Block 2 Harris Flashcards
(156 cards)
0
Q
the MBC for most bactericidal drugs is…
A
4-5x the MIC
1
Q
define MIC and MBC
A
MIC=minimum inhibitory growth= lowest [antibiotic} that inhibits bacterial growth after 24 hrs in a specific medium
MBC= minimum bactericidal concentration= lowest [antibiotic} that prevents growth on antibiotic-free subculture (aka kills 99.9% of bacteria with antibiotic then replate on antibiotic free plate)
2
Q
microbiostatic drugs are rarer… name them
A
antibacterial 1. chloroamphenical 2. clindamycin 3. macrolides 4. tetracycline antifolates 1. Trimethoprim= TMP 2. Sulfonamides
Antifungal
- fluconazole
- ketoconazole
- Itraconazolew
- terbafine
3
Q
why would you not give chloramphenical (=other protein syn -) to a premature infant
A
you need to glucaronate the drug which is a phase 2 rxn, which babies cant do therefore you get
1. flaccid baby
2. cardiovascular collapse
GRAY BABY SYNDROME
4
Q
what are the aminoglycosides and what is a classic side effect of them
A
- gentamicin
- amikacin
- streptomycin
SIDE EFFECTS= NO
- Nephrotoxicity
- Ototoxicity–> if taken more than 5 days–> can cause permanent hearing loss
- NM paralysis–> seen with patients with Myastenia gravis
- at high doses–>-ACh release like myasthenia gravis
5
Q
clindamycin is another protein syn - which causes….
A
SUPERINFECTIONS FROM CLOSTRIDIUM DIFFICILE
–> pseudomembranous colitis (= inflammation of colon which causes antibiotic associated diarrhea)–> treat with metronidazole
6
Q
vancomycin (non-B lactam penicillin) if administered in less than 1 hrs (rapid infusion) causes
A
red man syndrome
1. hypotension and flushing
7
Q
tetrecyclines (which are protein syn - of 30s) can cause
A
- photosensitivity
- discoloration of tooth and bone (bc it deposits here)
- -> = reason you dont give tetracyclines to kids - liver toxicity–> if given in high doses during pregnancy
8
Q
if you taking tetracycline (30s -) you should not take it with
A
dairy food–> will cause gastric discomfort
9
Q
chloroamphenical (50s -) is…
A
- too toxic for minor use and can cause
- gray baby syndrome–> if given to infants because they can do phase 2 rxns and the drug must be glucuronated
- anemia–> reversible and dose related
10
Q
sulfonamides which are anti-folates can cause
A
- hypersensitivity if given orally for long periods
- -> can cause steven-johnson syndrome= epidermis separates from dermis–> crust around lips and oral mucosa - kernicterus= bilirubin induced brain dysfunction
- -> increased amount of unbound drug in neonate is problem
- neonates have a premature liver and cant conjugate bilirubin
- sulfonamides displace bilirubin from the protein–> excess unconjugated bilirubin= highly neurotoxic
11
Q
fluroquinolines (FQ) are normally well tolerated but can cause
A
- cartilage toxicity–> reason you dont give FQ to kids or preg women
- musculoskeletal issues–> tendon ruptures
- photosensitivity
12
Q
metronidazole a misc. DNA antibiotics thats is metabolized to its active form by ferrodoxin can cause
A
- Gi issues–>metallic taste in mouth
2. if drinking alcohol–> it can cause disulfiram like effects
13
Q
define synergy and give an example
A
when 2 antibiotics work at 2 different sites in either the same or different metabolic pathways
EX:
1. ampicillin + gentamicin–> ampicillin facilitates entry of gentamicin
2. TMP+SMX= trimethoprim+ sulfamethoazole
–>both - folate metabolism but affect different steps of the pathway
-TMP–> - dihydrofolate reductase which takes folate and makes tetrahydro folic acids
-sulfamethoazole–> - dihydropteroate synthetase which takes PABA and makes folic acid
14
Q
which drug is good for aerobic infections
A
aminoglycosides
15
Q
which drug is good for anaerobic infections
A
metronidazole
16
Q
what are the B lactam drugs
A
- penicillins
- cephalosporins
- other
17
Q
what are the penicillins
A
- natural pens
- anti staph pens
- amino-pens
- anti pseudomonal
18
Q
what are the natural pens
A
- penicillin V
2. procaine or benzathine + penicillin G
