Download Allergic Rhinitis

Allergic Rhinitis
Megan D. Pendley, RPh, PharmD
PPS 946
Spring 2015
Lecture Objectives
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Describe the etiology, risk factors, and pathophysiology of allergic rhinitis
Identify common presenting signs and symptoms of allergic rhinitis and distinguish
between other types of rhinitis
Discuss the pharmacology, side effects, drug interactions, and proper dosing of
commonly used medications for allergic rhinitis
Given a patient case, select an appropriate treatment regimen, monitoring
parameters and patient related consultation recommendations considering the
patient's diagnosis and unique characteristics
Assess a patient’s pharmacotherapeutic regimen for safety and efficacy using
clinical signs, symptoms and laboratory data
Counsel patients on the appropriate use of nasal preparations
Allergic Rhinitis
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IgE mediated response
Characterized by
– Sneezing
– Nasal itching
– Watery rhinorrhea
– Nasal congestion
– Itching of throat, eyes, & ears
Seasonal
Symptoms occur at predictable times of the
year (spring/fall)
Perennial
Symptoms are year-round, chronic and
subtle
Allergens: pollen from trees, grasses and
weeds
Allergens: NON seasonal antigens (dustmites, animal dander, and molds
Why do we care?
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VERY COMMON problem
6th most prevalent chronic illness in the US
20-30% of adults affected
>40% of children affected
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Many complications:
– Limited ability to perform ADLs
– Mental fatigue/ Insomnia/ Malaise
– Poor work/school performance
– Loss of smell or taste
– Chronic cough, hoarseness, vocal polyps
– Anxiety
– Depressive disorders
– Asthma (more prevalent in perennial AR)
– Sinusitis
– OM
– Nasal polyposis
– URIs
– Orthodontic problems
Predisposing Factors
• Genetics
• Allergen exposure
• Microbial exposure in early life
• Eczema
• Second hand smoke exposure
• Increased levels of IgE before 6 years of age
Nasal Physiology
Three primary functions in preparing the air for the lungs:
 Heating
 Humidifying
 Cleaning
Immediate Reaction
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Occurs within minutes
Mediators of hypersensitivity:
– Histamine
– Leukotrienes
– Prostaglandins
– Tryptase
– Kinins
Symptoms include:
Rhinorrhea
Late Phase Reaction
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Occurs in 50% of patients
4 – 8 hours after initial exposure with
symptoms peaking within 12-24 hours
Due to mast cell cytokine release
Persistent, chronic symptoms
Primarily nasal congestion
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Itching
Sneezing
Nasal obstruction
Vasodilation
↑ vascular permeability
Production of nasal secretions
Allergic Rhinitis Clinical Presentation
Symptoms:
Clear rhinorrhea
Sneezing
Nasal congestion
Post-nasal drip
Pruritic eyes, ears, nose, or palate
Physical Exam:
Allergic shiners
Transverse nasal crease
Adenoidal breathing
Pale, bluish edematous nasal turbinates coated with thin, clear secretions
Tearing and conjunctival injection and edema
Periorbital swelling
Pharyngeal “cobblestone” appearance
Diagnostic Tests:
• Nasal cytology
– Nasal secretions stained
– Eosinophils→allergic
– Neutrophils→infection
• Skin tests
– Scratch test (percutaneous)
• Make superficial wound on outermost layer of the skin
• A drop of antigen is then placed in the wound
– Intradermal
• Diluted allergen injected between layers of the skin
Common Cold
Sore throat and cough predominate
+/- Fever
Sore or scratchy throat on 1st day and is short
lived
Nasal symptoms by 2nd or 3rd day and d/c may
be purulent
