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ID Review > B&B: Penicillins > Flashcards

B&B: Penicillins Flashcards

1
Q

Beta lactam rings are found in

A

Penicillins
Carbapenems
Aztreonam
Cephalosporins

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2
Q

3 components of penicillin

A
  1. Beta lactam ring
  2. Thiazolide Ring
  3. Side Chain (variable component)
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3
Q

Thiazolide rings are found

A

only in penicillins

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4
Q

Penicillin MOA is same as

A

MOA of all Beta lactam antibiotics

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5
Q

Bacteria are

A

constantly breaking down/remaking cell wall

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6
Q

Bacterial transpeptidases

A

Cross-link peptidoglycan in cell walls by binding to alanine residues

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7
Q

Transpeptidases are also called

A

Penicillin binding proteins

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8
Q

Transpeptidase MOA

A

Bind ala-ala residues

Link lysine-alanine residues to cross-link cell wall

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9
Q

Configuration of alanine in bacteria vs humans

A

Human: L-ala
Bacteria: D-ala

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10
Q

Peniciliin mimics

A

alanine residues (D-analyl-D-alanine)

  • inactivates transpeptidase
  • rate of cell wall breakdown becomes greater than rate of cell wall proliferation
  • result is autolysis of cell: enzymes that hydrolyze cell wall continue to work so bacteria kills itself
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11
Q

What are the two natural penicillins?

A 
Penicillin G (IM and IV)
Penicillin VK (oral)
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12
Q

Why are Penicillin G and Penicillin VK co-administered with Probenicid (gout drug)?

A

Probenicid inhibits renal secretion of penicillin so they can be co-administered to increase penicillin levels

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13
Q

Natural penicillins (Penicillin G and Penicillin VK) have a very low spectrum of activity due to

A

common bacterial resistance mechanisms

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14
Q

Modified penicillin binding proteins

A

Bacterial resistance mechanism modified by genetic mutations

-Often produced by Strep Pneumonia

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15
Q

Reduced Bacterial Cell Penetration

A

Bacterial resistance mechanism

-Bacteria decreases the number of porins they have to decrease drug penetration

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16
Q

Gram Negative Bacteria

A

Very poor bacterial cell penetration (higher resistance to penicillins)

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17
Q

Porins

A

Gram negative proteins that transport nutrients/waste

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18
Q

Beta Lactamase enzyme

A

Bacterial resistance mechanism that degrades beta lactam compounds. Used by many gram-negative bacteria and staphylococcus aureus.

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19
Q

Beta Lactamase

A

Family of bacterial enzymes that degrade beta lactam compounds:

  • Penicillin G and VK
  • Some other penicillins
  • Some cephalosporins
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20
Q

Beta Lactamase =

A

Penicillinase

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21
Q

Beta lactamase in gram negative bacteria is found in

A

Cytoplasm

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22
Q

Beta lactamase in gram positive bacteria (eg. S. Aureus)

A

There is no periplasm, so beta lactamase secreted into EC space. Generally produces more enzymes than gram negative.

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23
Q

Beta-lactamase inhibitors

A

Clavulanic Acid, Sulbactam, Tazobactum

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24
Q

Beta-lactamase inhibitors

A

Little/no effect if used alone
Added to some penicillins to expand coverage
-Aminopenicillins
-Antistaphylcoccal penicillins

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25
Q

Clinical uses of Penicillin G and VK

A 
Narrow spectrum: few specific modern uses
Gram positives:
-Strep pyrogenes (strep throat)
-Actinomyces
Treponema Pallidum (syphilis)
Rare uses (only in susceptible isolates)
-Neisseria Meningitides
-Strep Pneumonia
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26
Q

Penicillin Adverse Effects

A

Hypersensitivity (allergic reaction)
1st exposure: Sensitization
2nd exposure: Hypersensitivity reaction
Symptoms resolve on stopping drug

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27
Q

Penicillin Hypersensitivity (allergic) reactions

A

Acute (immediate)

