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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
Clinical uses of Penicillin G and VK
``` 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 ```
26
Penicillin Adverse Effects
Hypersensitivity (allergic reaction) 1st exposure: Sensitization 2nd exposure: Hypersensitivity reaction Symptoms resolve on stopping drug
27
Penicillin Hypersensitivity (allergic) reactions
Acute (immediate) - Type I, IgE-mediated - Usually within 1 hour of taking drug - Histamine release - Itching, urticarial - Bronchospasm - Anaphylaxis
28
Penicillin Adverse Effects
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
29
Penicillin Maculopapular Rash
More common with viral infection - EBV pharyngitis - Amoxicillin given for pharyngitis leads to maculopapular rash - MOA unknown
30
Penicillin Adverse Effects: SJS
``` 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
Penicillin Adverse Effects: SJS and TEN
``` Immune mediated drug reaction -CD8 T cells -Re-challenge with same drug can cause recurrence Antibiotic associations: -Sulfonamides (TMP-SMX) -Aminopenicillins -Cephalosporins ```
32
Penicillin Adverse Effects: Interstitial Nephritis
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
Classic Presentation of Interstitial Nephritis
``` Fever Oliguria Increased BUN/Cr Eosinophils in urine White cells and WBC casts (sterile pyuria) ```
34
High dose of Penicillin can lead to
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
Penicillin Adverse Effects: Serum Sickness
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
Penicillin Type I Reaction
Acute IgE Anaphylaxis
37
Penicillin Type II Reaction
Hemolysis, IgG
38
Penicillin Type III Reaction
``` Serum Sickness IgG Fever Urticaria Arthritis ```
39
Penicillin Type IV Reaction
T cells, Skin, Nephritis
40
Penicillin Adverse Effect: C. Difficile Infection
C. difficile growth leads to pseudomembranous colitis | May occur with any antibiotic
41
What are some common antibiotics associat3ed with C. Difficile Infection?
Penicillin Cephalosporins Clindamycin Fluoroquinolones
42
Jerisch-Herxheimer Reaction
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
Oxacillin, Nafcillin, Dicloxacillin
Antistaphylococcal Penicillins
44
How do Antistaphylococall Penicillins work
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
Antistaphylococal Penicillins are effect for
``` Staph Aureus (Non-MRSA) Most strep ```
46
What is the advantage of Antisphylococcal Penicillins
Cover same infections as Penicillin but have advanced effectiveness for staph aureus -Side chain to protect beta-lactam results in staph penicillinase resistance
47
Antistaphylococcal Penicillins
``` Oxacillin, Nafcillin, Dicloxacillin Commonly used for -Community acquired cellulitis -Impetigo Staph endocarditis based on culture data S/E similar to penicillin ```
48
Amoxicillin and Ampicillin are
Aminopenicillins
49
Amoxicillin is administered
orally
50
Ampicillin is administered
IV due to poor bioavailability with oral administration
51
How do Aminopenicillins work?
Penetrate porin channels of gram-negative bacteria
52
All penicillins are sensitive to beta lactamase enzymes except
Antistaphylococcal Penicillins (can resist staph penicillinase)
53
What is advantage of Aminopenicillins
Cover same infections as Penicillin and some gram negatives that express low amounts of beta-lactamase enzymes.
54
Aminopenicillins are effective for which bacteria?
``` 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
Main clinical uses of Aminopenicillin
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
Maculopapular rash is most common with which type of penicillin?
Aminopenicillin | -Note: Maculopapular rash is more common in viral infections
57
Maculopapular Rash Classic Case
EBV infection w/ sore throat Amoxicillin given for presumed bacterial pharyngitis Maculopapular rash
58
Which type of penicillin are SJS and TEN classically associated with?
Aminopenicillins
59
Beta-Lactamase inhibitors are often administered with aminopenicillins
Clavulanic Acid, Sulbactam, Tazobactam
60
Augmentin =
Amoxicillin + Beta-Lactamase Inhibitor
61
Unasyn =
Ampicillin + Beta-Lactamase Inhibitor
62
What does adding a beta-lactamase inhibitor to an amiinopenicillin do?
Increase activity of aminopenicillins against staph aureus and H. flu. Also increases activity against anaerobes (B. fragilis)
63
Common uses for aminopenicillin/beta-lactase inhibitor drugs
``` Otitis media/sinusitis (broad spectrum) Bite wounds (Polymicrobial with anaerobes) ```
64
Antipseudomonal Penicillins
Ticarcillin: Carboxypenicillin Piperacillin: Piperazine penicillin
65
Advantage of antipseudomonal penicillins
Have greater porin channel penetration than aminopenicillins (more gram (-) coverage) Effective against pseudomonas aeruginosa
66
Even through antipseudomonal penicillin have significant porin channel penetration, they remain susceptible to
Beta-lactamase | Administer with beta-lactamase inhibitor
67
All penicillin drugs are susceptible to Beta-lactamase except
Anti-staphylococcal drugs | Have resistance to staph penicillinase enzyme
68
Timentin =
Ticarcillin + beta-lactamase inhibitor (clavulanic acid)
69
Zosyn =
Piperacillin + taxobactam (beta-lactamase inhibitor)
70
Antipseudomonal Penicillins (Ticarcillin, Piperacillin)
Broad-spectrum antibiotics - Most gram (+) but not MRSA - More gram (-) eg. pseudomonas - Most anaerobic bacteria

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