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OTC 2015

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REFERENCES Cough and the Common Cold. ACCP Evidence-Based Clinical Practice Guidelines. Chest 2006;129;72S-74S. Cough Suppressant and Pharmacologic Protussive Therapy. ACCP Evidence-Based Clinical Practice Guidelines. Chest 2006;129;238S-249S. Treatment of the Common Cold. American Academy of Family Physicians. Am Fam Physician 2007;75:515-20, 522. The common cold. Lancet 2003; 361: 5159. Examining the evidence for the use of vitamin C in the prophylaxis and treatment of the common cold. American Academy of Nurse Practitioners. Journal of the American Academy of Nurse Practitioners 21 (2009) 295300 2

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OVERVIEW Pathophysiology of common cold. Diagnostic considerations for common cold. Non-pharmacologic management. Pharmacologic management. Tips to the pharmacist. Conclusions. 3

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Introduction. The common cold is a conventional term for a mild upper respiratory illness, the hallmark symptoms of which are nasal stuffiness and discharge, sneezing, sore throat and cough. Every year, in the USA, about 25 million people visit their family doctors with uncomplicated upper respiratory infections and the common cold syndrome results in about 20 million days of absence from work and 22 million days of absence from school 4

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Children younger than 1 year experience an average of 6-8 episodes of common cold infections. This figure decreases to 3-4 episodes per year by adulthood. Some reports indicate a male predominance of infection in children younger than 3 years, which switches to a female predominance in children older than 3 years. No difference in rates of infection in adults is apparent. Common cold is one of the most common categories of self-medication that requires pharmacist advice and patient counseling. 5

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Incidence of common colds per age group 6

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Pathophysiology 7

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Rhinovirus infection begins with the deposition of viruses in the anterior nasal mucosa or in the eye, from where they get to the nose via the lacrimal duct. The viruses are then transported to the posterior nasopharynx by mucociliary action. In the adenoid area, the viruses gain entrance to epithelial cells by binding to specific receptors on the cells. About 90% of rhinovirus serotypes use intercellular adhesion molecule-1 (ICAM-1) as their receptor 8

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The absence of epithelial destruction during rhinovirus infections has led to the idea that the clinical symptoms of the common cold might not be caused by a direct cytopathic effect of the viruses, but instead are primarily caused by the inflammatory response of the host. Extensive research into the role of inflammatory mediators in the pathogenesis of the common cold has produced evidence for increased concentrations of several mediators, such as kinins, leukotrienes, histamine, interleukins 1, 6, and 8, tumour necrosis factor, and RANTES (regulated by activation normal T cell expressed and secreted) in the nasal secretions of patients with colds. The concentrations of interleukin 6 and interleukin 8 in nasal secretions correlate with the severity of the symptoms 9

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Common cold is usually benign and self limiting. Typically symptoms begin slowly 18-48 hrs after exposure to the virus, but could start as early as 10 hours after exposure. The 1 st symptoms are typically scratchy, sore throat followed by a runny nose, watery-itchy eyes, sneezing and fatigue. The soreness of the throat usually disappears quickly, whereas the initial watery rhinorrhoea turns thicker and more purulent, tenacious consistency lasting about 4-5 days. Symptoms gradually diminish and usually disappear after 10 days or so. 10

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Although the common cold is usually a self- limited illness of short duration, the viral infection is sometimes accompanied by a bacterial complication. In children, the most common bacterial complication is acute otitis media, which occurs in about 20% of children with viral upper respiratory infections. The seasonal incidence rates of otitis media closely parallel the general occurrence of viral respiratory infections and the complication is diagnosed most frequently on days 3 or 4 after the onset of upper respiratory symptoms. 13

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Diagnostic considerations. The soreness of the throat caused by streptococcal pharyngitis often resembles the initial symptoms of the common cold. However, nasal stuffiness and discharge, which are the primary symptoms of the common cold, are not typical to streptococcal pharyngitis. 14

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How to differentiate between bacterial & viral sore throat? Bacterial sore throatViral sore throat OnsetRapidSlower SorenessMarkedLess severe Constitutional symptoms MarkedMild URT & LRT symptoms Not always presentUsually present Lymph nodesLarge, tenderSlight enlargement, not tender

