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Module 7: Multisystem > Antibiotics > Flashcards

Antibiotics Flashcards

(71 cards)

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1
Q

What makes an antibiotic bacteriostatic?

A

They inhibit growth reversibly (prevents further replication)

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2
Q

What are characteristics of Ketolides?

A

Inhibitors of Translocation

First ketolide approved by FDA: Telithromycin

New family of antimicrobials structurally related to macrolides

Mechanism:
binding within exit tunnel of 50S subunit, thus blocking exit of nascent polypeptides
Strongly binds simultaneously to two domains of subunit (macrolides only bind to one)

Bactericidal or bacteriostatic depending on bacterium

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3
Q

What are the aminopenicillins?

Which is has greater oral availability?

A

Ampicillin

AmOxicillin (greater Oral availability)

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4
Q

Side effect of linezolid?

A

Bone Marrow suppression

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5
Q

Clinical use of tetracyclines?

A

Borrelia burdorferi
M. pneumonia
Rickettsia
Chlamydia

Demeclocycline- ADH agoinst acts as a Diuretic in SIADH

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6
Q

What is the clinical use of Fluoroquinolones?

A

Gm- rods of urinary and GI tracts

Pseudomonas
Neisseria

some Gm+ organisms

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7
Q

What’s the clinical use of trimethoprim?

A

SMX-TMP used for treating UTIs

Shigella
Salmonella
PCP

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8
Q

What antibiotics cause photosensitivity?

A

Sun Too Quick

Sulfonamides
Tetracyclines
Quinolones

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9
Q

How do bacteria become resistant to beta-lactam antibiotics?

A
  • Inactivation through beta-lactamases
  • Altered PBP (mecA-PBP2a)
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10
Q

What antibiotics target Formation of initiation complexes in bacteria?

A
  1. Linezolid
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11
Q

What are characteristics of Tetracyclines?

A

Inhibitors of recognition:

Broad Spectrum

Bacteriostatic

Hydrophobic

Used to Treat:
Chlamydia, Mycoplasma, Rickettsia (intracellular pathogens)
and certain G+ and G- bacterial infections

Selective Toxicity: high affinity uptake of drugs by acterial cells and increased targeting of 70S

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12
Q
A
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13
Q

What are the characteristics of aztreonam?

A

monobactam resistant to B-lactamases

Synergistic with Aminoglycosides

No cross allerginicity with penicillins

Can use in patients with renal insufficiency

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14
Q

When do bactericidal drugs have a higher efficacy than bacteriostatic?

A

When the body’s defenses are insufficient to clear the invading agents.

i.e. bacterial endocarditis, bacterial meningitis, and infections in patients with low circulating neutrophils (agranulocytopenia)

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15
Q

Clinical use of chloramphenicol?

A

Meningitis

H. influenzae
N. meningitidis
S. pneumoniae

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16
Q

What are the 3 mechanisms of action of Streptomycin?

A
  1. Misreading: at low concentrations, or in case of ribosomes engaged in elongation, we see insertion of incorrect AA
  2. Cyclic Polysomal Blockade: 70S complex forms but is unstable and falls apart; results in cell death due to inability to make proteins
  3. Faulty outer Membrane Proteins: Translational misreading results in mutant membrane proteins that cause bacterial membrane to be leaky, thus more drug is taken into cell and acts at 30S subunit
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17
Q

What organisms are not covered by Cephalosporins?

A

LAME

Listeria
Atypicals (Chlamydia, Mycoplasma)
MRSA
Enterococci

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18
Q

What are the clinical uses for 3rd Gen cephalosporins?

A

CefTriaxone, cefotaxime, ceftazidime

Serious Gm- infections resistant to other B-lactams

Ceftriaxone-meningitis and gonorrhea

Ceftazidime- Pseudomonas

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19
Q

What are the antipseudomonals?

