Combined Lectures. REFERENCES Cough and the Common Cold. ACCP Evidence-Based Clinical Practice Guidelines. Chest 2006;129;72S-74S. Cough Suppressant and.

Combined Lectures

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: 51–59.

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) 295–300

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OVERVIEW

Pathophysiology of common cold.

Diagnostic considerations for common cold.

Non-pharmacologic management.

Pharmacologic management.

Tips to the pharmacist.

Conclusions.

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Common ColdIt is a self-limiting viral infection of the upper

respiratory tractAccounts for ½ of all ilnesses in adults and ¾

of all illnesses in infantscauses more time off work/school than any

other illnessCommon cold cannot be prevented or curedAntibiotics: ineffective

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.

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Incidence of common colds per age group

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Common Cold“coryza”, “acute infectious rhinitis”, “catarrh”.

The main and common causative agents: 5 viruses- rhinoviruses 50% of cases

- coronaviruses, respiratory syncytial virus (RSV), influenza virus (types A,B,C); echovirus; coxackie virus, adenovirus, parainfluenza virus

Pathophysiology

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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

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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

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Predisposing Factors The factors that increase the

susceptibility to viral URT infections are:1. Smoking, poor nutrition, sedentary lifestyle2. Chronic psychological stress (e.g. ≥ 1 month)3. Increased population density4. Seasonal variation: opening of schools (Sep-

April) and cold weather that prompt people to spend more time indoors. Seasonal changes in humidity too affect prevalence of colds (National Institue of Allergy & Infectious Diseases).

contrary to common beliefs!

cold environments or sudden chilling do not increase susceptibility to viral upper respiratory infections

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 1st 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.

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ComplicationsVirus-induced inflammatory changes in the

nose may spread to other nearby structures (e.g. Sinuses, Eustachian tube)

This may lead to sinusitis, Eustachian tube obstruction, otitis media & secondary bacterial infection

Complications in LRT: bronchitis, bacterial pneumonia, exacerbation of asthma & COPD

How to differentiate between bacterial & viral sore throat?

Bacterial sore throat Viral sore throat

Onset Rapid Slower

Soreness Marked Less severe

Constitutional symptoms

Marked Mild

URT & LRT symptoms

Not always present Usually present

Lymph nodes Large, tender Slight enlargement, not tender

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Non-pharmacologic management

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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.

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ControversiesVitamin C: Long-standing controversy since 1940sProposed: antioxidant effect, neutralizes that

high amount of oxidizing compounds released by neutrophils decreases the incidence and severity of common cold

Vitamin C: cannot prevent a cold even in gram/day dose but in megadoses (1-4 g/day) decreases the severity of symptoms by as much as 29%

Vitamin C& common coldWalker 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

Vitamin C

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ControversiesZinc:It is proposed that zinc has an antiviral effect

and if administered frequently in form of lozenges decreases severity of symptoms if therapy started within hours of onset of symptomsRef: Efficacy of Zinc Against Common Cold Viruses: An Overview. Darrell Hulisz J Am Pharm Assoc 44(5):594-603, 2004.

ZincEntry of rhinovirus into the nasal epithelium is

mediated by binding to a cellular receptor, intercellular adhesion molecule-1 (ICAM-1)

A leading hypothesis is that Zn2+ is a competitive inhibitor of ICAM-1 in both rhinovirus particles and the nasal epithelium

By attaching to the ICAM-1 receptor sites, zinc ions prevent the rhinovirus from binding with ICAM-1 and also from effectively entering the cell and replicating

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.

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EchinaceaEchinacea 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.

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Pharmacologic Management

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Symptomatic OTC drugs for common coldSymptom Treatment

Nasal congestion & discharge

Decongestants

Cough Hydration, demulcents, antitussive, expectorants/steam vapors

Sore throat Demulcents, saline gargles, local anesthetics, systemic analgesics

Laryngitis Cool mist/steam vapors

Feverishness and headache

Systemic analgesics

ACCP Practice Guidelines 2006

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overviewDrugs 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. 35

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.

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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.

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Ethylenediamines.Pyrilamine: 25-50 mg q 6-8 hrs.Thonzylamine: 50-100 mg q 6-8 hrs.

Ehthylenediamines have more frequent GI side effects like nausea, stomach upset

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.

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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.

Diphenhydramine has antitussive properties. It acts centrally on the cough center in a way similar to codiene.

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Common cold medications DO

NOT have proven

efficacies in children

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

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.

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Expectorants, mucloytics and antitussivesCough 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.

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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. Dextromethorphan 30 mg q 6-8 hrs

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.

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Expectorants decrease the viscosity of thickened secretions.

Action is best obtained by drinking plenty of 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.

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

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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

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NOT FDA APPROVED

NOT INDICATED FOR COMMON

COLD

Tips to the pharmacist and conclusions

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Unless otherwise contraindicated, NSAIDs should be a part of pharmacologic management of common cold EVEN IF THE PATIENT HAS NO FEVER OR PAIN. Naproxen is preferred in adults, ibuprofen

in children less than 12 years of age. Paracetamol is inferior to NSAIDs and should not be recommended unless NSAIDs are contraindicated.

Centrally acting anti-tussives are superior to expectorants and mucolytics in suppressing acute cough and should be preferred over the latter agents in case of severe coughing regardless whether the

cough is productive or not.

Decongestants: Do not use in patients less than 6 months.

PLEASE PAY ATTENTION TO THE ALCOHOLIC CONTENT IN THE FORMULATION.

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