Antibiotics Flashcards
(190 cards)
1
Q
Antibiotics are based on naturally occurring compound but are modified chemically to do what?
A
- extend their range of action
- improve potency and pharmacokinetics
- avoid resistance mechanisms
2
Q
Narrow vs. broad spectrum antibiotics
A
N: specific against a few bacteria
B: active against many different bacterial types
3
Q
Define therapeutic index
A
- lowest dose that is toxic to the patient divided by the dose used to typically treat a patient
- LARGER THE INDEX THE BETTER
4
Q
3 general types of adverse events from ABx
A
- allergic reactions: hypersensitivity to a specific drug
- toxic effects: can be drug specific
- Suppression of normal flora: one reason to use narrow-spectrum ABx
5
Q
How do disinfectants differ from antibiotics?
A
- disinfectants (detergents, peroxide) have a NONSPECIFIC mechanism of action and so are BROADLY active and not tolerated by the host
- usually need higher concentration relative to antibiotics due to lack of specificity
- remember: ABx have specific spectrum of activity that is related a specific mechanism of action
6
Q
5 major mechanisms by which antibiotics work:
A
- inhibit cell wall synthesismost common
- Inhibit protein synthesis second most common
- Inhibit nucleic acid function or production
- Disrupt metabolic pathways, like folate metabolism
- Disrupt cell membrane (Not cell wall, cell membrane)
7
Q
ABx that target the bacterial cell wall work best against _________ bacteria while ABx that target cell membrane typically work best against ________ bacteria.
A
- gram positive where cell wall is far more prominent
- gram negative where cell membrane is on outer surface
8
Q
3 mechanisms that confer selectivity to antibiotics
A
- absence of target from the host: high therapeutic indexes
- permeability differences: bacteria take it up, our cells dont
- structural differences in the target: different ribosome size
9
Q
Drugs that gain selectivity by permeability differences need to be given by IV, not the mouth…why?
A
-our cells will not pick up the drug, so it cannot reach infections internally
10
Q
Bacteriostatic vs. bactericidal antibiotics
A
- Static: reversibly inhibit bacterial growth; growth resumes when drug is removed
- cidal: kill bacteria; usually requires bacteria to be growing actively
11
Q
Drugs that target metabolic processes typically fall into (bacteriostatic/bactericidal) categories. Drugs that target the cell wall or membrane tend to be _______.
A
- bacteriostatic
- bactericidal
12
Q
Define Minimum Inhibitory Concentration
A
-lowest concentration of an antibiotic that effectively inhibits growth of a microorganism
13
Q
2 ways to test susceptibility of bacteria to various antibiotics
A
- Tube dilution assay for antibiotic sensitivities
2. Disc diffusion method
14
Q
Tube dilution assay for antibiotic sensitivies
A
- bacteria are gown in small cultures in the presence of different concentrations of antibiotics
- tells you sensitivies of a given bacterial isolate to a range of drug concentrations
15
Q
Disc diffusion method for antibiotic sensitivies
A
- bacterial isolate is spread over plate and grown into “bacterial lawn”
- small antibiotic impregnanted discs are placed on the agar, and drug diffuses in
- if isolate is not sensitive, it will continue to grow, but if it is sensitive, you will see clear area around disk
16
Q
In a disk diffusion method, the width of the clear area is related to the _______. Does this procedure inform us if the drug is bacteriostatic or bactericidal?
A
- MIC: minimum inhibitory concentration
- no
17
Q
Generally, we prescribe one drug whenever possible and it is usually the simplest to minimize evolution of drug resistance. What are some cases when 2 or more ABx will be prescribed?
A
- chronic infections
- emergencies: cannot wait for cultures to come back
- mixed infections
- drug synergies
18
Q
What are the 4 possible outcomes that can arise if more than 1 drug is being used?