A

Ticarcillin
Carbenicillin
Piperacillin

TCP: Takes Care of Pseudomonas

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20
Q

What is the clinical use of carbapenems?

A

Broad Spectrum

Gm+ cocci
Gm- rods
Anaerobes

GI distress, skin rash, and CNS toxicity (seizures) at high levels limit use of Imipenem to 2nd tier or life threatening infections

Meropenem has reduced risk of seizures at high plasma levels and is dihydropeptidase I resistant

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21
Q

What’s the clinical use of Clindamycin?

A

Anaerobic infections above the diaphram

Bacteroides fragilis
Clostridium perfrigens

aspiration pneumonia

S. aureus osteomyelitis

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22
Q

What’s the mechanism of Metronidazole?

A

Forms free radical toxic metabolites in the bacterial cell that damages DNA

Bactericidal, antiprotozoal

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23
Q

Clinical use of sulfonamindes

A

Gm+
Gm-

Nocardia
Chlamydia

Triple sulfas or SMX for simple UTI

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24
Q

What bacteria are treated with Streptogramins?

A

Staphylococci

Streptococci

Enterococcus faecium
(Restricted for treating vancomycin-resistant forms)

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25
What are the clinical uses for 2nd Gen cephalosporins?
cefoxitin, cefaclor, cefuroxime Gm+ cocci HEN PEcKS H. influenzae Enterobacter aerogenes Neisseria spp. Proteus mirabilis E. coli Klebsiella pneumonia Serratia marcescens
26
What's the mechanism of Trimethoprim?
inhibits bacterial dihydrofolate reductase Causes megaloblastic anemia, leukopenia, granulocytopenia (may be fixed with folic acid supplementation)
27
What are characteristics of Chloramphenicol?
An inhibitor of Peptidyl transfer: Broad Spectrum Bacteriostatic Mechanism: Binds reversibly to 50S ribosomal subunit and alters the tRNA structure blocking peptidyl transfer Selective Toxicity: Cannot enter mitochondria Does not bind to host 60S subunit Resistance: plasmid-encoded acetyltransferase that catalyze the acetylation of -OH groups; preventing 50S binding
28
What are the characteristics of Linezolid?
- Only clinically significant drug taht inhibits formation of 70S complex - First of new class of antibiotics called **oxazolidinones** - prevents formation of N-formylmethionyl-tRNA-mRNA-70S ribosomal ternary complex **Activity:** Bacteriostatic for Staphylococci and enterococci Bactocidal for Streptococci NOT approved for catheter-related blood stream, catheter-site, or gram(-) infections
29
What's the MOA mechanism of beta-lactam antibiotics?
1. Bind penicillin-binding proteins 2. Block transpeptidase cross-linking of peptidoglycan 3. Activate autolytic enzymes
30
What are the 4 steps of peptide chain synthesisn and which antibiotics target each step?
1. Recognition: - Aminoglycosides - Spectinomycin - Tetracyclines 2. Peptidyl Transfer: - Chloramphenicol - Lincomycin - Clindamycin 3. Translocation: - Macrolides - Ketolides - Streptogramins 4. Release: - None
31
What causes grey baby syndrome?
Chloramphenicol Premature neonates because they lack UDP-glucuronyl transferase, the drug builds up in the fetus, displacing bilirubin.
32
Clinical use of Aminoglycosides?
Gm- rods Neomycin for bowel surgury
33
What are Positive and Negative aspects of aminoglycoside therapy?
Positive: Rapid bactericidal effect Broad spectrum effective against *Pseudomonas* (notoriously antibiotic resistance) Negative: Resistance Ototoxicity and nephrotoxicity Antagonized by anaerobiasis low pH ineffective against intracellular bacteria induce biofilm production
34