19
Q
what are the anti-staph penicillins
A
anti staph=coNDOM Nafcillin Dicloxacillin Oxacillin Methicillin
20
Q
what are the amino penicillins
A
- ampicillin
2. amoxicillin
21
Q
what are the antipseudomonal penicillins
A
- pipercillin
2. ticarcillin
22
Q
what do Beta lactamase - do
A
they bind to the beta-lactam ring and protect it–> preventing B-lactamase from cleaving the B-lactam ring
23
Q
which penicillins are B lactamase susceptible
A
mostly natural penicillins
- cephalosporins are more B-lactamase resistant
- carbapenems are resistent to most B-lactamases
24
what are the 3 MOA for all the B-lactam drugs (penicillins, cephalosporins, monobactams, and carbapenems)
1. - PBP (penicllin binding proteins) on cell membranes
PBP--> synthesis of the cell wall
2. block transpeptidase rxn of some PBPs that catalyze cross-linkage of peptidoglycan chains--> decreases cell wall integrity
2. gram + cocci--> produce autolysins
--> block cell wall formation of gram + cocci= unopposed autolysin activity which degrades cell wall
25
gram - bacteria have
porins in their outer membrane--> antibiotic must you this to get into the periplasmic space where PBP are found
therefore--> change the porin and drug cant get in
26
how B-lactamase - work (AKA MOA)
B-lactamase - bind to conserved region or B-lactamase and changes the B-lactamases structure--> this prevents the lactamase from binding to the B-lactam ring
27
name the B-lactamase - combinations
1. clavulanic acid +
- amoxicillin= amino
- ticaricillin= anti-pseudo
2. tazobactam+
- pipercillin= anti-pseudo
3. sulbactam +
- ampicillin= amino
28
How is resistance to B-lactam drugs developed
1. natural= organism has no cell wall
2. acquired
- due to acquiring plasmid of B-lactamase to bacteria
- decreased penetration of the drug intro outer membrane
- -> cant reach PBP
- modify PBPs so drug cant bind
29
what is the only oral combination of penicillin drugs
clavulanic acid + amoxicillin= duh amoxicillin= bubble gum medicine
30
which other penicillins are give IV or IM only
1. anti-pseudomonals
and all the other combinations
31
which penicillins do you give slow release over time
pen. G + procaine or benzathine
benzathine+ pen G--> DOC for syphillis
32
generally how is the absorption of penicillins
most penicillins are incompletely absorbed
EXCEPTION= amoxicillin= almost completely absorbed
33
all penicillins...
gross the placenta BUT ARE NOT TERATOGENIC= safe in pregnancy
34
what is the only penicillin excreted by the biliary and renal route?
ANTI-STAPH
most penicillins excreted just by the kidneys= must adjust dose in renal failure
35
penicillins cause hypersensitivity--> why?
bc their metabolite PENICILLOIC ACID triggers an immune rxn
36
which penicillin kills gram + cocci (strept) the best
natural penicillin
37
which penicillin has the narrowest spectrum
anti-staph--> use for staph inf
| 1. MSSA=methicillin sensitive staph. aureus
38
if you want to use a broad penicillin--> good gram + coverage with decent gram- coverage, you would use
amino pens
39
which pen has the broadest spectrum and why
anti-pseudomonal, bc it kills more gram -s
often need to add aminoglycerides (gentamicin) with anti-pseudomonals if you are treating serious infections
40
when are cephalosporins used
in hospital setting for prophylaxis vs. surgical wound infections due to their broad spectrum
41
what are the 1st gen cephalosporins
1. cef-azolin
| 2. ceph-alexin
42
what are the 2nd gen cephalosporins and the saying
1. ce-fac-lor
2. ce-fox-itin
3. ce-furo-xime
4. ce-faman-dole
its a FACt I love FOXy FURry FAMAN
43
what are the 3rd gen cephalosporins
1. cefo-peraz-one
2. cefo-tax-ime
3. ceft-azid-ime
4. ceft-riax-one
44
what is the only 4th gen cephalosporin
cefe-pime
45
what is the new cephalosporin and what is it used for?
ceft-arol-ine
for
1. acute bacterial SKIN AND SKIN STRUCTURE INFECTIONS (ABSSSI)--> think MSSA and MRSA
2. community acquired bacterial pneumonia
46
how are most cephalosporins administered?