Cough predominates by 4th or 5th day
Allergic Rhinitis
Congestion, rhinorrhea and itching
predominate
Fever not present
Nasal d/c thin and clear
Classic PE findings present
Pharyngeal cobblestoning
Pale, boggy nasal turbinates
Conjunctival irritation
Allergic shiners
Absence of characteristic PE findings found in
allergic rhinitis
Treatment
Goals:
– Minimize and prevent symptoms
– Maintain a normal lifestyle
Three approaches
- Allergen avoidance
- Pharmacotherapy
- Immunotherapy
Allergen Avoidance
Pollens
 Keep windows and doors closed during pollen season
 Avoid fans that draw in outside air
 Use air conditioning
 If possible, eliminate outside activities during times of high pollen counts
 Shower, shampoo, and change clothes following outdoor activity
 Use a vented dryer rather than an outside clothes line
Molds
 Use similar controls as above
 Avoid walking through uncut fields, working with compost or dry soil, and raking leaves
 Clean indoor moldy surfaces
 Fix all water leaks in home
 Reduce indoor humidity to <50% if possible
House dust mites
 Encase mattresses, pillows, and box springs in an allergen-impermeable cover
 Wash bedding in hot water weekly
 Remove stuffed toys from bedroom
 Minimize carpet use and upholstered furniture
 Reduce indoor humidity to <50% if possible
Animal allergens (if removal of pets not acceptable)
 Keep pet out of patient’s bedroom
 Isolate pet from carpet and upholstered furniture
 Wash pet weekly
Cockroaches
 Keep food and garbage in tightly closed containers
 Take out garbage regularly
 Clean up dirty dishes promptly
 Use roach traps
Other recommendations
 Do not allow smoking around the patient, in the patient’s home, or in the family car
 Minimize the use of wood burning stoves and fireplaces
Pharmacotherapy
Nasal Steroids (See Nasal Steroid Chart provided on Bb)
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Best choice for perennial rhinitis and good for seasonal when used in advance of symptomatic season
The most effective single maintenance therapy for allergic rhinitis and causes few side effects
Particularly useful for predominant nasal congestion
 Produces significantly greater relief of nasal blockage, nasal discharge, sneezing, nasal itch,
post-nasal drip, and total nasal symptoms than oral antihistamines
Considered 1st line therapy in those with “significant enough” symptoms to seek medical treatment
MOA:
 Binds to glucocorticoid receptors in inflammatory cells
 ↓ inflammation by decreasing mediator release
 ↓ neutrophil infiltration
 ↓intracellular edema, causing mild vasoconstriction
 Inhibits mast cell mediated late-phase reactions
 All agents are equally efficacious.
 Peak response 2-3 weeks
 HPA Axis issues in children---o Limited to no effect on HPA axis and growth in children
o Agents dosed once daily preferred
o Agents approved for children ≥ 2 years of age:
 Fluticasone furoate (Veramyst®)
 Mometasone (Nasonex®)
 Triamcinolone (Nasacort AQ)
o Additive effects of intranasal steroids with other glucocorticoid preparations
 Effects on IOP and BMD---- Insignificant data to estimate risk for effects on bone mineral density and
intraocular pressure, but may be reasonable to inform patients if they have concerns
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Side effects:
o Sneezing, stinging, HA, epistaxis, drying of nasal mucosa, concern with local infection with
Candida (rare)
Administration
o Start with max dose for age and taper down to lowest effective dose that controls symptoms
(usually done at weekly intervals once symptoms are controlled)
o Benefits may not be seen for a few days with peak responses observed in 2-3 weeks
o May use decongestant 1st to open up nasal passages, then use nasal steroid
