Antibiotics Flashcards
(134 cards)
1
Q
Drugs with highest risk of CDAD
A
clindamycin, ampicillin, cephalosporins and fluoroquinolones
2
Q
Drugs to treat CDAD
A
metronidazole or vancomycin
3
Q
What should you use to treat UTI empirically
A
co-trimoxazol
4
Q
How are most antibiotics cleared
A
excretion by the kidney, consideration for young and elderly
5
Q
antibiotics cleared by the kidney (7)
A
aminoglycosides, vancomycin, cephalosporins, sulfonamides/trimethoprim, extended spectrum penicillins, carbapenems, ethambutol
6
Q
antibiotics cleared by the liver (7)
A
Clindamycin, macrolides, chloramphenicol, tetracyclines, metronidazole, isoniazid, rifampin
7
Q
Which drugs are class D for birth defects
A
aminoglycosides and tetracyclins
8
Q
antibiotics with placental and breast milk transfer
A
1) aminoglycoside ototoxicity during fetal development
2) sulfonamide induced kernicterus in nursing infants
9
Q
Most common sources of antibiotic allergy (4)
A
beta lactams (penicillin), sulfonamides, trimethoprim, and erythromycin
10
Q
What is the most important difference between gram+ and gram- bacterial
A
gram negative bacteria have an outermembrane which makes them more difficult to penetrate with antibiotics
11
Q
What is the main MOA of penicillin
A
irreversible inhibition of transpeptidases
12
Q
structure of penicillins
A
Beta-lactam ring fused to a 5-member thiazolidine
13
Q
Main mechanisms of penicillin resistance (3)
A
- Inability to penetrate G- outermembrane
- Acquired mutations in PBPs that lower affinity for B-lactam
- Beta-lactamases
14
Q
What are the standard, narrow-spectrum penicillins?
A
Penicillin G, penicillin V
15
Q
Which standard, narrow-spectrum penicillin is orally effective?
A
Penicillin V
16
Q
What is the DOC for syphilis?
A
Penicillin G,V
17
Q
What are the penicillinase-resistant penicillins
A
Nafcillin
18
Q
What are the aminopenicillins?
A
amoxicillin
19
Q
What unique property do aminopenicillins have?
A
Positive charge that makes them effective against G-
20
Q
Antipseudomonal penicillins
A
ticarcillin, piperacillin
21
Q
Which penicillins are prescribed with Beta-lactamases
A
Amoxicillin, ticarcillin, piperacillin
22
Q
Repository prep of penicillin and what it is used for
A
Pen G benzathine, syphilis and rheumatic fever
23
Q
What is a Jarisch-Herxheimer reaction
A
rash, fever, flushing after shot due to death of pathogen, typically syphilis
24
Q
What is a side effect specific to ticarcillin
A
sodium overload can be a problem in CHF
25
What is SJS
Steven Johnson's syndrome is a separation of the dermis from the epidermis covering less than 10% of the body. If it covers more it is called toxic epidermal necrolysis (TEN).
26
What are the first generation cephalosporins
cefazolin
27
First generation cephalosporins have which features (3)
1) high activity against G+ MSSA and strep
2) Alternative to penicillin when mild allergy exist
3) Prophylaxis before surgery
28
What are the second generation cephalosporins
cefoxitin
29
Second generation cephalosporins have which features (3)
1) Better G- than 1st gen
2) Little CNS penetration
3) Largely replaced by gen 3
30
What are the third generation cephalosporins
ceftriaxone
31
Third generation cephalosporins
ceftriaxone
32
Third generation cephalosporins have which features (4)
1) higher activity against G-
2) CNS penetration
3) Most widely used
4) meningitis, gonorrhea, empiric chlamydia
33
Fourth generation cephalosporins
cefepime
34
Fourth generation cephalosporins have which features (3)
1) highly resistant to beta-lactamases
2) good CNS penetration
3) treatment of hospitalized patients when resistance is suspected
35
What is special about 5th gen cephalosporins
acitivity against MRSA
36
What are the carbapenems
imipenum, cilastatin
37
What are the important features of carbapenems
1) Beta-lactam
2) broad spectrum
3) Highly resistant to beta-lactamases
4) only given parenterally
38
What is a unique toxicity of imipenem?