  • Type I, IgE-mediated
  • Usually within 1 hour of taking drug
  • Histamine release
  • Itching, urticarial
  • Bronchospasm
  • Anaphylaxis
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28
Q

Penicillin Adverse Effects

A

Maculopapullar rash

  • Non-immediate reaction
  • Most common with aminopenicillins
  • Maculopapules
  • Itchy or non-pruritic
  • Absence of fever, wheezing, joint pain
  • Days or weeks after starting drug
  • Type IV (T-cell mediated) mechanism
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29
Q

Penicillin Maculopapular Rash

A

More common with viral infection

  • EBV pharyngitis
  • Amoxicillin given for pharyngitis leads to maculopapular rash
  • MOA unknown
30
Q

Penicillin Adverse Effects: SJS

A 
SJS:
-Fever, necrosis
-Sloughing of skin
-Dermal-epidermal junction
-Vesicles, blisters
Toxic epidermal necrolysis
-Severe form SJS (>30% skin)
Mortality: SJS 1-5%; TEN 25-35%
31
Q

Penicillin Adverse Effects: SJS and TEN

A 
Immune mediated drug reaction
-CD8 T cells
-Re-challenge with same drug can cause recurrence
Antibiotic associations:
-Sulfonamides (TMP-SMX)
-Aminopenicillins
-Cephalosporins
32
Q

Penicillin Adverse Effects: Interstitial Nephritis

A

Drug acts as hapten (triggers immune response in kidneys)
Hypersensitivity (allergic) reaction with complex mechanism
Considered a Type IV hypersensitivity reaction
T-cells, Mast cells

33
Q

Classic Presentation of Interstitial Nephritis

A 
Fever
Oliguria
Increased BUN/Cr
Eosinophils in urine
White cells and WBC casts (sterile pyuria)
34
Q

High dose of Penicillin can lead to

A

Extrinsic hemolytic anemia
Penicillin binds to RBC and leads to immune response (drug acts as hapten)
Antibodies against penicillin are bound to RBCs
Direct Coombs test: positive
Type II Hypersensitivity

35
Q

Penicillin Adverse Effects: Serum Sickness

A

Immune complex disorder related to IgG antibodies
Days/Weeks after exposure
Antigen-antibody complex made of Penicillin-IgG molecules will deposit in tissues and lead to complement activation
Type III hypersensitivity reaction
Urticaria, fever, arthritis, lymphadenopathy

36
Q

Penicillin Type I Reaction

A

Acute
IgE
Anaphylaxis

37
Q

Penicillin Type II Reaction

A

Hemolysis, IgG

38
Q

Penicillin Type III Reaction

A 
Serum Sickness
IgG
Fever
Urticaria
Arthritis
39
Q

Penicillin Type IV Reaction

A

T cells, Skin, Nephritis

40
Q

Penicillin Adverse Effect: C. Difficile Infection

A

C. difficile growth leads to pseudomembranous colitis

May occur with any antibiotic

41
Q

What are some common antibiotics associat3ed with C. Difficile Infection?

A

Penicillin
Cephalosporins
Clindamycin
Fluoroquinolones

42
Q

Jerisch-Herxheimer Reaction

A

Occurs with penicillin therapy for spirochete infections

  • Classically occurs in syphilis
  • Fever, chills, flushing, hyperventilation
  • Usually 2 hours after starting therapy
  • Not a hypersensitivity (allergic) reaction: Caused by immune response to bacterial cell death.
43
Q

Oxacillin, Nafcillin, Dicloxacillin

A

Antistaphylococcal Penicillins

44
Q

How do Antistaphylococall Penicillins work

A

Have side chain that prevents beta-lactam from staph penicillinase
Prototype: Methicillin no longer used b/c high frequency of adverse effects (interstitial nephritis)

