3) Anti-Allergy Drugs

What are the common eye structures that are involved in allergy?

• eyelids

• conj

• cornea

What are allergens? What is the consequence of exposure to an allergen for the first time and reexposure?

→ initiate an allergic response in a susceptible individual

• First-time exposure - immune system forms a memory response without clinical manifestations

• Reexposure - causes rapid, exaggerated immune reaction

Differentiate between a normal immune response and a hypersensitivity reaction.

Normal Immune Response: removes an antigen via an inflammatory rxn with minimal tissue damage

Hypersensitivity (Allergic) Reaction: inappropriate, exaggerated immune response to an antigen → tissue damage

Which Hypersentivities rxn play a significant role in the pathophys of allergic eye disease?

 Types 1 & Type 4

Name the 4 types of conjunctivitis associated with an allergic response.

1. Seasonal allergic conjunctivitis (SAC)

2. Giant papillary conjunctivitis (GPC)

3. Vernal keratoconjunctivitis (VKC)

4. Atopic keratoconjunctivitis

Explain the mechanism and sequence of events involved in Type I hypersensitivity response.

1. Allergen activates B-cells → make IgE antibodies

2. IgE binds to the surface of mast cells and basophils, sensitizing them

3. Re-exposure to the allergen → Ca²⁺ influx into the mast cell

4. Ca²⁺ entry triggers phospholipase A2 leading to:

   • mast cell degranulation

   • preformed mediators (e.g., histamine, tryptase) release

   • breakdown of phospholipids → arachidonic acid

5. Arachidonic acid is metabolized via the cyclooxygenase pathway (forming prostaglandins, prostacyclin, thromboxane A) & lipoxygenase pathway (forming leukotrienes)

List the 4 common clinical signs of inflammation following a Type I hypersensitivity response.

• Mucus secretion

• Smooth muscle contraction

• Vasodilation

• ↑ vascular permeability and itching

Differentiate between the immediate and late phase allergic response.

Immediate Allergic Response

• begins 5 to 30 mins after allergen exposure

• resolves in 30 to 60 mins

Late-Phase Reaction

• Develops 4 to 6 hours after the initial response

• Lasts ~2 days

• results in severe tissue damage involving neutrophils, eosinophils, macrophages, lymphocytes, basophils & mast cells

What is histamine and the cells involved in its release as well as its common storage sites?

→ main chemical mediator involved in Type I allergic rxns

• made and released primarily by mast cells & basophils

• Storage sites: all tissues, lungs, skin, stomach, duodenum & nasal mucosa

List 4 common effects due to histamine release.

1. Smooth muscle contraction

2. Vasodilation

3. ↑ vascular permeability

4. Sensory nerve stimulation

What are the main types of histamine receptors and the type of receptors present in the eye?

1. H1

2. H2

3. H3

4. H4

-Actively involved in allergic response = H1 and H2

-Eye = H1 and H2

What is the major role of H2 Receptor?

regulates the secretory function of gastric parietal cells

What are the effects of stimulation of H1 receptors?

1. Vasodilation

2. smooth muscle contraction

3. ↑ vascular permeability

4. itching

What are 4 main ocular allergic effects of histamine?

1. Itching (due to conj nerve stimulation)

2. Tearing, chemosis, conjunctival and lid edema

3. Conj blood vessels dilation

4. Papillary reaction

What are the consequences to the eye due to topical administration or injection of histamine?

1. Hyperemia + edema in the uvea and conj

2. ↑ IOP

3. Mild pupillary constriction

4. Blood–aq barrier breakdown

What is the onset of a Type 4 immune response and the time involved in sensitization?

Onset: Delayed response appearing 12 to 72 hours after exposure, peaking at 48 to 72 hours

Sensitization time: Takes 1 to 2 weeks after 1^st exposure to the antigen

What are the major cell types involved in Type 4 response? Give the sequence of events involved.

Major cells

• T-cells

• APCs (Langerhans cells)

• Macrophages

1. Langerhans cells present the antigen to T cells, activating them (sensitization)

2. Upon reexposure, activated T cells release cytokines (interleukins, interferon)

3. Cytokines recruit and activate macrophages, inducing cytotoxic tissue destruction through enhanced phagocytosis and lytic enzymes

What are the common treatment options for allergic eye disease?

