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Flashcards in Antibiotics Deck (134)
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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
  1. Inability to penetrate G- outermembrane
  2. Acquired mutations in PBPs that lower affinity for B-lactam
  3. 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
Q

What is SJS

A

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
Q

What are the first generation cephalosporins

A

cefazolin

27
Q

First generation cephalosporins have which features (3)

A

1) high activity against G+ MSSA and strep
2) Alternative to penicillin when mild allergy exist
3) Prophylaxis before surgery

28
Q

What are the second generation cephalosporins

A

cefoxitin

29
Q

Second generation cephalosporins have which features (3)

A

1) Better G- than 1st gen
2) Little CNS penetration
3) Largely replaced by gen 3

30
Q

What are the third generation cephalosporins

A

ceftriaxone

31
Q

Third generation cephalosporins

A

ceftriaxone

32
Q

Third generation cephalosporins have which features (4)

A

1) higher activity against G-
2) CNS penetration
3) Most widely used
4) meningitis, gonorrhea, empiric chlamydia

33
Q

Fourth generation cephalosporins

A

cefepime

34
Q

Fourth generation cephalosporins have which features (3)

A

1) highly resistant to beta-lactamases
2) good CNS penetration
3) treatment of hospitalized patients when resistance is suspected

35
Q

What is special about 5th gen cephalosporins

A

acitivity against MRSA

36
Q

What are the carbapenems

A

imipenum, cilastatin

37
Q

What are the important features of carbapenems

A

1) Beta-lactam
2) broad spectrum
3) Highly resistant to beta-lactamases
4) only given parenterally

38
Q

What is a unique toxicity of imipenem?

A

seizures

39
Q

What are the monobactams

A

aztreonam

40
Q

What is the structure of monobactams

A

contains beta-lactam ring, but not fused with a second ring. Is not an allergen like penicillin

41
Q

What are the features of monobactams (4)

A

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
Q

What are the glycopeptides

A

vancomycin

43
Q

What are glycopeptides used for

A

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
Q

Route of administration for glycopeptides

A

IV for systemic and viral infections

orally to treat GI infections

45
Q

What are the adverse reactions to glycopeptides (3)

A

1) Ototoxic
2) red man syndrome (histamine reaction)
3) Thrombophlebitis

46
Q

Which cell wall synthesis inhibitor is commonly used for UTI with G- bacteria

A

Fosfomycin

47
Q

What is the MOA of fosfomycin

A

inhibits production of murein monomers by inhibiting enolpyruvate transferase

48
Q

What is unique about fosfomycin that allows it to treat G- bacteria

A

It enters through a transporter, but mutations confer resistance

49
Q

Which cell wall synthesis inhibitor is a component of Neosporin

A

Bacitracin

50
Q

Why is bacitracin only effective against G+ bacteria

A

It works inside the bacteria to inhibit bactoprenol dephosphorylation, it cannot penetrate G- outer membrane

51
Q

Which classes of cell wall inhibitors work inside or outside the bacterial cell

A

inside- fosfomycin and bacitracin

outside- vancomycin and beta lactams

52
Q

What are the classes of beta-lactams (4)

A

Penicillins, cephalosporins, carbapenems, and monbactams

53
Q

What are the sizes of the mammalian and bacterial ribosomes and their subunits

A

Bacterial 70S, 30S and 50S

Mammalian 80S, 40S and 60S

54
Q

What is the structure of aminoglycosides and what are the consequences?

A

2 or more amino sugars connected by glycoside linkages. Large bulky, cationic, hydrophilic structure. Does not cross membranes attracted to negative LPS

55
Q

What are the aminoglycosides (4)

A

gentamicin, amikacin, streptomycin, neomycin

56
Q

How do aminoglycosides get into bacteria

A

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
Q

Aminoglycosides MOA (3)

A
Binding to 30S
1) inhibits formation of initiation complex
2) misreading of mRNA
3) blockade of translocation 
Note: has post antibiotic effect
58
Q

Therapeutic considerations for aminoglycosides

A

Narrow spectrum, diminished therapeutic resistance

59
Q

Aminoglycoside used as second line drug for TB

A

Streptomycin

60
Q

aminoglycoside used in hospitals where resistance is common due to susceptibility to inactivation

A

Amikacin

61
Q

Aminoglycoside in neosporin effective against G- bacteria

A

neomycin

62
Q

What are the two Ototoxic antibiotic classes

A

aminoglycosides and glycopeptides (vancomycin)