seizures
39
What are the monobactams
aztreonam
40
What is the structure of monobactams
contains beta-lactam ring, but not fused with a second ring. Is not an allergen like penicillin
41
What are the features of monobactams (4)
1) only active against G- bacteria including pseudomonas
2) Given IV, reduced in renal insufficiency
3) resistant to most beta-lactamases
4) Safe for patients with penicillin allergy
42
What are the glycopeptides
vancomycin
43
What are glycopeptides used for
Generally serious infections with G+ bacteria
Parenteral- sepsis or endocarditis caused by MRSA or sensitive enterococci
In combination with 3rd gen cephalosporins for meningitis
Oral for CDAD if metronidazole is ineffective
Alternative to penicillin
44
Route of administration for glycopeptides
IV for systemic and viral infections
| orally to treat GI infections
45
What are the adverse reactions to glycopeptides (3)
1) Ototoxic
2) red man syndrome (histamine reaction)
3) Thrombophlebitis
46
Which cell wall synthesis inhibitor is commonly used for UTI with G- bacteria
Fosfomycin
47
What is the MOA of fosfomycin
inhibits production of murein monomers by inhibiting enolpyruvate transferase
48
What is unique about fosfomycin that allows it to treat G- bacteria
It enters through a transporter, but mutations confer resistance
49
Which cell wall synthesis inhibitor is a component of Neosporin
Bacitracin
50
Why is bacitracin only effective against G+ bacteria
It works inside the bacteria to inhibit bactoprenol dephosphorylation, it cannot penetrate G- outer membrane
51
Which classes of cell wall inhibitors work inside or outside the bacterial cell
inside- fosfomycin and bacitracin
| outside- vancomycin and beta lactams
52
What are the classes of beta-lactams (4)
Penicillins, cephalosporins, carbapenems, and monbactams
53
What are the sizes of the mammalian and bacterial ribosomes and their subunits
Bacterial 70S, 30S and 50S
| Mammalian 80S, 40S and 60S
54
What is the structure of aminoglycosides and what are the consequences?
2 or more amino sugars connected by glycoside linkages. Large bulky, cationic, hydrophilic structure. Does not cross membranes attracted to negative LPS
55
What are the aminoglycosides (4)
gentamicin, amikacin, streptomycin, neomycin
56
How do aminoglycosides get into bacteria
Concentration dependent, passive diffusion through porins, active transport across membrane is O2 dependent. only effective against aerobes. Can be synergistic with cell wall inhibitors
57
Aminoglycosides MOA (3)
```
Binding to 30S
1) inhibits formation of initiation complex
2) misreading of mRNA
3) blockade of translocation
Note: has post antibiotic effect
```
58
Therapeutic considerations for aminoglycosides
Narrow spectrum, diminished therapeutic resistance
59
Aminoglycoside used as second line drug for TB
Streptomycin
60
aminoglycoside used in hospitals where resistance is common due to susceptibility to inactivation
Amikacin
61
Aminoglycoside in neosporin effective against G- bacteria
neomycin
62
What are the two Ototoxic antibiotic classes
aminoglycosides and glycopeptides (vancomycin)
63
What are the adverse reactions to aminoglycosides (3) and what is a way to avoid them
1) ototoxicity
2) nephrotoxicity (mostly bad due to reduced clearance)
3) Neuromuscular blockade with high doses, respiratory paralysis
Can administer once daily in large dose
64
Tetracyclines (3)
tetracycline, tigecycline, doxycycline
65
Which two antibiotic classes bind to the 30S ribosomal subunit
tetracyclines and aminoglycosides
66
How are tetracyclines transported into the bacterial cell
active transport system only present in bacterial cells
67
Administration of tetracyclines
Orally (except tigecycline), do not administer with dairy widely distributed
68
Therapeutic profile of tetracyclines
broad spectrum antibiotics, rickettsial infections, peridontal disease, acne, prophylaxix of malaria
69
Adverse reactions of tetracyclines (6)
1) GI irritation
2) Deposition in bone and teeth, staining
3) renal toxicity, especially if outdated
4) superinfection
5) hepatotoxicity at high doses, esp in preg women
6) photosensitivity
70
Macrolydes (2)
erythromycin, azithromycin
71
MOA of macrolydes
binds to 50S inhibits translocation
72
Resistance to macrolydes
plasma-encoded methylation of 50S
73
Adverse reactions to macrolydes
Generally very safe
1) GI irritation is most common, increases motility
2) Cholestatic hepatitis
3) Prolonged Q-T interval
74
What is the prototype oxizolidinone?