IV--> due to poor oral absorption
EXCEPTIONS= those given orally
1. ceph-alexin= 1st gen
2. ce-fac-lor= 2nd gen
3. ce-furo-xime= 2nd gen
47
which cephalosporins can adequately get into the CSF
1. ce-furo-zime= 2nd gen
| 2. all 3rd gens
48
most cephalosporins are only excreted via the kidney but what is the exception
ceft-riax-one= 3rd gen
| --> excreted through the bile into feces--> use in pts with renal insufficiency
49
which 2 cephalosporins produce disulfiram like effects like metronidazole
1. ce-faman-dole= 2nd gen
2. cefo-peraz-one= 3rd gene
- aldehyde dehydrogenase which cause the accumulation of acetaldehyde
50
which cephalosporins can cause bleeding and why
same ones that produce disulfiram like effects
1. ce-faman-dole= 2nd gen
2. ceft-peraz-one= 3rd gen
they cause anti- vit K effects--> NEED TO GIVE THEM VIT K TO CORRECT
51
what is the only narrow spectrum cephalosporin and what does it kill
1st gen cephalosporins
```
kill gram + cocci
some gram - rods
1. E. coli
2. Klebsiella
3. Proteus
```
52
what is the only broad spectrum cephalosporin and what is it good at killing
2nd gen cephalosporins--> BEST CEPH FOR KILLING ANAEROBES
1. non difficile clostridium
2. bacteroides--> ce-fox-itin
53
if you think its a gram - infection and your thinking about using a cephalosporin you would use
3rd gen cephalosporin
gram - cocci--> Neisseria
1. N. meningitidis
- -> ceft-riax-one or cefo-tax-ime
2. gonorrhea--> ceft-riax-one
gram - rods--> enterics
54
if you want to use a cephalosporin in neonates but are afraid bc you know neonates can do phase 2 rxns (glucuronidation), you might give
cefo-tax-ime= 3rd gen
| bc its only eliminated by the kidney
55
2nd gen cephalosporins are good for treating
1. otitis media
2. UTIs
DONT USE FOR MENINGITIS--> you dont achieve sufficient levels in CSF
EXCEPTION:
1. ce-furo-xime= 2nd gen
2. 3rd gens= more effective in penetrating CSF
56
when do you use 3rd gen cephalosporins
1. aerobic gram - bacteria
2. best agents for
- -> aerobic gram - meningitis
- -> biliary tract infections
alt to 2nd gen cephalosporin
57
characteristics of 4th gen cephalosporins
cephalosporin with greatest stability vs. B-lactamase
58
what are the other B-lactam drugs
1. carbapenems
| 2. Monobactams
59
what are the carbapenems (other B-lactam drugs)
1. imi-penem + cilastatin--> which protects imipenem from being cleaved into a NEPHROTOXIC METABOLITE
2. mero-penem
3. erta-penem
4. dori-penem
60
which carbapenem do you have to combine with another drug and why
imipenem +cilastatin
cilastatin protects imipenem from being cleaved into a NEPHROTOXIC METABOLITE
61
what is the broadest spectrum B-lactam antibiotic prep available
imipenem + cilastatin
carbapenems= broadest spectrum drug we have--> kill almost anything
62
what is a side effect commonly associated with imipenem
seizures in ppl with renal problems
| --> they cant clear the drug
63
monobactams (other B-lactam) have...
no gram + or anaerobic coverage!!
