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Pharmacology Test 3 > Antibiotics 1: Drugs that target protein and DNA synthesis > Flashcards

Antibiotics 1: Drugs that target protein and DNA synthesis Flashcards

1
Q

Antibiotic Targets

A
  • differences between bacterial and human cells

- mitochondria have similarities and can be effected

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2
Q

Important concepts of antibiotic therapy

A

1) selective toxicity (therapeutic index)
2) spectrum of activity (varies per bacteria/antibiotic
3) Bacteriostatic vs. Bactericidal

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3
Q

Bacteriostatic

A
  • by time for immune system to kill bacteria on its own

- protein synthesis inhibitors

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4
Q

Bactericidal

A
  • kill bacteria
  • cell wall-active agents
  • TMP-SMX
  • quinolones
  • aminoglycosides
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5
Q

Aminoglycosides

A
  • bactericidal
  • protein synthesis inhibitors
  • – inhibit 30S ribosomal subunit
  • ** Streptomycin ***

First drug to treat TB

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6
Q

quinolones

A

bactericidal

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7
Q

TMP-SMX

A

bactericidal

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8
Q

Protein Synthesis Inhibitors

A
  • exploit differences between BACTERIAL 70S and MAMMALIAN 80S ribosomes
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9
Q

Protein Synthesis Inhibitors

Inhibitors of 30S Ribosomal Subunit

A
  • Aminoglycosides: Streptomycin

- Tetracyclines: Doxycycline

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10
Q

Tetracycline

A
  • inhibit 30S ribosomal subunit

* ** Doxycycline ***

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11
Q

Protein Synthesis Inhibitors

Inhibitors of 50S Ribosomal Subunit

A
  • Macrolides: Erythromycin
  • Clindamycin
  • Streptogramins
  • Linezolid
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12
Q

Macrolides

A

Protein Synthesis Inhibitors
Inhibitors of 50S Ribosomal Subunit
** Erythromycin **

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13
Q

Clindamycin

A

Protein Synthesis Inhibitors

Inhibitors of 50S Ribosomal Subunit

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14
Q

Streptogramins

A

Protein Synthesis Inhibitors

Inhibitors of 50S Ribosomal Subunit

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15
Q

Linezolid

A

Protein Synthesis Inhibitors

Inhibitors of 50S Ribosomal Subunit

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16
Q

Aminoglycosides

Mechanism of Action

A
  • bind to 30S subunit and interfere with protein synthesis in 3 ways:
  • – blocks initiation
  • – blocks elongation and promotes termination
  • – promotes incorporation of incorrect amino acids: MISCODING
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17
Q

Aminoglycosides

Features

A
  • bactericidal: Gram -
  • IV: poor bioavailability
  • exhibit significant POSTANTIBIOTIC EFFEC
  • act SYNERGISTICALLY with PENICILLINS and other B-lactams
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18
Q

Postantibiotic effect

A
  • bacteria continue dying after drug is removed from system

- due to miscoding

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19
Q

Streptomycin

Clinical uses

A
  • aminoglycoside
  • 2nd line agent for treatment of TB
  • used in combination with other agents

NOT ORAL: IV or other routes

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20
Q

Aminoglycosides

Primary Adverse Reactions

A
  • ** nephrotoxic and ototoxic (ear) ***
  • due to mitochondrial effects
  • both occur when therapy is continued for >5 days
  • – USE SHORT TERM
  • nephrotoxicity: reversible
  • ototoxicity: irreversible even upon discontinuation of therapy
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21
Q

Aminoglycoside Effects

A
  • rapidly bactericidal vs many aerobic gram - bacteria

- associated with significant post-antibiotic effect

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22
Q

Tobramycin & Gentamicin Primary Clinical Indication

A
  • treatment of serious systemic infections caused by gram - organisms
  • used in combination with B-lactam
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23
Q

Amikacin Primary Clinical Indication

A
  • used in many cases of resistance to tobramycin and gentamicin caused by inactivating enzymes
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24
Q

Neomycin and Kanamycin Primary Clinical Indications

A
  • limited to topical use (skin/eyes)
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25
Q

Tetracyclines

Mechanism of Action

A
  • bind to 30S ribosomal subunit and interfere with protein synthesis
  • ** BLOCKING PEPTIDE ELONGATION ***
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26
Q

Tetracycline Effects

A
  • bacteriostatic vs. many aerobic and anaerobic gram (+) and gram (-) bacteria
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27
Q

Tetracyclines

Pharmacokinetics

A
  • similar effects
  • different t1/2
  • short t1/2 = compliance issues (inconvenient)
28
Q

Tigecycline

A
  • active against bacteria resistant to other tetracyclines

- active against MDR bacteria

29
Q

Tetracycline Clinical Indications

A
  • rickettsial infections
  • STI
  • respiratory infections
  • skin and soft tissue infections
  • infections caused by MDR bacteria (tigecycline only)
30
Q