linezolid
75
What is the MOA of oxizolidinones
binding to 23S of the 50S subunit, blocks formation of initiation complex. Bacteriostatic
76
What are the Streptogramins?
quinupristin-dalfopristin
77
What are the therapeutic uses of oxizolidines
MDR G+ pathogens when other agents are not available, due to negative effects like anemia and neuropathy. Have to do blood counts weekly
78
What is the MOA of streptogramins?
inhibits Dalfopristin directly inhibits peptidyl transferase center of the 23S rRNA (50S)
Quinupristin binds at the same site as the macrolides
A 30:70 fixed dose combination is bactericidal
79
What is the fluoroquinolones prototype drug
ciproflaxin
80
What is the structure of fluoroquinolones
fluorinated derivatives of the quinolone, nalidixic acid
81
MOA of fluoroquinolones
Inhibits one of the two topoisomerase II enzymes. Bactericidal
82
Pharmacokinetics of fluoroquinolones
orally available and widely distributed, cleared renally
83
What is the unique side effect of fluoroquinolones?
Tendon rupture, do not give to patients <18
84
What are the therapeutic uses of fluoroquinolones (3)
1) Widely used for urogenital, respiratory and GI infections Aerobic G-
2) Prophylaxis for anthrax
3) Respiratory fluoroquinolones
85
Which protein synthesis inhibitor is associated with CDAD?
Clindamycin presents in up to 5% patients and may develop weeks after drug withdrawl
86
What other drug class has a similar mechanism to clindamycin?
macrolides
87
What type of bacteria is clindamycin used to treat
most anaerobic and G+ aerobes
88
Which drug is cheap and effective against a broad spectrum, but not commonly used in the developed world due to toxicities
Chloramphenicol
89
Chloramphenicol's MOA
binds to peptidyl transferase center of 50S, prevents attachment of incoming tRNA to A-site
90
What is one condition where chloramphenicol is still used
bacterial meningitis
91
What are the main adverse reactions of chloramphenicol (3)
1) gray baby syndrome
2) bone marrow suppresion
3) aplastic anemia
92
What are oxizolindones primarily used for therapeutically
MDR G+ bacteria, only when others are not effective
93
Adverse reactions to oxizolindones
Reversible myelosuppression, blood counts weekly
| Neuropathy
94
What drug interaction does linezolid have
MAOIs and SSRIs, serotonin syndrome
95
What organisms is quinupristin-dalfopristin affective against
G+, G- activity limited
96
Adverse reactions to quinupristin-dalfopristin
hyperbilirubinemia (jaundice)
arthralgia /myalgia (joint and muscle pain)
Inhibits CYP3A4
97
Which protein synthesis inhibitors are bacteriocidal
aminoglycosides and quinupristin/dalfopristin
98
What are the major resistance mechanisms to protein synthesis inhibitors
decreased uptake or efflux
| bacterial enzymes that inactivate the drug
99
Major side effects from protein synthesis inhibitors
1) ototoxicity
2) tooth discoloration
3) CDAD
4) aplastic anemia
1) aminoglycosides
2) tetracyclines
3) Clindamycin
4) chloramphenicol
100
Protein synthesis that bind the 50S and 30S subunits
50S- macrolides and miscellaneous
| 30S- aminoglycosides and tetracyclins
101
What are the adverse reactions associated with fluoroquinolones
1) tendon rupture
2) confusion, visual disturbances in elderly
3) prolong Q-T interval,
4) CDAD
102
What drug interactions do fluoroquinolones have
increase theophylline and warfarin
| oral absorption reduced if taken with multivalent cations
103
What is the drug of choice to treat CDAD
Metronidazole
104
