Allergic Rhinitis 2: Pharm Management Flashcards
AR - Antihistamines
What is Histamine?
Histamine is found in most tissues
•Higher concentration in tissues exposed to outside world (lungs, skin, GIT)
•Released from mast cells during allergic/inflammatory reactions
AR - Antihistamines
Name the 4 types of histamine receptors?
H 1 , H 2 , H 3 , and H 4
H 1 receptors are the site of action for antihistamines
AR - Antihistamines
List the histamine binding to H 1 receptors causes
- Smooth muscles to contract in the bronchi
- Dilation of blood vessels and increased permeability
- Increases heart rate and cardiac output
- Reddening of the skin, itch, wheal with a surrounding flare (hives)
AR - Antihistamines - PK
What are the effects from Antihistamines - PK
- Absorbed well from the GIT
- Peak plasma concentration achieved in 2-3 hrs
- Duration of effect varies (1st & 2nd generation)
AR - Antihistamines - 1st gen
List the effects from 1st gen
- Rapid onset but short duration of action (short T 1⁄2)
- Poorly selective for H 1 receptors
- Highly lipophilic 🡪 Penetrate readily into the brain (sedation)
- Have effects on muscarinic receptors (anticholinergic effects)
- Decrease rhinorrhea but can thicken mucus secretions
- Duration of effect varies: Chlorpheniramine maleate = 24 hrs & Diphenhydramine HCI = 12 hrs
AR - Antihistamines - 1st gen
List the side effects from 1st gen
• Anticholinergic: dry mouth and nasal passages, difficulty voiding urine, constipation, tachycardia
Note: elderly more susceptible to anticholinergic
effects
• Central H 1 receptor effects: sedation and cognitive and/or performance impairment:
- Lower work/academic performance, slowed reaction
times, decreased visual-motor coordination
- Even if taken at bedtime
• Can have paradoxical excitation in children
AR - Antihistamines - 1st gen
List the precautions from 1st gen
• Drug-Disease interactions
◦ Narrow-angle glaucoma
◦ Symptomatic prostatic hypertrophy
◦ Bladder-neck obstruction
• Drug-Drug interactions
◦ CNS depressants: alcohol, sedatives
◦ Drugs with anticholinergic side-effects: TCAs
◦ Drugs metabolized by CYP2D6 may be affected
AR - Antihistamines - 2nd gen
List the effects from 2nd gen
• Drug of choice for treatment of mild allergic rhinitis
• Rapid absorption from GIT
• Less lipophilic 🡪 limited penetration of BBB
• Highly selective for H 1 receptors
• Minimal anticholinergic effects
• Longer duration of action than 1 st generation
• All similar in efficacy
• Less effective than intranasal corticosteroids
especially for congestion:
- Desloratadine, fexofenadine, and cetirizine have shown modest improvement in congestion
AR - Antihistamines - 2nd gen
List the duration of effects from 2nd gen
- Cetirizine HCl = 12-24 hrs (schedule 1 at 20 mg strength)
- Loratidine = 24 hrs
- Desloratidine = 24 hrs
- Fexofenadine = 12-24 hrs
- Bilastine = 26 hrs (schedule 1)
- Rupatadine = 24 hrs (schedule 1)
AR - Antihistamines - 2nd gen
List the side effects from 2nd gen
• Usually well tolerated
• Less sedation, cognitive and performance impairment
compared to 1 st gen:
- Cetirizine can cause mild sedation and somnolence
in 10% of the population, especially in higher doses
• Headache, nausea, xerostomia, pharyngitis,
dyspepsia
AR - Antihistamines - 2nd gen
List the drug interactions from 2nd gen
• CNS depressants
• Drugs with anticholinergic side-effects
• Fexofenadine:
- Antacids (aluminum and magnesium containing)
- Fruit juices (apple, grapefruit, orange) may decrease
bioavailability
• Loratidine, desloratidine:
- PgP inhibitors may increase levels (erythromycin, ketoconazole)
- PgP inducers may decrease levels (carbamazapine)
- QTc prolongation with amiodarone (loratadine)
AR - Antihistamines - 2nd gen
What are the 2 new Rx drugs?
