Allergic Rhinitis

Rhinitis

inflammation of the nasal mucous membrane with one or more of the following: nasal congestion, rhinorrhea (runny nose), sneezing, and itching.
There are several types of _____ including nonallergic ____ and occupational _____, and allergic ____.

Allergic rhinitis

Rhinitis caused by a mucous membrane exposure to inhaled allergenic materials that elicit a specific response mediated by IgE

Seasonal allergic rhinitis

allergic rhinitis that occurs in response to specific allergens present at predictable times of the year

Perennial allergic rhinitis

allergic rhinitis that occurs year round

Episodic allergic rhinitis

allergic rhinitis that occurs by sporadic exposures to allergens that are not usually en- countered in the patient's indoor or outdoor environment (e.g., visiting a home with pets when the patient has no pet exposure in their own home or work environment)

Allergic conjunctivitis

inflammation of the conjunctiva that is medicated by IgE and is associated with itching, erythema (i.e., redness), and tearing

Conjuctiva

i. The outer layer of the eye (which is a thin epithelium)
ii. A thin, transparent mucous membrane that lines the eyelids and covers the visible part of the eye
iii. Functions to lubricate the eye by secreting oils and mucus

Allergen

A protein that elicits an allergic response

Seasonal Allergic Rhinitis Allergens include:

i. Tree pollens (spring)
ii. Grass pollens (late spring-early summer)
iii. Weed pollens (late summer-early fall)

Perennial Allergic Rhinitis Allergens

i. Mold spores
ii. House dust mite fecal proteins
iii. Animal dander
iv. Cockroaches

Tree pollen allergen (season)

(Season): Spring

Grass pollen allergen (season)

(Season): Late Spring - Early Summer

Weed pollen allergen (season)

(Season): Late Summer - Early Fall

Risk factors for allergic rhinitis

a. Family history of atopy
b. Higher Socioeconomic classes
c. Higher serum IgE levels (>100 IU/mL) before age six
d. Positive allergy skin prick test

Atopy

state of hypersensitivity to an allergen

IgE

Antibody present on the surface of basophils.
Results in release of histamine and heparin during allergic and inflammatory reactions.

Most Common Causes of Drug-Induced Rhinitis

a. Ace inhibitors
b. ?-receptor antagonists
c. Phosphodiesterase-5 selective inhibitors

Nose

i. Provides airway for respiration
ii. Moistens and warms entering air
iii. Filters and cleans inspired air
iv. Serves as a resonating chamber for speech
v. Houses the olfactory (smell receptors)

Nasal Cavity:

i. Lies posterior to the external nose
ii. Comprises large surface area lined by an epithelial mucous membrane

Mucous Membrane

i. Consists of an epithelium (sheet of cells)
ii. Supported by an underlying layer of connective tissue
iii. Coated with viscous fluid (mucus) secreted by either goblet cells strewn throughout the epithelium and/or underlying mucous glands

Serous glands:

i. Resident to the nasal cavity
ii. Release watery fluid containing lysosome (chemically destroys bacteria)

Nasal mucosa

i. Continuous with pharynx, larynx

Paranasal sinuses:

a. Air filled spaces located within the bones of the face
Continuous with the nasal cavity and produce mucus and fluids that drain into the nasal cavity.

Nasal turbinates

(also called nasal conchae) extend the length of the nasal cavity and can increase the mucosal surface area when they become engorged with blood.

As a consequence of increased blood flow, ___________ swell and reduce the airflow through the nose causing nasal congestion.

the conchae (turbinates)

hypersensitivity reaction (general definition)

An immune response in itself, if excessive or aberrant, that can also cause tissue injury and disease

Hypersensitivity reaction (mechanism

Upon subsequent exposure to allergen, the allergen binds to and cross-links the IgE molecules. This event causes mast cells and basophils, to rapidly release the contents of their secretory vesicles, a process called degranulation, as well as to synthesiz

histamine (term)

(function): causes vasodilation, increased vascular permeability (edema), and the transient contraction of smooth muscle;

proteases (term)

(function): causes damage to local tissues

prostaglandins (term)

(function): arachidonic acid metabolite that causes
vascular dilation;

leukotrienes (term)

(function): arachidonic acid metabolite that stimulates prolonged smooth muscle contraction; and

cytokines (term)

(function): induce local inflammation, and stimulate the recruitment of immune cells (eosinophils, neutrophils, and TH2 cells).

