Sweatman Antmicrobial Drugs Flashcards
1
Q
4 MOA’s of antimicrobial agents
A
- inhibition of cell wall
- inhibition of protein synthesis
- inhibition of folic acid biosynthetic pathways
- Inhibition of DNA/RNA synthesis
2
Q
Ampicillin: DRUG CLASS
A
penicillin (beta lactam)
3
Q
Aztreonam: DRUG CLASS
A
Penicillin (monobactam)
4
Q
penicillin G: DRUG CLASS
A
Penicillin (beta lactam)
5
Q
Piperacillin
A
penicillin (beta lactam)
6
Q
Imipenem
A
penicillin (Carbapenem) also a beta lactam
7
Q
Amoxicillin
A
penicillin
8
Q
Clavulanic acid
A
penicillin (beta lactamase inhibitor)
9
Q
cilastatin
A
penicillin (renal dihydropeptidase inhibitor)
10
Q
Sulbactam
A
penicillin (beta lactamase inhibitor)
11
Q
Tazobactam
A
penicillin (beta lactamase inhibitor)
12
Q
Methicillin
A
penicillin
13
Q
Nafcillin
A
penicillin
14
Q
oxacillin
A
penicillin
15
Q
penicllin V
A
penicillin
16
Q
other inhibitors of cell wall synthesis
A
ceftriaxone (IV; 3rd generation) cephalexin (oral; 1st generation) Vancomycin Cefazolin (IV) Cefepime (IV)
17
Q
penicillins, carbapenems, and cephalosporins belong to a class of antibiotics known as….
A
Beta-lactams
4 membered ring where a N is adjacent to carboxy C–> all bind PBP’s
18
Q
Narrow Spectrum Penicillins and their MOA
A
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)
19
Q
Aminopenicillins and their MOA’s
A
Ampicillin, Amoxicillin
*added NH2 group makes molecule more hydrophillic–>more able to cross LPS barrier and thus increased efficacy against gram-nagative bacteria
20
Q
Broad-Spectrum Penicillins
A
Piperacillin
21
Q
Prototypical Penicillins
A
Penicillin G and Penicillin V
22
Q
MOA for beta lactam antibiotics
A
- binding to penicillin-binging proteins (transpeptidases)
2. destruction of cell wall
23
Q
Action of transpeptidases that is disrupted by beta-lactam antibiotics
A
Cross-linking of peptidoglycan molecules in bacterial cell walls–> lack of cross-links makes them weak and the cell will lyse
24
Q
Type of bacteria susceptible to beta lactam activity
A
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
25
Beta Lactamase inhibitors
1. clavulanic acid (added to amoxicillin)
2. tazobactam (added to piperacillin)
3. 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
26
contains a thiazolidine ring
penicillins and cephalosporins
27
Monobactam with a sulfonic acid attached to beta lactam ring
aztreonam (bactericidal-->binds transpeptidases inside the cell wall)
28
major difference between carbapenem and other penicillins
carbon atom in 5 membered ring as opposed to sulfer atom
29
Why does Imipenem need cilastatin
in the kidneys--> cilastin inhibits an enzyme that breaks down the drug, this increases imipenem activity and decreases nephrotoxicity
30
D.O.C for Staph. Aureus and Staph epi
| *Gram-positive cocci
Penicillinase resistant penicllins
| methicillin, nafcillin, oxacillin,
31
DOC for Strep (GROUPS A,B,C,G) and S. bovis
| *(Gram-Positive cocci)
Pen G, Pen V, Ampicillin
32
DOC for Clostridium
| (*bacilli)
Pen G
33
DOC for E. faecalis UTI
| * Gram-Positive cocci
ampicillin and amoxicillin
34
DOC for Strep. pneumonia
| *gram-positice cocci
Pen G, Pen V, Ampicillin
35
DOC for E. coli
| *gram-negative bacilli
ampicillin, (*ampicillin+sulbactam), (Amoxicillin + Clavulanate)
36
DOC for P. Aeurginosa
| gram-negative bacilli
piperacilli n/ tazobacta m
37
Unique features of cephalosporins
1. more acid stable than penicillins
2. possess 6 membered ring attached to a beta lactam ring
3. 4 generations (gram positive activity is lost and gram negative activity is gain with each generation)
38
List the Cephalosporins
Cefazolin-->1st
Cephalexin-->1st
Ceftriaxone-->3rd
Cefepime-->3rd
39
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
40
Vancomycin is a ( ) that interupts ( ) activity during cell wall formation.
