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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
Tetracyclines | Mechanism of Action
- bind to 30S ribosomal subunit and interfere with protein synthesis * ** BLOCKING PEPTIDE ELONGATION ***
26
Tetracycline Effects
- bacteriostatic vs. many aerobic and anaerobic gram (+) and gram (-) bacteria
27
Tetracyclines | Pharmacokinetics
- similar effects - different t1/2 - short t1/2 = compliance issues (inconvenient)
28
Tigecycline
- active against bacteria resistant to other tetracyclines | - active against MDR bacteria
29
Tetracycline Clinical Indications
- rickettsial infections - STI - respiratory infections - skin and soft tissue infections - infections caused by MDR bacteria (tigecycline only)
30
Tetracycline Primary Toxicities
- 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
Anything good for MDR
not used first line
32
Tetracyclines
very broad spec
33
Macrolides | Mechanism of Action
- bind to the 50S ribosomal subunit and interfere with protein synthesis * ** BLOCKS TRANSLOCATION STEP ***
34
Macrolides Effects
- bacteriostatic vs aerobic gram + and some gram - bacteria
35
Telithromycin
active against MDR
36
Macrolides | Primary Clinical Indications
V broad spectrum - respiratory infections - skin and soft-tissue infections - acute otitis media - strep throat - chlamydial infections - diptheria - pertussis
37
Macrolides | Primary Adverse Reactions
- GI Disturbances * ** Cardiac Toxicity *** - Hepatotoxicity
38
Clindamycin | Mechanism of Action
- binds 50S ribosomal subunit | - blocks ribosomal translocation step
39
Clindamycin | Effects
- Bacteriostatic vs. aerobic and anaerobic gram + bacteria
40
Clindamycin | Primary Clinical Indications
- skin and soft tissue infections | - acne cream
41
Clindamycin | Primary Toxicity
- diarrhea | - skin rashes
42
Streptogramins | Mechanism of Actions
- bind 50S ribosomal subunit - blocks translocation step - inhibits peptide elongation
43
Streptogramins | Effects
- active vs most gram + bacteria | - bactericidal and bacteriostatic depending on combination
44
Streptogramins | Primary Clinical Indications
- treatment of infections caused by VRE | - treatment of complicated skin lesions caused by MSSA
45
Streptogramins | Primary Toxicity
- infusion related effects of IV combination - Arthralgias - Myalgias
46
Linezoid | Mechanism of Action
- binds 50S ribosomal subunit | - interferes with protein synthesis by blocking the initiation step
47
Linezoid | Effects
- active vs aerobic and anaerobic gram + bacteria | - bacteriostatic but can also be bactericidal
48
Linezoid | Primary Clinical Indications
- treatment of infections caused by MDR Gram + bacteria | - -- MRSA, VRE
49
Linezoid
VRE RESISTANT
50
Antifolate Drugs
Inhibit bacterial BIOSYNTHESIS OF NUCLEOTIDES and thus synthesis of DNA - sulfonamides - trimethoprim - trimethoprim-sulfonamide combination
51
Sulfonamides
Antifolate Drugs
52
Trimethoprim
Antifolate Drugs
53
DNA Gyrase/Topo IV Inhibitors
Block BACTERIAL DNA REPLICATION by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV - Fluoroquinolones
54
DNA Synthesis Inhibitors | 2 Functional Classes
1) Antifolate Drugs | 2) DNA Gyrase/Topo IV Inhibitors
55
Antifolate Drugs | Mechanism of Action
- SMX is a competitive antagonists of dihydropteroate synthase - TMP is a competitive antagonist of dihydrofolate reductase
56
Sulfonamides and TMP | Effects
- bacteriostatic vs gram - and some gram + bacterial
57
TMP-SMX | Effects
- bactericidal
58
TMP-SMX
Sulfonamide & Trimethoprim combination: changes effects
59
Sulfonamides | Adverse Reactions
Allergies
60
Sulfonamides Clinical Uses
- used to treat UTIs | - rarely used as monotherapy
61
TMP-SMX Clinical Uses
- first choice for UTIs *** COMBINATION IS BACTERICIDAL *** (bacteriostatic when administered as single agents)
62
TMP-SMX Adverse Reactions
- allergy - urticaria (hives) * ** ONLY USED FOR SHORT PERIOD OF TIME ***
63
Fluoroquinolones
DNA Gyrase/Topo IV inhibitors
64
Fluoroquinolones Mechanism of Actions
- inhibitors of DNA gyrase in Gram - bacteria | - inhibitors of topoisomerase IV in gram + bacteria
65
Fluoroquinolones | Effects
- bactericidal vs both gram - and gram + bateria
66
Fuoroquinolones Clinical Uses
broad spec - ANTHRAX - CF - UTI but not used first line (TMP-SMX)
67
Fluoroquinolones | Adverse Reactions
- 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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