This document discusses ocular allergies and antihistamines. It begins by explaining the role of histamines as mediators of inflammation released during allergic reactions. It then covers the different types of hypersensitivity reactions before discussing the various white blood cells involved in the immune response. The remainder of the document focuses on the types and mechanisms of action of antihistamines, both oral and topical, as well as mast cell stabilizers that are used to treat ocular allergies and their symptoms.

1. OCULAR
Antihistamines and anti-allergics
Dr Gauri Sr Shrestha
IOM, TU

2. Histamines
Histamines Mediators of inflammation, which are released by mast
cells (induced by antigens) and basophils in type I
hypersensitive reaction
Consequences in
the cells
Anaphylactic shock, rhinitis, itching, tearing, and red-
eye
Ocular tissues
having high levels of
histamine activities
Conjunctiva and Uvea > Iris and ciliary body > retina
and sclera

3. Hypersensitivity (Allergic) reactions
TYPE I
(ANAPHYLACTIC
RXN)
TYPE II (CYTOTOXIC
RXN)
TYPE III ( SYSTEMIC
IMMUNE DISEASE)
TYPE IV (CELL-
MEDIATED
IMMUNITY)
Hypersensitivity reactions are abnormal physiological conditions in
which exaggerated or uncontrolled immunologic responses occur in
response to an antigen or allergen.

5. White Blood cells (WBC)
Granulocytes Agranulocytes
Neutrophils Basophils Eosinophils Monocytes Lymphocytes
Myeloid cells Mast cells Dendritic cell
Phagocytes
Macrophages
T-cell B-cell
Helper T
cytotoxic T
Memory T
Natural killer cells
Plasma cell Memory B

6. Mast cells
Granule contents Membrane phospholipids Cytokines
Histamine
Proteases
Chemokines
e.g., IL-4,
IgE IgA IgG
adenosine, C3a,
chemokines,
cytokines, and
pathogen-associated
molecular patterns
(PAMPs), as well as
toll-like receptors
(TLRs)
Prostanoids
Leukotrienes
heparines
Phospolipase A2, Free fatty acids

7. Parameters Type of Hypersensitivity Reaction
Type I Type II Type III Type IV
Reaction Anaphylactic cytotoxic Immune complex T-cell dependent
Antigen Exogenous Cell surface Soluble Tissues and organs
Antibody IgE IgG Antigen-antibody
complex (IgG, IgM)
None
Complement involved No Yes Yes No
Cells involved Mast cells, basophils,
eosinophil
Effector cells Macrophages,
PMNs leukocytes
Macrophages, Mast
cells, Neutrophils
Antigen-specific T-cell
(monocytes and lymphocytes)
Cytokine involved Yes No Yes Yes
Comparative
description
Antibody mediated,
immediate
Antibody dependent,
complement or cell
mediated
Immune complex
mediated
T-cell mediated, delay
Response time 15 – 30 mins Min – hours 3 – 8 hours 48 – 72 hours
Mechanism of tissue
injury
Allergic and
anaphylactic
reactions
Target cell lysis, cell
mediated cytotoxicity
Immune complex
deposition,
inflammation
Inflammation, cellular
infiltration
Example Hay fever, Vernal KC,
Atopic KC, GPC,
asthma
Moore’s ulcer, myasthenia
gravis, ocular cicatricial
pemphigoid, autoimmune
diseases, Graves diseases
SLE, polyarthritis
nodosa, S-J syndrome,
disciform keratitis
Contact dermatitis, graft
rejection, phlyctenule,
interstitial keratitis, arthritis
Sympathetic ophthalmia

8. Medicine used in ocular allergies
Antihistamines
Mast-cell stabilisers
Corticosteroids
NSAIDs

9. Types and action of histamine
receptors
• Types
• H1 receptor:
• Found in nerve endings and causes itching
• An important receptor to target in ocular allergies
• Involves in the Type I hypersensitivity reaction
• H2 receptor:
• vascular tissues and causes redness
• Promotes gastric acid production and immune cells activation
• H3 receptor:
• Neurons: presynaptic feedback inhibitions,
• H4 receptor:
• Immunomodulation, inflammation, Has nociception roles
•Actions
• Symptoms:
itching, redness,
tearing, and
chemosis
• Signs:
conjunctival and
lid oedema,
dilatation of
conjunctival
vessels, and
papillary
reaction