What are the penicillinase-resistant penicillins used for clinically?
S. aureus (not MRSA) "Use naf(cillin) for staph"
35
What antibiotics are included in the family of Aminoglycosides?
Streptomycin Kanamycin Tobramycin Gentamycin Neomycin Amikacin Paramomycin
36
What are the characteristics of Aminoglycosides?
Inhibitors of activated tRNA recognition: Broad Spectrum (G+/-) Bactericidal Target specific proteins in the 30S ribosomal subunit Selective Toxicity: 1. 30S vs 40S subunit 2. actively transported into bacteria, not euks.
37
What's the clinical use of vancomycin?
Gm+ only Serious multidrug resistant organisms S. aureus Enterococci C. difficile
38
What are the B-lactamase inhibitors?
CAST Claulanic Acid Sulbactam Tazobectam Added to penicillins to prevent beta-lactamase destruction
39
What is the mechanism of Macrolides?
Not entirely clear, but likely to: 1. Prevent elongation 2. prevent release of empty tRNA 3. blockage of transpeptidation
40
Clinical use of Penicillin
Gm+ (Staph pneumoniae, pyogenes; Actinomyces) Treponema pallidum
41
What are the clinical uses for 1st Gen cephalosporins?
Cefazolin, cephalexin Gm+ Cocci PEcK Proteus mirabilis E. coli Klebsiella pneumoniae
42
What antibiotics target the amino acid activation of bacteria?
None - there are NO clinically significant inhibitors of AA activation (possibly due to the fact that prokaryotic and eukaryotic processes are so similar)
43
What are some beta-lactam antibiotics?
Penicillin (G, V) Methicillin, nafcillin, dicloxacillin (penicillinase-resistant) Ampicillin, amoxicillin (aminopenicillins) Ticarcillin, carbenicillin, piperacillin (antipseudomonals) Cephalosporins Aztreonam Carbapenem
44
How do many antibiotics specifically target bacteria, and not humans?
They target bacterial ribosomes and inhibit protein synthesis
45
What makes an antibiotic bactericidal?
They kill microorganisms rapidly
46
What are the sulfonamides?
Sulfamethoxazole (SMX) sulfisoxazole sulfadiazine PABA antimetabolites inhibit dihydropteroate synthetase
47
How do bacteria become resistant to Aminoglycosides?
1. Altered target in 30s ribosomal subunit 2. Decreased cellular uptake 3. Enzymatic modifications of the aminoglycoside (typically by enzymes coded on transposons or plasmids) Gentamicin specifically has: Potential sites for acetylation Potential sites of adenylylation or phosphorylation - both of which alter the antibiotic activity, rendering it useless
48
What is the mechanism of action of Vancomycin?
Binds D-ala, D-ala portion of cell wall precursors inhibiting mucopeptide formation Bacteriocidal
49
What are characteristics of Lincomycin and Clindamycin?
Inhibitors of Peptidyl Transferase: Narrow Spectrum Bacteriostatic Mechanism: Similar to chloramphenicol Selective Toxicity: Very effective for treatment of G+ bacterial infections Clindamycin: Very effective for staphylococcal and anaerobic G- infections Resistance: Methylation of 23S ribosomal RNA which prevents drug binding to 50S subunit
50
What are penicillinase resistant penicillins?
Methicillin Nafcillin Dicloxacillin
51
Penicillin is bactericidal for:
Gm+ cocci Gm+ rods Gm- cocci Spirochetes
52
What are characteristics of Macrolides?
Inhibitors of Translocation: Characterized by macrocyclic lactone structure Medium Spectrum Bacteriostatic Treatment: infections caused by *Mycoplasma, Legionella, Chlamydia,* and *Campylobacter* and G+ bacteria in patients allergic to penicillins Azithromycin and Clarithromyin: certain Mycobacteria
53
Clinical use of Macrolides
Atypical Pneumonias (mycoplasma, chlamydia, legionella) URIs STDs Gm+ cocci Neisseria
54
What are some broad-spectrum antibiotics?
Amoxicillin Carbapenems Piperacillin/tazobactam Fluoroquinolones Streptomycin Tetracycline Chloramphenicol