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Non-pharmacologic management 18

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Increase fluid intake. Humidifiers and Vaporizers. Intranasal saline sprays/drops/washes. Breathe Right nasal strips. Lozenges and demulcents. Warm salt gargles. 19

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Vitamin C 20

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Vitamin C& common cold Walker and Schwartz, gave half of their volunteers a placebo and the rest 3,000 mg of vitamin C daily for several days before inserting live cold viruses directly into their noses; and then continued 3,000 mg of vitamin C (or placebo) for seven more days. All of the volunteers got colds, which were of equal severity

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Zinc The use of zinc has been shown to inhibit viral growth, and an RCT suggested that zinc could reduce the duration of cold symptoms. However, this has not been substantiated in subsequent RCTs. Specifically, four of eight subsequent trials showed no benefit, and the other four may have been biased by the patients ability to recognize the adverse effects of zinc. Because of these inconsistent study results, zinc cannot be recommended for adults. 23

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Echinacea Echinacea purpurea has recently been studied and did not show any differences in rates of infection or severity of illness when compared with placebo. Although reports of improved symptoms have been described, validation and standardization of products is necessary. Echinacea angustifolia has also been examined in the prophylaxis and treatment of experimental rhinoviral infection. Neither the rate of infection nor the severity of symptoms were found to be statistically significantly affected when E angustifolia was used either prophylactically or at the time of challenge. In contrast, a recent meta-analysis of echinacea indicated that, in properly designed studies, patients receiving placebo were 55% more likely to experience cold symptoms than patients taking echinacea. The most striking part of this meta-analysis was that 231 of 234 articles identified were excluded because they did not control for the type of viruses causing the colds. Echinacea extracts will continue to be evaluated. 25

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Pharmacologic Management 26

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ACCP Practice Guidelines 2006 27

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overview Drugs used in the symptomatic treatment include nonsteroidal anti- inflammatory drugs (NSAIDs), antihistamines, and anticholinergic nasal solutions. These agents have no preventive activity and appear to have no impact on complications. The combined effect of NSAIDs and antihistamines often relieves nasal obstruction; therefore, decongestion therapy may not be needed. Oral (pseudoephedrine) and topical (oxymetazoline and phenylephrine) decongestants are commonly used for symptomatic relief. First-generation antihistamines reduce rhinorrhea by 25-35%, as do topical anticholinergics and ipratropium bromide. Second-generation or nonsedating antihistamines appear to have no effect on common cold symptoms. Corticosteroids may actually increase viral replication and have no impact on cold symptoms. 28

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As a result of viral infection; kinins are released which cause inflammation in the lining of the nose. The cold symptoms are believed to be a result of kinin release not histamine so the rationale for the use of antihistamines is generally viewed as questionable. Observations indicate that antihistamines may decrease symptoms like sneezing and runny nose. FDA announced in 2000 that it will allow the indications of sneezing and runny nose caused by common cold to be part of the monographs of the first generation antihistamines. 29

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First generation antihistamines are classified based on their chemical structures into. Alkylamines: Brompheniramine : 4 mg q4-6 hrs. Dexbrompheniramine: 6 mg q12 hrs. Chlorpheniramine: 4 mg q4-6 hrs. Pheniramine: 12.5-25 mg q4-6 hrs. Triprolidine: 2.5 mg q 6-8 hrs. Have lower incidence of drowsiness and may cause CNS stimulation in children. 30

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Ethylenediamines. Pyrilamine: 25-50 mg q 6-8 hrs. Thonzylamine: 50-100 mg q 6-8 hrs. Ethanolamines. Diphenhydramine: 25-50 mg q 4-6 hrs. Doxylamine: 7.5 mg q 4-6 hrs. Clemastine: 1.34 mg q 12 hrs. Carbinoxamine: 4-8 mg 3-4 times daily. The most sedative of first generation antihistamines. 31