1. glycopeptide
| 2. transglycosylase
41
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
42
Glycopeptide antibiotics are only effective against _______
gram-positive bacteria
gram-negatives have LPS layers that protects their peptidoglycan wall from being disrupted
43
Aminoglycosides
```
GENTAMICIN
Amikacin
neomycin
straptamycin
tobramycin
```
44
lincosamides
clindamycin
45
macrolides
```
AZITHROMYCIN
CLARITHROMYCIN
ERYTHROMYCIN
erythromycin
telithryomycin
```
46
oxazolidinones
LINEZOLID
47
streptogramins
quinipristin/dafropristin
48
tetracyclines
DOXYCYLINE
TIGECYCLINE
minocycline
tetracycline
49
(OTHERS) monoxycarbolic acid
mupriocin
50
MOA for aminoglycosides
1. 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
51
classes that inhibit cell walls
Penicillins, Cephalosporins & Vancomycin
52
beta lactams MOA
disrupt transpeptidase (PBP's), destruction of cell wall
53
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
```
54
Penicillin + aminoglycoside
Combination of cell wall and protein synthesis inhibitor
55
Sulfamethexazole + trimethoprim
act in sequential steps in the folic acid biosynthesis pathway
56
amoxicillin + clavulanic acid
(augmentin) beta lactam + beta lactamase inhibitor
57
prokaryote ribosome
70S ribisomes
Small 30S subunit
Large 50S (23S and 5S and 34 other proteins)
58
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.
59
Aminoglycosides work well on which type of bacteria
Gram-negative
60
Azithromycin (macrolide) MOA
Binds the 23s subunit of the 50S RSU (bacteriostatic)
61
Clindamycin (lincosamide) MOA
binds the 23s of 50s RSU (bacteriostatic)
62
Tetracycline MOA
bind to 16s subunit
63
streptogramins MOA
quinipristin and dalfopristin bind the 50s (large) RSU (these two have a synergistic effect)
64
mupriricin MOA
binding and inhibition of Isoleucyl transfer rna sythetase--> works on MRSA
65
Antimicrobials
Antibiotics
antifungals
antiparasitics
NOT antivirals--> they are not technically alive
66
MBC
minimum bacteriostatic concentration
| *the lowest concentration of an antibacterial agent required to kill a particular bacterium
67
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
68
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)
69
Penicillin + aminoglycoside synergistic MOA
combination of cell wall and protein synthesis inhibition
70
Sulfamethexazole + Trimethoprim (septra or bactrim) synergistic MOA
sulfa inhibits incorporation of PABA into folic acid
trimethoprim inhibits reduction of DHF to THF
*sequential steps
71
monobactam
aztreonam
72
carbapenem
impenem
73
Beta Lactams...name them and their MOA
Penicillins, Carbapenems, Cephalosporins
1. bind to transpeptidases and inhibit cell wall cross-linking
2. destruction of bacterial cell wall
74
end result of beta lactam activity
cell lysis
75
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
76
Do beta lactamase inhibitors contain a beta lactam
yes-->but are not toxic to the cell
| *they merely bind to beta lactamase
77
BLI added to amoxicillin
clavulanic acid (augmentin)
78
BLI added to piperacillin
tazobactam (zosyn)
79
Narrow spectrum penicillin MOA's
bulk adduct on penicllin side chain making them
1. resistant to Beta lactamase cleavage
2. unable to contort into may sterioisomers--> inhibiting their range of activity
80
amino penicillins are best used against
gram negative bacteria
81
Broad spectrum penicillins are modifications of...