Histamine often causes the following symptoms associated with allergic rhinitis:

-rhinorrhea
-itching & sneezing
-nasal congestion, redness, heat

rhinorrhea results from:

reflexive stimulation of the parasympathetic nervous system leading to secretion of mucus from mucous glands,

itching and sneezing result from:

histamine stimulation of H1 receptors on sensory nerve endings, and

nasal congestion, redness, heat result from:

submucosal edema and engorgement of the nasal turbinates as a result of vasodilation and increased vascular permeability of the blood vessels in the nasal cavity.

Conjunctivitis is associated with

redness of the eyes due to vasodilation of the peripheral small blood vessels.

In patients with allergic rhinitis, an abnormally large number of helper _______ differentiate into ______,

T cells, TH2 Cells

Eosinophils

IgE-mediated WBC present in increased numbers during an allergic reaction
Release chemical mediators that promote the migration of additional immune cells to the site, as well as chemicals that are destructive to epithelial tissues.

TH2 cell role

stimulate mast cell- and eosinophil-mediated immunity, as well as the secretion of mucus

____is central to allergic rhinitis by binding to and activating histamine-1 (H1) receptors.

histamine

IgE allergen tests are indicated in patients to:

-provide an allergic basis for the patient's symptoms
-to confirm suspected causes of the patient's symptoms
-to assess the sensitivity to a specific allergen for avoidance measures and/or allergen immunotherapy

Epicutaneous skin test

[Diagnostic Tes]: (aka scratch or prick test)
? Performed by making a superficial wound in the outermost layer of the skin. Then a drop of antigen is placed in the wound and allowed to diffuse into the underlying skin.
? Fastest and least expensive screen

Intradermal skin test

[Diagnostic Test]:
? Performed by injecting diluted allergen between the layers of the skin
? Useful in patients who have negative epicutaneous tests, but who are suspected of having an allergic etiology for their symptoms
? A positive test produces a whe

Radioallergosorbent test (RAST)

[Diagnostic Test]:
? In vitro assay that is more expensive and less sensitive than skin tests
? Useful when skin test extracts are not available, when negative controls produce a reaction, when antihistamine therapy cannot be discontinued, or in the prese

Allergic Rhinitis Complications Include:

-inability to sleep
-fatigue
-poor work or school efficiency
-post nasal drip with cough
-loss of smell or taste
-high arched, V-shaped palate due to chronic edema and venous stasis (blood pooling in veins)
-permanent transverse crease across the lower pa

Goals of therapy for allergic rhinitis

Minimize or prevent symptoms.
Minimize side effects of medications.
Maintain a normal lifestyle, including participating in outdoor activities, yard work, and playing with pets as desired.

Nonpharmacologic therapy typically consists of: (summary)

identifying triggers and avoiding triggers when practical

Nonpharmacologic patient counseling includes the following:

Identify triggers and avoid triggers when practical
Mold growth can be reduced by maintaining household humidity below 50% and removing obvious growth with bleach or disinfectant.
Exposure to dust mites can be reduced by encasing mattresses and pillows wi

Why is intranasal drug delivery advantageous?

Nasal tissue is the site of allergic rhinitis
Intranasal drug delivery minimizes systemic drug exposure. >Drug does not distribute into and affect the rest of the body nearly to the same extent as oral delivery (often translates into fewer adverse effects

Counseling points for intranasal drug delivery:

Nasal passages should be cleared prior to administration (i.e., blow your nose before using this drug).
Avoid clearing nasal passage for about 10 minutes after administration (i.e., don't blow your nose right away after using this drug).
Direct the spray

Imumunotehrapy:

Slow, gradual process of injecting increasing doses of antigens responsible for eliciting allergic symptoms in a patient with the hope of increasing tolerance to the allergen when natural exposure occurs.

