Allergic Rhinitis, Cough/Cold, Nasal Congestion, Sore Throat

Allergic rhinitis is clinically defined as a ______________________ of the nose induced by an _____________________ after allergen exposure of the membranes lining the nose.

symptomatic disorder, IgE-mediated inflammation

Pathophysiology steps of allergic rhinitis

1.) Initial Sensitization

2.) Mast Cell Sensitization

3.) Early Phase

4.) Late Phase

Pathophysiology steps of allergic rhinitis

Step 1: The process of allergic sensitization involves _______________________ in nasal tissues, subsequent presentation to other immune response cells like T lymphocytes, and production of allergen-specific _____________________ by ___________________

the uptake of the allergens by antigen-presenting cells (dendritic cells)

immunoglobulin E (IgE) by B lymphocytes

Pathophysiology steps of allergic rhinitis

Step 2: The IgE binds to high-affinity ____________________ on the surface of nasal ____________________, thereby sensitizing them to the offending allergen but not yet causing any ____________________.

FcεRI receptors

mast cells and circulating basophils

symptoms

Pathophysiology steps of allergic rhinitis

Step 3: Upon re-exposure, the offending allergen is recognized by IgE on sensitized mast cells and basophils, which induce early- and late-phase responses that lead to the clinical symptoms of allergic rhinitis. Within minutes (early phase), the allergen–IgE interaction causes _____________________, leading to the release/ production of mediators, including _____________________________

degranulation of the sensitized cells,

histamine, tryptase, leukotrienes, and prostaglandins.

Pathophysiology steps of allergic rhinitis

Step 4: Approximately 50% of patients with allergic rhinitis then experience a late-phase response that may persist for hours after allergen exposure. The late-phase response is characterized by the influx and _________________________, including _______________________, as well as by an increase in ________________ number in the nasal submucosa and epithelium, and is thought to be mediated by cytokines and chemokines released by the local activation of Th2 cells. Nasal congestion is the most prominent symptom during the late-phase response.

activation of multiple inflammatory cells

T cells, eosinophils, basophils, neutrophils, and monocytes

mast cell

Pathophysiology steps of allergic rhinitis

Step 4: Approximately 50% of patients with allergic rhinitis then experience a late-phase response that may persist for hours after allergen exposure. The late-phase response is characterized by the influx and activation of multiple inflammatory cells, including T cells, eosinophils, basophils, neutrophils, and monocytes, as well as by an increase in mast cell number in the nasal submucosa and epithelium, and is thought to be mediated by _______________________ released by the local activation of Th2 cells. _____________________ is the most prominent symptom during the late-phase response.

cytokines and chemokines

Nasal congestion

Histamine activates H1 receptors on sensory _____________________, as well as both H1 and H2 receptors on mucosal ______________________

nerve endings to cause sneezing and nasal secretion

blood vessels to cause nasal congestion.

The leukotrienes act on receptors located in ____________________ to induce ____________________

blood vessels and mucus glands

nasal congestion and mucus secretion.

The role of IgE antibodies in allergic response is also called _______________________. Initial contact to induce IgE then in subsequent challenge, allergen will bind to IgE.

type 1 hypersensitivity

Histamine is present in mast cells as a preformed mediator and is the major mediator of allergic rhinitis. It stimulates the sensory nerve endings of the fifth cranial nerve and induces __________________. Histamine also stimulates the mucous glands causing the secretion of _________________ Histamine and the newly formed leukotrienes and prostaglandins to act on the blood vessels causing _____________________

sneezing

mucous (rhinorrhea)

nasal congestion

pharmacologic treatment of allergic rhinitis includes

- antihistamines

- decongestants

- intranasal corticosteroids, anticholinergics, and cromolyn

Histamine, an ___________________, is a biological chemical that acts like a local hormone with a short duration. It binds to various histamine receptors (H1 - H4), all of which are ____________________ in the cell membrane. Histamine causes increased permeability of the capillaries to white cells and proteins and inflammatory cytokine, leading to _____________________

autocoid

G-protein-coupled receptors

tissue edema

Histamine is also produced in the hypothalamus and the gut by the _____________________ that control gastric acid secretion. In the CNS, it affects sleep, wakefulness, food intake, locomotion, memory and learning, and emotions including aggressive behavior.

enterochromaffin cells

Antihistamines block the action of histamine at the receptor. Antihistamines cannot displace already-bound histamines. Histamine receptors (all of which are ___________________) have constitutive activity, meaning that they exist in inactive or active forms. Antihistamines are _____________________, that preferentially binds to the receptor in the inactive form, preventing the binding of a ligand to the receptor