amino penicillins
| *inreases the range of bacteria that are susceptible to them
82
Are Broad Range Penicillins sensitve to beta lactamase cleavage
yes--> frequently administered with beta lactamase inhibitor "pip/tazo"
83
where are PBP's located
inside the bacterial cell wall
84
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
85
renal dehydropeptidase inhibitor
cilistatin
| *prevents renal metabolism of Imipenem, increasing the urinary concentration and minimizing nephrotoxicity o the drug
86
Major advantage of cephalosporins regarding administration
acid stable so can be given WITHOUT FOOD
87
IST GENERATION CEPHALOSPORINS ARE USEFUL FOR TREATING
SKIN INFECTION
| CEFAZOLIN AND CEPHALEXIN
88
2ND GENERATION CEPHALOSPORINS ARE USEFUL FOR TREATING?
GRAN NEGATIVE BACTEROIDES
89
CEFTRIAXONE IS USEFUL IN TREATING
STD'S AND PEDIATRIC MENINGITIS
90
CEFEPIME IS USEFUL in treating
pseudomonal infection
91
Solubility of aminoglycosides
insoluble--> they are very polar and therefore penetration is poor
92
Aminoglycosides are toxic in the
kidneys
93
small ribosomal subunit
30 s
94
large RSU
50 S
95
50 S RSU is composed of
23 S 5 S 34 other proteins
96
Aminoglycosides will not work on
anaerobes
| *aminoglycosides require energy for uptake--> anaerobic bacteria lack much energy
97
aminoglycosides are bacteriostatic/cidal
-cidal
*holes + protein inhibition
other protein synthesis inhibitors are mainly bacteriostatic
98
macrolide nomenclature
-Thromycin
99
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
100
Macrolides are phagocytosed by?
macrophages at the site of infection
101
MOA for lincosamides
23s/50s-->promote premature dissociation of peptidyl transferase
102
Clinda is most useful in
toxin producing infections
103
Tetracylin MOA
bind to 16 S of 30s RSU--> and inhibit amino-acyl tRNA binding
104
tetracylcins static/cidal
cidal
| they completely stop protein synthesis-->whereas other protein synthesis inhibitor stop initiation
105
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
106
bactericidal protein synthesis inhibitors
aminoglycosides (for 2 reasons)
streptogramins (synergitic effect)
tetracycline (prevents trna from ever binding to A site
mupirocin
107
Mupriocin inhibits...
isoleucyl tRNA synthetase
108
chloramphenicol should not be given with?
macrolide or lincosamide Ab's--> binds at B site as well
109
floruoquinolones
cipro
| levofloxacin
110
Nitroimdazoles
metronidazole
111
sulfonamides
cotromoxazole
| sulfamethexazole
112
rifamycins
rifampin
| rifamixin
113
DHFR inhibitors
cotrimoxazole
| trimetoprim
114
Flouroquinolones MOA
bactericidal
bind to and inhibit Gyrase (gram negative) and TOPO IV (gram positive)
*after the cutting step-->there is no re-anealing
115
rifampin MOA
binds RNA polymerase--> prevents INITIATION...not ELONGATION
116
RIFAMPIN is useful in treating
| HIGHLY lipophillic
```
Mycobacterium
Biofilms
Bacterial menengitis (cns penetration is high)
intracellular bacteria
abcesses
```
117
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
118
cotrimoxazole is made up of
Sulfa and trimethoprim
119
sulfa MOA
inhibits incorporation of PABA into folic acid
120
trimethoprim MOA
inhibits DHF being reduced into THF
121
in vivo concentration of sulfa to trimethoprim
20:1
