Cough, Cold, Flu JIMMY NGUYEN, PHARMD ASSISTANT PROFESSOR, CLINICAL SCIENCES AMERICAN UNIVERSITY OF HEALTH SCIENCES LEARNING OBJECTIVES  Differentiate between signs and symptoms of cold and flu  Describe the mechanism of action of drugs used for treatment of symptoms associated with the common cold  Assess the patient to determine if the cause of his/her symptoms are due to cold, influenza or other cause.  Identify the patients that require referral or can be self-treated with nonpharmacological or OTC medications  Describe the pharmacology of decongestants, antitussives, protussives, local anesthetics, and complementary medicines used for the treatment of signs and symptoms.  Recommend OTC medication for self-treatment based on individual patient specific information.  Counsel patients on how to optimally treat sign and symptoms with OTC medication Common Cold: Background  A viral infection of the upper respiratory tract.  1 billion cases per year  Children usually have 6-10 colds per year.  Adults younger than 60 years typically have 2-4 colds per year, whereas adults older than 60 years usually have 1 cold per year.  Colds are usually self-limiting; however, because symptoms are bothersome, patients frequently self-medicate and spend an estimated $3 billion annually on nonprescription cold and cough products. Pathophysiology of Colds  Colds are limited to the upper respiratory tract and primarily affect the following respiratory structures: pharynx, nasopharynx, nose, cavernous sinusoids, and paranasal sinuses.  Over 200 viruses cause colds. The majority of colds in children and adults are caused by rhinoviruses.  Other viruses known to cause colds include coronaviruses, parainfluenza, adenoviruses, echoviruses  Peak viral concentration occur 2-4 days after initial inoculation. Virus present for 16-18 days  Infected cells release chemokine “distress signals” cascade of active inflammatory mediators and neurogenic reflexes Pathophysiology of Colds Etiology  The most efficient mode of viral transmission is self- inoculation of the nasal mucosa or conjunctiva after contact with viral-laden secretions on animate or inanimate objects.   Aerosol transmission is also common.   Hand shake, door knobs, telephones Coughing or sneezing Increased susceptibility to colds has been linked to:  Higher exposure rates (e.g., increased population density in classrooms or day care centers)  Allergic disorders affecting the nose or pharynx; less diverse social networks;  Weakened immune system due to smoking, a sedentary lifestyle, chronic psychological stress, or sleep deprivation. Common Cold: Clinical Presentation  Symptoms appears 1-3 days after infection.  Sore throat is the first symptom to appear, followed by nasal symptoms, which dominate 2-3 days later.  Nasal symptoms include: congestion, rhinorrhea, sneezing  Cough, although an infrequent symptom ( 3 months of age with rectal temperature ≥104 F or equivalent  < 3 months of age with rectal temperature ≥100.1 F or equivalent Non-pharmacologic Treatment  Rest  Maintain adequate fluid intake, good nutrition  Humidification  Upright position for nasal drainage  Saline gargles or nasal irrigation  Bulb syringe for infants and toddlers Cough: Background  Cough is the most common symptom for which patients seek medical care.  Cough is also a common reason for emergency department visits.  In 2010, cough was the second most common reason for children younger than 15 years to visit emergency departments and the seventh most common reason for adults.  Americans spend more than $4 billion annually on nonprescription cough/cold and related medications, more than any other nonprescription sales category.  In most cases, cough is protective – facilitates removal of inhaled foreign particles and excessive secretions Coughs: Clinical Presentation  Cough is a symptom of diverse infectious and noninfectious disorders, classified as : acute (duration of less than 3 weeks), • subacute (duration of 3-8 weeks), or • chronic (duration of more than 8 weeks) • • Productive cough (wet cough): expels secretions from the lower respiratory lungs ability tract; could impair ventilation and the to resist infection (e.g., bacterial infections) • Non-productive cough (dry cough) e.g., GERD, drug induced cough, viral respiratory tract infection Cough: Pathophysiology  Defense mechanism to rid the airway of mucus, foreign bodies, and cellular debris  The “cough control center” is located in the medulla, but separate from the respiratory control center, coordinate the complex cough response.  Cough is initiated by stimulation of chemically and mechanically sensitive, vagally mediated sensory pathways in pharyngeal, laryngeal, esophageal, and tracheobronchial airway epithelium.  