10. Papillae versus follicles (Self reading)
Papillae
1. shows a cobblestone arrangement
of flattened nodules with central
vascular cores.
2. associated with an allergic immune
response. e.g., VKC, AKC, CL, ocular
prosthesis.
3. Contains numerous eosinophils,
lymphocytes, plasma cells, and
mast cells in the stroma
surrounding a central vascular
channel
4. Are red at the surface and pale at
the base.
Follicles
1. Shows small, dome-shaped nodules
without a prominent central vessel.
2. Associated with inflammation
associated with virus, bacteria and
toxins
3. Contains immature proliferating
lymphocytes surrounded by mature
lymphocytes and plasma cells.
4. Appears more pale on its surface
and red at its base

11. • Papillae • Follicles

12. Role of antihistamines
Block capillary
dilatation, capillary
permeability, and
associated itching
and pain.
Prevent further
histamine release
and action, do not
reverse the clinical
manifestations,
which are already
present.
Maybe helpful in
relieving
anaphylactic shock
and angioedema

13. Oral Antihistamines
1. Strongly sedating, highly lipophilic, enter
Blood-brain barrier
• Diphenhydramine, Promethazine.
2. Moderately sedating
• Clemastine, Carbinoxamine, Tripelennamine,
Trimeprazine, Azatadine.
3. Mildly sedating:
• Pyrilamine, Brompheniramine,
Chlorpheniramine, Dexchlorpheniramine,
Triprolidine, Cyproheptadine, Methdilazine
4. Nonsedating:
• Fexofenadine, Loratadine, Cetirizine
• Actions
• Affect CNS
• Anticholinergic actions (parasympatholytic
action. e.g., pupil dilatation)
• Antiemetic actions (cure motion sickness)
• Sedative action (variable)
• Indication
• More effective than topical
• Moderate to severe eyelid edema and
chemosis.
• When topical administration would be
ineffective
Generation 4, Low anticholinergics and antiemetics
Generation 1, High anticholinergics and antiemetics

14. Non-sedative antihistamines (Oral)
Properties
• Mild cholinergic-blocking properties
• Mild antiemetic properties
• Long half-life (prescribe OD or BD)
Children <2 –
4 years
Children below
2 - 6 years
Children 6 –
11 years
Children >12
years
Adult
Fexofenadine No supervised 60 mg OD 120 mg OD 180 mg OD
Loratadine supervised 2.5 mg/5ml OD 5 mg/5ml
OD
5 mg/5ml OD
– BD
10 mg OD - BD
Cetirizine

15. Non-sedative antihistamines (Oral)
• Indications
• atopic conjunctivitis (hay fever), vernal conjunctivitis, eczema, urticaria,
reactions to insect bites, food allergies
• Side effects
• dry throat and bronchi, anorexia, nausea, vomiting, diarrhea, constipation,
dysuria, palpitation
• Eye: decrease tear and mucus secretion, accommodation and vision, risk of
ACG with mydriasis
• Contraindications
• Allergy to peanuts or soya, kidney failure, epilepsy, difficulty with urination,
third trimester of pregnancy, prostate hypertrophy, peptic ulcer

16. Topical H1 Antihistamines
•Generation 1 (strong
sedative, anticholinergics
and antiemetics):
• Pheniramine maleate and
antazoline phosphate
• Available in combination with
naphazoline (adrenergic agonist-
vasoconstriction, pupil dilation,
increase blood pressure, reduce
irritation)
Antihistamine and decongestant

17. Topical H1 Antihistamine
Generation 1
• Composition:
• CHLORPHENIRAMINE
• ZINC SULPHATE-10MG
• OXETACAINE-10MG
• BORIC ACID

