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Pharm > Antibacterials Pt. 2 > Flashcards

Antibacterials Pt. 2 Flashcards

1
Q 
General Mechanisms of Action
Aminoglycosides:
Tetracycline and Chloramphenicol:
Chloramphenicol:
Erythromycin and Clindamycin:
A

Aminoglycosides: Premature release of ribosome from mRNA - misreading of mRNA
Tetracycline and Chloramphenicol: Prevent tRNA from binding
Chloramphenicol: Blocks peptide bond formation
Erythromycin and Clindamycin: Block translocation step

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2
Q

Aminoglycosides

A

Gentamicin
Tobramycin
Amikacin

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3
Q

Tetracyclines

A

Doxycycline
Minocycline
Tigecycline (Glycycline)

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4
Q

Macrolides

A

Erythromycin
Clarithromycin
Azithromycin

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5
Q

Oxazilidinones

A

Linezolid

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6
Q

Aminoglycosides - General Properties
Bactericidal or Static?
Administration:
Mechanism:

A

Bactericidal
Administration: IV, IM, topical
Mechanism: Transported into bacteria by energy requiring aerobic process
- Binds to several ribosomal sites (30S/50S interface)
- Stops initiation and causes premature release of ribosome
- Causes mRNA misreading

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7
Q

Uses of Aminoglycosides

A

Primarily for gram-neg. ‘aerobic’ bacilli (Often in combination with cell wall inhibitors or quinolones) - synergism
Poor activity against anaerobes
Gram positive activity requires drug combinations
- Cell wall inhibitors enhance permeability of aminoglycosides
Use restricted to serious infections (due to side effects)

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8
Q

Why don’t you mix aminoglycosides with β-lactams in vitro?

A

Chemical reaction inactivates the aminoglycosides

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9
Q

Post antibiotic effect of aminoglycosides

A

Sustained activity for several hours after aminoglycoside concentration has dropped below effective levels
- Concentration dependent killing
Less frequent dosing
Problem: Toxicity is dose-related

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10
Q

When do you use amikacin?

A

Choice agent for gentamicin and tobramycin -resistant strains

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11
Q

Aminoglycosides side effects

A

Narrow therapeutic window
Nephrotoxicity (usually reversible)
Ototoxicity (mostly irreversible)
Nueromuscular blockade

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12
Q

Tetracyclines: Mechanism

A

Bacteriostatic
Transported into the cells by protein carrier system
Prevent attachment of aminoacyl-tRNA bind to 30S ribosomal subunits

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13
Q

Tetracycline Resistance

A

Drug efflux pump

- Resistance to one tetracycline often implies resistance to them all

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14
Q

Uses of Tetracyclines (no longer broad spectrum)

A

Preferred agents for “unusual” bugs

  • Rickettsia
  • Lyme Disease
  • Chlamydia, Mycoplasma, Ureaplasma
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15
Q

Doxycycline
Uses:
Half Life:

A

Uses: For patients with impaired renal function; alternative for PenG-sensitive syphilis and uncomplicated N. gonorrhoeae
Half Life: 24 hours

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16
Q

Minocycline
Uses:
Half Life:

A

Uses: Alternative for PenG-sensitive syphilis and uncomplicated gonorrhea
Half Life: 11-26 hours

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17
Q

Tetracyclines Administration:

What slows absorption?

A

Oral, Parenteral
Binds calcium which inhibits absorption
- Tetracycline > minocycline > doxycycline
- Do not take with high-calcium foods

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18
Q

Side effects of Tetracyclines

A 
Gastrointestinal disturbances including enterocolitis
Candida superinfection in coon
Photosensitization with rash
Teeth discoloration
- Avoid use in children <8 years old
- Contraindicated in pregnancy
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19
Q

Tigecycline (New drug class - Glycylcyclines)
Mechanism:
Resistance:

A

Mechanism: Bacteriostatic; like tetracyclines but also binds additional sites in the ribosomes
Resistance: No cross resistance with other antibacterials including tetracyclines

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20
Q

Tigecycline Uses:
Gram negatives:
Gram Positives:
Anaerobes:

A
  • Skin/Skin structure infections
  • Complicated intra-abdominal infections
  • CAP (community-acquired pneumonia)

Gram negatives: E. Coli, Citrobacter, Klebsiella, Enterobacter (NOT pseudomonas)
Gram Positives: Staphylococcus (MSSA and MRSA), Streptococcus
Anaerobes: Bacteroides, Clostridium Perfringens