45
Q

Antistaphylococal Penicillins are effect for

A 
Staph Aureus (Non-MRSA)
Most strep
46
Q

What is the advantage of Antisphylococcal Penicillins

A

Cover same infections as Penicillin but have advanced effectiveness for staph aureus
-Side chain to protect beta-lactam results in staph penicillinase resistance

47
Q

Antistaphylococcal Penicillins

A 
Oxacillin, Nafcillin, Dicloxacillin
Commonly used for
-Community  acquired cellulitis
-Impetigo
Staph endocarditis based on culture data
S/E similar to penicillin
48
Q

Amoxicillin and Ampicillin are

A

Aminopenicillins

49
Q

Amoxicillin is administered

A

orally

50
Q

Ampicillin is administered

A

IV due to poor bioavailability with oral administration

51
Q

How do Aminopenicillins work?

A

Penetrate porin channels of gram-negative bacteria

52
Q

All penicillins are sensitive to beta lactamase enzymes except

A

Antistaphylococcal Penicillins (can resist staph penicillinase)

53
Q

What is advantage of Aminopenicillins

A

Cover same infections as Penicillin and some gram negatives that express low amounts of beta-lactamase enzymes.

54
Q

Aminopenicillins are effective for which bacteria?

A 
H. Influenza (gram negative bacteria)
E. Coli
Proteus
Salmonella
Shigella
Listeria (gram positive bacteria)
-Aminopenicillins are administered with Listeria to prevent comorbid infections by gram negative bacteria
55
Q

Main clinical uses of Aminopenicillin

A

Situations where there are both gram positives and some gram negatives that are potential causes of infection

  • Otitis Media and bacterial sinusitis are often caused by strep as well as H. flu
  • Meningitis in newborns and elderly (at risk for Listeria)
56
Q

Maculopapular rash is most common with which type of penicillin?

A

Aminopenicillin

-Note: Maculopapular rash is more common in viral infections

57
Q

Maculopapular Rash Classic Case

A

EBV infection w/ sore throat
Amoxicillin given for presumed bacterial pharyngitis
Maculopapular rash

58
Q

Which type of penicillin are SJS and TEN classically associated with?

A

Aminopenicillins

59
Q

Beta-Lactamase inhibitors are often administered with aminopenicillins

A

Clavulanic Acid, Sulbactam, Tazobactam

60
Q

Augmentin =

A

Amoxicillin + Beta-Lactamase Inhibitor

61
Q

Unasyn =

A

Ampicillin + Beta-Lactamase Inhibitor

62
Q

What does adding a beta-lactamase inhibitor to an amiinopenicillin do?

A

Increase activity of aminopenicillins against staph aureus and H. flu.
Also increases activity against anaerobes (B. fragilis)

63
Q

Common uses for aminopenicillin/beta-lactase inhibitor drugs

A 
Otitis media/sinusitis (broad spectrum)
Bite wounds (Polymicrobial with anaerobes)
64
Q

Antipseudomonal Penicillins

A

Ticarcillin: Carboxypenicillin
Piperacillin: Piperazine penicillin

65
Q

Advantage of antipseudomonal penicillins

A

Have greater porin channel penetration than aminopenicillins (more gram (-) coverage)
Effective against pseudomonas aeruginosa

66
Q

Even through antipseudomonal penicillin have significant porin channel penetration, they remain susceptible to

A

Beta-lactamase

Administer with beta-lactamase inhibitor

67
Q

All penicillin drugs are susceptible to Beta-lactamase except

A

Anti-staphylococcal drugs

Have resistance to staph penicillinase enzyme

68
Q

Timentin =

A

Ticarcillin + beta-lactamase inhibitor (clavulanic acid)

69
Q

Zosyn =

A

Piperacillin + taxobactam (beta-lactamase inhibitor)

70
Q

Antipseudomonal Penicillins (Ticarcillin, Piperacillin)

A

Broad-spectrum antibiotics

  • Most gram (+) but not MRSA
  • More gram (-) eg. pseudomonas
  • Most anaerobic bacteria

ID Review (23 decks)

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