The number of afferent nerves activated and the intensity of activation may influence the cough threshold. Coughs: Exclusions to Self-Treat Treatment Options  Pharmacological  Antitussives & Protussives  Decongestants  Antihistamines  Local Anesthetics  Systemic Analgesics  Non-pharmacological  Fluid intake, adequate rest, a nutritious diet as tolerated, and increased humidification with steamy showers, vaporizers, or humidifiers  Interventions to promote nasal drainage  Proper hand hygiene Antitussives and Protussives  FDA-approved nonprescription oral antitussives include:  codeine (Schedule C-V available by Rx in CA only)  dextromethorphan,  diphenhydramine  Protussives (expectorants)  Guaifenesin Codeine (Schedule V)  Indication: the suppression of nonproductive cough caused by chemical or mechanical respiratory tract irritation.  MOA: Codeine acts centrally on the medulla to increase the cough threshold (suppress the central cough control center).  Codeine is methylmorphine; morphine may be the active antitussive.  Codeine is well absorbed orally with a 15- to 30-minute onset of  action and a 4- to 6-hour duration of effect. The elimination half-life is 2.53 hours.  FDA 2018: Cough and cold medicines containing codeine or  hydrocodone should not be used in those under 18 years of age because the risks of these medicines outweigh their benefits. Codeine: ADRs  Usual antitussive codeine dosages have low toxicity and little risk of addiction.  The lethal dose of codeine in adults is 0.5- 1 gram, with death from marked respiratory depression and cardiopulmonary collapse.  Codeine-containing Schedule CV products must contain one or more noncodeine active ingredients and no more than 200 mg of codeine per 100 milliliters.  The most common side effects associated with antitussive codeine dosages are nausea, vomiting, sedation, dizziness, and constipation. Codeine: Warnings/Precautions/Pr egnancy/DDI  Pregnancy category: C  CI: Codeine is contraindicated in patients with known codeine (or codeine derivatives) hypersensitivity and during labor when a premature birth is anticipated.  DDI: concomitant use of codeine and central nervous system (CNS) depressants (e.g., barbiturates, sedatives, or alcohol) causes additive CNS depression.  Patients with impaired respiratory reserve (e.g., asthma or COPD) or preexisting respiratory depression, drug addicts, and individuals who take other respiratory depressants or sedatives, including alcohol, should use codeine with caution. Dextromethorphan (DXM) – Robitussin DM, Delsym  Indication: suppression of nonproductive cough caused by chemical or mecha nical respiratory tract irritation.  MOA: acts centrally in the medulla to increase the cough threshold  It is well absorbed orally with a 15- to 30-minute onset of action and a 3to 6-hour duration of effect.  Dextromethorphan exhibits polymorphic metabolism, with a usual  elimination half-life of 1.2-2.2 hours. However, the half-life may be as long as 45 hours in people with a poor metabolism phenotype.  Public Health Advisory: FDA Recommends that Over-the-Counter (OTC) Cough and Cold Products not be used for Infants and Children under 2 Years of Age.  Currently, FDA does not recommend nonprescription cold medications for children younger than 2 years because of the lack of efficacy and risk of misuse or overuse leading to adverse events and death.  Manufacturers have voluntarily updated product labeling to statement “Do not use in children under four years of age. include the DXM: ADRs  Side effects with usual doses are uncommon but may include drowsiness, nausea or vomiting, stomach discomfort, or constipation.  Dextromethorphan overdoses & abuse can cause confusion, excitation,  nervousness, irritability, restlessness, drowsiness, as well as severe nausea and vomiting; respiratory depression may occur with very high doses.  CI: Patients who have known hypersensitivity to dextromethorphan or who have a prior history of dextromethorphan dependence should not take it.  DDI:  Additive CNS depression occurs with alcohol, antihistamines, and psychotropic medications.  Dextromethorphan should not be taken for at least 14 days after the MAOI is discontinued.  CA Law requires purchasers of DXM ≥18 yo – verify with proper ID (no recording keeping required) Guaifenesin – Robitussin, Tussin, Mucinex  Indication: only FDA-approved expectorant, is indicated for the symptomatic relief of acute, ineffective productive cough.  MOA: increases the effective hydration of the respiratory tract, loosens and thins lower respiratory tract secretions, facilitating its removal by natural clearance processes.  Few data support its efficacy, especially at nonprescription dosages.  Although the pharmacokinetics of guaifenesin is not well described, guaifenesin appears to be well absorbed after oral administration, with a half-life of about 1 hour.  Do not use extended-release tablets in children 12 years: Formulation Immediate Release​ Extended Release​ Dose​ 200-400mg​ 600 mg​ Frequency​ Q4hrs​ Q12hrs​ Max/day​ 2400 mg​ 2400 mg​ Counseling point​ Take with plenty of water​ • Do NOT crush/chew​ • Take with plenty of water​ Knowledge Check  What is the max daily dose of guaifenesin for adults?  2400 mg  600 mg  1200 mg  3200 mg  4200 mg Knowledge Check  What is the max daily dose of guaifenesin for adults?  