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21
Q

Tigecycline
Administration:
Adverse reactions:

A

Administration: IV only (does not inhibit P450s)
Adverse reactions: Nausea, vomiting (35%), enterocolitis
- Other side effects similar to tetracylines including calcium binding
- FDA alert: increased risk of DEATH

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22
Q

Chloramphenicol
Mechanism:
Resistance:

A

Mechanism: Interferes with binding of aminoacyl-tRNA to 50S ribosomal subunit and inhibits peptide bond formation
Resistance: Acetylation by CAT (chloramphenicol transacetylase)

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23
Q

Chloramphenicol

Spectrum of activity:

A

Broad

  • Aerobes and anaerobes
  • Gram-pos. and gram-neg.
  • Including Bacteroides fragilis
24
Q

Chloramphenicol - Current Indications

A

Meningitis - alternative for those with serious cephalosporin allergy (N. Meningitidis, S. Pneumoniae)
Brain abscesses (often anaerobes)
H. Influenzae
Salmonella Typhi/Invasive salmonella infections
* Generally bacteriostatic

25
Q

Chloramphenicol - Side Effects

A

Bone Marrow Depression - Fatal aplastic anemia (1 in 30,000)
Grey baby syndrome
Optic Neuritis and Blindness
GI effects including enterocolitis

26
Q

Macrolides
Drugs:
Mechanism:

A

Drugs: Erythromycin; Clarithromycin; Azithromycin
Mechanism: Bacteriostatic - binds to 50S subunit, blocks translocation along ribosomes

27
Q

Erythromycin - Uses

A

Primarily against gram positive
- Streptococcus - Recommended for Strep. throat in penicillin-allergic patients
- Some Staph
Also effective against “unusual” or “atypical” bugs:
- Chlamydia, Mycoplasma
- Legionella (azithromycin now preferred)
- Bordetella

28
Q

Erythromycin - Side Effects

A

Nausea, vomiting (20-40%) - from enhance GI motility
Inhibits CYP3A4 metabolism/excretion of many drugs
Increases risk of arrythmias and cardiac arrest (doubles the risk on its own)

29
Q

Clarithromycin
Mechanism:
Differences from Erythromycin:

A 
Mechanism: Similar to erythromycin
Differences from Erythromycin:
- Better kinetics: less frequent dosing
- Less GI motility effects (50% less)
- Somewhat wider antibacterial spectrum
* Also some CV risk
30
Q

Clarithromycin Uses:

3 drug combo:

A 
Same as erythromycin plus:
- Haemophilus influenzae, Moraxella
- Penicillin-resistant Strep. pneumoniae
- Atypical mycobacteria
- Lycensed for Helicobacter pylori
3 drug combo: 2 antibacterials: clarithromycin + amoxicillin + acid blocker
31
Q

FDA-approved treatments for Helicobacter eradication

A

1) Clarithromycin + amoxicillin + omeprazole
2) Metronidazole + tetracyline + bismuth subsalicylate + PPI

  • combinations are more effective than single antibiotic
32
Q

Azithromycin - Uses

A
  • Very common for outpatient respiratory tract infections
  • Genital infections (chlamydia)
  • Gonorrhea (CDC recommends ceftriaxone + azithromycin or doxycycline)
33
Q

Macrolides Adverse Reactions:

A

Erythromycin > Clarithromycin > Azithromycin
Azithromycin has few effects on CYP3A4
- QT prolongation

34
Q

Clindamycin

Mechanism:

A

Binds to 50S ribosomal subunit, locks translocation along ribosomes
- Significant cause of enterocolitis

35
Q

Clindamycin Uses

A

Gram Pos. cocci (Strep and MSSA)
- NOT for enterococcus or hospital acquired MRSA
- Suppresses bacterial toxin production (Strep. and Staph.)
Many anaerobes including Bacteroides fragilis
- NOT FOR C. DIFFICILE!!