G-protein-coupled receptors

inverse agonists

The main use of anti-histamines is for _____________________ purposes. The first-generation antihistamines are ________________ and can enter through the _________________, it is not metabolized and is a poor substrate for the p-glycoprotein pump, therefore it does not exit the brain, and can cause drowsiness

anti-allergic and anti-emetic

lipophilic

blood-brain barrier into the brain

The first-generation antihistamines, being that it does not exit the brain, also interact with the _____________________ and block adrenergic activities, causing side effects such as, ______________________ such as tachycardia, hypotension, dry mouth, vertigo, and increased apatite

cholinergic receptors

urinary retention, drowsiness, and cardiotoxicity

The second generation anti-histamines have substituted _________________ groups, so they do not cross the blood-brain barrier. Therefore, they do not penetrate the brain, and will ___________________. They are generally more selective for the ___________________, and have lower affinity for other receptors, and have less ______________________ and negligible sedative effect

hydrophilic

not cause drowsiness

H1 receptor

cardiotoxicity

Some examples of anti-histamines include

1st Generation:

- Propyl amines: e.g. Chlorpheniramine

- Ethanol amines: e.g. Diphenhydramine (Benadryl)

2nd Generation:

- Piperazines: e.g. Cetirizine (Zyrtec)

- Piperidines: e.g. Loratadine (Claritin)

Pseudoephedrine (Sudafed) is a ______________________ with mixed mechanisms of action, direct and indirect. It indirectly stimulates ______________________________ from the neurons, while it also ___________________________

sympathomimetic

α-adrenergic receptors, causing the release of norepinephrine (NE)

directly stimulates β-adrenergic receptors

Pseudoephedrine works as a decongestant to ______________________. Active ingredients in OTC nasal decongestants include ______________________

relieve nasal congestion and sinus pressure

vasopressors

Nasal _____________________ helps unclog a congested nose and dry a postnasal drip. They belong to the class of _____________________ that stimulate _____________________ (agonists).

decongestants

sympathomimetic amines

alpha receptors

Nasal decongestants work by _________________________ in the lining of the nose so that the swollen tissue shrinks and decreases mucous production. Air can then pass through more easily. Prolonged use may cause ___________________ congestion.

narrowing the blood vessels, rebound

Intranasal corticosteroids (INCS) are steroid-based nasal sprays or drops that are used to treat a range of conditions, including _____________________, and nasal polyps. Cromolyn sodium is a _____________________ that ______________________________, including histamine and leukotrienes, which cause allergic symptoms and bronchoconstriction.

allergic rhinitis, sinusitis

mast cell stabilizer

prevents the release of inflammatory mediators

The common cold, also known as _____________________, is an acute, self-limited viral infection of the upper airway. Many types of viruses cause URI, the most common one is ____________________ with at least 100 serotypes. that infect both children and adults. Other viruses that cause URIs are Coronavirus, RSV, influenza virus, etc.

upper respiratory tract infection (URI)

rhinovirus

Mechanism of human rhinovirus (HRV) infection in the nasal epithelium

Human rhinoviruses are ____________________. To produce infection, HRVs must first attach to ______________________ in the plasma membrane

RNA viruses

ICAM-1 cellular receptors

Mechanism of human rhinovirus (HRV) infection in the nasal epithelium

After binding to the ICAM-1 cellular receptors, the rhinovirus capsule ___________________ to develop a hydrophobic pocket and interacts with the cell membrane to deliver the RNA into the epithelial cell. Antiviral drugs bound to this hydrophobic pocket ‘‘lock’’ the viral particle in a state, thus ______________________

changes conformation

preventing uncoating

The symptoms of the common cold are due to the _______________________ and other mediators from infected nasal epithelial cells. For instance, the goblet cells in the nasal mucus are stimulated to produce more mucus (snot) in order to clear the invading organism. Subsequent white or yellow nasal discharge may result from an increased number of ______________________ and other inflammatory cells.

release of cytokines

polymorphonuclear cells (PMNs)

A symptom of the common cold is white or yellow nasal discharge that may result from an increased number of polymorphonuclear cells (PMNs) and other inflammatory cells. The nasal discharge may turn green due to ________________________