• Corticosteroids

• Dual-action agents

• Environmental allergen avoidance (pollen, dust, grass)

• Mast cell stabilizers

• NSAIDs

• Topical decongestants

• Topical/oral antihistamines

Name the 4 common ocular decongestants.

1. Phenylephrine

2. Naphazoline

3. Oxymetazoline

4. Tetrahydrozoline

What type of agent is phenylephrine? How does it act and what symptoms does it alleviate?

→ Synthetic adrenergic agonist

• 💊 Directly stimulates α-adrenergic receptors on conj blood vessels → vasoconstriction

• 💊↓ conj hyperemia and edema

What are the drawbacks of long term use of phenylephrine?

1. Rebound conj congestion

2. Conjunctivitis medicamentosa

3. Occasional pupillary dilation (even at 0.12%)

What are the advantages of other decongestants over phenylephrine?

Imidazole derivatives (naphazoline, oxymetazoline, tetrahydrozoline)

• show greater α-receptor selectivity

• Less likely to cause rebound congestion or pupillary dilation

What are the clinical uses of decongestants?

💊 Counteract histamine-induced erythema

• Naphazoline - conj inflammation

• Oxymetazoline - allergic conjunctivitis/hyperemia

• Tetrahydrozoline - allergic/chronic conjunctivitis

What are the common side effects of decongestants?

• Stinging upon instillation

• Pupillary dilation

• Blurred vision

• Epithelial erosions

• Rebound congestion

What are the main contraindications to the use of decongestants?

• CVD

• Angle-closure GLC

• DM

• Hyperthyroidism (↑TH)

• Diseased or traumatized cornea (systemic vasopressor response risk)

What are antihistamines? What are the common effects blocked by antihistamines?

→ inverse agonists that inhibit histamine’s action by blocking:

• histamine-induced capillary dilation

• ↑ capillary permeability

• itching

• pain

What are H1 antihistamines and how are they classified? Give examples and mechanism of action.

First-Generation (Sedating)

• Chlorpheniramine - Crosses the BBB to depress/stimulate the CNS → blocks muscarinic, α-adrenergic & serotonin receptors

Second-Generation (Non-sedating)

• Fexofenadine, Loratadine, Cetirizine - Lipophobic with minimal CNS penetration → selectively block H1 receptors → inhibit mast cell mediator release

Give the adverse effects of H1 antihistamines due to blockade of other receptors.

Muscarinic blockade: Dry mouth, dry eyes, urinary retention, sinus tachycardia, mydriasis, constipation.

α-Adrenergic blockade: Hypotension, dizziness, reflex tachycardia

Serotonin blockade: ↑ appetite

Cardiac I_Kr channels: Prolonged QT interval & ventricular arrhythmias

What are the advantages of 2^nd gen antihistamines » 1^st gen?

• (+) ↓/non-sedating with minimal CNS penetration

• (+) Inhibit histamine release in addition to receptor blockade

• (+) ↓ affinity for cholinergic and α-adrenergic receptors

• (+) Longer elimination t^1/2 allowing once-daily dosing

Give the common clinical uses of oral H1 antihistamines.

• Relief of nasal and conjunctival itching

• Sneezing

• Congestion

• Watery/red eyes

• Moderate-to-severe eyelid edema (angioedema)

• Chemosis

What are the ocular side effects of oral H1 antihistamines?

• ↓ Tears and mucus secretion(dry eyes)

• Mydriasis (acute angle-closure GLC risk)

• ↓ accommodation and blurred vision with prolonged use

Why should alcohol and H1 antihistamines not be taken together?

synergistic sedative actions → enhances CNS depression

What are the key clinical contraindications for H1 antihistamines?

• Hypersensitivity to individual agents

• Nursing mothers and pregnancy

• Peptic ulcer disease

• Prostatic hypertrophy

• Pyloroduodenal obstruction

• Narrow-angle GLC

Classify topical H1 antihistamines with examples. What is the advantage of second generation topicals?

1^st gen: Chlorpheniramine maleate, Antazoline phosphate

2^nd-gen: Emedastine, Azelastine, Ketotifen, Olopatadine

What is an advantage of 2^nd gen topical H1 antihistamines?

• ↑ H1 receptor selectivity w/out off-target α-adrenergic or muscarinic binding

• Have dual mast-cell stabilizing properties

What is the main application of emedastine? What concentration is used?

→ Relieves itching and redness in allergic conj within 10 mins

• Concentration: 0.05% Emadine

What are the main side effects of Topical ocular antihistamines and its contraindication?