64
monobactams are good against
aerobic gram - rods
65
what B-lactam drug has no cross-reactivity in pts allergic to penicillin
monobactams
66
what is the main non- B lactam cell wall drug
VANCOMYCIN
67
what are the other non B-lactam cell wall drugs
1. bacitracin
2. polymyxins
3. teicoplanin
68
what is the MOA of vancomycin
prevents peptidoglycan elongation by binding to the D-ala-D-ala terminal
69
how do bacteria get resistance to vancomycin
change the D-ala to a D-lactate which prevents binding of vancomycin
VR-SA
VR-EF
70
vancomycin is the DOC for
1. hospital acquired MRSA
life threatening gram +!!
71
if vancomycin which is administered via IV is given to quickly you get...
red man syndrome
| -histamine mediated (due to mast cell degranulation) flushing of the upper torso and hypotension
72
what are the protein synthesis inhibitors
1. tetracyclines
2. aminoglycosides
3. macrolides
4 others
73
what are the 2 main tetracyclines
1. tetracycline
| 2. doxycycline
74
what are the aminglycosides
1. gentamicin
2. amikacin
3. streptomycin
75
what are the macrolides
1. ery-thromycin
2. azi-thromycin
3. clari-thromycin
76
MOA for tetracyclines
bind to the 30s ribosomal subunit
--> blocks access of the acyl tRNA to the mRNA-ribosome complex at the acceptor site
therefore if the tRNA never binds you cannot add on AA to the growing peptide chain
77
tetracyclines are
broad spectrum but their use is limited by resistance
78
resistance mechanism for tetracyline
naturally occuring R factor--> confers inability of the organism to accumulate the drug
--> due to a Mg2+ dependent active efflux of drug by the protein TetA!!
79
what drug has a mechanism similar to tetracycline and how is it different
tige-cycline
it binds with 5x greater affinity for the 30s subunit
80
spectrum of tige-cycline
most gram + including
1. MRSA
2. VREF
used for complicated skin and intra-abdominal infections
81
how is tigecycline different from tetracycline
tigecycline is not affected by efflux pumps (TetA)
82
tetracyclines should not be taken with
1. dairy foods--> tetracyclines chelate with Ca2+--> form NONABSORBABLE PRODUCTS
not as big of a problem with doxycycline
2. antacids--> tetracyclines chelate with Mg2+ and Al3+
if pt takes tetracycline tell them it can cause GI upset but to not take antacids bc it will make it worse
83
basically tetracylines can...
chelate with dairy products and antacids--> will reduce [plasma] of tetracycline
1. Ca
2. Mg
3. Al
84
tetracyclines can...
1. bind to tissues undergoing calcification like teeth and bones--> deposit here causing discoloration
2. cross the placenta and concentrate in fetal bones and dental area
85
tetracyclines are metabolized by...
glucuronidation (phase 2) in the liver
86
___________________ is the exception and is excreted in bile
doxycycline
87
tetracyclines can cause
1. upset GI--> dont take with dairy
2. deposit in bones and teeth--> discoloration
3. lover and renal toxicity esp in preg women
4. PHOTOTOXICITY
88
aminoglycosides are the mainstay treatment for
aerobic gram - rods
synergistic with ampicillin
89
how do aminoglycosides get into bacteria
1. passive diffusion
2. active O2 transport
- ->low pH or anaerobic conditions--> inhibit entry
90
MOA for aminoglycosides
bind to 30s ribosomal subunit--> interfering with initiation complex of peptide formation
--> induces misreadings of mRNA--> incorporation of incorrect AA into growing peptide chain--> NON-FUNCTIONAL OR TOXIC
91
aminoglycosides are good vs.
gram - organisms--> bc they cant get through thick peptidoglycan wall
92
aminoglycosides are...
for 2 drug bugs (gentimicin + ampicillin)--> ampicillin helps break down peptidoglycan wall
1. enterococcus faecalis--> endocarditis
2. listeria--> meningitis
93
side effects of aminoglycosides
NO
1. nephrotoxicity--> due to drug accumulating in the kidneys
2. ototoxicity--> due to high peak plasma levels and using aminoglycosides for longer than 5 days
3. NM paralysis at very high doses--> - Ach release
can cause resp paralysis
94
since aminoglycosides have long lasting effects you dose...