A
- indifference: 2 drugs have no effect on eachother
- Additive response: response is the same as the sum of the 2 drugs individually
- Synergistic response: response is greater than the sum of the two drugs used individually
- antagonistic response: response is less than sum of the two drugs used individually
19
Q
2 drug examples of synergism
A
- Bactrim: Sulfamethoxazole (inhibits production of THF-acid, but not utilization of current pool)+ Trimethoprim (prevents use of THF-acid pool, but not its synthesis)
- Augmentin: amoxicillin (extended spectrum penicillin)+ beta-lactamase inhibitor clavulanic acid
20
Q
Drug example of antagonistic response
A
- penicillin and erythromycin
- erythomycin is bacteriostatic and slows bacterial growth that is necessary for penicillin (bacterocidal) to function properly
- if E is used first, it will make subsequent application of the cell wall inhibitors less effective
21
Q
Name 4 issues that can limit successful antimicrobial therapy
A
- location: some drugs cannot cross BBB and some bacteria are intracellular
- abscess formation and necrosis: decreased circulations in the area of an abscess will limit drug concentrations; low nutrients may slow bacterial growth that makes some ABx less effective
- presence of foreign bodies and obstructions: adhere to objects and make biofilms
- drug resistance
22
Q
5 general mechanisms of drug resistance
A
- enzymatic inactivation of the antibiotic
- Inadequate or decreased uptake of the drug into the microbe (mutate porins)
- Increased efflux of the antibiotic out of the microbe (active transport)
- Alteration of drug target (mutations in PBPs)
- Altered metabolic pathways (new enzyme expression)
23
Q
Many bacteria, as a form of resistance, produce an enzyme called a beta lactamase that does what?
A
-cleaves the beta-lactam ring present in penicillins, cephalosporins, and carbapenems
24
Q
Are community acquired or hospital acquired bacterial infections more likely to be resistant to drugs?
A
-hospital
25
If you know what bacterium is causing the infection, you should prescribe drugs that are as ____________. When would you want to do the opposite?
- narrow spectrum as possible
| - if life threatening, you need to treat more broadly since you can't run the risk of guessing wrong
26
Gram positive vs. gram negative structure
+: thick, exposed peptidoglycan layer
| -: thinner peptidoglycan layer that is beneath an outer membrane
27
Peptidoglycan has repeating units of disaccharides that are crosslinked to each other via ________. What catalyzes formation of these cross-linked?
- peptide bonds
| - transpeptidase
28
Penicillins bind to __________, so these enzymes are also referred to as __________.
- transpeptidase
| - penicillin binding proteins (PBPs)
29
Beta lactams are competitive inhibitors of __________ and inhibit its function. What is the result of this?
- transpeptidase
- do not destroy existing cross-links but prevent formation of new ones; causes weak points at growth sites and become fragile
30
In general, Beta-lactam ABx are more effective against what type of bacterial cells?
- gram-positives because the cell wall is exposed
| - those that are effective against G(-) cells must cross the cell membrane
31
Beta-lactams are __________ and work more effectively against rapidly/slowly growing bacteria?
- bactericidal
| - rapidly growing bacteria
32
What do the 3 classes of penicllins have in common? Describe this feature
- common structure of the beta-lactam ring
| - 4 sided ring with a nitrogen in it
33
Are penicillins the only ABx to have a beta-lactam ring?
- no; cephalosporins, carbapenems, and monobactams
| - different side groups can alter the properties of the drug
34
Penicillins, cephalosporins, and carbepenems are drug classes that ALL contain a beta-lactam ring and target ________.
- bacterial cell wall
| - called beta-lactam antibiotics
35
Name the 3 classes of penicillins
1. Natural penicillins
2. Penicillinase-resistant penicillins
3. Extended spectrum penicillins
36
List the 2 natural penicillins and how they are taken
- Penicillin G: inactivated by low pH so given by IV
| - Penicillin V: acid stable, so can be taken PO
37
List the 5 penicillinase-resistant penicillins
1. Methicillin
2. Oxacillin
3. Naficillin
4. Cloxacillin
5. Docloxicillin
* *VERY NARROW SPECTRUM**
38
What is unique about penicillinase-resistant penicillins?
-they are resistant to beta-lactamases and were developed to combat Staph
39
Give the 4 examples of extending spectrum penicillins
1. Ampicillin
2. Amoxicillin
3. Carbenicillin
4. Pipericillin
40
What is unique about extending spectrum penicillins?
-must improved activity against gram-negatives, but less effective against gram positives
41
Extended spectrum penicillins are often used in conjunction with ____________.
-beta lactamase inhibitors
42
Penicillins are safe drugs, but have one significant side effect. Name it and describe a little bit about its risk.
- hypersensitivity reactions
- can be severe, causing anaphylaxis and can become more severe if a person is exposed to these drugs multiple times
- can include hives, maculopapular-measles-like, include itchy skin, wheezing swollen lips, etc
43
Anaphylactic reactions to penicillins occur _________ and include what symptoms? What symptoms do they not include?