- myeloperoxidases of PMNs

- bacterial infections

During human rhinovirus (HRV) infection, proinflammatory cytokines are produced, resulting in ____________________ that causes the exudation (release) of plasma proteins that contain ___________________ which causes ____________________

increased vascular permeability,

bradykinin

sore throat

A cough is an innate ____________________ and acts as part of the body's immune system to protect against foreign materials. The most common causes of chronic cough are ________________________ from the stomach

primitive reflex

postnasal drip, asthma, and acid reflux

____________________ is an illness with a classic clinical finding of paroxysmal episodes of intense coughing lasting up to several minutes followed by a loud gasp for air. It is an infection of the respiratory tract by Bordetella pertussis, where the bacterium produces a toxin, ______________________, that affects the cyclic AMP signaling through _________________________

Pertussis (whooping cough)

pertussis toxin

inhibition of Gi

Two types of cough include

- Non-Productive (Dry Cough)

- Productive Cough (Wet Cough)

Non-productive (Dry Cough) needs to be _____________. Constant non-productive cough leads to _____________________ and syncope.

suppressed

- loss of sleep

- rib fractures

- rupture of surgical wounds

Productive Cough (Wet Cough) is ___________________, and is needed to ______________________ It is beneficial as it expels irritating substances such as dust, pollen, fluids, and inflammatory cells from the upper respiratory airways

dangerous to suppress, clear airways

Antitussives vs Expectorants vs. Demulcents

- Antitussives are cough suppressants

- Expectorants loosen mucus so that it can be coughed out

- Demulcents provide soothing relief by coating the mucous membrane

Antitussives suppress cough via the following two mechanisms:

1.) Via the CNS, by raising the threshold of cough centers

2.) Via the periphery to reduce cough impulse

CNS Acting Cough Suppressants (Antitussives) include opioids and non-opioids.

Opioid antitussives cross the ____________________ to suppress cough reflex on the cough center (medulla) via ____________________. Examples of opioid antitussives include ____________________

blood-brain barrier

mu and kappa opioid receptors

Codeine (which has a black box warning for respiratory depression), and Hydrocodone

CNS Acting Cough Suppressants (Antitussives) include opioids and non-opioids.

Non-opioid antitussives cross the ____________________ to suppress cough reflex on the cough center (medulla) via ____________________. Examples of non-opioid antitussives include ____________________.

blood-brain barrier

sigma receptors

Dextromethorphan, Diphenhydramine, Benzonatate

Benzonatate is an antitussive with ________________________, which helps control cough by suppressing reflexes in airways and lungs.

numbing and anesthetic properties

Throat sprays, cough drops, and lozenges fall under the category of pharyngeal ________________________ and provide soothing and symptomatic relief by coating the surface. ____________________ help thin and loosen mucus so you can cough it up more easily. The active ingredient in OTC cough expectorants is ___________________

demulcents

Expectorants

Guaifenesin

Allergic rhinitis is aka _________________________ It is inflammation (redness and swelling) of the inside of the nose that's caused by an allergen, such as pollen, dust, mold, or flakes of skin from certain animals.

hay fever/allergies

The clinical presentation of allergic rhinitis consists of bilateral symptoms that are worst upon awakening, improve during the day, then may worsen at night. These bilateral symptoms include ________________________

- Sneezing

- Rhinorrhea (Watery nasal discharge)

- Pruritus (Itching in the eyes, nose, or palate)

- Nasal obstruction

- Conjunctivitis (Red, irritated eyes)

- Systemic symptoms (fatigue, irritability, malaise, and cognitive impairment)

- Pain (Sinus pain from congestion and throat pain from postnasal drip)

Allergic rhinitis classification

Duration

- Intermittent (seasonal): Symptoms occur ≤4 days per week OR ≤4 weeks

- Persistent (perennial): Symptoms occur ≥4 days per week AND ≥4 weeks

Severity

- Mild: Symptoms do not impair sleep or daily activities; no troublesome symptoms

- Moderate-Severe: One or more of the following occurs: impairment of sleep; impairment of daily activities; troublesome symptoms

Allergic Rhinitis Exclusions for Self-Treatment

- Children under 12 years old unless previously diagnosed.

- Pregnant or lactating women unless previously diagnosed.

- Presence of non-allergic rhinitis symptoms, infections (e.g., sinusitis, otitis media), or other conditions such as uncontrolled asthma, wheezing, SOB, COPD, or undiagnosed respiratory diseases.