• Stinging/burning on instillation

• mydriasis (pheniramine + tetrahydrozoline combination)

• verticillate-type keratopathy (long-term antazoline-naphazoline)

Contraindications: pt with narrow anterior chamber angles

What type of allergic response do mast cell stabilizers inhibit? How do they act?

inhibits Type I immune responses by blocks Ca²⁺ influx across mast cell membranes → prevents mast cell degranulation → mediator release

What are the main effects of lodoxamide? Compare the potency of lodoxamide to that of cromolyn sodium.

→ Inhibits mast cell degranulation, eosinophil migration, and leukotriene synthesis (LTB4, LTC4)

• Potency: Lodoxamide is 2500x more potent than cromolyn sodium

What are the common adverse effects of mast cell stabilizers?

Ocular: Stinging or burning upon instillation

Systemic: HA

Name 4 drugs with a dual antihistamine and mast-cell stabilizing effect. Give their mechanism of action.

→ Selective H1 receptor antagonism + inhibit mast cell mediator release, basophil degranulation, and eosinophil chemotaxis

1. Epinastine (Elestat)

2. Azelastine (Optivar)

3. Ketotifen (Zaditor)

4. Olopatadine (Patanol)

How does ketorolac tromethamine act to relieve allergic conjunctivitis?

Ketorolac (0.5% / Acular LS 0.4%)

• inhibits cyclooxygenase → ❌ arachidonic acid to prostaglandins conversion (this is the 1er itch-producing mediators in the conj)

What are the common contraindications to the use of NSAIDs for ocular allergy?

• Soft CL pt

• Pt w/ known sensitivity to acetylsalicylic acid or phenylacetic acid derivatives

List 3 ways by which steroids act to counter allergic response. Give an example of an approved steroid.

1. ↓ histamine levels

2. Inhibit degranulation of mast cells, basophils, and neutrophils

3. Inhibit inflammatory mediator synthesis

Approved Steroid: Loteprednol etabonate (Alrex 0.2%, Lotemax)

Write the Trade Name to Generic Name & Dosage Matching for the following:

• Clear Eyes

• Visine LR

• Visine

• Zaditor

• Alaway

• Acular LS

Clear Eyes: Naphazoline HCl 0.012%

Visine LR: Oxymetazoline HCl 0.025%

Visine: Tetrahydrozoline HCl 0.05%

Zaditor: Ketotifen fumarate 0.035%

Alaway: Ketotifen fumarate 0.035%

Acular LS: Ketorolac tromethamine 0.4%

Write the Trade Name to Generic Name & Dosage Matching for the following:

• Lastacaft

• Livostin

• Optivar

• Naphcon-A

• Vasocon-A

• Tilade / Nedocromil

• Zyrtec

Lastacaft: Alcaftadine 0.25%

Livostin: Levocabastine 0.05%

Optivar: Azelastine HCl 0.05% (BID)

Naphcon-A: Pheniramine maleate 0.3% + Naphazoline HCl 0.025%

Vasocon-A: Antazoline phosphate 0.5% + Naphazoline HCl 0.05%

Tilade / Nedocromil: Nedocromil sodium

Zyrtec: Cetirizine (5 mg or 10 mg)

Write the Trade Name to Generic Name & Dosage Matching for the following:

• Benadryl

• Bepreve

• Claritin

• Clarinex

• Crolom

• Elestat

• Emadine

Benadryl: Diphenhydramine

Bepreve: Bepotastine besilate 1.5% / etabonate 0.2%

Claritin: Loratadine (10 mg)

Clarinex: Desloratadine (5 mg)

Crolom: Cromolyn sodium 4%

Elestat: Epinastine HCl 0.05%

Emadine: Emedastine difumarate 0.05%

Write the Trade Name to Generic Name & Dosage Matching for the following:

• Alamast

• Alrex

• Allegra

• Alocril

• Alomide

Alamast: Pemirolast potassium 0.1%

Alrex: Loteprednol etabonate 0.2%

Allegra: Fexofenadine

Alocril: Nedocromil sodium 2%

Alomide: Lodoxamide tromethamine 0.1%

Write the Trade Name to Generic Name & Dosage Matching for the following:

• Patanol

• Pataday

• Pazeo

Patanol: Olopatadine HCl 0.1%

Pataday: Olopatadine HCl 0.2%

Pazeo: Olopatadine HCl 0.7%