- immediately
- difficulty breathing, decreased blood pressure leading to dizziness and weak pulse, swelling of throat and tongue
- Nausea and vomiting are NOT allergic reactions to the drug
44
Before administering a penicillin, what do physicians have to do?
-ask if there is a history of having taken these drugs before/allergies to medications
45
Any allergic reaction to penicillin can occur quickly, but more commonly _____________________.
-it takes a while, sometimes a day or two
46
3 mechanisms of Beta-lactam resistance
1. Beta-lactamases are produced that destroy the drug
2. Transpeptidases (major PBP) acquires a mutation the prevents drug binding
3. Gram negatives can have membrane pumps that remove drug from pepiplasmic space
47
Describe the function of Beta-lactamase inhibitors
-little or no antimicrobial activity on their own, but can make beta lactam antibiotics more effective by binding to and inactivating beta lactamases
48
List 3 beta lactamase inhibitors
1. clavulanate
2. sulbactam
3. tazolbactram
49
List 4 common combinations of penicillins and beta-lactamase inhibitors
1. Amoxicillin-clavulanate = Augmentin
2. Ampicillin-sulbactam
3. Piperacillin-tazolbactam= Zosyn
4. Ticarcillin-clavulanate= Timentin
50
When are natural penicillins the drug of choice and when are they not used?
- drug of choice for community-acquired Strep, pneumococci, meningococci
- treatment of choice for syphilis (a spirochete)
- NOT effective against STAPH due to drug resistance
51
What genra of bacteria are natural penicillins not effective against and why?
-Staph!!! due to drug resistance
52
What is Staph's method of resistance against natural penicillins? What is then used to treat them and are issues arising in this?
- beta lactamases
- use beta-lactamase resistant penicillins (oxacillin, methicillin, naficillin) but many strains are now resistant to these drugs--MRSA
- now try to use oxacillin to treat Staph but this resistance is now rising
53
Characteristics of Ampicillin and Amoxicillin.
- extended spectrum penicillins
- similar to natural penicillins but can cross the membranes of some gram negatives and inactivate their transpeptidase enzymes
54
What are Ampicillin and Amoxicillin commonly prescribed for?
-uncomplicated urinary tract infections, otitis media, and uncomplicated community acquired penumonia, H. influenza, Lyme disease, and listeria meningitis
55
Characteristics and issue with Ticarcillin, Mexlocillin, and Piperacillin
- extended spectrum penicillins
- nice coverage of gram negatives, but at expense of not hitting gram positives as effectively
- still sensitive to beta lactamases, which is a huge issue
56
What class of penicillins are often coadministered with beta lactamase inhibitors?
-extend spectrum penicillin
57
Summary of categories of bacterium natural penicillins are good at fighting against.
- Strep
- Meningococci
- Spirochetes
- Most other gram positive anaerobes
- NOT STAPH
58
Why is selective toxicity crucial to antibiotics?
-due to specific mechanism of action, are typically well-tolerated by the host but lethal to harmful micrones
59
Define disinfectant and give 4 characteristics
- an agent, such as heat, radiation, or a detergent, that destroys, neutralizes, or inhibits the growth of disease-carrying microorganisms
- Nonspecific spectrum of action
- Nonspecific mechanism of action
- Not tolerated by host
- Usually need high concentrations due to lack of specificity
60
Are bactericidal or bacteriostatic drugs better?
- often believed that bactericidal is more beneficial, though massive bacterial death can enhance inflammatory response
- bactericidal drugs are clearly better for meningitis and endocarditis
61
Efflux systems can be shared between bacteria via exchange of _________.
-Pathogenicity islands
62
3 ways antibiotics are used
1. empiric therapy: given for proven or suspected infection, but organism not identified
2. Definitive therapy: given for proven identification and based on a causative organism
3. Prophylaxis: given to prevent infection
63
Hypersensitivity to penicillins are ______ mediated.
-IgE
64
MRSA's method of resistance to penicillins
-transpeptidase acquires a mutation that prevents drug bindings
65
Staph's method of resistance to penicillins
-beta lactamases
66
Mechanism of action of beta lactamase inhibitors
-irreversibly bind and inactivate certain beta-lactamases
67
Is amoxicillin or ampicillin used more?