18. Topical H1 Antihistamines
• Generation 2 (moderate sedative, anticholinergics and antiemetics):
• Levocabastine (0.05%), emedastine (0.05%), azelastine (0.05%), ketotifen
(0.4%) and olopatadine (0.1%, BD for 3 years and above)
• Inhibit the release of histamine and other mediators from mast cells
• These drugs provide immediate relief against released histamine and prevent
the future degranulation of mast cells.
• Do not affect the α-adrenergic, dopamine, muscarinic or serotonin receptors
H1-antagonist/ mast-cell stabiliser

19. Side effects of topical H1 Antihistamines
• Burning, stinging and discomfort
• Pheniramine 0.3% with tetrahydrozoline 0.05% causes mydriasis
• Antazoline-naphazoline causes keratopathy on long-term use

20. Mast Cell Stabilisers
Controls mast cell-related systemic and ocular conditions
Drugs
Sodium cromoglycate (Cromolyn Sodium)
Lodoxamide
Nedocromil sodium
Pemiroblast

21. Cromolyn Sodium (2%, 4% solutions)
• Inhibits mast cell degranulation and the release of
mediators of allergic disease.
• Exhibit no antihistaminic activity
• Inhibit interaction of IgE with the corresponding
antigen on the mast cell surface.
• Cromolyn may also prolong the tear breakup time
in patients with chronic conjunctivitis
• It shows a lag period for 2 – 3 weeks

22. Cromolyn Sodium (2%, 4% solutions)
• Indication:
• vernal keratoconjunctivitis, allergic keratoconjunctivitis
• giant papillary conjunctivitis (less effective, but increase CL tolerance).
• Side effects:
• stinging and burning sensation, conjunctival injection, watery or itchy eyes,
dryness around the eye, puffy eyes and styes.
• Doses: 2% QID, 4% BD

23. Olopatadine
0.1% BD vs
cromolyn
sodium 2%
QID
• A comparison of the efficacy and tolerability
of olopatadine hydrochloride 0.1%
ophthalmic solution and cromolyn sodium
2% ophthalmic solution in seasonal allergic
conjunctivitis has found that Six weeks’
installation of olopatadine 0.1% ophthalmic
solution two times a day had a significantly
greater effect on the ocular signs and
symptoms of allergic conjunctivitis compared
with 6 weeks’ installation of cromolyn 2%
(sodium Cromoglycate) ophthalmic solution
4 times a day dose. Both treatments were
well tolerated by patients in all age groups;
however, olopatadine appeared to have
better local tolerability in children aged <11
years.

24. Lodoxamide (0.1%)
• Inhibits mediator release from mast cells and
eosinophil migration
• Decreases the level of leukotrienes (LTB4 & LTC4)
and other inflammatory cells.
• 2500 times more potent than cromolyn in the ability
to inhibit mediator release.
• The clinical superiority may be due to its greater
effect on CD4+ cells, which play a significant role in
the pathogenesis of VKC.
• Efficient in treating several types of allergic
conjunctivitis, including VKC.
• Side effects: discomfort, nausea (rare).

25. FDA approved Ophthalmic NSAIDs
Drug Trade name Indication Contraindication
Ketorolac
tromethamine
0.5%
Acular, Ketlur • Temporary relief from
ocular itching-related
to seasonal allergic
conjunctivitis
• Post-operative
inflammation
(cataract surgery)
• soft contact lens wearers
• Hypersensitivity
• may cause dystocia with
systemic medication (difficult
or obstructed labor)
• Lactation

26. Summary
• Primary episode of ocular allergy: antihistamine is better
• Secondary episode or prevention of allergy: Mast cell stabiliser is
better.
• Mast-cell stabilizers and antihistamines have fewer and less
dangerous adverse effects and can be used singly or in combination.
• olopatadine, ketotifen and azelastine, have a mast cell–stabilizing
effect as well as H1-antagonism

27. Thank you