2400 mg  600 mg  1200 mg  3200 mg  4200 mg Cough: Product Selection  Targeted towards productive or non-productive cough  Combinations of antitussives and protussives are potentially counterproductive.  Antitussives should not be used to treat productive cough unless the potential benefit outweighs the risk (e.g., significant nocturnal cough).  What kind of cough are they experiencing?  Phlegmy, chest congestion, productive  Tight, dry and hacking, non-productive Cough: Non-pharmacological  Non-medicated lozenges may reduce cough by decreasing throat irritation.  Babies and young children up to about 2 years of age cannot blow  their noses; a rubber bulb nasal syringe may be used to clear the nasal passages and reduce cough if postnasal drip causes cough.  Propping infants upright when they sleep and raising the head of the bed at night promotes drainage of nasal secretions.  Less viscous and thus easier-to-expel secretions are formed when a person is well hydrated. Maintain adequate fluid intake– water!  Cautious hydration is recommended for patients with lower respiratory tract  infections, heart failure, renal failure, or other conditions potentially exacerbated by over-hydration. Cough: Non-Pharm – humidifiers  Humidifiers (ultrasonic, impeller, and evaporative) increase the amount of moisture in inspired air, which may soothe irritated airways.  High humidity may increase environmental mold, dust mites, minerals, and microorganisms.  Vaporizers (humidifiers with a medication well or cup for volatile inhalants) produce a medicated vapor.  Cool-mist humidifiers and vaporizers are preferred because fewer bacteria grow at the cooler temperatures and there is less risk of scalding if they are tipped over.  Humidifiers and vaporizers must be cleaned daily and disinfected weekly. Knowledge Check  John Smith comes into your pharmacy complaining of a hacking sound cough that has lasted for 2 weeks. He reports no other symptoms. Patient was exposed to COVID positive patient last month and suspect it may be “late COVID”. He has repeated test and all have been negative. Smith read online that delysrum is a good medicaiton to use to suppress his cough and wanted recommendation.  Is this patient a good candidate for self-treatment? Knowledge Check  You are a pharmacist working in a busy retail pharmacy. Doctor sends in a prescription for Mucinex 1200 mg every 4 hours. Your technicians types up: Dextromethorphan 400 mg tablet: Take 3 tablet by mouth every 4 hours  What is wrong with this prescription? Knowledge Check  You are a pharmacist working in a busy retail pharmacy. Doctor sends in a prescription for Mucinex 1200 mg every 4 hours. Your technicians types up: Dextromethorphan 400 mg tablet: Take 3 tablet by mouth every 4 hours  What is wrong with this prescription?  Generic for Mucinex is guaifenesin  Max daily dose of guaifenesin is 2400 mg per day Oral H1-Antihistamines  Indication: Allergy, rhinorrhea (runny nose), nausea / vomiting (N/V), and insomnia  Two generations: 1st generation and 2nd generation Oral H1-Antihistamines  1st Generation Antihistatmine  Selective for H1-receptors and cross blood brain barrier  Cross BBB: reason for sedation effect  Sedative and anticholinergic  Anticholinergic: blurred vision, constipation, dry mouth, tachycardia, urine retention Diphenhydramine – Benadryl  MOA: Nonselective (first-generation) antihistamine with significant sedating and anticholinergic properties, acts centrally in the medulla to increase the cough threshold.  Indication: Diphenhydramine is indicated for the suppression of nonproductive cough caused by chemical or mechanical respiratory tract irritation.  Diphenhydramine is well absorbed following oral administration, with a bioavailability of 40%-70%, an onset of action of about 15 minutes, and a duration of action of about 4-6 hours.  Use in those ≥ 6 years of age Diphenhydramine: ADRs  Side effects of diphenhydramine include drowsiness, disturbed  coordination, respiratory depression, blurred vision, urinary retention, dry mouth, and dry respiratory secretions.  Diphenhydramine may cause excitability, especially in children.  Pregnancy: B  Warnings: Diphenhydramine should be used with caution in patients  with diseases potentially exacerbated by drugs with anticholinergic activity, including:  narrow-angle glaucoma, stenosing peptic ulcer, pyloroduodenal obstruction,  symptomatic prostatic hypertrophy, bladder-neck obstruction, asthma and  other lower respiratory tract disease, elevated intraocular pressure, hyperthyroidism, cardiovascular disease, or hypertension. Chlorpheniramine (Chlor-Trimeton)  1st generation antihistamine  Indication: relieve symptoms of allergy, hay fever, and the common cold  Temporarily relieve sneezing, runny nose, itchy/watery eyes, itching of nose or throat Chlorpheniramine (Chlor-Trimeton)  Dosing: 12 mg BID  ADR: drowsniess, dizziness, blurred vision, dry mouth/nose/throat, constipation, some memory or concentration problems Oral H1-Antihistamines  2nd Generation:  