once a day even though they have a short half life
95
MOA of macrolides= protein syn -
bind to 50s subunit--> - aminoacyl translocation reaction
96
spectrum for macrolides
broad spectrum--> atypical bacteria
gram - rods
1. Haemophilus
2. Legionella
3. chlamydia, chlamydophila
4. mycobacterium avium
ACs for MAC
97
when do you use macrolides
as an alt. to B-lactams in pts allergic to penicillin that require treatment for NON-LIFE THREATENING GRAM + INFECTIONS
98
macrolides are also specifically used for
1. mycoplasma pneumonia
| 2. legionella pneumonia
99
combo used to eradicate H. pylori
1. clari-thromycin
2. amoxicillin
3. lansoprazole
100
macrolides=
Macrolides
methylation of binding site= resistance
motilin +--> increased gastric motility= side effect
101
how does bacteria develop resistance to macrolides
1. decrease antibiotic uptake
2. methylation of the binding site--> this decreased affinity of the 50s subunit for the antibiotic
3. bacteria produces esterases which cleave the antibiotic
102
what is the new drug similar to macrolides and what are its properties
Teli-thromycin
binds 10x tighter to 2 different sites on the ribosome
has less resistance compared to macrolides
103
what is the only fluid macrolides dont distribute
CSF
104
whats abnormal about macrolides
ery-thromycin penetrates prostatic fluid well
105
macrolides from least to greatest p450 -
Azi-thromycin
Clari-thromycin
Ery-thromycin--> interacts with alot of drugs
C and E--> inhibit theophylline and warfarin
106
macrolides as a group...
dont need to be adjusted in renal failure
clari-thromycin only needs to be adjusted in severe renal failure
107
side effects of macrolides
1. increase Gi motility due to + motilin receptors
- -> good for diabetic patients with peripheral neuropathy to vagus nerve which causes decrease in gastric emptying
2. teratogen--> some ery-thromycin and clari-thromycin
108
what are the other protein synthesis inhibitors
1. chlor-amphenical
2. clindamycin
3. strepto-gramins
4. line-zolid
109
what is the MOA of all the other protein synthesis -
similar to macrolides
bind to 50s subunit and - peptidyl transferase
= - transfer of the peptide chain
110
when would you use chlor-amphenicol
as an alt when you have a pt with a rickettsial infection like typhus or rocky mt spotted fever who can not have tetracycline
CHLORAMPHENICOL IS TO TOXIC TO USE FOR MINOR INFECTIONS
111
SE of chloramphenicol
neonates cant glucuronidate the drug (which is needed for metabolism)--> phase 2
--> results in gray baby syndrome
112
what is the main use of clindamycin
anaerobes--> severe infection due to bacteroides
113
clindamycin is only cleared by the...
liver--> must adjust in liver failure
114
clindamycin can cause
a C. dif superinfection= pseudomembranous colitis= inflamm of colon--> antibiotic induced diarrhea
treat with metronidazole or give vancomycin if its resistant
115
streptogramins is used for
gram + cocci
life threatening infections due to
VREF= enterococcus faecium
VRSA
for complicated skin or skin structure infections due to MSSA
116
linezolid is
back up to back up
for gram + cocci
for
VREF
VRSA
117
what are the antifolates
1. sulfonamides
| 2. TMP/SMX= trimethoprim-sulfamethoazole
118
MOA of sulfonamides (sulfa-metho-azole)
competes with PABA for dihydro-pteroate synthetase, preventing PABA from being converted to folic acid
bacteria must synthesize folic acid
humans cant and have to get from diet
119
how is resistance to sulfonamides developed
1. change dihydro-pteroate synthase by mutation or plasmid transfer
2. decrease the uptake of sulfonamides
3. increase PABA synthesis--> can outcompete the drug
120
sulfonamides can be used for
conjunctivitis
121
sulfonamides if given orally for a long time can cause
Stevens-Johnson syndrome
122
MOA of TMP= trimethoprim
competitively inhibits dihydrofolate reductase
| prevents folic acid--> tetrahydrofolic acid--> AA, purines, pyrimidine synthesis