-amoxicillin because it can be used 3 times a day instead of 4, and it is absorbed better
68
Extended spectrum penicillins with the addition of a beta-lactamase inhibitor have activity against _______.
- improved activity against staph and gram negatives
| - pseudomonas
69
Compare cephalorsporins mechanism of action to the penicillins. What are some differences?
- same mechanism: inhibit peptidoglycan synthesis via PBPs--bactericidal
- wider antibacterial spectrum
- resistance to many beta-lactamases
- improved pharmacokinetics
70
Are cephalosporins bactericidal or bacteriostatis?
-bactericidal
71
How do cephalosporins ring structures compare to penicillins?
-both have beta lactam rings, but cephalosporins are connected to a 6-member ring while penicillins are connected to a 5 member ring
72
In general, cephalosporins are resistant to _______ produced by __________ and common gram-negatives.
-beta-lactamases produced by staph
73
Cephalosporins do NOT cover ________.
-enterococci
74
Cephalosporin drugs have been described as "generations" from first generation (oldest) to fourth. Newer generations have better _______________.
-gram-negative coverage and poorer gram + coverage
75
Like penicillins, cephalosporins can induce ____________.
- hypersensitivity reactions
| - 5% of patients with penicillin reactions have reactions to cephalosporins as well
76
1st generation cephalosporins start with "ceph" except for ________ and _________.
- Cefazolin
| - Cefadroxil
77
What types of bacteria are cephalosporin (1st gen) active against and what are they commonly prescribed for?
- very active against gram positives including Staph (except MRSA)
- moderate use against some gram negatives, esp. E. coli and Klebsiella
- used for community acquired UTIs and respiratory infections
- Cefazolin is used for surgical prophylaxis
78
For what instances are 1st generation cephalosporins commonly prescribed?
- community acquired UTIs and respiratory infections
| - Cefazolin for surgical prophylaxis
79
When are 2nd generation cephalosporins prescribed?
- otitis media in children
- increased activity, esp. against gram negatives including H. influenzae
- respiratory infections, UTIs
80
3rd generation cephalosporin activity
-less activity against G+, more effective G- coverage
81
What are 3rd generation cephalosporins prescribed for?
- management of hospital-acquired (G-) bacteremia, inpatient pneumonia and UTIs
- some can penetrate CNS!!! unlike 1st and 2nd generation)
- gonococcal infections
82
Single dose of __________ is used for gonococcal infections. It is also used to treat meningitis
-Ceftriaxone, a 3rd generation cephalosporin
83
________ is the only licensed 4th generation cephalosporin in the US. What activities does it have?
- Cefipime
- enhanced activity to enterobacter, citrobacter, and pseudomonas
- can be used when resistance is seen to a 3rd generation drug
84
Side effects of Cephalosporins
- overall relatively safe since drugs that target cell wall have a very high therapeutic index
- hypersensitivity reactions just like penicillin
- patients with significant PCN allergies should NOT be given cephalosporins, but you can risk it if PCN allergies are mild
- greater incidence of GI problems due to better gram negative coverage- can lead to C. difficile colonization and colitis
85
3 mechanisms of resistance to cephalosporins
- Same to penicillin!
1. beta lactamases
2. increased efflux from periplasmic space of gram negatives
3. change the target; mutate PBPs so they dont bind ABx well
86
As you increase the generation of cephalosporins, you increase the ________ coverage.
-gram negative
87
3 common first generation cephalosporins used at Penn
1. Cafadroxil
2. Cefazolin
3. Cephalexin
88
2nd generation cephalosporin commonly used at Penn
1. Cefuroxime
89
Name the 4 3rd generation cephalosporins used at penn
1. Cefixime
2. Cefotaxime
3. Ceftazidime
4. Ceftriaxone
90
What 3rd generation cephalosporin is used to treat pseudomonas?
-Ceftazidime
91
Carbapenems mechanism of action; how is it similar to penicillins? how is it different?
- same as penicillins: inhibit PBPs
| - wider antibacterial spectrum than other beta lactamases, resistance to beta-lactamases, improved pharmackkinetics
92
4 carbapenems commonly used
1. Imipenem
2. Meropenem** commonly used at Penn and restricted**
3. Ertapenem
4. Doripenem
93
Are Carbapenems bacteriostatic or bacterocidial? How are they administered?
- bactericidal
| - usually given IV
94
What types of bacterial are carbapenems effective against?