Immunotherapy diminishes ______ production, increases _____ production, changes T-lymphocytes, reduces inflammatory mediator release from sensitized cells, and diminishes tissue responsiveness.

IgE, IgG

In general, very dilute solutions are given _____ times per week. The concentration is increased until the maximum tolerated dose is achieved. This maintenance dose is continued every ______ weeks, depending on clinical response.

1-2, 2-6

Adverse effects of immunotherapy include:

Mild local reactions (e.g., induration and swelling at the site of the injection), generalized urticaria, bronchospasm, laryngospasm, vascular collapse, and anaphylactic reactions.

When patients use the term "antihistamine" they are nearly always referring to ____ receptor antagonists

H1

H1 receptors

histamine receptors responsible for allergic symptoms

H2 receptors

Located in stomach
Stimulation results in secretion of hydrochloric acid

Antihistamines block histamine from activating H1 receptors, and preventmost of the effects of histamine on _______.

smooth muscle

H1 receptor antagonists also block muscarinic acetylcholine receptors, producing:

anticholinergic" effects (i.e., dry mouth and eyes, blurry vision, urinary retention, constipation

Second Generation Oral Antihistamines

Acrivastine/Pseudoephedrine (Semprex-D�) (Rx)
Cetirizine (Zyrtec�) (OTC)
Levocetirizine (Xyzal�) (Rx)
Fexofenadine (Allegra�) (OTC)
Loratadine (Claritin�) (OTC)
Desloratadine (Clarinex�) (Rx)

First Generation Oral Antihistamines

Brompheniramine (Dimetapp�) (OTC)
Chlorpheniramine (Chlor-Trimeton�) (OTC)
Carbinoxamine (Arbinoxa�, Palgic�) (Rx)
Clemastine (Tavist�) (Rx, OTC)
Cyproheptadine (Periactin�) (Rx)
Diphenhydramine (Benadryl�) (Rx, OTC)
Promethazine (Phenergan�) (Rx)
Pyrilam

Intranasal Antihistamines

Azelastine (Astelin�, Astepro�) (Rx)
Azelastine/Fluticasone (Dymista�) (Rx)
Olopatidine (Patanase�) (Rx)

Ophthalmic Antihistamines

Alcaftadine (Lastacaft�) (Rx)
Azelastine (Optivar�) (Rx)
Bepotastine (Bepreve�) (Rx)
Emedastine (Emadine�) (Rx)
Epinastine (Elestat�) (Rx)
Ketotifen (Zaditor�) (OTC)
Olopatidine (Patanol�, Pataday�) (Rx)

Oral second generation agents are listed before oral first generation agents to indicate that

There is a preference of second generation antihistamines over first generation histamines

Second generation agents have little to no __________and do not cause significant ______________ effects

M ACh receptor blockade, anticholinergic

Second generation agents have _________ distribution into CNS and cause ______ CNS-related adverse effects than 1st generation agents

little, less

First generation agents have __________ distribution into CNS and cause ________ CNS-related adverse effects

extensive, extensive

sympathomimetic

refers to a drug that mimics the neurotransmitters released at the terminus of sympathetic nerves (norepinephrine and epinephrine). Some of these drugs are chemical mimics of epinephrine and norepinephrine, while others are close chemical analogs

?1-Adrenergic Agonist Decongestants (Sympathomimetics)

Epinephrine
Norepinephrine
Phenylephrine
Pseudoephedrine
Naphazoline
Tetrahydrozoline
Oxymetazoline

______ and _____ are close chemical mimics of norepinephrine and epinephrine,

Phenylephrine,pseudoephedrine