o Avoid sneezing or blowing nose for at least 10 minutes after administering
How to administer the nasal spray
o Shake well
o Prime (if first time use or more than a week since last use)
o Patient can use nasal saline to clean the nose if mucous crusting is present
o Hold one nostril closed
o Tuck chin slightly with head slightly downward
o In opposite nose, place spray tip just inside nose, direct away from septum, and while breathing in
actuate spray and sniff slightly
o Breathe out through mouth
o If using 2 sprays, repeat the above then switch to the other nostril and repeat above
Antihistamines: General Information
 H-1 receptor antagonists- bind to H1 receptors preventing histamine binding and action
 Available in oral, ophthalmic and intranasal dosage forms
 Oral antihistamines are most commonly used
 Agents are more effective in PREVENTING the actions of histamine than in reversing these
actions once they have taken place (better at preventing symptoms than reversing them once they
start)
o Most effective when taken about 1-2 hours before anticipated exposure to allergen
 Reversal of symptoms primarily due to anticholinergic effects:
o Drying effect
o Antagonize the increase in capillary hyperpermeability, wheal and flare formation, and
itching
o Effective at reducing itching, sneezing, and rhinorrhea, with LESS impact on nasal
congestion
o Considered less effective than intranasal corticosteroids (INCS) at symptom control
o In general, these agents are used in combination with INCS for symptom control or alone
when symptoms are predictable and intermittent
Antihistamines
First Generation
Adult
Child
Diphenhydramine
25-50 mg q6-8h
5 mg/kg/day q6-8h
Second Generation
Adult
Child
Cetirizine
5-10 mg qd
6-12 mos: 2.5mg qd
12-23 mos: 2.5 mg qd-bid
2-5 yr: 2.5-5 mg qd
**Fexofenadine
(sometimes
called 3rd
generation)
60mg bid OR
180mg qd
6 mos - <2 yr: 15mg bid
2-11 yrs: 30 mg bid
**Desloratadine
(sometimes
called 3rd
generation)
Loratadine
5mg qd
6-11 mos: 1mg qd
1-5 yrs: 1.25 mg qd
6-11 yrs: 2.5 mg qd
10mg qd
2-5 yrs: 5mg qd
(up to 25 mg/dose)
Chlorpheniramine
IR: 4mg q4-6h
SR: 8-12mg q812h
IR: 2-6 yo: 1mg q4-6h (do
not exceed 6 mg in 24 hr)
IR: 6-12 yo: 2mg q4-6h
(do not exceed 12 mg/day)
SR: 6-12 yo: 8 mg HS
Hydroxyzine
(Rx)
25mg 3-4x/day
2mg/kg/day div q6-8 hrs
Brompheniramine
See Box Label
(dose varies
with brand)
ER: 6-16mg
q12h
IR: 4-8mg 3-4
x/day
See Box Label
(dose varies with brand)
Carbinoxamine
(Karbinal ER®,
Palgic ®,
Arbinoxa®)
(Rx)
ER: 2-<4yo: 3-4mg q12h
4-<6yo: 3-8mg q12h
6-<12: 6-12mg q12h
IR: 2-<6yo 1-2mg 3-4
x/day
6-<12yo: 2-4mg 3-4
x/day
First Generation Information:
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Non-selective
High incidence of CNS effects, primarily sedation and has been implicated in several MVAs, including
several fatal accidents, impaired work and school performance
Use prohibited in many states for transportation workers
Can cause paradoxical agitation in young children
Significant anticholinergic side effects, therefore use with caution in:
o ↑ IOP
o Hyperthyroidism
o Cardiovascular disease
Place in therapy:
o Considered 2nd line compared with the 2nd generation antihistamines
o OK for mild-moderate intermittent symptoms
o Symptoms primarily at night interfering with sleep
o Patients who have significant cost issues
o Patients who can stand a little sedation (i.e. not transportation workers, etc)
o Not ideal in the elderly and in children
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COMBO PRODUCT!! Hydrocodone/Chlorpheneramine (TussiCaps®, Tussionex Pennkinetic ER®,
Vituz ®)----available as 5-4mg and 10-8mg ER Capsule, 10-8mg/5mL controlled release liquid; 54mg/5mL Solution.
