract–>orally because ti would not need to be absorbed to have an affect
- if ANYWHERESE ELSE–> IV
Glycopeptide antibiotics are only effective against _______
gram-positive bacteria
gram-negatives have LPS layers that protects their peptidoglycan wall from being disrupted
Aminoglycosides
GENTAMICIN Amikacin neomycin straptamycin tobramycin
lincosamides
clindamycin
macrolides
AZITHROMYCIN CLARITHROMYCIN ERYTHROMYCIN erythromycin telithryomycin
oxazolidinones
LINEZOLID
streptogramins
quinipristin/dafropristin
tetracyclines
DOXYCYLINE
TIGECYCLINE
minocycline
tetracycline
(OTHERS) monoxycarbolic acid
mupriocin
MOA for aminoglycosides
- Irreversibly bind 30s subunit
low concentrations–Cause misreading of mRNA
–>high conecntrations– halt protein synthesis
2.bore giant f’ing holes in the outer cell membrane
(leads to leakage of intracellular materials and increase Ab uptake)
*holes are more detrimental
classes that inhibit cell walls
Penicillins, Cephalosporins & Vancomycin
beta lactams MOA
disrupt transpeptidase (PBP’s), destruction of cell wall
Beta Lactams are most potent inhibitors of which type of bacteria and why?
Gram positive (thick peptidoglycan layer) *gram negative bacteria have the LPS layer that protects the peptidoglycan layer from beta lactam activity
Penicillin + aminoglycoside
Combination of cell wall and protein synthesis inhibitor
Sulfamethexazole + trimethoprim
act in sequential steps in the folic acid biosynthesis pathway
amoxicillin + clavulanic acid
(augmentin) beta lactam + beta lactamase inhibitor
prokaryote ribosome
70S ribisomes
Small 30S subunit
Large 50S (23S and 5S and 34 other proteins)
Aminoglycosides are bactericidal because?
The action on the outer bacterial membrane, in addition to its protein synthesis inhibition, is thought to be the reason that aminoglycosides are bactericidal.
Aminoglycosides work well on which type of bacteria
Gram-negative
Azithromycin (macrolide) MOA
Binds the 23s subunit of the 50S RSU (bacteriostatic)
Clindamycin (lincosamide) MOA
binds the 23s of 50s RSU (bacteriostatic)
Tetracycline MOA
bind to 16s subunit
streptogramins MOA
quinipristin and dalfopristin bind the 50s (large) RSU (these two have a synergistic effect)
mupriricin MOA
binding and inhibition of Isoleucyl transfer rna sythetase–> works on MRSA
Antimicrobials
Antibiotics
antifungals
antiparasitics
NOT antivirals–> they are not technically alive
MBC
minimum bacteriostatic concentration
*the lowest concentration of an antibacterial agent required to kill a particular bacterium
MIC
minimum inhibitory concentration
*n microbiology, minimum inhibitory concentration (MIC) is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation
Therapeutic index
The therapeutic index (also known as therapeutic ratio) is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death (in animal studies) or toxicity (in human studies)
Penicillin + aminoglycoside synergistic MOA
combination of cell wall and protein synthesis inhibition
Sulfamethexazole + Trimethoprim (septra or bactrim) synergistic MOA
sulfa inhibits incorporation of PABA into folic acid
trimethoprim inhibits reduction of DHF to THF
*sequential steps
monobactam
aztreonam
carbapenem
impenem
Beta Lactams…name them and their MOA
Penicillins, Carbapenems, Cephalosporins
- bind to transpeptidases and inhibit cell wall cross-linking
- destruction of bacterial cell wall
end result of beta lactam activity
cell lysis
why are Gram Negative bacteria more resistant to beta lactams
LPS layer protects the thin (2 layered) peptidoglycan wall–>BL’s cannot reach the thang
Do beta lactamase inhibitors contain a beta lactam
yes–>but are not toxic to the cell
*they merely bind to beta lactamase
BLI added to amoxicillin
clavulanic acid (augmentin)
BLI added to piperacillin
tazobactam (zosyn)
Narrow spectrum penicillin MOA’s
bulk adduct on penicllin side chain making them
- resistant to Beta lactamase cleavage
- unable to contort into may sterioisomers–> inhibiting their range of activity
amino penicillins are best used against
gram negative bacteria
Broad spectrum penicillins are modifications of…
amino penicillins
*inreases the range of bacteria that are susceptible to them
Are Broad Range Penicillins sensitve to beta lactamase cleavage
yes–> frequently administered with beta lactamase inhibitor “pip/tazo”
where are PBP’s located
inside the bacterial cell wall
3 reasons Imipenem has a broader range spectrum of activity than other beta lactams
5 membered ring contains a carbon atom rather than sulfer
1. more efficient penetration thru cell wall
2 resistance to bacterial enzymes
3. affinity for all PBP’s
renal dehydropeptidase inhibitor
cilistatin
*prevents renal metabolism of Imipenem, increasing the urinary concentration and minimizing nephrotoxicity o the drug
Major advantage of cephalosporins regarding administration
acid stable so can be given WITHOUT FOOD
IST GENERATION CEPHALOSPORINS ARE USEFUL FOR TREATING
SKIN INFECTION
CEFAZOLIN AND CEPHALEXIN
2ND GENERATION CEPHALOSPORINS ARE USEFUL FOR TREATING?
