Respiratory Diseases

Allergic Rhinitis
LECTURE- 3 PHAR 514
Learning Outcomes …
By the end of the lecture, students would be able to:
- Define allergic rhinitis and its types.
- Explain pathophysiology and immune response in allergic rhinitis.
- List signs, symptoms & complications of allergic rhinitis.
- Identify management methods including pharmacological & non-
pharmacological strategies.
- Case Study
 Allergic Rhinitis
• Inflammation of nasal mucous membranes in sensitized individuals as
a result of inhalation of allergens.
• Immune response mediated by immunoglobulin E (IgE).
 Pathophysiology – Immediate response
• Inhalation of airborne allergen leads to immune response which result in
production of specific IgE (bound to mast cells).

• Within seconds to minutes: immediate hypersensitivity reaction.

• Stimulates the release of inflammatory mediators including histamine,

leukotrienes, prostaglandin, tryptase, and kinins.

• These mediators cause vasodilation, increased vascular permeability, and

production of nasal secretions.

• Histamine causes rhinorrhea, itching, sneezing, and nasal obstruction.

 Pathophysiology – Late response
• A late-phase reaction may occur 4 to 8 hours after initial allergen
exposure.

• Due to cytokine release from mast cells and T helper lymphocytes.

• This inflammatory response causes persistent chronic symptoms,

including nasal congestion.
 Clinical Presentation
1. Seasonal – hay fever
• Associated with pollens in certain seasons e.g. pollen from trees, grasses, and
weeds. Acute symptoms.

2. Persistent allergic rhinitis

• Occurs year-round in response to non-seasonal allergens e.g. dust mites, animal
dander, and molds. Seasonal allergic rhinitis who experience symptoms in the
spring are most likely allergic due to trees
 Subtle, chronic symptoms.
Many patients have a combination of both types, with symptoms year-round and
seasonal exacerbations.
In Allergic rhinitis, headache that usually appears as a symptom immediately
after exposure to an allergen
 Signs & Symptoms
• Clear rhinorrhea.
• Sneezing.
• Nasal congestion.
• Postnasal drip.
• Allergic conjunctivitis.
• Pruritic (itchy) eyes, ears, or nose.
 Complications
• Loss of smell or taste.
• Cough or hoarseness.
• Recurrent and chronic sinusitis.
• Epistaxis (nose bleeding).

 Untreated rhinitis symptoms may lead to:

- insomnia, malaise, fatigue, and poor work or school performance.
 Management
• Goals:
- Minimize or prevent symptoms
- Minimize or avoid medication side effects
- Provide economical therapy
- Maintain normal lifestyle

• Non-pharmacological strategies involve:

- Remove allergen if feasible (washing bed linen, cleaning molds, no pets)
- Avoid exposure especially if seasonal allergen (staying indoor, masks)
- Stay away from known allergens is the best way to prevent allergic rhinitis
 Pharmacological Treatment
Options include:
• Antihistamines
• Decongestants
• Nasal corticosteroids
• Cromolyn sodium
• Ipratropium bromide
• Monteulukast
• Immunotherapy
 Antihistamines - Mechanism
Act through:
1. Histamine H1-receptor antagonists (Beneficial in Certain type I allergic reactions only)
 Nonselective (first-generation or sedating antihistamines)
 Selective (second-generation or non-sedating antihistamines)
 Why sedative?

2. Anticholinergic drying effect that reduces nasal, salivary, and lacrimal gland
hypersecretion.
 Antihistamines – Dosage Forms
• Oral:
- Non-selective: Chlorpheniramine, diphenhydramine.
- Selective: Cetirizine, levocetrizine, loratadine, desloratadine,
fexofenadine (Headache possible adverse drug reactions).
• Intranasal: Azelastine (topically in the nose), olopatadine. (2nd
generation H1 antihistamine in nasal spray)
• Ophthalmic: Levocabastine, olopatadine, and bepotastine.
 Antihistamines – Side Effects
• Drowsiness is the most common side effect (interferes with daily life
activity),
 Beneficial?
 Individual variation in response to sedative effect.

• Dry mouth, difficulty voiding & constipation.

• Loss of appetite, nausea, vomiting, and epigastric distress.

 Less when medication taken with meals or a full glass of water.
 Decongestants - Mechanism

• Sympathomimetic agents.

• Alpha-adrenergic receptors agonist – act on nasal mucosa.

• Vasoconstriction, shrink swollen mucosa, and improve ventilation.

 Decongestants – Dosage forms
• Systemic (oral):
 Pseudoephedrine*.
 Phenylephrine.
 Usually combined with anti-histamines.

• Topical (intranasal): drops or sprays.

 Short-acting: Phenylephrine
 Intermediate-acting: Naphazoline & Tetrahydrozoline
 Long-acting: Oxymetazoline & Xylometazoline
 Decongestants - Precaution

• These products should be used only when absolutely necessary.