Tetracycline Primary Toxicities

A
  • GI Disturbances: nausea, vomiting, diarrhea
  • – disrupts microbiome because so broad spec
  • Teeth and Bone: tooth discoloration, growth deformity
  • – contraindicated for children under 8 years: CA absorption effect
  • photosensitization
  • hepatotoxicity during pregnancy
31
Q

Anything good for MDR

A

not used first line

32
Q

Tetracyclines

A

very broad spec

33
Q

Macrolides

Mechanism of Action

A
  • bind to the 50S ribosomal subunit and interfere with protein synthesis
  • ** BLOCKS TRANSLOCATION STEP ***
34
Q

Macrolides Effects

A
  • bacteriostatic vs aerobic gram + and some gram - bacteria
35
Q

Telithromycin

A

active against MDR

36
Q

Macrolides

Primary Clinical Indications

A

V broad spectrum

  • respiratory infections
  • skin and soft-tissue infections
  • acute otitis media
  • strep throat
  • chlamydial infections
  • diptheria
  • pertussis
37
Q

Macrolides

Primary Adverse Reactions

A
  • GI Disturbances
  • ** Cardiac Toxicity ***
  • Hepatotoxicity
38
Q

Clindamycin

Mechanism of Action

A
  • binds 50S ribosomal subunit

- blocks ribosomal translocation step

39
Q

Clindamycin

Effects

A
  • Bacteriostatic vs. aerobic and anaerobic gram + bacteria
40
Q

Clindamycin

Primary Clinical Indications

A
  • skin and soft tissue infections

- acne cream

41
Q

Clindamycin

Primary Toxicity

A
  • diarrhea

- skin rashes

42
Q

Streptogramins

Mechanism of Actions

A
  • bind 50S ribosomal subunit
  • blocks translocation step
  • inhibits peptide elongation
43
Q

Streptogramins

Effects

A
  • active vs most gram + bacteria

- bactericidal and bacteriostatic depending on combination

44
Q

Streptogramins

Primary Clinical Indications

A
  • treatment of infections caused by VRE

- treatment of complicated skin lesions caused by MSSA

45
Q

Streptogramins

Primary Toxicity

A
  • infusion related effects of IV combination
  • Arthralgias
  • Myalgias
46
Q

Linezoid

Mechanism of Action

A
  • binds 50S ribosomal subunit

- interferes with protein synthesis by blocking the initiation step

47
Q

Linezoid

Effects

A
  • active vs aerobic and anaerobic gram + bacteria

- bacteriostatic but can also be bactericidal

48
Q

Linezoid

Primary Clinical Indications

A
  • treatment of infections caused by MDR Gram + bacteria

- – MRSA, VRE

49
Q

Linezoid

A

VRE RESISTANT

50
Q

Antifolate Drugs

A

Inhibit bacterial BIOSYNTHESIS OF NUCLEOTIDES and thus synthesis of DNA

  • sulfonamides
  • trimethoprim
  • trimethoprim-sulfonamide combination
51
Q

Sulfonamides

A

Antifolate Drugs

52
Q

Trimethoprim

A

Antifolate Drugs

53
Q

DNA Gyrase/Topo IV Inhibitors

A

Block BACTERIAL DNA REPLICATION by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV
- Fluoroquinolones

54
Q

DNA Synthesis Inhibitors

2 Functional Classes

A

1) Antifolate Drugs

2) DNA Gyrase/Topo IV Inhibitors

55
Q

Antifolate Drugs

Mechanism of Action

A
  • SMX is a competitive antagonists of dihydropteroate synthase
  • TMP is a competitive antagonist of dihydrofolate reductase
56
Q

Sulfonamides and TMP

Effects

A
  • bacteriostatic vs gram - and some gram + bacterial
57
Q

TMP-SMX

Effects

A
  • bactericidal
58
Q

TMP-SMX

A

Sulfonamide & Trimethoprim combination: changes effects

59
Q

Sulfonamides

Adverse Reactions

A

Allergies

60
Q

Sulfonamides Clinical Uses

A
  • used to treat UTIs

- rarely used as monotherapy

61
Q

TMP-SMX Clinical Uses

A
  • first choice for UTIs
    ** COMBINATION IS BACTERICIDAL **
    (bacteriostatic when administered as single agents)
62
Q

TMP-SMX Adverse Reactions

A
  • allergy
  • urticaria (hives)
  • ** ONLY USED FOR SHORT PERIOD OF TIME ***
63
Q

Fluoroquinolones

A

DNA Gyrase/Topo IV inhibitors

64
Q

Fluoroquinolones Mechanism of Actions

A
  • inhibitors of DNA gyrase in Gram - bacteria

- inhibitors of topoisomerase IV in gram + bacteria

65
Q

Fluoroquinolones

Effects

A
  • bactericidal vs both gram - and gram + bateria
66
Q

Fuoroquinolones Clinical Uses

A

broad spec

  • ANTHRAX
  • CF
  • UTI but not used first line (TMP-SMX)
67
Q

Fluoroquinolones

Adverse Reactions

A
  • generally well tolerated
  • GI disturbances
  • may damage growing carilage
  • – contraindicated for children under 18 unless CF

Pharmacology Test 3 (9 decks)

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