What is the MOA of metronidazole
Initiates strand breaks and loss of helical structure, cannot be metabolized by human cells
105
Therapeutic uses of metronidazole (5)
1) anaerobic bacterial infections
2) bacterial vaginosis
3) CDAD
4) with tetracycline and bismuth subsalicylate for H.pylori in peptic ulcer disease
5) antiparasitic agent
106
Adverse reactions to metronidazole
headache, GI, metallic taste, dark brown urine
107
Drug interactions with metronidazole
disulfiram-like reaction with ethanol
| inhibits metabolism of warfarin-bleeding
108
Sulfonamine prototype
sulfamethoxazole
109
Sulfonamine MOA
Structural analog of PABA, bacteriostatic
110
Resistance mechanisms to sulfonamine
1) synthesis of PABA to overcome inhibition
2) mutation in dihydropteroate synthase
3) decreased uptake
111
Therapeutic uses of sulfonamides
Broad specturm against G-/G+
diminished due to development of resistance and safer alternatives
Mostly in combination with trimethoprim
112
Adverse reactions to sulfonamides
1) kernicterus
2) hypersensitivity- Stevens-Johnson syndrome
3) Hemolytic anemia
113
What are the 2 types of folic acid inhibitors
sulfonamides, trimethoprim (TMP)
114
What is the MOA of trimethoprim
inhibits dihydrofolate reductase (DHFR)
115
Resistance to Trimethoprim
1) increased synthesis of DHFR
2) mutated DHFR
3) reduced uptake
116
Adverse reactions to trimethoprim
Bone marrow suppression in folate deficient patients
| Fatal fetal malformations in experimental animals
117
What is co-trimoxazole
Fixed-dose combination of trimethoprim and sulfamethoxazole that has a synergistic bactericidal effect due to inhibition of sequential steps of folate biosynthesis.
118
Therapeutic uses of co-trimoxazole (5)
1) UTI, chronic and recurrent
2) oportunistic pneumonia
3) ear infections
4) MSSA + MRSA
5) Shigellosis (diarrhea)
119
What is the third line drug for CDAD
Fidoxomicin after metronidozol and vancomycin.
120
What features does fidoxomicin have relative to other treatments for CDAD
minimally disruptive to normal GI flora and lowers risk of recurrence.
121
What Nucleic acid synthesis inhibitor is a pro-drug
Metronidazol causes DNA strand breaks in anaerobic bacteria
122
Which drug class inhibits bacterial DNA gyrase
Fluoroquinolones
123
Which drugs inhibit bacterial RNA polymerase
Fidoxamicin and rifampin
124
Major side effects of nucleic acid synthesis inhibitors and their causative agents
1) tendon rupture- fluoroquinolones
2) kernicterus, hemolytic anemia- sulfonamides
3) Myelosuppression- SMX and TMP
125
What is the prototype Lipopeptide
daptomycin
126
What is the MOA of lipopeptides
Calcium dependent insertion of lipophilic tail into plasma membrane forms an ion-permeable channel that permits efflux of intracellular K+
127
Therapeutic uses for daptomycin
administered IV, complicated skin, bacteremia and right-sided endocarditis with resistant microbes
128
Adverse reactions to daptomycin
myopathy
129
What are the polymyxins?
colistin, polymyxin B
130
MOA of polymyxins
Binds to neg charged LPS in G- bacteria , disrupts plasma membranes
131
What are the two formulations of colistin?
```
Colistin sulfate (cationic)- oral and GI
Colistimethate (anionic)- parenteral use, prodrug
```
132
What are the therapeutic uses of colistimethate
treatment of last resort for serious MDR G- infections
133
Colistin sulfate therapeutic uses
topical for infection of skin, mucous membranes, eye, ear
134
What are the side effects of colistin
reversible nephrotoxicity and neurotoxicity
