Download PRACTICE GUIDELINES FOR THE MANAGEMENT OF COMMON

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 Cold
 It is a self-limiting viral infection of the upper
respiratory tract
 Accounts for ½ of all ilnesses in adults and ¾ of all
illnesses in infants
 causes more time off work/school than any other
illness
 Common cold cannot be prevented or cured
 Antibiotics: 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

1.
2.
3.
4.
The factors that increase the susceptibility to
viral URT infections are:
Smoking, poor nutrition, sedentary lifestyle
Chronic psychological stress (e.g. ≥ 1 month)
Increased population density
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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Complications
 Virus-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
Rapid
Slower
Soreness
Marked
Less severe
Constitutional
symptoms
URT & LRT
symptoms
Lymph nodes
Marked
Mild
Not always present
Usually present
Large, tender
Slight enlargement,
not tender
Onset
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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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Controversies
Vitamin C:
 Long-standing controversy since 1940s
 Proposed: 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 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
Vitamin C
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Controversies
Zinc:
 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 symptoms
Ref: Efficacy of Zinc Against Common Cold Viruses: An Overview.
Darrell Hulisz J Am Pharm Assoc 44(5):594-603, 2004.
Zinc
 Entry 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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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.
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Pharmacologic Management
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Symptomatic OTC drugs for
common cold
Symptom
Treatment
Nasal congestion &
discharge
Cough
Decongestants
Sore throat
Demulcents, saline gargles, local
anesthetics, systemic analgesics
Laryngitis
Cool mist/steam vapors
Feverishness and
headache
Systemic analgesics
Hydration, demulcents, antitussive,
expectorants/steam vapors
ACCP Practice Guidelines 2006
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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.
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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.
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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.
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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.
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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.
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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.

NOT FDA APPROVED
NOT INDICATED FOR
COMMON COLD
Capsule:
Once Daily
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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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