Selective for peripheral H1 receptors  Decrease side effect of sedation  Sedation can still occur  Less CYP450 drug interaction  2nd Generation Drugs:  Cetirizine (Zyrtec)  Fexofenadine (Allegra)  Loratadine (Claritin) Loratadine (Claritin)  Dosing: 10 mg once daily  Least sedative – along with Fexofenadine (Allegra) of the 2nd generations  Onset of action 3 hours Cetirizine (Zyrtec)  Dosing: 10 mg once daily  Most sedative of the 2nd generation antihistamine  NO CYP450 substrate  Onset of action 1 hour (works faster) Oral H1-Antihistamines QUESTIONS?? Allergic Rhinitis CS 713 “Do everything without complaining or arguing, so that you may become blameless and pure, children of God without fault in a crooked and depraved generation, in which you shine like stars in the universe.” Philippians 2:14-15 2 Objectives 1. Describe the pathophysiology of allergic rhinitis 2. Identify common triggers and risk factors of allergic rhinitis 3. Differentiate between the common cold, non-allergic rhinitis, and allergic rhinitis based on patient presentation 4. Recognize exclusion/inclusion criteria to self-care for allergic rhinitis and identify cases that warrant referral 5. Recommend an appropriate patient-specific treatment to manage allergic rhinitis, including pharmacologic and non-pharmacologic therapies 6. Provide accurate counseling on pharmacologic and non-pharmacologic treatments for allergic rhinitis 3 Background ❖ Allergic rhinitis: ➢ Also commonly known as “Hay Fever” ➢ A systemic disease with prominent nasal symptoms due to inflammation of the nasal mucous membranes caused by inhaled allergenic materials ➢ ❖ Elicits a specific response mediated by immunoglobulin E (IgE) Affects adults and children ➢ Symptoms usually begin after the second year of life ➢ Highest prevalence in adults 18-64 years old ➢ After age 65 number of cases decrease 4 Epidemiology ❖ 8% of adults and 11% of children are newly diagnosed each year ❖ Affects up to 30% of adults and up to 40% of children in industrialized countries worldwide ❖ About $2.4 billion spent on prescription and over-the-counter medications 5 Pathophysiology https://www.youtube.com/watch?v=y3bOgdvV-_M 6 Pathophysiology Figure 1. Adapted by Eilidh Clark from Naish J, Revest P, Court DS 2009 Saunders Elsevier’s Medical Sciences, Edinburgh. 7 Guidelines ❖ Allergic Rhinitis and its Impact on Asthma (ARIA) ❖ Joint Council of Allergy, Asthma & Immunology (JCAAI) ❖ American Academy of Otolaryngology – Head and Neck Surgery (AAO-HNS) 8 Classifications ❖ Seasonal allergic rhinitis ➢ Intermittent Allergic Rhinitis (IAR) ❖ Perennial allergic rhinitis ➢ Persistent Allergic Rhinitis (PER) ❖ Depends on the timing and duration of symptoms ❖ Symptoms also classified as moderate or moderate-severe Allergic Rhinitis and its impact on Asthma (ARIA) 2019 9 Common Triggers ❖ ❖ Indoor Allergens ❖ Occupational Allergens ➢ House dust mites ➢ Wool dust ➢ Cockroaches ➢ Latex ➢ Mold spores ➢ Resins ➢ Cigarette smoke ➢ Biologic enzymes ➢ Pet dander ➢ Organic dusts (flour) ➢ Various chemicals Outdoor Allergens ➢ Pollen ➢ Mold spores ➢ Pollutants (ozone and diesel exhaust) 10 What Are Some Signs & Symptoms of AR? 11 Signs & Symptoms Coughing Blocked or Runny Nose Ear Discomfort Watery or Itchy Eyes with redness Dry Itchy Skin Sneezing Avoid Allergies 2019. www.allergistatlanta.info Breathing Problem 12 Facial, Nasal, and Throat Features 1. “Allergic shiners” 2. “Dennie-Morgan lines” 3. “Allergic salute” 4. “Allergic crease” 5. “Allergic gape” 6. Nonexudative cobblestone appearance of posterior oropharynx 1 2 3 4 6 13 Allergic Rhinitis vs. Non-Allergic Rhinitis Symptoms/Findings Non-Allergic Rhinitis Allergic Rhinitis Symptom presentation Bilateral symptoms, worse upon Unilateral symptoms common but can awakening, improve during the day, be bilateral; constant day and night then worsen at night Sneezing Little or none Common, paroxysmal Runny nose Posterior, thick, cloudy, green or yellow discharge (infection) Anterior, watery Itchy eyes Not present Common Congestion Usually present and often severe Variable Red eyes Not present Common Aches and pains Variable depending on cause Sinus pain may be present; throat pain due to post nasal drip possible Anosmia Common Rare Epistaxis Recurrent Rare 14 Allergic Rhinitis vs. Common Cold Symptom Common Cold Allergic Rhinitis Sneezing Usual Usual Congestion Common Common Runny nose Common Common Sore throat Common Sometimes Cough Common Sometimes Fatigue, weakness Sometimes Sometimes Body aches and pains Slight Never Fever Rare Never Itchy eyes Rare – never Common Duration New, recent, 3-14 days Recurrent, prior diagnosis, weeks 15 Exclusions to Self-Treatment ❖ Children < 12 years old ❖ Pregnant or lactating women ❖ Symptoms of nonallergic rhinitis ❖ Symptoms of otitis media, sinusitis, bronchitis, or other infection ❖ Symptoms of undiagnosed or uncontrolled asthma (wheezing, shortness of breath), COPD, or other respiratory disorders ❖ Moderate-to-severe persistent allergic rhinitis or symptoms unresponsive to