55
What's the toxicity of vancomycin?
Well tollerated in general does NOT have many problems Nephrotoxicity Ototoxicity Thrombophlebitis Redman syndrome preventable with slow infusion rate and antihistamines
56
What's the clinical use of Ticarcillin, carbenicillin, and piperacillin?
Pseudomonas spp. Gm- rods Use with beta-lactamase inhibitors
57
What are the carbapenems?
Imipenem/cilastatin Meropenem beta-lactamase resistant Cilastatin inhibits renal dehydropeptidase I and decreases inactivation of the drug in renal tubules
58
What's the clinical use of aminopenicillins?
Ampicillin, Amoxicillin HELPSS kill enterococci Extended spectrum penicillin Haemophilus influenzae E. Coli Listeria monocytogenes Proteus mirabilis Salmonella Shigella enterococci
59
What are characteristics of Streptogramins?
Inhibitors of Translocation: Class of natural cyclic peptide antibiotics produced by certain subspecies of Streptomyces Mechanisms: **Dalfopristin:** binds to 50S subunit; prevents elongation and facilitates binding of quinupristin to 50S **Quinupristin**: premature release of peptide chains from ribosome **Synercid** (quinupristin+dalfopristin) Alone = bacteriostatic Together = bactericidal
60
Clinical use of Metronidazole
GET GAP on the Metro Giardia Entamoeba Trichomonas Gardnerella Anaerobes (Bacteriodes, C. diff) H. Pylori
61
What are the protein systhesis inhibitors?
Target bacterial ribosome (70S) buy AT 30, CCEL (sell) at 50 Aminoglycosides Tetracyclines Chloramphenicol, Clindamycin Erythromycin Linezolid
62
What are characteristics of Spectinomycin?
Inhibitor of Recognition: Bacteriostatic Causes formation of unstable 70S initiation complexes (does not cause misreading or inhibit polysomal ribosomes) Exclusively for treatment of gonorrhea caused by beta-lactamase-producing gonococci or to treat gonorrhea in patients allergic to penicillins
63
What are two common antibiotics in the Macrolide family?
Azithromycin and Clarithromycin | (modified forms of erythromycin)
64
Antibiotics to avoid in pregnancy:
Clarithromycin-embryotoxic Sulfonamides-kernicterus Aminoglycosides-ototoxic Fluoroquinolones-cartilage damage Metronidazole-mutagenesis Tetracyclines-discolored teeth, bone growth problems Ribavinin-teratogen Griseofulvin-teratogen Chloramphenicol- "gray baby" Countless SAFe Moms Take Really Good Care
65
Toxicity of Sulfa drugs?
hypersensensitivity hemolysis if G6PD nephrotoxicity photosensitivity kernicterus in infants displace drugs from albumin
66
Explain the tenants of selective toxicity
Characteristics of antibiotics that reduce side-effects: - Absence of target from host - permeability differences (effective [antibiotic] is too low to cause side effects in humans) - structural differences in target
67
What bugs is Aztreonam used against?
Gm- rods only no activity against Gm+ or anaerobes
68
How do bacteria become resistant to tetracyclines?
1. Decreased uptake (often due to mutations in the OmpF porin) 2. Efflux from the bacterial cell; actively pump drug out of cell before it's able to bind to 30S ribosomal subunit 3. Elongation factor-like proteins that protect 30S subunit
69
What is the mechanism of action for tetracyclines?
Tetrcyclines bind to 30S ribosomal subunit and inhibit bindign of aa-tRNA to the A site
70
What contributes to Macrolide resistance?
1. Methylation of 23S RNA of teh 50S subunit; which prevents binding of drug 2. Hydrolysis of lactone ring by and esterase 3. Efflux of drug
71
That's the mechanism of quinolones?
-floxacins inhibit DNA gyrase (topoisomerase II) Bactericidal

Module 7: Multisystem (15 decks)

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