123
TMP/SMX works synergistically to prevent the formation
of tetrahydrofolic acid
124
uses of TMP/SMX
1. back up for listeria= gram + rod
2. gram - cocci= neisseria meningitidis
DOC for Pneumocystis jiroveci pneumonia--> give IV
125
what is common to antifolates
bone marrow suppression
1. megaloblastic anemia
2. leukopenia= low # leukocytes
3. thrombocytopenia
126
what are the miscellaneous DNA antibiotics
1. metronidazole
| 2. daptomycin
127
MOA of metronidazole
bacteria has ferrodoxin--> which metabolizes metronidazole to its active form which interacts with DNA
128
metronidazole is used for
Giardia lamblia
Entamoeba histolytica
Trichomonas vaginalis
Bacteroides
Clostridium
on the
METRO
Garderella= bacterial vaginosis
129
metronidazole is generally considered the DOC for
susceptible anaerobic infections
130
metronidazole causes
1. metallic taste in mouth
| 2. disulfiram like effects if taken with alcohol
131
what drugs do you not have to adjust for in a pt with renal failure
1. anti-staph
2. 3rd gen cephalosporin
3. doxycycline
4. macrolides
5. metronidazole
132
MOA for daptomycin
binds to bacterial cell membrane--> rapid depolarization--> loss of membrane potential--> - protein, DNA, RNA synthesis
133
use daptomycin= miscellaneous DNA antibiotic
susceptible complicated skin and skin structure infections--> think MRSA
good for gram + cocci
134
FQ are limited to
gram - organisms
135
MOA of fluoroquinolines
- bacterial DNA gyrase/topoisomerase 2
topoisomerase 2--> relaxes positive supercoils in DNA= required for normal transcription and replication
+ supercoiling=tension=inhibited replication
136
name the fluoroquinolines
2nd gen
1. cipro-floxacin
2. o-floxacin
3rd gen
1. levo-floaxacin
2. moxi-floxacin
4th gen= gemi-floxacin
137
which generations of FQ are very broad
3rd and 4th gen
138
FQ are active against practically
all aerobic gram - rods--> except pseudomonas (use cipro to kill)
139
3rd and 4th gen FQ kill
anaerobes
1. bacteroides
2. clostridium--> but not difficile
referred to as resp RQ some active vs penicillin/macrolide resistant Strept. pneumoniae
levofloxacin= candy
140
resistance to FQ
1. mutation of bacterial DNA gyrase/topoisomerase 2
| 2. decreased FQ accumulation in bacteria
141
FQ can cause
1. problems with collagen metabolism and cartilage development
2. tendonitis and tendon ruptures
3. phototoxicity
142
like tetracyclines, when on FQ you should avoid
antacids or iron and zinc supplements
143
ciprofloxacin...
- p 450 enzymes
interfers with metabolism of theophylline
144
see phototoxicity with...
1. tetracyclines
2. sulfonamides
3. fluoroquinolines
145
drug for urinary tract antiseptic
Nitro-furan-toin
146
MOA of nitrofurantoin= UTI
bacteria metabolize drug to active form
| active form--> inhibits enzymes and damages DNA
147
use of nitrofurantoin
uncomplicated UTI
148
nitrofurantoin
turns urine brown
149
pathphys of UTIs
ascend to urinary tract due to the short proximity of the peri-rectal area to the female urethra
--> migration to the bladder--> ascend the ureters to the kidneys
150
use of what may promote colonization of urinary tract
use of spermicides and diaphragms as method of contraception
151
if you have an uncomplicated UTI treatment is...
1st--> TMP-SMX
| if that doesnt work then you use fluroquinolines
152
if you have a complicated UTI you use
anti-pseudomonal penicillin + gentamicin
153
if preg and you get a UTI use
nitrofurantoin
154
what is pro-bene-cid and what is its MOA
probenecid is an antigout drug
| MOA= inhibits tubular reabsorption of uric acid --> which increases the urinary excretion of uric acid
155
purpose of learning about probenecid
it inhibits the tubular secretion of acids, such as
1. penicillins
2. cephalosporins
3. fluroquinolines
aka, if pt is on antigout med (probenecid) it will increase the half life of penicillins, cephalosporins and FQ by preventing their secretion