36
Q

Clindamycin side effects

A

GI irritation, Diarrhea (about 20%)
Antibiotic-associated enterocolitis (3-5%)
Hepatotoxicity

37
Q

Linezolid

Mechanism:

A

Bacteriostatic

  • Inhibits protein synthesis
  • Binds to 50S ribosomal subunit, interfering with formation of 70S initiation complex
38
Q

Linezolid Uses
Skin infections:
Nosocomial pneumonia:

A 
Gram positive spectrum
Skin infections
- VRE: vancomycin resistant Enterococcus faecium
- Staph Aureus
- Streptococcus, group. A and B
Nosocomial pneumonia
- Strep. Pneumoniae
- Staphylococcus
39
Q

Linezolid Side effects

A 
Non selective inhibitor of MAO
- Avoid foods with tyramin
- Possible drug interactions
Diarrhea, superinfection including enterocolitis
Headache, nausea/vomiting
Bone marrow suppression
40
Q

Anti-folates

Drugs:

A

Sulfonamides: Sulfamethoxazole, Sulfadiazine

Trimethoprim

41
Q

Sulfonamides

Mechanism of Action:

A

Bacteriostatic

Competitive analogs of p-aminobenzoic acid, a precursor in folate synthesis

42
Q

Sulfonamide - Uses

A

Today, most commonly used sulfonamides are combined with other antibacterials

43
Q

Which sulfonamide is used with trimethoprim and why?

A

Sulfamethoxazole (synergistic combination)

Best pharmacokinetic match to trimethoprim (proper ratio)

44
Q

Silver sulfadiazine use

A

Used topically for infection in burn patients

45
Q

Sulfonamides - Side Effects

A 
Hypersensitivity - Rashes, serum sickness (sunlight UV makes rash worse)
GI disturbances
Renal damage (crystalluria)
Potentiate action of other drugs
- Inhibit CYP2C9
46
Q

Trimethoprim

Mechanism:

A

Inhibits folate synthesis in bacteria by competitively inhibiting dihydrofolate reductase
- Dihydrofolate analog

47
Q

Trimethoprim Uses:

TMP/SMX combination:

A

Usually in combination with sulfamethoxazole:
- Synergistic effect
- 2 static drugs = 1 cidal combination
TMP/SMX combination:
- First choice therapy for uncomplicated UTIs
- Upper respiratory tract ear infections (H. influenzae, Moraxella, Strep. pneumoniae)
- GI infections (Salmonella, Shigella)
- Pneumocystis jiroveci - 1st choice treatment and prophylaxis

48
Q

TMP/SMX side effects

A

All of the other sulfonamide side effects
Trimethoprim adds:
- Nausea, vomiting, diarrhea, rashes
- Bone marrow suppression
* side effects especially pronounced with long-term use (AIDS)

49
Q 
Drug selection
Prophylactic:
Empiric:
Pathogen-directed:
Susceptibility-guided:
A

Prophylactic: Based on predominant flora at site of interest
Empiric: Which drugs have good activity against most common pathogens
Pathogen-directed: Which drugs likely target this pathogen
Susceptibility-guided: susceptibility results

50
Q

Empiric Diagnosis: Diagnostic Steps

A

1) Obtain culture/diagnostic tests
2) Empiric therapy
3) Diagnostic results - sensitivity profile
4) Modify therapy as needed
5) Cure

51
Q

Once common use of empiric therapy

A

Uncomplicated cystitis in nonpregnant women

- 1st choice: TMP-SMX

52
Q

Reasons for Antibacterial Failures

A 
Drug Choice
- Susceptibility of pathogen
- Site of infection
Host Factors
- Do abscesses need draining
- Immune response OK
- Are there foreign bodies, implants, mechanical devices, indwelling lines
53
Q

Widespread overuse of antibacterials has led to…

A
  • Large numbers of antibiotic resistant strains
  • Ever-increasing need for new drugs
  • > 50% of us carry multiply-resistant strains
54
Q

CDC 2013 - Urgent threats

A

C. Difficile
- Rapid increase in hypertoxigenic strains assoc. with antibacterial use
N. gonorrhoeae
- Ceftriaxone is the only agent left (use with either doxycycline or azithromycin)
Carbapenem-resistant Enterbacteriaceae
- Resistant to most drugs including carbapenems

55
Q

CDC 2013 - Serious threats

A 
Multi-drug resistant Acinetobacter
Multi-drug resistant Pseudomonas Aeruginosa
Drug-resistant Campylobacter
ESBL gram negs (extended-spectrum β-lactamases)
Salmonella/Salmonella Typhi
Strep Pneumoniae
VRE (Vancomycin-resistant Enterococcus)
MRSA
56
Q

Drugs for MRSA
Hospital-acquired:
Community-acquired:

A 
Hospital-acquired:
- Vancomycin
- Linezolid
- Daptomycin
- Tigecycline
Community-acquired:
- Linezolid
- Doxycycline, minocycline
- Clindamycin
- TMP-SMX

Pharm (16 decks)

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