Allergic Rhinitis Pharmacology

which drug classes are used in AR?

intranasal corticosteroids, antihistamines, decongestants, cromolyn, ipratropium, leukotriene receptor antagonists

MOA of INCS in allergic rhinitis

reduce antigen-induced hyperresponsiveness of the nasal mucosa to subsequent challenge by antigen and histamine release; target early steps in the inflammatory process, effectively blocking the allergic cascade

what do INCS have an effect on?

congestion, rhinorrhea, sneezing, nasal itching, ocular symptoms

onset of INCS

ranges from 3-5 hours to 36 hours after first dose

when is efficacy reached for INCS

after 1 week of continuous use (peak response may take up to 2-3 weeks)

T/F: all INCS preparations are comparable in efficacy

true

ADRs of INCS

HA, dryness, burning, stinging, blood-stinged secretions, epistaxis

who should avoid using INCS?

patients with nasal septum ulcers, recent nasal surgery, or trauma

what is long-term use of INCS linked to?

changes in vision, glaucoma, and cataract formation

T/F: HPA suppression is unlikely with INCS (patients with HIV may have more systemic absorption)

true

T/F: fluticasone, mometasone, triamcinolone appear to have no effect on growth suppression

true

which INCS are OTC

budesonide (Rhinocort Allergy 12+), Fluticasone propionate (Flonase ALlergy Relief 4+), fluticasone furoate (Flonase Sensimist 2+), and triamcinolone (Nasacort Allergy 24 hour 2+)

which INCS are Rx

beclomethasone (Qnasl, Qnasl Childrens 4+), flunisolide (generics 6+), fluticasone propionate (Xhance), mometasone (Nasonex 2+), ciclesonide (Omnaris 12+)

MOA of antihistamines

competitively antagonizes histamine-1 receptors to prevent receptor activation

which oral antihistamine generation is lipophilic, crosses BBB, anticholinergic effects and excessive sedation

1st generation

which oral antihistamine generation is highly selective for H1 receptors and has limited penetration into CNS

2nd generation

ADRs of 1st generation oral antihistamines

dry eyes, dry mouth, urinary retention, constipation, changes in appetite

T/F: 2nd generation OAH have more favorable SE profile but can still cause drowsiness

true

which generation OAH is not recommended for routine use in allergic rhinitis?

1st generation

caution use of 1st generation OAH in which patients?

elderly patients, use of other CNS depressants or anticholinergic agents, urinary retention issues/BPH, slowed GI motility, narrow-angle glaucoma, combination products

which medications are ethanolamines (1st gen OAH)

diphenhydramine, doxylamine

which medications are alkylamines (1st gen)

brompheniramine, chlorpheniramine

which drugs are piperazines (2nd generation)

cetirizine, levocetirizine

which drugs are piperidines (2nd generation)

fexofenadine, loratadine, and desloratadine

properties of ethanolamines

highly sedating, strong anticholinergic effects

properties of alkylamines

moderately sedating, strong anticholinergic effects, higher risk of paradoxical CNS stimulation vs. other classes

properties of piperazines

minimally to moderately sedating

properties of piperidines

nonsedating

PK considerations for 1st generation OAH

onset: 15 minutes - 1 hour

duration: 4-6 hours

PK considerations for 2nd generation OAH

onset: 1-3 hours

duration: > 24 hours

what do oral antihistamines have an effect on

minimal effect on congestion, rhinorrhea, sneezing, nasal itching, ocular symptoms

which OAH is prescription only

desloratadine (Clarinex)

brand of cetirizine

Zyrtec

brand of levocetirizine

Xyzal

brand of loratadine

Claritin

brand of fexofenadine

Allegra

PK considerations for INAH

rapid onset of action 15-30 minutes

what is the advantage of using INAH vs OAH?

more targeted delivery which allows for increased dosage to nasal tissue while limiting systemic effects

what do intranasal antihistamines have an effect on

congestion, rhinorrhea, sneezing, nasal itching

ADRs of INAH

bitter taste, epistaxis, HA, somnolence and nasal burning (taste and BID dosing may limit adherence)