Second Generation Information
 Peripherally selective
 Non-sedating (at least less sedating than the 1st generation)
 Little or no CNS effects
 Very few anticholinergic effects
 Tend to be longer acting and are thus dosed once or twice daily
 Oral preparations are all equally efficacious
 Oral preparations – all are similarly efficacious
o Loratidine, cetirizine
o Fexofenadine, desloratidine, levocetirizine – “3rd generation”
 Topical preparations:
o Olopatadine, azelastine
 Place in therapy:
o Considered 1st line among the antihistamines
o OK for mild-moderate intermittent –persistent symptoms
o Best choice for most patients including children and elderly and those who cannot tolerate
sedation
o Good for patients in whom cost not an issue (more of a concern for prescription products)
Intranasal antihistamines
 Azelastine (Astelin®, Astepro®)
 COMBO Product: Azelastine/Fluticasone (Dymista®)
o Nasal route is an alternative to switching to another oral route if oral agents have not been
effective
 Pros:
o Produces rapid effects
o Good for nonallergic rhinitis as well as the allergic type
o Good for predominately nasal symptoms (sneezing, postnasal drip, congestion, rhinorrhea)
 Cons:
o Bitter taste in ~20% of patients
o Significant drying effects, headache and decreased efficacy over time
o Systemic absorption ~40% so can cause drowsiness
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Additional option for intranasal preparations: Olopatadine (Patanase®) – 2 sprays each nostril bid
Ophthalmic antihistamines
 Used for predominately ocular symptoms (allergic conjunctivitis)
 Rx: Azelastine (Optivar®): 1 gtt to each affected eye bid
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Rx: Olopatadine (Patanol®): 1 gtt to each affected eye bid @ intervals of 6-8 hours
OTC: Visine® Allergy (naphazoline/ pheniramine)
 Contains both an antihistamine and ocular decongestant
 1-2 gtts in affected eye(s) 3-4 times daily
 Caution with glaucoma and other eye disorders
 May cause pupillary enlargement
Decongestants
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Sympathomimetic agents that act on adrenergic receptors in the nasal mucosa, producing vasoconstriction
Shrink swollen mucosa
Improve ventilation
Good in combination with antihistamines
Decongestants
Topical
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Systemic
Applied directly to swollen nasal mucosa
via drops or sprays
Results in little to no systemic absorption
Available OTC (↓$)
Rapid onset of relief
Side effects:
o Burning, stinging
o Sneezing, nasal dryness
o Rhinitis medicamentosa (rebound
vasodilation) – associated with use
beyond 3-5 days
Place in therapy:
o NOT for routine use
o Good for prn occasional congestion
relief
Counseling points
o No more than3-5 days of use (less
is better)
o Use as small a dose as possible as
infrequently as possible and only
when absolutely necessary
Short Acting
Phenylephrine HCl
(Neosynephrine®)
1-2 sprays/ drops
each nostril q4h
prn
Lasts up to 4 hours
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Not as effective on an immediate basis as the
topical agents but the effects sometimes last
longer and cause less local irritation
Rhinitis medicamentosa NOT a problem
Side effects:
o Mild CNS stimulation
o Insomnia, irritability, HA
o Stroke a concern in those with HTN
&/or vasospasm
o Elevates BP
o Heart palpitations
o Tremor, nervousness
o Contraindicated in those taking
MAOIs
Caution in those with:
o Closed angle glaucoma
o Cardiovascular or cerebrovascular
disease
o Hyperthyroidism
o Bladder neck obstruction
Place in therapy:
o Alone for occasional nasal congestion
o In combination with antihistamines for
relief of rhinitis symptoms where
congestion is a predominant problem
Intermediate
Acting
Naphazoline
(Privine®)
Tetrahydrozoline
(Tyzine®)Rx
Long Acting
Oxymetazoline
(Afrin®)
1-2 sprays/ drops
each nostril q6h
prn
Pseudoephedrine
2-5 yrs: 15mg q4-6h
6-12 yrs: 30mg q4-6h
Adults: IR: 30-60mg q4-6h
SR: 120mg q12h OR
240mg q24h
Phenylephrine
2-6 yrs: 1.8-3.75 mg q12h
6-12yrs: 10 mg q4h
Adults: 10-20 mg q4h
Both last up to 4-6
hours
2-4 drops or 3-4
sprays q3-4h prn
2-3 sprays each
nostril bid
Lasts up to 12
hours
Cromolyn sodium (Nasalcrom®)
 MOA: mast cell stabilizer
o Inhibits allergen triggered mast cell degranulation and release of mediators (including histamine)
o Has no DIRECT antihistaminic, anticholinergic or anti-inflammatory properties
 Available OTC
 Dose: Adults and children > 2yo: 1 spray each nostril 3-4x/day spaced about q4-6h
 Side effects: sneezing, irritation, nasal stinging
 Pearls:
o For greatest efficacy, must cover entire nasal lining
o Blow nose before administering
o Dosing really should be spaced q6h to maintain effect
 Efficacy:
o less effective than nasal steroids or second generation antihistamines
o most effective for allergic rhinitis when initiated just prior to the allergy season, rather than after
symptoms have begun
 Place in therapy:
o Blocks symptoms associated with the immediate and late phase nasal allergen challenge and is
effective in doing so even when used shortly before allergen inhalation. This makes cromolyn
particularly useful for individuals who experience episodic symptoms to allergens, such as a
cat, where it may be used 30 minutes prior to exposure
o Used most commonly in pediatric patients with mild allergic rhinitis whose parents wish to avoid
nasal steroids
Montelukast (Singulair®)
 Nasal congestion in experimental allergic rhinitis correlates best with with leukotriene C4 (LTC4) levels,
whereas sneezing and nasal itching correlate with histamine levels
 1st leukotriene receptor antagonist approved for the treatment of seasonal allergic rhinitis
 Inhibits inflammatory mediator release from mast cells
 Dose:
o Adults: 10 mg once daily in the evening
o 12 – 23 months: 4 mg (oral granules) once daily, in the evening
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Place in therapy:
o Less effective than nasal steroids
o In combo with 2nd generation antihistamine: better than any agent alone
o Usually reserved for patients who have epistaxis or intolerance to nasal steroids or azelastine
o Also useful in people with concomitant asthma (kill two birds with one stone) and in patients who
also have nasal polyposis
Ipratropium bromide
 Anticholinergic nasal spray
 Exhibits drying properties, therefore most effective for symptoms of rhinorrhea
 Dose: 2 sprays each nostril 2-3 times per day
 Side effects: HA, epistaxis, nasal dryness
 Caution in glaucoma and BPH
 Place in therapy:
o not recommended as a first-line drug in allergic rhinitis, but sometimes useful in children or
adults who have profuse rhinorrhea not otherwise controlled with topical nasal steroids, a
complaint most commonly observed in adult patients with concomitant allergic and nonallergic
(or vasomotor) rhinitis.
Adjunct Therapy
 Nasal Saline therapy
o Useful with mild symptoms, or for use before using other topical medications
o Commonly performed once or twice daily, or as needed
Immunotherapy (“Allergy shots”)
 $$$$ and very time consuming
 Patients must commit to the time it requires to do this
 Slow gradual process of injecting increasing doses of antigen responsible for allergic symptoms in the
hope of inducing tolerance
 Several proposed mechanisms:
o Induces IgG antibodies
o Decreases specific IgE
o Decreases recruitment of effector cells
o Altered T cell cytokine balance
o T cell anergy
o Induction of regulatory T cells
 Start with very dilute solutions 1-2 x/week then increase concentration until max tolerated dose is
achieved and continue
 Immunotherapy usually done for 3-5 years
 Best in people with:
o Strong h/o severe symptoms unsuccessfully controlled by avoidance and PTX
o Patients with strong propensity for the development of asthma (allergy shots may postpone the
onset or prevent it altogether)
o Intolerable side effects to most pharmacotherapy
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Side effects:
o Mild local skin reactions: induration and swelling @ injection site
o Generalized urticaria, bronchospasm, laryngospasm, and vascular collapse (rare)
o Death from anaphylaxis
o Treat with epi, antihistamines, and systemic steroids if occurs
Avoid immunotherapy in:
o Those unable to tolerate anaphylactic type reaction (usually those with severe, brittle, systemic
steroid dependant asthmatics)
o Unstable cardiovascular disease
o Those on significant doses of beta blockers
o Immunocompromise
o h/o nonadherence to PTX treatment
Summary points:
 In most pediatric and adult patients, allergic rhinitis is a persistent condition that requires ongoing therapy
over a period of years. The current approach to management combines allergen avoidance and
pharmacologic therapy, with allergen immunotherapy added for refractory or severe cases.
 The patient’s specific triggers should be determined whenever possible, either by history or by specific
allergy testing. Patients whose symptoms are severe or refractory to pharmacotherapy should be referred
to an allergy specialist.
 Intranasal steroids are the most effective single therapy for allergic rhinitis in most patients with
significant or persistent symptoms