63
Q

What are the adverse reactions to aminoglycosides (3) and what is a way to avoid them

A

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
Q

Tetracyclines (3)

A

tetracycline, tigecycline, doxycycline

65
Q

Which two antibiotic classes bind to the 30S ribosomal subunit

A

tetracyclines and aminoglycosides

66
Q

How are tetracyclines transported into the bacterial cell

A

active transport system only present in bacterial cells

67
Q

Administration of tetracyclines

A

Orally (except tigecycline), do not administer with dairy widely distributed

68
Q

Therapeutic profile of tetracyclines

A

broad spectrum antibiotics, rickettsial infections, peridontal disease, acne, prophylaxix of malaria

69
Q

Adverse reactions of tetracyclines (6)

A

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
Q

Macrolydes (2)

A

erythromycin, azithromycin

71
Q

MOA of macrolydes

A

binds to 50S inhibits translocation

72
Q

Resistance to macrolydes

A

plasma-encoded methylation of 50S

73
Q

Adverse reactions to macrolydes

A

Generally very safe

1) GI irritation is most common, increases motility
2) Cholestatic hepatitis
3) Prolonged Q-T interval

74
Q

What is the prototype oxizolidinone?

A

linezolid

75
Q

What is the MOA of oxizolidinones

A

binding to 23S of the 50S subunit, blocks formation of initiation complex. Bacteriostatic

76
Q

What are the Streptogramins?

A

quinupristin-dalfopristin

77
Q

What are the therapeutic uses of oxizolidines

A

MDR G+ pathogens when other agents are not available, due to negative effects like anemia and neuropathy. Have to do blood counts weekly

78
Q

What is the MOA of streptogramins?

A

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
Q

What is the fluoroquinolones prototype drug

A

ciproflaxin

80
Q

What is the structure of fluoroquinolones

A

fluorinated derivatives of the quinolone, nalidixic acid

81
Q

MOA of fluoroquinolones

A

Inhibits one of the two topoisomerase II enzymes. Bactericidal

82
Q

Pharmacokinetics of fluoroquinolones

A

orally available and widely distributed, cleared renally

83
Q

What is the unique side effect of fluoroquinolones?

A

Tendon rupture, do not give to patients <18

84
Q

What are the therapeutic uses of fluoroquinolones (3)

A

1) Widely used for urogenital, respiratory and GI infections Aerobic G-
2) Prophylaxis for anthrax
3) Respiratory fluoroquinolones

85
Q

Which protein synthesis inhibitor is associated with CDAD?

A

Clindamycin presents in up to 5% patients and may develop weeks after drug withdrawl

86
Q

What other drug class has a similar mechanism to clindamycin?

A

macrolides

87
Q

What type of bacteria is clindamycin used to treat

A

most anaerobic and G+ aerobes

88
Q

Which drug is cheap and effective against a broad spectrum, but not commonly used in the developed world due to toxicities

A

Chloramphenicol

89
Q

Chloramphenicol’s MOA

A

binds to peptidyl transferase center of 50S, prevents attachment of incoming tRNA to A-site

90
Q

What is one condition where chloramphenicol is still used

A

bacterial meningitis

91
Q

What are the main adverse reactions of chloramphenicol (3)

A

1) gray baby syndrome
2) bone marrow suppresion
3) aplastic anemia

92
Q

What are oxizolindones primarily used for therapeutically

A

MDR G+ bacteria, only when others are not effective

93
Q

Adverse reactions to oxizolindones

A

Reversible myelosuppression, blood counts weekly

Neuropathy

94
Q

What drug interaction does linezolid have

A

MAOIs and SSRIs, serotonin syndrome

95
Q

What organisms is quinupristin-dalfopristin affective against

A

G+, G- activity limited

96
Q

Adverse reactions to quinupristin-dalfopristin

A

hyperbilirubinemia (jaundice)
arthralgia /myalgia (joint and muscle pain)
Inhibits CYP3A4

97
Q

Which protein synthesis inhibitors are bacteriocidal

A

aminoglycosides and quinupristin/dalfopristin

98
Q

What are the major resistance mechanisms to protein synthesis inhibitors

A

decreased uptake or efflux

bacterial enzymes that inactivate the drug

99
Q

Major side effects from protein synthesis inhibitors

1) ototoxicity
2) tooth discoloration
3) CDAD
4) aplastic anemia

A

1) aminoglycosides
2) tetracyclines
3) Clindamycin
4) chloramphenicol

100
Q

Protein synthesis that bind the 50S and 30S subunits

A

50S- macrolides and miscellaneous

30S- aminoglycosides and tetracyclins

101
Q

What are the adverse reactions associated with fluoroquinolones

A

1) tendon rupture
2) confusion, visual disturbances in elderly
3) prolong Q-T interval,
4) CDAD