- gram positive, gram negative, aerobic, and anaerobic bacteria
- typically cover everything except enterococci
95
When are carbapenems administered?
- often used as empiric therapy for critically ill patients
| - last resort for E. Coli and Klebsiella infections
96
Where are carbapenems metabolized? By what enzyme and can this be blocked?
- Kidney by dehydropeptidase
| - blocked by cilastatin, which is sometimes coadministered
97
Why is the use of carbapenems so controlled?
-we dont want overuse as resistance to them so far is rare
98
Resistance to carbapenems
-Carbapenemases (beta lactamases) have been found in enteric bacteria
99
How do carbapenems penetrate gram negative rods?
- bia OprD porins
| - carbapenem resistant pseudomonas aeruginosa mutants lack OprD
100
In summary, beta lactam drugs are generally more active against __________ bacteria, with variable coverage of ___________ bacteria.
- gram positive
| - gram negative
101
Beta lactam side effects summary
-hypersensitivity is major side effect, along with GI disturbances with more potent cephaloporins
102
What type of molecule is vancomycin?
-glycopeptide
103
Function of vancomycin
- interactions with D-alanine-D-alanine termini of the pentapeptide side chains interfering with formation of bridges between peptidoglycan chains
* *Thus it works a step BEFORE beta-lactams in preventing transpeptidation**
104
Is there cross resistance to vancomycin and beta-lactams?
-no; though V inhibits cell wall synthesis, it does so differently than beta-lactams
105
How is vancomycin usually administered?
-IV due to poor absorption from intestinal tract, unless you are trying to treat a GI infection
106
What coverage is vancomycin best at providing?
- excellent gram positive coverage against Staph and Strep
| - NO gram negative coverage
107
Why does vancomycin not providing gram negative coverage make sense?
-it is a glycopeptide and is too big to pass through porins in the gram negative membranes
108
Compare vancomycin and oxacillin effectiveness against MRSA
-vancomycin is inferior to oxacillin, but V is still used
109
What is vancomycin prescribed for?
- Staph and Strep infections
- MRSA and othwr beta-lactam resistant gram positive organisms
- oral form used for C. difficile colitis
110
Vancomycin can cause a hypersensitivity reaction; rarely this can be more severe, leading to what is called ____________. In general, it is well tolerated but must be infused slowly. What else can it cause?
- Red Man Syndrome with a red rash on the face, neck, and trunk
- occurs monutes after administration due to secondary mast cell degranulation and histamine release
- can also cause thrombophlebitis
111
Bacitracin, like vancomycin, is a ________.
-peptide; although, B is technically a mixture of cyclic peptides
112
How does bacitracin function?
-inhibits cell wall synthesis by preventing the transport of peptidoglycan precursors across the bacterial cytoplasmic membrane
113
How is bacitracin used and what is it most effective against?
- only used topically; toxicity issues if taken orally
| - most effective against gram-positives
114
Where is bacitracin a common ingredient?
-in non-prescription first-aid ointments
115
Daptomycin
- lipophilic peptide that disrupts the membranes of gram positives
- can be given IV
116
Daptomycin is approved for _____________ infections and is active against _________.
- gram positive skin infections and S. aureus bacteremia
| - MRSA
117
What is the target of many antimicrobials that function by inhibiting protein synthesis?
- prokaryotic ribosome
| - it is different enough from the eukaryotic ribosomes responsible for selective toxicity
118
4 drugs comprising class of antimicrobials that act via inhibiting protein synthesis
1. Macrolides**
2. Aminoglycosides**
3. Tetracyclins
4. Chloramphenicol
119
What are the 4 macrolides commonly used at penn?
1. Azithromycin
2. Clarithromycin
3. Clindamycin
4. Erythromycin
120
Mechanism of macrolides
-reversibly bind to 50S ribosome and prevent protein elongation
121
Are macrolides bactericidal or bacteriostatic?
-Bacteriostatic
122
Macrolides have broad activity against __________ and some _______.
- gram positive
| - some gram negatives
123
When are macrolides prescribed?
- first line agents for community acquired pneumonia and often drugs of choice for those allergic to penicillin
- good activity against strep pneumonia
- atypical pathogens like legionella, chlamydia, and mycoplasma
- skin infections not due to MRSA
- URTI
124
Usual form of resistance to macrolides
- usually due to altered binding sites
| - can also be due to hydrolysis of drug and enhanced efflux
125
Macrolide side effects
-no unusual side effects
126
Eukaryotic ribosome have _____ and _____ subunits, while prokaryotes have ____ and ______ subunits.