• In doses as small and infrequent as possible.
• Duration of therapy should be limited to 3 to 5 days.

 Pseudoephedrine is dispensed in limited monthly amount (behind the

counter not OTC); why?
 Pseudoephedrine is a phenethylamine.
 Component in the illegal manufacture of methamphetamine.
 Decongestants – Side effects
Oral decongestants:
• Alpha-agonists may cause a rise in blood pressure and heart rate especially
with higher doses.
• Severe hypertension if given with MAOIs.
• Slight CNS stimulation.
 Decongestants – Side effects
Topical decongestants:
• Less systemic absorption so less systemic side effects.

• Rhinitis medicamentosa (rebound vasodilation with congestion) may occur with

prolonged use of topical agents (>3–5 days).
₋ Nasal steroids could help (but take several days to work).
₋ Weaning off: by decreasing dosing frequency or concentration over several weeks.
₋ Combining the weaning process with nasal steroids may be helpful.

• Other adverse effects of topical decongestants are burning, stinging, sneezing, and
dryness of the nasal mucosa.
 Nasal Corticosteroids
• Mechanism: Reduce inflammation by:
- blocking mediator release
- suppressing neutrophil chemotaxis
- mild vasoconstriction
- inhibiting late-phase reactions

• Very effective for persistent rhinitis.

• In seasonal rhinitis, more effective when given before symptoms.
• Beclomethasone, budesonide, fluticasone, mometasone &
triamcinolone.
• Some patients improve within a few days, but peak response may
require 2 to 3 weeks.
 Nasal Corticosteroids – Side effects
• Less side effect than if used systemically.
• Side effects include:
- Sneezing
- Stinging
- Headache
- Epistaxis
- Infections with Candida albicans (rarely).
 Cromolyn Sodium
• A mast cell stabilizer – inhibits release of inflammatory
mediators including histamine.
• Available as a nonprescription nasal spray for symptomatic
prevention and treatment.
• May cause local irritation (sneezing and nasal stinging).
 Ipratropium Bromide
• Anticholinergic agent with anti-secretory effect.
• Nasal spray.
• Useful in persistent allergic rhinitis to relief rhinorrhea.
• Adverse effects are mild and include:
- Headache
- Epistaxis
- Nasal dryness
 Monteulukast
• A leukotriene receptor antagonist.

• Approved for:
- persistent allergic rhinitis - even in children > 6 months.
- seasonal allergic rhinitis - even in children > 2 years.

• Taken orally.
• Dosage form: tablets, chewable tablets or granules.

• Third-line after antihistamines & nasal corticosteroids.

 Immunotherapy
• Injecting gradual doses of antigen (allergen) to induce tolerance.
• Indicated for patients with:
1. strong history of severe symptoms
2. unsuccessful control by avoidance of allergen and pharmacotherapy
3. inability to tolerate adverse effects of drug therapy
• Contraindicated for immune compromised patients.
• Local reactions include induration and swelling at the injection site.
• More severe reactions (generalized urticaria, bronchospasm, laryngospasm,
vascular collapse, and death from anaphylaxis) occur rarely.
• Severe reactions are treated with epinephrine, antihistamines, and systemic
corticosteroids.
 Therapy Assessment

• Monitor symptoms progression.

• Medication side effects.
• Assess effect of disease on normal lifestyle.
• Seasonal allergic rhinitis cannot avoid the allergen and drug treatment with
corticosteroids, antihistamines, and/or decongestants is ineffective, then most appropriate
next step in management is desensitization immunotherapy.
 CASE-1
A 13-year-old boy presents to your pharmacy with his mother and she states he is complaining of
runny nose, itchy and watery eyes, and nasal congestion. It has been going on for one month without
relief. He is having trouble focusing in school because of his symptoms. He has no past medical
history. He lives at home with his mom, dad, and two brothers (ages 4 years and 6 months). His
mother reports he is exposed to tobacco in the home because dad smokes approximately half of a
pack/day. The family has two pets (one dog and one cat). He says he enjoys playing soccer but lately
has not felt well enough to participate.
Allergies: NKDA
Medications: None
Physical Exam/Other Studies:
Wt. 68 lb Ht 52 in T 97.6°F
Physical exam reveals positive Dennie’s lines, no purulent nasal discharge.
This patient is suffering from nasal congestion and allergic rhinitis symptoms. When asked, his
mother tells you he does know how to swallow tablets and would prefer this to a nasal spray.
In addition to an oral decongestant for his congestion, what medication would you recommend for
this patient?
Loratadine Antihistamine (nonselective: brompheniramine, chlorpheniramine, dexchlorpheniramine, carbinoxamine,
clemastine, diphenhydramine, pyrilamine, tripelennamine, promethazine, cyproheptadine,
phenindamine, azelastine; selective: loratadine, desloratadine, fexofenadine, cetirizine, levocetirizine)