Bilastine
Rupatadine
AR - Antihistamines - 2nd gen
New Rx drugs - Bilastine info:
- H 1 receptor antagonist
- Indicated for ages 12 and over
- Available as 20 mg tab daily
- Taken on empty stomach
- Grapefruit juice can decrease bioavailability
AR - Antihistamines - 2nd gen
New Rx drugs - Rupatadine info:
• H 1 receptor antagonist
• Indicated for ages 2 and over
• Available as 10 mg tab and 1mg/ml solution daily
• Grapefruit juice can decrease metabolism
• Caution
- QTc prolongation
- Don’t use with CYP 3A4 inhibitors
AR - Intranasal Corticosteroids
1 st line therapy for ___ to ___ allergic rhinitis
moderate to severe
AR - Intranasal Corticosteroids
It’s more effective therapy than:
antihistamines, decongestants, and cromoglicate for allergic rhinitis
symptoms
AR - Intranasal Corticosteroids
How does it show effectiveness?
• Can be used prn but more effective with continuous use
• Some benefit seen in the 1 st day of therapy (after 6-8 hrs) but max effect may take 2-4 weeks
• Effective for nasal congestion, sneezing, rhinorrhea, and pruritus
• Modest effect on ocular symptoms (effect increases with long-term use)
- Mometasone furoate and fluticasone furoate are most effective for ocular symptoms
AR - Intranasal Corticosteroids
What cause it to fail?
If excessive nasal mucus secretions, may fail to reach site of action (clear secretions with
saline irrigation and then use the spray)
AR - Intranasal Corticosteroids
What are the Mechanism of Actions?
• Inhibit allergic inflammation at the nose at many levels
• Down-regulate inflammatory responses by binding to intracellular glucocorticoids receptors in inflammatory cells, causing the production of anti-inflammatory
proteins and suppressing cytokines and chemokines that promote inflammation
AR - Intranasal Corticosteroids
List the side effects
- Burning, stinging, or nose bleeds
- Case reports of nasal septal perforation (aim away from septum)
- Rare infections with Candida albicans
- Quickly metabolized once absorbed so adrenal suppression not seen at therapeutic doses
- Beclomethasone (high dose) can cause growth suppression (0.9cm after 1 year of continuous use)
AR - Intranasal Corticosteroids
List the Drugs/Sprays
- fluticasone propionate 50mcg (Flonase®) - Schedule I and II
- triamcinolone 55mcg (Nasocort®) - Schedule I and II
- beclomethasone 50mcg (Beclonase®)
- budesonide 64 or 100mcg (Rhinocort® Aqua or
Turbuhaler) - ciclesonide 50mcg (Omnaris®)
- fluticasone furoate 27.5mcg
- mometasone 50mcg (Nasonex®)
AR - Decongestants
See slide re: Allergic Cascade
- some mediators cause vasodilation of nose
- results in decreased ability to breathe
- decongestants decrease blood vessel size/vasoconstriction in nasal cavity via alpha1 agonist activity
AR - Decongestants
Describe the Oral Decongestants
- Only work for nasal congestion, no other AR symptoms
- Affect smooth muscle around the blood vessels throughout the body (vasoconstriction throughout!)
- Pseudoephedrine acts on beta 1 receptors in the heart (not ideal for patients with heart disease)
- Combination products with antihistamine available
AR - Decongestants
Describe the Oral Decongestants
• Only work for nasal congestion, no other AR
symptoms
• Affect smooth muscle around the blood vessels
throughout the body (vasoconstriction throughout!)
• Pseudoephedrine acts on beta 1 receptors in the heart
(not ideal for patients with heart disease)
• Combination products with antihistamine available