- Severe adverse drug reactions to treatment.

non-pharmacologic treatment of allergic rhinitis includes:

- Avoid allergens

- Nasal irrigation

- Nasal wetting agents

Examples of sedating oral antihistamines used to treat allergic rhinitis

- Diphenhydramine

- Clemastine

- Doxylamine

Examples of less sedating oral antihistamines used to treat allergic rhinitis

- Chlorpheniramine

- Brompheniramine

- Triprolidine

Examples of low sedating oral antihistamines used to treat allergic rhinitis

- Cetirizine

- Levocetirizine

Examples of non sedating oral antihistamines used to treat allergic rhinitis

- Loratadine

- Fexofenadine

Characteristics of sedating oral antihistamines (e.g. Diphenhydramine, Clemastine, Doxylamine)

- Strong anticholinergic effects

- CNS depressant effect

- Caution with alcohol

Characteristics of less sedating oral antihistamines (e.g. Chlorpheniramine, Brompheniramine, Triprolidine)

- Strong anticholinergic effects

- Higher risk of paradoxical CNS stimulation compared with other classes

Characteristics of low sedating oral antihistamines (e.g. Cetirizine, Levocetirizine)

- Caution with liver/kidney disease

- Labeling includes drowsiness precautions

Characteristics of non sedating oral antihistamines (e.g. Loratadine, Fexofenadine)

- Caution with liver/kidney disease

key counseling point for Loratadine (Claritin)

First choice oral antihistamine for children 2 - 12 years old

key counseling point for Fexofenadine (Allegra)

- Separate from aluminum/magnesium containing antacids

- Should not be taken with fruit juices

These are all conditions negatively impacted by anticholinergic drugs and are prevalent in elderly populations. That said, first-generation oral antihistamines should be used with caution in people _______________ and in people with these conditions: ___________________

over 65 years old

- glaucoma

- hyperthyroidism

- tachyarrhythmia

- prostate hypertrophy

Azelastine HCl (Astepro) is the first OTC intranasal antihistamine that can be used as needed. The patients that can use this are ___________________ and is effective in ___________________

- children over 6 years old

- effective in 15-30 minutes

Azelastine HCl (Astepro) cannot be used for

children under 6 years old

Cromolyn sodium nasal spray is a mast cell stabilizer that is _______________________, and is more effective if started ___________________. It may take 3–7 days for initial improvement and 2–4 weeks of continued therapy to achieve full benefit

safe for pregnancy and children over 2 years old

before symptoms occur

intranasal corticosteroids used to treat allergic rhinitis include ______________________, with the adverse side effects being _______________________

triamcinolone acetonide, fluticasone propionate (over 4 years old), fluticasone furoate, mometasone furoate, and budesonide (over 6 years old)

nose bleeds, sneezing, cough, pharyngitis

Intranasal corticosteroids are the most effective drugs available for allergic rhinitis, as the onset occurs ______________________. It should be reduced to 1 spray on each nostril daily after 1 week of improvement.

within 12 hours

Long-term use of intranasal corticosteroids has been linked to ____________________

changes in vision, glaucoma, cataract formation, increased risk of infection, and growth inhibition in children

Oral (systemic) and topical nasal decongestants used to treat allergic rhinitis

Oral (systemic) nasal decongestants

- Pseudoephedrine

- Phenylephrine

Topical nasal decongestants

- Oxymetazoline

- Phenylephrine

- Xylometazoline

Symptoms/clinical presentation of colds and how long they last

- Sore throat

- Nasal symptoms (congestion and pain)

- clear, thin nasal secretions, progressing to yellow or green before returning to thin and clear

- coughing

- Low-grade fever of less than 100.4℉

Symptoms usually last 7-14 days

Self Care Exclusions for people with the common cold

- Fever greater than 100.4℉

- Chest pain

- Shortness of breath, asthma, COPD, CHF

- AIDS or chronic immunosuppressant therapy

- Elderly and Infants less than 3 months old

- Hypersensitivity to OTC therapies

Non-pharmacologic therapy for the common cold

- Prevent transmission (Hand hygiene, disinfectants, etc.)

- Increased fluids

- Rest

- Nutritious diet

- Increased humidification (Hot showers, humidifiers)

- Eucalyptus oil

Complementary Therapy for the common cold

- Zinc

- Vitamin C

- Probiotics (e.g. Lactobacillus)

Classification of cough

acute: <3 weeks

subacute: 3-8 weeks

chronic: >8 weeks

A productive cough is a wet cough that comes in two different forms

Effective - expels secretions

Ineffective - difficult to expel secretions

Pharmacologic therapy used to treat cough

- Codeine

- Dextromethorphan

- Diphenhydramine

- Menthol

- Camphor

- Guaifenesin

uses, MOA, and adverse effects of codeine

Useful for a non-productive cough for people 18 and up

MOA: Acts centrally on the medulla to increase the cough threshold

Adverse effects: drowsiness (respiratory depression)

uses, MOA, and adverse effects of dextromethorphan (DM)

