Types of hypersensitive reaction and drugs used for the treatment

1. HYPERSENSITIVITY
REACTIONS
By
M.ASIYABI.,M.PHARM (PHARMACOLGY)
ASST PROFESSOR
DEPARTMENT OF PHARMACY

2. HYPERSENSITIVITY REACTIONS
• Allergies Greek – “altered reactivity”
• 1906 – Von pirquet coined term:
hypersensitivity
• Hypersensitivity reactions – ‘over reaction’ of
the immune system to harmless
environmental antigens

3. THE IMMUNE SYSTEM IN HEALTH AND
DISEASE
How does your
everyday life
affect your immune
system?

4. Exercise and stress
• Exercise has been shown to boost the immune
response
• Moderate exercise increases the immune
response in all age groups
• Intensive exercise can stress the immune system
• Lack of sleep and exhaustion decrease immune
function
• Psychological stress has also been found to
decrease immune function

5. ENVIRONMENT
Exposure to certain things in their environment may
activate the immune systems of some people
• Chemicals
–dioxin • Viruses
–pesticides
–solvents • Bacteria
•Sunlight
•Medication • Food

6. Disorders of the immune system
1
•Allergy
2
•Autoimmune disease
3
•Immuno deficiency

7. Hypersensitivity Reactions
• The immune system is an integral part of
human protection against disease, but the
normally protective immune mechanisms can
sometimes cause detrimental reactions in the
host.
• Such reactions are known as Hypersensitivity
reactions, and the study of these is termed
Immunopathology.

8. Definition
• Undesirable side effect of immunity
manifesting trivial discomforts such as itching
of the skin to potentially fatal disease such as
bronchial asthma.
• Initiated by the interaction of antigen with
humoral antibody or by cell-mediated immune
mechanisms

9. Gell and Coomb’s classification
• Type I reactions
Immediate hypersensitivity reactions
• Type II reactions
Cytotoxic hypersensitivity reactions
• Type III reactions
Immune-complex reactions
• Type IV reactions
Delayed hypersensitivity reactions, cell-mediated
immunity

11. Sell et al Classification
1. Inactivation/activation antibody reactions
2. Cytotoxic or cytolytic antibody reactions
3. Immune-complex reactions
4. Allergic reactions
5. T-cell cytotoxic reactions
6. Delayed hypersensitivity reactions
7. Granulomatous reactions

12. Globally approved classification of Hypersensitivity reactions
• Type I: Immediate hypersensitivity
- onset within minutes of antigen challenge
- examples are allergies to molds, insect bites
• Type II: Cytotoxic hypersensitivity
- onset within minutes or a few hours of antigen challenge
- examples are adult hemolytic anemia and drug allergies
• Type III: Immune complex-mediated hypersensitivity
- onset usually within 2-6 hours
- examples include serum sickness and systemic lupus
erythematosus
• Type IV: Delayed Hypersensitivity
- inflammation by 2-6 hours; peaks by 24-48 hours
- examples include poison ivy and chronic asthma 14

13. Type I: Immediate hypersensitivity

14. • Rapidly developing immunologic reaction
occurring within minutes after the
combination of an antigen with antibody
bound to mast cells or basophils in individuals
previously sensitized to the antigen.
• May occur as a systemic or as a local reaction

15. Etiology
Allergic reactions
• Reactions can be elicited by various
aeroallergens (eg, pollen, animal dander),
drugs, or insect stings.
• Other possible causes are latex, drug, and
food allergy

16. Insect stings
Pollen grains

18. • Antigens (red dots) from inhaled pollen are ingested and
presented by macrophages to T cells. Activated T cells produce
cytokines leading to the production of IgE, which binds to
receptors on mast cells and causes the release of histamine,
which is responsible for allergy symptoms. Onset is usually
within minutes of contact with antigen.

19. Local symptoms
• Nose: swelling of the nasal mucosa (allergic rhinitis)
• Eyes: redness and itching of the conjunctiva (allergic
conjunctivitis)
• Airways: bronchoconstriction, wheezing, sometimes
outright attacks of asthma
• Ears: feeling of fullness, possibly pain, and impaired
hearing due to the lack of eustachian tube drainage.
• Skin: various rashes, such as eczema, hives and
contact dermatitis.
• Head: while not as common, headaches are seen in
some with environmental or chemical allergies.

20. Systemic allergic response
• Is also called anaphylaxis
• Depending of the rate of severity, it can cause
cutaneous reactions, bronchoconstriction,
edema, hypotension, coma and even death

21. Laboratory testing
• CBC
–Increased WBC – eosinophil count
•Increased serum IgE levels
–Normal values 39IU/ml
–Does not determine indicate specific antigen
•Radioallergosorbent Test (RAST)
–Determines the blood concentration of IgE
directed against a specific antigen and thus can
determine specific antigen

22. Allergy testing
• Scratch test
• Intradermal test
• Oral food challenge
• In vitro testing

23. Medications
• Decongestants
- vasoconstriction in the inflamed tissue thereby
reducing the edema
- Caution in patients with HPN, glaucoma
• Antihistamines
- blocks histamine from binding with its receptor
preventing vasodilation and capillary
permeability
- Sedation

24. Cont….
Corticosteroids
decrease inflammation by preventing the
synthesis of mediators
Nasal
Beclomethasone
Fluticasone
Oral
Prednisolone
Prednisone

25. Cont…
Mast Cell Stabilizers
Prevent mast cell membranes from opening
when allergen binds to IgE
• Cromolyn sodium
Leukotriene Inhibitors
• Zileuton
• Zafirlukast

26. Allergic Rhinoconjunctivitis
• Congestion
• Sneezing
• Itchy , runny nose and eyes;
• Itching of the palate and inner ear.
• postnasal drip, which can cause sore throat,
coughing, or throat clearing

27. Management
• Topical nasal decongestants can provide
immediate relief of nasal congestion and can
be used temporarily and as needed.
• Note: Patients should be cautioned not to use
them for more than a few days, however, as
they can cause rebound congestion (rhinitis
medicamentosa).