102
Q

What drug interactions do fluoroquinolones have

A

increase theophylline and warfarin

oral absorption reduced if taken with multivalent cations

103
Q

What is the drug of choice to treat CDAD

A

Metronidazole

104
Q

What is the MOA of metronidazole

A

Initiates strand breaks and loss of helical structure, cannot be metabolized by human cells

105
Q

Therapeutic uses of metronidazole (5)

A

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
Q

Adverse reactions to metronidazole

A

headache, GI, metallic taste, dark brown urine

107
Q

Drug interactions with metronidazole

A

disulfiram-like reaction with ethanol

inhibits metabolism of warfarin-bleeding

108
Q

Sulfonamine prototype

A

sulfamethoxazole

109
Q

Sulfonamine MOA

A

Structural analog of PABA, bacteriostatic

110
Q

Resistance mechanisms to sulfonamine

A

1) synthesis of PABA to overcome inhibition
2) mutation in dihydropteroate synthase
3) decreased uptake

111
Q

Therapeutic uses of sulfonamides

A

Broad specturm against G-/G+
diminished due to development of resistance and safer alternatives
Mostly in combination with trimethoprim

112
Q

Adverse reactions to sulfonamides

A

1) kernicterus
2) hypersensitivity- Stevens-Johnson syndrome
3) Hemolytic anemia

113
Q

What are the 2 types of folic acid inhibitors

A

sulfonamides, trimethoprim (TMP)

114
Q

What is the MOA of trimethoprim

A

inhibits dihydrofolate reductase (DHFR)

115
Q

Resistance to Trimethoprim

A

1) increased synthesis of DHFR
2) mutated DHFR
3) reduced uptake

116
Q

Adverse reactions to trimethoprim

A

Bone marrow suppression in folate deficient patients

Fatal fetal malformations in experimental animals

117
Q

What is co-trimoxazole

A

Fixed-dose combination of trimethoprim and sulfamethoxazole that has a synergistic bactericidal effect due to inhibition of sequential steps of folate biosynthesis.

118
Q

Therapeutic uses of co-trimoxazole (5)

A

1) UTI, chronic and recurrent
2) oportunistic pneumonia
3) ear infections
4) MSSA + MRSA
5) Shigellosis (diarrhea)

119
Q

What is the third line drug for CDAD

A

Fidoxomicin after metronidozol and vancomycin.

120
Q

What features does fidoxomicin have relative to other treatments for CDAD

A

minimally disruptive to normal GI flora and lowers risk of recurrence.

121
Q

What Nucleic acid synthesis inhibitor is a pro-drug

A

Metronidazol causes DNA strand breaks in anaerobic bacteria

122
Q

Which drug class inhibits bacterial DNA gyrase

A

Fluoroquinolones

123
Q

Which drugs inhibit bacterial RNA polymerase

A

Fidoxamicin and rifampin

124
Q

Major side effects of nucleic acid synthesis inhibitors and their causative agents

A

1) tendon rupture- fluoroquinolones
2) kernicterus, hemolytic anemia- sulfonamides
3) Myelosuppression- SMX and TMP

125
Q

What is the prototype Lipopeptide

A

daptomycin

126
Q

What is the MOA of lipopeptides

A

Calcium dependent insertion of lipophilic tail into plasma membrane forms an ion-permeable channel that permits efflux of intracellular K+

127
Q

Therapeutic uses for daptomycin

A

administered IV, complicated skin, bacteremia and right-sided endocarditis with resistant microbes

128
Q

Adverse reactions to daptomycin

A

myopathy

129
Q

What are the polymyxins?

A

colistin, polymyxin B

130
Q

MOA of polymyxins

A

Binds to neg charged LPS in G- bacteria , disrupts plasma membranes

131
Q

What are the two formulations of colistin?

A
Colistin sulfate (cationic)- oral and GI
Colistimethate (anionic)- parenteral use, prodrug
132
Q

What are the therapeutic uses of colistimethate

A

treatment of last resort for serious MDR G- infections

133
Q

Colistin sulfate therapeutic uses

A

topical for infection of skin, mucous membranes, eye, ear

134
Q

What are the side effects of colistin

A

reversible nephrotoxicity and neurotoxicity