GRAN NEGATIVE BACTEROIDES
CEFTRIAXONE IS USEFUL IN TREATING
STD’S AND PEDIATRIC MENINGITIS
CEFEPIME IS USEFUL in treating
pseudomonal infection
Solubility of aminoglycosides
insoluble–> they are very polar and therefore penetration is poor
Aminoglycosides are toxic in the
kidneys
small ribosomal subunit
30 s
large RSU
50 S
50 S RSU is composed of
23 S 5 S 34 other proteins
Aminoglycosides will not work on
anaerobes
*aminoglycosides require energy for uptake–> anaerobic bacteria lack much energy
aminoglycosides are bacteriostatic/cidal
-cidal
*holes + protein inhibition
other protein synthesis inhibitors are mainly bacteriostatic
macrolide nomenclature
-Thromycin
Macrolide MOA
bind 23s of 50s–>BIND to P site inhibit peptidyl transferase–>this blocks the transfer of the new amino acid onto the growing chain
*bacteriostatic except for in high concentrations
Macrolides are phagocytosed by?
macrophages at the site of infection
MOA for lincosamides
23s/50s–>promote premature dissociation of peptidyl transferase
Clinda is most useful in
toxin producing infections
Tetracylin MOA
bind to 16 S of 30s RSU–> and inhibit amino-acyl tRNA binding
tetracylcins static/cidal
cidal
they completely stop protein synthesis–>whereas other protein synthesis inhibitor stop initiation
what are the streptogramins and how are they synergistic
BASTERICIDAL
Quinipristin bind to P site on 50sRSU, inhibits elongation, and promotes early termination of protein synthesis
Dalfopristin binds at a spot nearby and causes a conformation change in the 50sRSU which makes the RSU bind more tightly to quinipristin at the P site
bactericidal protein synthesis inhibitors
aminoglycosides (for 2 reasons)
streptogramins (synergitic effect)
tetracycline (prevents trna from ever binding to A site
mupirocin
Mupriocin inhibits…
isoleucyl tRNA synthetase
chloramphenicol should not be given with?
macrolide or lincosamide Ab’s–> binds at B site as well
floruoquinolones
cipro
levofloxacin
Nitroimdazoles
metronidazole
sulfonamides
cotromoxazole
sulfamethexazole
rifamycins
rifampin
rifamixin
DHFR inhibitors
cotrimoxazole
trimetoprim
Flouroquinolones MOA
bactericidal
bind to and inhibit Gyrase (gram negative) and TOPO IV (gram positive)
*after the cutting step–>there is no re-anealing
rifampin MOA
binds RNA polymerase–> prevents INITIATION…not ELONGATION
RIFAMPIN is useful in treating
HIGHLY lipophillic
Mycobacterium Biofilms Bacterial menengitis (cns penetration is high) intracellular bacteria abcesses
METRONIDAZOLE IS MOST USEFUL IN TREATING
anaerobic bacteria–> it acts as the terminal electron acceptor (aerobic bacteria use O2 for this and metronidazole is never converted from its prodrug state
cotrimoxazole is made up of
Sulfa and trimethoprim
sulfa MOA
inhibits incorporation of PABA into folic acid
trimethoprim MOA
inhibits DHF being reduced into THF
in vivo concentration of sulfa to trimethoprim
20:1