treatment ❖ Severe or unacceptable side effects of treatment Unless already diagnosed with AR and approved for self-treatment by a PCP 16 Case Vignette 1 AC is a 22-year-old female presented to pharmacy for OTC recommendation with a cough, congestion, thick yellow nasal discharge and a slight loss of sense of smell that started 4 days ago. 1. What condition does she has? 2. Can she get OTC meds? 17 Case Vignette 2 JN is a 12-year-old male who has been experiencing coughing at night, congestion, and shortness of breath when he plays sports or exercises. His mom comes into the pharmacy asking for over the counter medication for allergy. Is he a candidate for self-care? Why or why not? 18 Treatment ❖ No cure ❖ Goals of therapy ➢ Reduce symptoms ➢ Improve patient’s functional status and sense of well being ➢ ❖ Quality of life Individualized treatment to provide optimal symptomatic relief 19 Approach to Treatment ❖ ❖ Three steps of treatment: 1. Allergen Avoidance 2. Non-Pharmacotherapy & Pharmacotherapy 3. Immunotherapy Maximize each step before moving to the next ➢ Allergen avoidance usually not sufficient alone; targeted therapy with single drug is usually indicated 20 Allergen Avoidance – Indoor House dust mites ■ ■ ■ ■ Lower household humidity to less than 40%, use acaricides Remove carpets, upholstered furniture, stuffed animals, and bookshelves Encase mattress, box springs, and pillows in mite-impermeable materials Wash un-encased bedding weekly in HOT (130F) water Cockroaches ■ ■ ■ Keep kitchen areas clean Keep food stored tightly Treat with baits or pesticides Mold spores ■ ■ ■ ■ Prevalent in late summer and fall Lower household humidity Remove houseplants Vent food preparation areas and bathroom 21 Allergen Avoidance – Indoor ❖ Cigarette smoke ❖ Pet dander ➢ ❖ Weekly cat baths (unproven) HEPA Filters ➢ Ventilation systems with high-efficiency particulate air (HEPA) filters ➢ Remove pollen, mold spores, and cat allergens from household air ➢ Do not remove fecal particles from house-dust mites, which settle to the floor too quickly to be filtered 22 Allergen Avoidance – Outdoor ❖ Pollen ➢ Pollen Counts – https://weather.com/forecast/allergy/l/USCA0412:1:US ➢ Trees pollinate in spring, grasses in early summer ➢ Ragweed pollinates from mid-August to the first fall frost Pollen counts highest early in the morning and lowest after a rainstorm ➢ ❖ Mold spores ➢ ➢ ❖ Prevalent in late summer and fall Avoid activities that disturb decaying plant material (e.g., raking leaves) Pollutants (ozone and diesel exhaust) ➢ Be aware of the air quality index (AQI; a measure of five major air pollutants per 24 hours) and plan outdoor activities when the AQI is low ➢ https://airnow.gov/index.cfm?action=airnow.local_city&zipcode=92840&submit=Go 23 Non-Pharmacologic Agents Nasal wetting agents ➢ Saline, polyethylene glycol sprays or gels ➢ Nasal irrigation with warm saline ■ Isotonic or hypertonic ■ Syringe or Neti-Pot ■ Use only distilled, sterile, or boiled tap water ➢ Relieve nasal mucosal irritation and dryness ➢ Decrease nasal stuffiness, rhinorrhea, sneezing ➢ Adverse effects: mild stinging or burning 24 http://www.neilmed.com/knowledgebase/article/58/how-come-the-saline-solution-does-not-drain-out-the-opposite-nostril-when-i-try-to-do-irrigation 25 How To Use Nasal Irrigation System https://www.youtube.com/watch?v=GR9bC_wVuVg 26 Pharmacologic Therapy ❖ Intranasal Corticosteroid ❖ Antihistamines: Oral and Ophthalmic ❖ Decongestants: Oral and Intranasal ❖ Mast cell stabilizer (cromolyn) 27 Intranasal Corticosteroids (INCS) ❖ Mechanism of action ➢ Inhibit multiple cell types and mediators stopping the “allergic cascade” ❖ Most effective treatment for moderate-severe IAR and both types of PER ❖ 1st line treatment for Allergic Rhinitis ❖ Common side effects: ➢ ❖ ❖ Nasal discomfort, bleeding, sneezing Rare but serious side effects: ➢ Changes in vision, glaucoma, cataracts ➢ Increased risk of infection, growth inhibition in children If no relief of symptoms after 2 weeks of use refer to PCP or allergist 28 Intranasal Corticosteroids (INCS) Triamcinolone Fluticasone Budesonide 29 INCS Comparison Brand Nasacort Flonase Rhinocort Generic Triamcinolone Fluticasone Budesonide Time to relief 7-8 hrs 2-12 hrs 10 hrs Max efficacy up to 2 weeks up to 3-4 days up to 2 weeks Direction 2 sprays in each nostril/day 2 sprays in each nostril/day 2 sprays in each nostril/day Age recommendations > 2 years old > 4 years old > 6 years old https://www.flonase.com/about/ http://www.rhinocort.com/ http://nasacort.com/otc-nasal-spray.aspx 30 Intranasal Spray Administration https://www.pharmacytimes.com/publications/issue/2015/july2015/rd362_july2015 31 Antihistamines ❖ Mechanism of action ➢ Compete with histamine at central and peripheral histamine receptor sites ➢ Prevent histamine from binding and subsequent mediator release ➢ Second generation antihistamines: inhibit release of mast cell mediators and may decrease cellular recruitment ➢ Highly selective for H1 receptors but have little effect on H2, H3, or