28. Allergic Asthma
• Bronchoconstriction
• Shortness of breath (eg, difficulty getting air
out), wheezing, cough, and/or chest tightness.
• Patients may be coughing or appear short of
breath.
• Wheezing may be present.
• Cyanosis of the lips, fingers, or toes (caused by
hypoxemia) may occur with severe asthma.

29. Management
• Therapy depends on the severity of disease.
• Salbuterol metered-dose inhaler (MDI) (or
nebulizers for young children) to use as
needed.
• Inhaled glucocorticosteroids should be added
if appropriate.
• In general, these medications are used if
symptoms occur more than twice weekly.

30. Anaphylaxis
• Most dramatic and life-threatening
• Occurs rapidly and systematically
• Affects many organs within seconds to
minutes after allergen exposure
• Not common
• Fatal

31. Symptoms
• Generalized pruritus and urticaria
• Erythema and angioedema
• Bronchoconstriction, mucosal edema and
excess mucus production
• Wheezes , crackles
• Anaphylactic shock
• Confusion and alteration of mental status can
occur.

33. Administer medications as prescribed
• Epinephrine 0.3-.05ml subq
• Antihistamines – diphenhydramine IM or IV
• Aminophylline – theophylline IV for severe
bronchospasm
• Corticosteriods – hydrocortisone, solumedrol
IV
• B2 agonists nebulization – Salbutamol,
terbutaline

34. Type II: Cytotoxic hypersensitivity

35. • Body makes special autoantibodies directed
against self-cells (antigens present on the
surface of cells or other tissue components)
• Antigen:
- May be intrinsic to the cell membrane
- May take the form of an exogenous antigen
adsorbed on the cell surface.
• Hypersensitivity results from the binding of
antibodies to normal or altered cell-surface
antigens

36. Examples
Transfusion reactions
cells from an incompatible donor react w/ the host’s antibody
Erythroblastosis fetalis
there is an antigenic difference between the mother & the
fetus, and antibodies (IgG) cross the placenta & cause
destruction of fetal red cells.
Hemolytic anemia, agranulocytosis, throbocytopenia
individuals produce antibodies to their own blood cells, w/c
are then destroyed.
Drug reactions
antibodies are produced that react w/ the drug.

37. Transfusion reactions Hemolytic anemia

38. Rh incompatibility
Occurs when the mother's blood type is Rh
negative and her fetus' blood type is Rh positive.

39. • If some of the fetus' blood passes into the
mother's blood stream, her body will produce
antibodies in response

40. Complications
• Possible complications include:
• Brain damage due to high levels of bilirubin
(kernicterus)
• Fluid buildup and swelling in the baby
(hydrops fetalis)
• Problems with mental function, movement,
hearing, speech, and seizures

41. Prevention
• Rh incompatibility is almost completely
preventable.
• Rh-negative mothers should be followed
closely by their obstetricians during
pregnancy.
• Special immune globulins, called RhoGAM, are
now used to prevent RH incompatibility in
mothers who are Rh negative

42. Two different blood groups mixed together
during blood tranfusion

43. Symptoms
The following are symptoms of ABO
incompatible transfusion reactions:
• Back pain
• Hematuria
• Feeling of "impending doom"
• Fever
• Jaundice

44. Type III hypersensitivity – immune
complex formation and deposition

45. • In sensitized individuals, allergen (antigen)
combined with antibody leads to the
formation of immune complexes, which
activate complement and the inflammatory
response.
• The location of the inflammation depends on
the location of the antigen - inhaled, under
skin, systemic.
• Onset is usually within 2-6 hours.

47. Immune complexes forming region
Generalized:
- if immune complexes are formed in the
circulation & are deposited in many organ
Localized to particular organs:
- kidney (glomerulonephritis), joints (arthritis),
- small blood vessels of the skin if the complexes
are formed and deposited locally (local Arthus
reaction
Note: wherever complexes deposit, the tissue
damage is the same

48. Arthus reaction
A dermal inflammatory reaction produced
under conditions of antibody excess, when a
second injection of antigen produces
intravascular antigen-antibody complexes
which bind complement, causing cell
clumping, endothelial damage, and vascular
necrosis

50. Examples
• Rheumatoid arthritis
• Systemic Lupus Erythematosus
• Serum sickness

51. Type IV. Cell-Mediated

52. Antigen (red dots)
are processed by
local APCs
T cells (blue cells)
that recognize
antigen are
activated and
release cytokines
Inflammatory
response
causes tissue injury.
Antigen is presented by APCs to antigen-specific
memory T cells that become activated and produce
chemicals that cause inflammatory cells to move
into the area, leading to tissue injury. Inflammation
by 2-6 hours; peaks by 24-48 hours.

53. Tuberculin reaction
The best known example of delayed-type hypersensitivity
- produced by intracutaneous injection of tuberculin
- In previously sensitized individual: reddening and
induration of the site(8-12 hours), peaks in 24-72 hours,
and thereafter slowly subside.

54. Other examples
• Transplant rejection
• Contact dermatitis
• Poison Ivy skin rashes
• Local response to insect stings

55. Stimulatory type
• Inappropriate stimulation of a normal cell surface
receptor by an autoantibody, resulting in an
continuous “turned-on” state for the cell
•Example – Graves Disease
–An autoantibody binds to
TSH receptor sites in the
thyroid gland stimulating it
to produce thyroid hormones
continually.

57. THANK YOU…..!!!