Useful in a non-productive cough

MOA: increases cough threshold by acting on the σ (sigma) receptor in the CNS

Adverse effects: drowsiness, constipation, nausea, vomiting

Dextromethorphan - Important Counseling Points

- avoid with alcohol

- Using monoamine oxidase inhibitors (MAOIs) and dextromethorphan may cause serotonin syndrome (Symptoms of serotonin syndrome include increased blood pressure and arrhythmias)

- Avoid DM for 14 days after MAOI has been discontinued

Diphenhydramine is a first generation antihistamine with sedating effects. What is/are the MOA and adverse effects?

MOA: works centrally in the medulla by increasing the cough threshold

Adverse Effects - drowsiness, dry mouth

Menthol and Camphor are the only FDA-approved ____________________

cough drops that are placed in the mouth to dissolve. Its MOA is not well described but may create local __________________ and a sense of improved airflow

topical antitussive

anesthetic sensation

Key counseling points of menthol and camphor

- May cause mouth numbness

- Avoid in children <2 years old

Guaifenesin (Mucinex) is the only FDA-approved _________________ that is indicated for __________________. Its MOA is that it _______________________

expectorant

ineffective productive cough

loosens respiratory tract secretions making the cough more productive

Non-pharmacologic therapy for the treatment of cough includes _________________. However, it is not used in ____________________ due to ______________________

honey

not used in children <1 - risk of botulism spores

all nonprescription cough and cold products should not be used for _________________________

children under 2 years old

Adverse effects of oral/systemic decongestants (e.g. Phenylephrine, Pseudoephedrine)

- CNS stimulation (insomnia, restlessness, anxiety)

- CV stimulation (increased blood pressure, tachycardia, palpitations)

Adverse effects of topical nasal decongestants (e.g. Oxymetazoline, Phenylephrine, Xylometazoline)

- burning, dryness, trauma from the tip

- rebound congestion - do not use for more than 3 days!

Systemic Decongestants: Phenylephrine vs. Pseudoephedrine

Phenylephrine

- Direct acting

Pseudoephedrine

- Direct and indirect activity - more effective

- Sold behind the counter since it can be synthesized into methamphetamine

Drug interactions and cautions with systemic decongestants (Phenylephrine, Pseudoephedrine)

- Caution in patients with thyroid disorders, heart disease, or enlarged prostate - may experience worsening of their underlying disease

- Patients with diabetes - closely monitor blood sugar levels

- Patients taking MAOI, ergot derivatives, or certain antibiotics should NOT take systemic decongestants

Pharmacologic therapy for the treatment of sore throat includes local anesthetics, such as ______________________. Important counseling points for these medications are that they _______________________

Benzocaine, Menthol, Pectin, Dyclonine, and Phenol

may cause mouth numbness and should not be used in children under 2 years old

Two types of pharmacologic therapies for the treatment of sore throat includes

local anesthetics

systemic analgesics

Pharmacologic therapy for the treatment of sore throat includes systemic analgesics, such as

Ibuprofen and Acetaminophen

MOA and adverse effects of Ibuprofen (Advil, Motrin)

MOA: reversibly inhibits COX-1 and COX-2 enzymes which results in decreased prostaglandin precursors

Adverse Effects: GI discomfort, bleeding

MOA and adverse effects of Acetaminophen (Tylenol)

MOA: activates the descending serotonergic inhibitory pathways in the CNS

Adverse Effects: hepatotoxicity, nausea

For pregnant populations, ____________________ are preferred for the treatment of cold and cough. ___________________ especially should be avoided, as it can cause congenital birth defects

non-drug measures

Codeine

Cough and cold symptoms - typically last for ________________ - if longer, ______________ is needed!

7-14 days

referral

Patients need to self-monitor daily throughout their cold and cough treatment. Monitoring parameters to look out for include _____________________

- Body temperature

- Nasal secretions

- Cough type (productive or unproductive)

- Worsening symptoms during treatment

- Shortness of breath

FDA Guidelines for Liquid OTC Products

- Dosing device included with all liquid products

- Device should be used only with the product it came with

- Device is calibrated to the recommended dose in the directions for the product

- Markings must remain visible when liquid is in device

Nasal congestion is caused by cholinergic stimulation leading to ____________________, resulting in congestion.

dilation of arterial blood flow