Mechanism of Action Blocks H1-receptors preventing mediator release; may also decrease cellular recruitment
Contraindications/ Hypersensitivity to loratadine or any component of the formulation/Hepatic impairment, renal impairment,
Precautions pediatrics less than 2 years of age; phenylalanine is contained in some formulations

Adverse Effects Headache, sedation (at higher doses), fatigue, xerostomia, possible CNS stimulation in children
Drug Interactions Moderate substrate of the CYP2C19 isoenzyme; loratadine may increase the level of alcohol,
anticholinergics, CNS depressants; levels of loratadine may be increased by P-glycoprotein inhibitors,
pramlintide; loratadine may decrease the levels of acetylcholinesterase inhibitors, betahistine; levels of
loratadine may be decreased by acetylcholinesterase inhibitors, amphetamines, peginterferon alfa-2b, P-
glycoprotein inducers

Monitoring Allergic rhinitis symptoms

Case Notes Loratadine is the best choice for this patient because it is a nonsedating antihistamine. He should be
advised to take this medication on an empty stomach, as food may delay the peak of the drug. Patients age
6 and older should take 10 mg po daily, and pediatrics ages 2 through 5 should take 5 mg po daily. A liquid
formulation is available for this medication. Nonselective antihistamines will most likely be a cheaper
alternative, but caution should be taken when recommending them because of their side effects of
drowsiness, dizziness, and somnolence. Nonpharmacologic recommendations should also be made for this
patient (eg, limit smoke exposure in home, removal of pet dander). Diphenhydramine, a sedating
antihistamine, is an FDA-approved sleep aid.
 CASE-2
A 29-year-old pregnant woman presents to your pharmacy one week after picking up her regular prescription refills of cetirizine and
birth control. She tells you that she has just taken four pregnancy tests, all of which have come back as positive. She believes she
conceived approximately five weeks ago. She has stopped her birth control pills, but wants your advice on if she should stop her
cetirizine as well. She has an appointment to see her OB/GYN in three weeks, but wanted to speak with you because her allergies
are really bothersome this time of year and she is concerned she will not have any relief if she stops her current antihistamine.
 Allergies: NKDA
Medications: Cetirizine 10 mg tablet (OTC) 1 po daily; ethinyl estradiol/drospirenone 0.02
mg/3 mg tablet 1 po daily (stopped 1 week ago)
Physical Exam/Other Studies:
Wt 125 lb Ht 64 in BP 118/76 HR 64
You recommend this patient discontinue her medications and keep her current appointment with
her OB/GYN. However, you do know that there is a medication that is safe in pregnancy to help
her with her allergic rhinitis.
What is the best medication to treat this patient’s allergic rhinitis during her pregnancy?
Intranasal Corticosteroid Beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, mometasone, triamcinolone

Mechanism of Action Reduces inflammation by reducing mediator release, suppresses neutrophil chemotaxis, reduces intracellular edema,
causes mild vasoconstriction, and inhibits mast cell-mediated late-phase reactions

Contraindications/ Hypersensitivity/Adrenal suppression, bronchospasm, delayed wound healing, immunosuppression, Kaposi’s

Precautions sarcoma, psychiatric disturbances; refer to individual product labeling for more information on precautions

Adverse Effects Sneezing, stinging, headache, cough, epistaxis, local Candida albicans infections, and possible growth suppression
with higher bioavailability (eg, beclomethasone); nasal steroids have been found to have no significant association
with hypothalamic-pituitary axis suppression, cataract formation, glaucoma, or bone mineral density changes.

Drug Interactions Avoid use with aldesleukin, BCG, natalizumab, live vaccines, and echinacea
Monitoring Growth, signs and symptoms of HPA axis suppression/adrenal insufficiency, eosinophilic conditions

Case Notes Because the patient is suffering from nasal symptoms of allergic rhinitis, a topical intranasal steroid is the best choice
to add to his regimen. Review individual agents for dosing recommendations. Some patients may notice an
improvement in symptoms in a few days, but with others, it may take two to three weeks to see a peak effect.
Counsel patients on continued use until efficacy can be determined. To administer a nasal spray, prime the pump by
spraying until a fine mist appears. Have the patient blow his or her nose or use a nasal saline spray or wash to clear
out mucus before using the nasal corticosteroid. Shake well prior to use. Have patient tilt head slightly forward and
keep bottle upright when administering sprays. Breathe in gently through the nostril, and then breathe out through
the mouth.
Reference ….
• Pharmacotherapy handbook; Terry L. Schwinghammer, Joseph T.
DiPiro, Cecily DiPiro, Barbara G. Wells; McGraw-Hill Education, NY;
2015; 9th edition.