H4 receptors 32 First Generation Antihistamines ❖ Commonly called sedating antihistamines ➢ ❖ ❖ Highly lipophilic molecules that readily cross the blood brain barrier Non-Selective ➢ Excessive H1 receptor and cholinergic receptor blockade ➢ Alpha adrenergic and serotonergic activity Side effects ➢ Anticholinergic ➢ Anti-serotonin ➢ Anti-alpha-adrenergic 33 Second Generation Antihistamines ❖ Commonly called non-sedating antihistamines ➢ Large protein bound molecules with charged side chains, do not readily cross the blood brain barrier ❖ 1st generation may be more effective for allergic rhinitis however side effect profile causes 2nd generation to be drugs of choice ➢ Cetirizine causes sedation in 10% of patients; most potent second generation antihistamine 34 Antihistamines Generic Product Drowsiness Anticholinergic Alkylamine class, 1st generation Bronpheniramine Chlorpheniramine Dimetane Chlor-Trimeton + ++ Ethanolamine class, 1st generation Clemastine Tavist ++ +++ Diphenhydramine Benadryl +++ +++ + +/- Piperazine class, 2nd generation Cetirizine Zyrtec Piperidine class, 2nd generation Loratadine Claritin/Alavert +/- +/- Fexofenadine Allegra +/- +/35 Ophthalmic Antihistamines Loratadine Ketotifen Cetirizine 36 Ophthalmics Administration http://www.safemedication.com/safemed/docs/Eye-Drop-Flyer.pdf 37 Ophthalmics Administration (Cont.) http://www.safemedication.com/safemed/docs/Eye-Drop-Flyer.pdf 38 Decongestants ❖ Mechanism of action: ➢ ❖ Adrenergic agonists: causing blood vessel constriction Indicated for temporary relief of sinus and nasal congestion and for cough associated with post-nasal drip ❖ Types of decongestants: ➢ Systemic decongestant ■ ➢ ➢ Pseudoephedrine and phenylephrine Intranasal short-acting: ■ Ephedrine, epinephrine, levmetamfetamine, naphazoline ■ Phenylephrine, propylhexedrine, tetrahydrozoline Intranasal long-acting: ■ Xylometazoline and oxymetazoline 39 Combat Methamphetamine Epidemic Act (2005) ❖ All pseudoephedrine products must now be kept in secure areas (e.g., behind a pharmacy counter or in a locked cabinet) ❖ The following information from each sale must be entered into a written or electronic logbook: product name, quantity sold, patient’s name and address, and time and date of sale. ➢ ❖ Patients must show valid identification to purchase pseudoephedrine and then sign the logbook. Allowed limits to be placed on sales of pseudoephedrine ➢ ➢ Daily: 3.6 grams Monthly: 9 grams 40 Decongestant Adverse Effects ❖ Cardiovascular stimulation (e.g., elevated blood pressure, tachycardia, palpitation, or arrhythmias) ❖ CNS stimulation (e.g., restlessness, insomnia, anxiety, tremors, fear, or hallucinations) ❖ Topical (intranasal) decongestants do not generally cause these ADRs because they are minimally absorbed ➢ ➢ ➢ ADRs include propellant – or vehicle-associated effects (e.g., burning, stinging, sneezing, or local dryness) and trauma from the tip of the device. Rhinitis medicamentosa (i.e., rebound congestion) has been associated with topical decongestants. Therapy should only be for 3 -5 days with these products. 41 Decongestants Warnings & Contraindications ❖ Decongestants are contraindicated in patients receiving concomitant MAO inhibitors (MAOIs). ❖ Decongestants may exacerbate diseases sensitive to adrenergic stimulation, such as hypertension, coronary heart disease, ischemic heart disease, diabetes mellitus, hyperthyroidism, elevated intraocular pressure, and prostatic hypertrophy. ❖ Patients with hypertension should use decongestants only with medical advice. ➢ No clear evidence exists that any one agent is safer than other agents in patients with hypertension. 42 Combination Products Brand Name Ingredients Actifed Allergy Nighttime Caplets Diphenhydramine HCl 25mg Pseudoephedrine HCl 30mg Advil Allergy Sinus Tablets Chlorpheniramine 2mg Pseudoephedrine HCl 30mg Ibuprofen 200mg Allerest Maximum Strength Tablets Chlorpheniramine 2mg Pseudoephedrine HCl 30mg Claritin-D 24 Hour Tablets Loratadine 10mg Pseudoephedrine sulfate 240mg Tylenol Severe Allergy Tablet Diphenhydramine HCl 12.5mg Acetaminophen 500mg 43 Intranasal Cromolyn Sodium ❖ Mechanism of action: ➢ Mast cell stabilizer- prevents release of mediators ❖ Approved for age >2 years old ❖ Treatment needs to be started before symptoms begin ❖ Requires 3-7 days for initial treatment to become effective and 2-4 weeks of continued therapy to get maximal benefit ❖ Side effects ➢ Sneezing, nasal stinging, burning 44 Pregnancy & Lactation ❖ Pregnancy is a common cause of allergic rhinitis – refer for dx ❖ Lactation – refer for dx ❖ Antihistamines: ■ Chlorpheniramine – Drug of choice due to long history of safety ■ Loratadine – low risk ■ Cetirizine – low risk ■ Fexofenadine – moderate risk ■ Take at bedtime after the last feeding 45 Pregnancy & Lactation (Cont.) ❖ Nasal Sprays ➢ Cromolyn (use if patient is breastfeeding) ➢ Triamcinolone (category C) ➢ Fluticasone (category C) ➢ Budesonide (category B) ❖ Decongestants ➢ AVOID phenylephrine ➢ Pseudoephedrine AFTER 1st trimester if no HTN