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Piperidines and piperazines. Phenindamine: 25 mg q 4-6 hrs. Hydroxyzine HCL: 50-100 mg daily in divided doses. Side effects may include dry mouth, blurred vision, difficulty urination, constipation, irritation, dizziness and drowsiness. Ehthylenediamines have more frequent GI side effects like nausea, stomach upset. Diphenhydramine has antitussive properties. It acts centrally on the cough center in a way similar to codiene. 32

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Decongestants are classified as adrenergic agonists that stimulate alpha-adrenergic receptors to constrict blood vessels. This consequently results in decreased mucosal edema. Pseudoephedrine (Sudafed) and phenylephrine (Sudafed PE) are common systematic decongestants found in OTC preparations. Topical decongestants such as naphazoline, oxymetazoline, phenylephrine, and xylometazoline are also available. 33

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Expectorants, mucloytics and antitussives Cough is a protective reflex to rid the host of inhaled irritants, foreign debris and mucus. Common cold causes cough by stimulating the cough receptors located within the epithelial lining of the tracheobronchial tree. Cough center in the medulla coordinates the cough response. Productive cough is commonly treated by increasing fluid intake and an expectorant / mucolytic. Dry cough is commonly treated by an anti-tussive. 34

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Anti-tussives act centrally by inhibiting the cough center. Dextromethorphan, Butamirate citrate, codeine. Volatile oils (Camphor, menthol) act as anti-tussives by inhibiting peripheral sensory nerve receptors within the respiratory tract. Codeine 10-20 mg q 4-6 hrs has been used, but recent studies show no benefit in common cold. It can still be used as antitussive for other indications. Dextromethorphan 30 mg q 6-8 hrs has been used in common cold. A dose of 30 mg dextromethorphan produces an equi-antitussive action as 20 mg of codiene. Camphor and menthol 4.7%-5.3% camphor and a 2.6-2.8% menthol in petrolatum or 6.2% camphor and 3.2% menthol in steam vaporizer. They produce a sense of coolness and act via a local anesthetic effect. 35

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Expectorants decrease the viscosity of thickened secretions. Action is best obtained by pushing fluids (8-10 glasses of water per day). Their major pharmacological action is to irritate receptors in the gastric mucosa. This promotes increased output from secretory glands of the GI and reflexively increases flow of fluids from glands lining the respiratory tract. Guaifenesin is the only expectorant approved by FDA for OTC due to safety and efficacy considerations. 36

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41 Am Fam Physician 2007;75:515-20, 522.

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Common Cold in Children 42

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Dimethindene maleate Dosage per Novartis: Average daily dosage (in three doses spread over the day): Drops: Infants up to 1 year, 10-30 drops; Infants of 1 to 3 years, 30-45 drops; Children over 3 years, 45-60 drops; Adults, 60-120 drops. Syrup: Infants up to 1 year, 1-3 teaspoons; Infants of 1 to 3 years, 3-4 teaspoons; Children over 3 years, 4-6 teaspoons; Adults, 6-12 teaspoons. Coated tablets: Adults, 3-6 tablets. Capsule: Once Daily 48 NOT FDA APPROVED NOT INDICATED FOR COMMON COLD

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49 Dimethindene maleate + Phenylephrine

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Guaiacol is a naturally occurring organic compound with the formula C 6 H 4 (OH)(OCH 3 ), Guaiacol is a precursor to various flavorants such as eugenol and vanillin Its derivatives are used medicinally as an expectorant, antiseptic, and local anesthetic. 50 Coldex-D Syrup Pseudoephedrine 30 mg Chlorpheniramine Maleate 1.25 mg Dextromethorphan 10 mg guaiacol 50 mg

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A new OTC product called Clofera containing clophedianol (also known as clofenadol) and pseudoephedrine is being introduced in the U.S. market. 51 Centrix Pharmacuetical is launching a new OTC product, Clofera, which contains clophedianol 12.5 mg and pseudoephedrine 30 mg per 5 mL, for temporary relief of cough and nasal congestions due to the common cold, hay fever, or other upper respiratory allergies in patients six years and older.1 The recommended Clofera dosage for patients >12 years of age is two teaspoonfuls every six to eight hours, not to exceed eight teaspoonfuls within a 24 hour period. For children six to