- 60S,40S
| - 50S,30S
127
6 commonly used aminoglycosides
- streptomycin
- gentamicin
- tobramycin
- amikacin
- neomycin
- spectinomycin
128
Mechanism of action of aminoglycosides
- IRREVERSIBLY binds to 30S ribosomal subunit
- causes distortion and malfunction of ribosome
- blocks initiation of translation
- causes misreading of mRNA
129
Are aminoglycosides bactericidal or bacteriostatic?
-bactericidal because they bind irreversibly
130
Are aminoglycosides effective against anaerobes? explain.
-no; penetration through membrane is an aerobic, energy-dependent process
131
Aminoglycosides are not effective against _____ and _______ unless...
- enterococci and streptococci
- UNLESS a Beta lactam drug is coadministered
- this allows aminoglycosides to enter cells that are often resistant
132
Typical uses of aminoglycosides
- good coverage against aerobic, gram negative rods (E. coli, Klebsiella, enterobacter, pseudomonas, shigella)
- usually reserves for serious gram negative infections (complicated UTIs with pylonephritis, penumonia and used with beta-lactam to cover G+ and G-, pseudomonas)
133
Are aminoglycosides used in everyday practice?
-no, issues with toxicity limit their use
134
How are aminoglycosides administered?
- not absorbed in the gut
| - thus given IV or IM
135
What are the 2 most commonly used aminoglycosides
- Gentamicin
| - Tobramycin
136
Why are aminoglycosides coadministered with beta lactams?
-beta lactams will damage cell wall and allow aminoglycosides to penetrate
137
Aminoglycoside resistance is increasing with _______ and _______.
- pseudomonas and enterococci
| - incidence of resistance is low for other organisms
138
3 resistance mechanisms to aminoglycosides
1. enzyme modification of the drug: typically on plasmids and results in high-level resistance
2. reduced uptake or decreased cell permeability: intermediate resistance since block is not complete
3. Altered ribosome binding site: not common
139
Why are there such strict concerns over aminoglycosides?
-these drugs have a low therapeutic index, so you need to follow drug levels
140
2 common side effects of aminoglycosides
1. nephrotoxicity: relatively common (10-20%), generally reversible toxicity, appears assoc. with high trough levels (lowest levels of drug seen in plasma)
2. Ototoxicity: appears assoc with high peak levels, can cause tinnitus and permanent deafness due to loss of hair cells; may not be reversible
141
Aminoglycosides being used with beta-lactams is a good example of _______.
-synergy
142
Why can administering aminoglycosides be of help to CF patients?
-important drug against pseudomonas which cause serious problems for patients with CF
143
3 common drugs used from tetracyclins
- tetracyclin
- doxycycline
- minocycline
144
Mechanism of action for tetracyclins
- REVERSIBLY bind to 30S ribosomal subunit
| - blocks attachment of tRNA to ribosome and prevents continuations of protein synthesis
145
Are tetracyclins bacteriostatic or bactericidal?
-bacteriostatic: reversibly! bind 30s
146
Common uses of tetracyclins
- good coverage of mycoplasma and chlamydia
- Drug of choice for lyme disease
- acne treatment
147
What class of drugs is the drug of choice for lyme disease?
-tetracyclins
148
3 common side effects of tetracyclins
- discolored teeth in children
- GI upset
- Phototoxic dermatitis
149
Who should NOT receive tetracyclins?
-children or pregnant women
150
Most common resistance mechanism to tetracyclins
-increased efflux from cells
151
Mechanism of action of chloramphenicol
- binds to 50S subunits
| - prevents peptide bonds from forming and blocking protein synthesis
152
Chloramphenicol is effective against a VERY wide variety of organisms, but used as drug of last resort for life-threatening infections. Why?
- has rare, but deadly side effects
| - aplastic anemia
153
Aplastic anemia
- rare, often fatal side effect of chloramphenicol
| - bone marrow is wiped out
154
Give 2 examples when Chloramphenicol is used
- young children and pregnant women with Rocky Mountain Spotted Fever, which is usually treated with tetracyclins but can't use these with these people
- meningitis if organism not known and patient has penicillin allergy
155
Who should not be given chloramphenicol under any condition?