or preeclampsia risk 46 Geriatrics ❖ Beer’s List ➢ ➢ ❖ Oral Antihistamines ➢ ➢ ❖ List of medication that should be used with caution or avoided in elderly (>65 years old) Increased risk of CNS-depressive adverse effects including sedation and hypotension ■ Increased risk of falls Avoid sedating 1st generation antihistamines Also assess for additive sedative effects from other medications Decongestants ➢ Do not recommend pseudoephedrine if patient has uncontrolled HTN ■ Also assess for drug-drug interactions with pseudoephedrine ➢ Combination products with NSAIDs should be avoided in possible due to increase cardiovascular and GI bleed risk. ❖ Drugs of choice: ➢ Antihistamine: Loratadine ➢ Nasal spray: Intranasal cromolyn 47 Pharmacotherapy Chart Summary Therapy Sneezing Rhinorrhea Itching Congestion ADRs Intranasal Corticosteroid +++ +++ +++ +++ + Intranasal Antihistamine +++ ++ +++ + – to + 1st generation Antihistamine +++ +++ +++ + +++ 2nd generation Antihistamine +++ ++ +++ + – to + 2nd generation Antihistamine + Decongestant +++ +++ +++ +++ +++ Cromolyn ++ + + + – Decongestant – + – +++ +++ 48 Summary Allergic Rhinitis and its impact on Asthma (ARIA) 2019. 49 References ❖ Handbook of Nonprescription Drugs: An Interactive Approach to Self-Care, 20th Edition. 2020. ❖ European Academy of Allergy and Clinical Immunology. Global atlas of allergic rhinitis and chronic rhinosinusitis. Zurich, Switzerland: EAACI; 2015. ❖ Skoner DP. Allergic rhinitis: definition, epidemiology, pathophysiology, detection, and diagnosis. J Allergy Clin Immunol. 2001;108(1 Suppl):S2-8. ❖ Brożek JL, Bousquet J, Agache I, et al. Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines-2019 revision. J Allergy Clin Immunol. 2019. ❖ Naish J, Revest P, Court DS 2009 Saunders Elsevier’s Medical Sciences, Edinburgh. 50 Allergic Rhinitis Part Two – Version 20231004 Dr. Transon Nguyen Please read through Part 1’s slides from the first hour of today’s lecture. https://docs.google.com/presentation/d/1rugRmjXPn_srV_jEW5bxeAJfQgnxOLbk2agVErbd4bw/edit?usp=sharing 1 2 Allergic Rhinitis (Endorsed 2014) (Reaffirmed, April 2020) The guideline, Allergic Rhinitis, was developed by the American Academy of Otolaryngology-Head and Neck Surgery and was endorsed by the American Academy of Family Physicians. https://journals.sagepub.com/doi/full/10.1177/0194599814561600 https://emedicine.medscape.com/article/134825-guidelines 3 Allergic Rhinitis (Endorsed 2014) (Reaffirmed, April 2020) The guideline, Allergic Rhinitis, was developed by the American Academy of Otolaryngology-Head and Neck Surgery and was endorsed by the American Academy of Family Physicians. https://journals.sagepub.com/doi/full/10.1177/0194599814561600 https://emedicine.medscape.com/article/134825-guidelines This … is a “Self-Care” course … is “self-care” equivalent to “OTC” ? Why do we have to learn the prescriptions in these lecture … Because we are ALWAYS learning … https://youtu.be/8mhadN-8oZE 4 ● ● ● ● ● ● The diagnosis of allergic rhinitis (AR) should be made when history and physical findings are consistent with an allergic cause (e.g., clear rhinorrhea, pale discoloration of nasal mucosa, and red and watery eyes) and one or more of the following symptoms: nasal congestion, runny nose, itchy nose, or sneezing . Individuals with AR should be assessed for the presence of associated conditions such as asthma, atopic dermatitis, sleep-disordered breathing, conjunctivitis, rhinosinusitis, and otitis media. Specific IgE testing (blood or skin) should be performed for patients with a clinical diagnosis of AR who do not respond to empiric treatment, or when diagnosis is uncertain, or when determination of specific target allergen is needed. Sinonasal imaging should not routinely be performed in patients presenting with symptoms consistent with allergic rhinitis. Intranasal steroids should be prescribed for patients with AR whose symptoms affect quality of life. Oral second-generation/less sedating antihistamines should be prescribed for patients with AR and primary complaints of sneezing and itching. 5 ● ● ● ● ● ● Intranasal antihistamines may be prescribed for patients with seasonal, perennial, or episodic AR. Oral leukotriene receptor antagonists should not be prescribed as primary therapy for patients with AR. Combination pharmacologic therapy may be prescribed for patients with AR who have inadequate response to monotherapy. The most effective combination therapy is an intranasal steroid and an intranasal antihistamine. Immunotherapy should be prescribed for patients with AR who have inadequate response to pharmacologic therapy. Avoidance of known allergens or environmental control may be considered in patients with AR who have identified allergens that correlate with their clinical symptoms. Inferior turbinate reduction may be considered for patients with AR with nasal airway obstruction and enlarged inferior turbinates who have failed medical management. 