Penicillin Allergy

References
• Laurence L Brunton, John S. Lazo, Keith L Parker,
Goodman&Gilman’s the pharmalogical basis of therapeutics
11th ed, 2006
• Abbas AK, Lichtman AH. Cellular and Molecular Immunology,
5th ed, 2003
• http://www.webmd.com/allergies/tc/penicillin-allergy-topic-
overview Last Updated: July 07, 2009
 Penicillin Allergy: Overview

• Penicillin antibiotics are the most common

cause of drug allergies
• An allergic reaction that occurs when your
body’s immune system overreacts to penicillin
antibiotics
• The most common adverse effects noted with
the penicillins
 Penicillin Allergy: Overview

• may occur with any dosage form of penicillin.

• Allergy to one penicillin exposes the patient to
a greater risk of reaction if another is given.
• However, the occurrence of an untoward
effect does not necessarily imply repetition on
subsequent exposures.
Manifestations of allergy to penicillins
Frequency
Anaphylaxis
Low
Stevens-Johnson
syndrome
Exfoliative dermatitis
Serum Sickness
Vasculitis
Brochospasm
Fever
Urticarial rash
High
Maculo-papular rash
Manifestations of allergy to penicillins

Anaphylaxis
Stevens-Johnson • Sudden, severe
syndrome hypotension
Exfoliative dermatitis • Brochoconstriction
Serum Sickness
Vasculitis
Brochospasm
Fever
Urticarial rash Sudden Death !!!
Maculo-papular rash
Manifestations of allergy to penicillins

Anaphylaxis
Stevens-Johnson
syndrome
Exfoliative dermatitis
Serum Sickness
Vasculitis
Brochospasm
Fever
Urticarial rash เป็ นผื่นมากจนทำให้ เกิดลอกทังตั
้ ว

Maculo-papular rash
Manifestations of allergy to penicillins

Anaphylaxis
Stevens-Johnson
syndrome
Exfoliative dermatitis
Serum Sickness
Vasculitis
Brochospasm
Fever
Urticarial rash ผิวหนังอักเสบ

Maculo-papular rash
Manifestations of allergy to penicillins

Anaphylaxis
Stevens-Johnson
syndrome
Exfoliative dermatitis
Serum Sickness
Vasculitis
Brochospasm
Fever
Urticarial rash ผื่นลมพิษ

Maculo-papular rash
Manifestations of allergy to penicillins

Anaphylaxis
Stevens-Johnson
syndrome
Exfoliative dermatitis
Serum Sickness
Vasculitis
Brochospasm
Fever
ผื่นแดง, ตุม่ นูนแดง
Urticarial rash
Maculo-papular rash
Manifestations of allergy to penicillins

Anaphylaxis The most serious

Stevens-Johnson hypersensitivity reactions
syndrome • Anaphylaxis
Exfoliative dermatitis • Angioedema (หนังตา, ปากบวม)
Serum Sickness
Vasculitis
Brochospasm
Fever
Urticarial rash
Maculo-papular rash
 Mechanism of penicillin allergy
Penicillin
Penicillin
Break down Isomers
Covalent bond
tissue&
plasma proteins
Hapten Carrier Complex

Hapten = Low molecular weight

substances that are able to produce
an allergic response
•By themselves they are unable to
induce antibody formation.

Immune
Response
Table1: Classification of Penicillin Reactions

Classification Time of onset Mediators Clinical Signs

1. Early Reaction

•Type I 15-30 mins IgE mediated •Anaphylaxis

Hypersensitivity •Angioedema
•Urticaria
•Type II Varies min to IgG, complement •Hemolytic anemia
Hypersensitivity hour •Granulocytopenia
•Type III Varies, 4-8 hr occasionally
is observed immune •Serum Sickness
IgG, IgM in
Hypersensitivity pharmacists, nurses,complexes
and physicians •Vasculitis
2. Late Reaction who prepare penicillin solutions
•Type IV 24-72 hr Cytokines Contact dermatitis
Hypersensitivity activate Tc cells
causing direct
cellular damage
•Idiopathic Usually >72 Maculopapular
hrs rash
 Type I:Immediate/Anaphylactic Hypersensitivity
Hapten
Carrier
Complex

ปฏิกิริยาภูมิแพ้ เฉียบพลันเรี ยกว่า

Anaphylaxis ซึง่ มีอาการ
• ลมพิษ
• ความดันโลหิตต่ำ
• คัน
• Angioedema
 Type II: Antibody-dependent cytotoxic Hypersensitivity
IgG IgM
3 mechanism
1. Opsonization/ Phagocytosis
2. Antibody dependent cell cytotoxicity
Penicillin (ADCC)
Isomers Covalent 1. Classical Complement Pathway
bond
tissue&
Plasma
proteins

Hapten Carrier Complex

Destruction of affected cell/tissues
• Soluble antigens โดยเฉพาะเซลล์ เม็ดเลือดทำให้ เกิด
that can attach to • Immune hemolytic anemia (เม็ดเลือดแดงแตก)
cell membranes
•Thrombocytopenia (เกล็ดเลือดต่ำ)
•Granulocytopenia (เม็ดเลือดขาวต่ำ)
Type III: Immune complex mediated hypersensitivity

IgG IgM
 Type III: Immune complex mediated hypersensitivity

1. Complement activation Neutrophil

(Classical Pathway) recruitment

Immune Complex
deposited 2. Activation of neutrophil/ Destructive enzymes
in BV cell wall, Phagocytosis Tissue And reactive oxygen
tissues damage species

Histamine
3. Activation of mast cell by
Leukotriene
immune complex&by c3a,
c5a (anaphylatoxin) Vasodilation

4. Activation of platelet Microthrombi

Tissue Necrosis
 Type III: Immune complex mediated hypersensitivity

1. Complement activation
(Classical Pathway)

Immune Complex
deposited 2. Activation of neutrophil/
in BV cell wall, Phagocytosis Tissue
tissues
อาการแพ้ ยา penicillin
damage • Serum Sickness
• Vasculitis
• Fever
3. Activation of mast cell by • Rash
immune complex&by c3a,
c5a (anaphylatoxin)

4. Activation of platelet
 Management of drug allergy
• Identify most likely drugs (based on history).
• Avoidance of identified drug or suspected drugs is essential.
• Perform allergy skin tests (if available).
• Avoid potential cross-reacting drugs (e.g. avoid Cephalosporins in penicillin-
allergic individuals).
• Use alternative medications, if at all possible.
• Desensitize to implicated drug, if this drug is deemed essential.(เริ่ มให้ จาก dose ต่ำๆภาย
ใต้ การดูแลของแพทย์)