T/F: INAH are equal or superior to OAH

true

which product is superior for nasal congestion, INAH or OAH

INAH

which INAH is available OTC

azelastine

which medications are INAH

azelastine, olopatadine, azelastine/fluticasone, olopatadine/mometasone

bran do azelastine/fluticasone

Dymista

brand of olopatadine/mometasone

Ryaltris

when to use ophthalmic antihistamines

relieves allergic conjunctivitis

T/F: ophthalmic antihistamines are appropriate as monotherapy or in combination with oral agents

true

ADRs of ophthalmic antihistamines

HA, blurred vision, burning/stinging of the eyes, discomfort, bitter taste, pharyngitis

what do ophthalmic antihistamines have an effect on?

ocular symptoms

which medications are ophthalmic antihistamines?

ketotifen, azelastine, olopatadine, alcaftdadine, epinastine, bepotastine, cetirizine

which ophthalmic antihistamines are available OTC

ketotifen, olopatadine, alcaftdadine

brand of ketotifen

Alaway, Zaditor

brand of olopatadine

Pataday, Pazeo

brand of alcaftdadine

Lastacaft

brand of bepotastine

Bepreve

brand of ophthalmic cetirizine

Zerviate

MOA of decongestants

sympathomimetic agents that target adrenergic receptors in the nasal mucosa to produce vasoconstriction

how can decongestants help allergic rhinitis?

reduce swollen nasal mucosa and improve ventilation (systemic and topical options)

PK of topical decongestants

rapid onset of action (within 10 minutes)

which medication should not be used for more than 3 days?

intranasal decongestants

ADRs of topical decongestants

sneezing, burning, stinging, drying of nasal mucosa

which medications are topical decongestants?

phenylephrine, naphazoline, oxymetazoline

T/F: topical decongestants are available OTC

true

which nasal decongestant does not have safety/efficacy data in children?

naphazoline

T/F: oral decongests are only used as monotherapy and are not in combination products

false

ADRs of oral decongestants

increases in BP (avoid use with MAOIs), CNS stimulation, urinary retention

which medications are oral decongestants?

pseudoephedrine and phenylephrine

brand of cromolyn

NasalCrom

when is cromolyn useful

useful for treating and preventing sinus symptoms (runny nose, stuffy nose, sneezing, itching)

MOA of cromolyn

mast cell stabilizer

ADRs of cromolyn

sneezing and nasal irritation

dosing for cromolyn

1 spray in each nostril 3-4 times daily (up to 6 times daily) in patients 2+

PK considerations for cromolyn

slow onset of action, response to treatment can take up to 1-2 weeks

what does ipratropium treat when used intranasally?

rhinorrhea

MOA of ipratropium

anticholinergic

ADRs of intranasal ipratropium

HA, nosebleeds, and nasal dryness

caution use of ipratropium in which patients?

narrow-angle glaucoma, myasthenia gravis, and bladder neck obstructions/BPH

dosing for intranasal ipratropium

2 sprays 2-4 times daily for patients 5 years and up

PK considerations for intranasal ipratropium

quick onset of action (within 15 minutes)

what can montelukast treat

symptoms of perennial and seasonal allergic rhinitis

dosing for montelukast

>/= 15 years old: 10 mg PO daily in the evening

children 6 years - 14 years: 5 mg PO daily

children 6 months-5 years: 4 mg daily (chewable tab or granule packet)

how long does it take to see the full effect of montelukast

~ 1 month

which medication is a monoclonal antibody for AR?

omalizumab (Xolair)

MOA of omalizumab

binds circulating IgE to prevent binding to mast cells

what is omalizumab approved for?

allergic asthma

what are the risks associated with omalizumab?

anaphylaxis, malignancy, acute asthma attacks, serum sickness

what is the last-line therapy for AR and typically requires specialist input prior to receiving?

omalizumab

describe immunotherapy in AR

gradual process of injecting increasing doses of allergens to induce tolerance, reserved for significant symptoms despite pharmacotherapy (expensive and considerable time commitment)

LTRA role in symptom management?

minimal resolution of congestion, rhinorrhea, sneezing, and nasal itching

what does cromolyn have an effect on?

congestion, rhinorrhea, sneezing, nasal itching

what does intranasal ipratropium have an effect on?

rhinorrhea and minimal effect on sneezing and nasal itching