6 Term Definition Allergic rhinitis (AR) Disease caused by an IgE-mediated inflammatory response of the nasal mucous membranes after exposure to inhaled allergens. Symptoms include rhinorrhea (anterior or posterior nasal drainage), nasal congestion, nasal itching, and sneezing. Seasonal allergic rhinitis (SAR) Disease caused by an IgE-mediated inflammatory response to seasonal aeroallergens. The length of seasonal exposure to these allergens is dependent on geographic location and climatic conditions. Perennial allergic rhinitis (PAR) Disease caused by an IgE-mediated inflammatory response to year-round environmental aeroallergens. These may include dust mites, mold, animal allergens, or certain occupational allergens. Intermittent allergic rhinitis Disease caused by an IgE-mediated inflammatory response and characterized by frequency of exposure or symptoms (4 weeks per year). Episodic allergic rhinitis Disease caused by an IgE-mediated inflammatory response that can occur if an individual is in contact with an exposure that is not normally a part of the individual’s environment. (ie, a cat at a friend’s house). 7 8 9 10 11 12 13 Intranasal Steroids and Oral Antihistamines When patients have no response to INS or incomplete control of nasal symptoms with an INS, oral antihistamines should not be routinely used as additive therapy. The largest trials have shown no benefit of taking an INS plus oral antihistamine compared with INS plus placebo in adults.259,260 A Cochrane review including only one study of adequate quality found no evidence to support this combination in children. 261 Oral Antihistamines and Oral Decongestants Oral antihistamines and oral decongestant combinations control AR symptoms better than either oral antihistamine or oral decongestant alone. This benefit has been consistently demonstrated in multiple randomized, placebo-controlled trials, each with more than 500 subjects enrolled.262-270 Adding an oral decongestant to a second-generation antihistamine increases side effects of insomnia, headache, dry mouth, and nervousness.263,264,267 Additionally, the potential for tolerance from chronic use of oral decongestants may be seen. In one study, 24-hour extended-release pseudoephedrine (240 mg) caused less insomnia than 12-hour extended-release pseudoephedrine (120 mg) taken twice daily (4% vs 15%, P < .01).271 A 2005 meta-analysis concluded that “pseudoephedrine caused a small but significant increase in systolic blood pressure (0.99 mm Hg; 95% CI, 0.08 to 1.90) and heart rate (2.83 beats/min; 95% CI, 2.0 to 3.6), with no effect on diastolic blood pressure (0.63 mm Hg, 95% CI, –0.10 to 1.35).” 272 Oral decongestant use is not recommended for patients under 4 years of age, and the extended-release, 120-mg, 12-hour dose is not recommended for patients under 12 years of age. 14 15 Oral Antihistamines and Leukotriene Receptor Antagonists There is conflicting evidence as to whether combined treatment with oral antihistamine and LTRA is superior to either as single treatment, and therefore routine use of combined therapy is not recommended. Combinations of oral antihistamines and LTRAs were equivalent to oral antihistamine alone within arms of several studies.273-277 Alternatively, some trials showed that oral antihistamine plus LTRA was superior to oral antihistamine alone278-280 or LTRA alone278,279 for AR symptoms. Other studies showed a benefit when combining oral antihistamine and LTRA compared with oral antihistamine or LTRA in preventing symptoms,281 in patients who had poor control with LTRA monotherapy,282 and specifically in nighttime symptoms.276 Combination of oral antihistamine and LTRA is either inferior to273,283-285 or less likely equivalent to277 INS monotherapy in control of AR symptoms. Intranasal Steroids and Leukotriene Receptor Antagonists LTRAs should not routinely be used as additive therapy for patients benefiting from INS for AR. 283,286,287 Three studies with arms that compared INS to INS + LTRA did not show a significant benefit to adding LTRA for their primary outcome. The largest trial enrolled 102 patients.287 Intranasal Steroids and Intranasal Antihistamines The combination of INS and intranasal antihistamine is more effective than INS or intranasal antihistamine monotherapy for AR.243,288-290 This benefit has been demonstrated across multiple symptoms of AR and in patients with moderate to severe symptoms.290 In patients who tolerate INS or intranasal antihistamine spray and have inadequate control of AR symptoms with a single agent, combined INS + intranasal antihistamine is an effective option.243,288-290 16 Intranasal Steroids and Intranasal Oxymetazoline The combination of INS and intranasal oxymetazoline is more effective in controlling AR symptoms than either monotherapy.291-294 The development of rhinitis medicamentosa (rebound nasal congestion from overuse of intranasal oxymetazoline) is a concern. The sizes and lengths of the currently available studies are insufficient to draw conclusions about the risk of rhinitis medicamentosa. Short-term use (
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