-neonates: they cannot metabolize the drug, resulting in high levels and vasomotor collapse
156
3 types of drugs that inhibit nucleid acid synthesis. Name them and if they work on DNA or RNA
DNA replication: quinolones/fluoroquinolones and metronidazole
RNA replication: Rifamycins
157
Quinolones target ________.
- DNA gyrase
| - DNA gyrase nicks and reannels DNA to relieve supercoiling, and relieves tension as DNA is unwound during replication
158
Drugs that target DNA gyrase inhibit ________.
-DNA replication
159
Commonly used fluoroquinolones
- levofloxacin
- norfloxacin
- Cirpofloxacin
160
What bacterium are fluoroquinolones not good against?
-gram positives or anaerobes
161
What are fluoroquinolones effective against?
-multi-drug resistant pseudomonas (Cipro is best)
-Enterics: E.coli, salmonella, shigella, campylobacter
-Complicated UTIs: usually caused by gram negs
-Anthrax
-GNR including pseudomonas
-
162
Levofloxacin is active against many _________.
-penicillin-resistant pneumococci
163
How are fluoroquinolines administered?
- PO
| - good tissue absorption
164
Resistance mechanism against fluoroquinolones
-due to mutations in drug binding site in gyrase
165
Side effects of fluoroquinolones
-generally safe, but can disrupt normal gut flora, increasing chance of getting C. difficile
166
Tradename of metronidazole
-Flagyl
167
Is metronidazole bacteriostatic or bactericidal?
-bactericidal
168
Mechanism of action of metronidazole
-inhibits DNA replication, causes DNA breaks and secondary mutations
169
Metronidazole is administered as a _________. What does this mean?
- pro-drug
- it is inactive (or significantly less active) until it is metabolized in vivo into an active form
- in metronidazole, the nitrogroup is chemically reduced by bacterial oxidoreductases to become active
170
What enzymes create the active form of metronidazole?
- bacterial oxidoreductases
| - it is activated INSIDE bacterial cells
171
Metronidazole is only active against ________.
- anaerobes
| - one of the most reliable anti-anaerobic agents available
172
Aside from anaerobes, metronidazole is also good against what other pathogens?
- good for C.difficile, behind vancomycin
| - Protozoa: trichomonas, giardia, amebic infections
173
Resistance mechanisms against metronidazole
- decreased uptake into the cell
| - reduced activation of the ABx
174
Mechanism of action of sulfonamides
-inhibit growth of gram + and gram - organisms through competitive inhibition of enzyme that aids in production of folic acid
175
What is sulonamides structurally similar to?
-para-aminobenzoid acid which is substrate in folic acid pathway
176
What is the basis of selective toxicity of sulfa-drugs?
-humans lack specific enzyme in folic acid pathway
177
Resistance mechanism to sulfa-drugs
- due to plasmid
| - plasmid codes for enzyme that has lower affinity to drug
178
Trimethoprim mechanism of action
- inhibits folic acid production
| - interferes with activity of enzyme following enzyme inhibited by sulfonamides
179
Trimethoprim is often used synergistically with _______.
-sulfonamide
180
Most common mechanism of resistance to trimethoprim
-plasmid-encoded alternative enzyme
181
Genes encoding resistance to sulfonamide and tripmethoprim are often ________.
-carried on the same plasmid
182
What is bactrim a combination of?
-trimethoprim and sulfamethaxazole
183
Bactrim has no _______ coverage.
-anaerobic
184
What is bactrim good for?
- strep and H. flu (otitis media, sinusitis, bronchitis)
- gram negatives causing diarrhea: shigella, salmonella, E. coli
- pneumocystis (seen in AIDS patients)
185
Bactrim side effects
- hypersensitivity
| - don't give to patients taking warfarin (blood thinner) as it increases warfarin levels and can lead to bleeding
186
List the 3 classes of drugs that target the cell wall
- Penicillins
- Cephalosporins
- Carbapenems
187
List the 1 class of drug that targets the cell membrane
-Glycopeptides/polypeptides
188
List the 4 classes of drugs that target protein synthesis
- Macrolides
- Aminoglycosides
- Tetracyclins
- Chloramphenicol
189
List the 3 classes of drugs that target nucleic acid synthesis
- Quinolones
- Rifampin
- Metronidazole
190
List the class of drugs that targets antimetabolites
- Sulfonamides
| - Trimethoprim
