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Upper respiratory tract infection

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1 Upper respiratory tract infection
Therapeutics 2 course N.B Upper respiratory tract infection

2 Introduction The respiratory tract is divided into upper and lower parts: The upper respiratory tract : sinuses, middle ear, pharynx….. The lower respiratory tract: bronchi, bronchioles and alveoli. Otitis media, rhinosinusitis, and pharyngitis are the three most common upper respiratory tract infections. Most URIs are caused by viruses, have nonspecific symptoms, and resolve spontaneously. Antibiotics are not effective for viral URIs, and their excessive use has contributed to resistance N.B

3 OTITIS MEDIA Is an inflammation of the middle ear.
Acute otitis media (AOM)is the most common reason for antimicrobial use in children, and is associated with expenditures of almost $3 billion annually. Acute otitis media is most common from the ages of 3 months to 3 years, although the highest incidence occurs between 6 and 2 years of age. By 3 years of age, more than 80% of children have at least one episode, and up to 65% have recurrent infections by 5 years of age. Most children will have had at least one episode by the time they reach 1 year of age N.B

4 Several risk factors for AOM have been identified and include:
Incidence is higher in the winter months, concurrent with viral upper respiratory illnesses. Several risk factors for AOM have been identified and include: N.B

5 There are three subtypes of otitis media: acute otitis media
otitis media with effusion chronic otitis media. The three are differentiated by acute signs of infection evidence of middle ear inflammation presence of fluid in the middle ear N.B

6 Etiology Approximately 40% to 75% of acute otitis media cases are caused by viral pathogens. Although AOM occurs frequently with viral URIs, bacteria are isolated from middle ear fluid in up to 90% of children with AOM Common bacterial pathogens include Streptococcus pneumoniae (35% to 40%), Haemophilus influenzae (30% to 35%), and Moraxella catarrhalis (15% to 18%). Antibiotic resistance heavily influences the treatment options for AOM. Penicillin-resistant S. pneumoniae (PRSP) exhibit intermediate resistance N.B S. pneumoniae, H. influenzae, and M. catarrhalis can all possess resistance to β-lactams. S. pneumoniae develops resistance through alteration of penicillin-binding proteins, whereas H. influenzae and M. catarrhalis produce β-lactamases. Up to 40% of S. pneumoniae isolates in the United States are penicillin nonsusceptible, and up to half of these have high-level penicillin resistance.9 Approximately 30% to 40% of H. influenzae and greater than 90% of M. catarrhalis isolates from the upper respiratory tract produce β-lactamases.1

7 PRSP are frequently resistant to other drug classes, including sulfonamides, macrolides, and clindamycin, but are usually susceptible to levofloxacin. Risk factors have been identified for amoxicillin- resistant bacteria(Amoxicillin resistance is less common). These include attendance at child care centers, recent receipt of antibiotic treatment (within the past 30 days), and age younger than 2 years. N.B

8 Pathophysiology The middle ear is the space behind the tympanic membrane, or eardrum. A noninfected ear has a thin, clear tympanic membrane. In otitis media, this space becomes blocked with fluid, resulting in a bulging and erythematous tympanic membrane. The bacteria proliferate and cause infection. Children tend to be more susceptible to otitis media than adults because the anatomy of their Eustachian tube is shorter and more horizontal, facilitating bacterial entry into the middle ear. N.B

9 Viscous effusions caused by allergy or irritant exposure contribute to impaired mucociliary clearance and AOM in susceptible individuals. Effusions can persist for up to 6 months after an episode of AOM. Atopic children experience chronic OME that may require tympanostomy tube placement to reduce complications such as hearing and speech impairment and recurrent AOM. Viral URIs impair eustachian tube function and cause mucosal inflammation, impairing mucociliary clearance and promoting bacterial proliferation and infection. N.B

10 Clinical Presentation
an acute onset of otalgia (ear pain). For parents of young children, irritability and tugging on the ear are often the first clues that a child has acute otitis media. A diagnosis of acute otitis media requires the following three criteria: acute signs of infection evidence of middle ear inflammation presence of fluid in the middle ear. N.B

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13 General Approach to Treatment
The first step is to differentiate acute otitis media from otitis media with effusion or chronic otitis media. The therapeutic strategy should be changed if complications develop or if symptoms fail to resolve within 3 days. Nonpharmacologic Therapy: Children with recurrent AOM or chronic OME with impaired hearing or speech may benefit from surgery (tympanostomy tube placement) N.B

14 Pharmacological therapy:
Acetaminophen or a nonsteroidal antiinflammatory drug, such as ibuprofen, should be offered early to relieve pain in acute otitis media….depend on age Eardrops with a local anesthetic, such as amethocaine, benzocaine, or lidocaine, provide pain relief when administered with oral pain medication to children aged 3 to 18 years Because of minimal benefit and increased side effects, neither decongestants nor antihistamines should be routinely recommended in cases of acute otitis media or otitis media with effusion N.B

15 Antibiotics N.B

16 Antibiotics Severe illness consists of otalgia, irritability, fussiness, lethargy, less interest in eating, and a temperature of at least 39◦C. Generally, infants 6 months of age and younger should receive antibiotic therapy in all cases. Infants and children 6 months to 2 years of age can be managed with observation for 48 to 72 hours in the case of an uncertain diagnosis and if illness is not severe. Children 2 years of age and older can be managed with observation even in the case of a certain diagnosis, although illness should be non severe N.B

17 If antibiotics are to be administered, then amoxicillin should be given to most children (80 to 90 mg/kg/day in two divided doses). High-dose amoxicillin (80–90 mg/ kg/day) is preferred over conventional doses (40–45 mg/kg/day) because higher middle ear fluid concentrations can overcome pneumococcal penicillin resistance without substantially increasing adverse effects. If pathogens that produce β-lactamase are known or suspected, then amoxicillin should be given in combination with a β-lactamase inhibitor: amoxicillin– clavulanate (90 mg/kg/day of amoxicillin with 6.4 mg/kg/day of clavulanate in two divided doses). N.B

18 In patients with moderate to severe illness (temperature greater than 39°C [102°F] and/or severe otalgia), amoxicillin– clavulanate is recommended N.B

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21 Use of trimethoprim–sulfamethoxazole and erythromycin–sulfisoxazole is discouraged because of high rates of resistance. Intramuscular ceftriaxone is the only antibiotic other than amoxicillin that achieves middle ear fluid concentrations above the MIC for greater than 40% of the dosing interval. Ceftriaxone should be reserved for severe and unresponsive infections or for patients for whom oral medication is inappropriate because of vomiting, diarrhea, or possible nonadherence N.B It is an expensive antibiotic, and the intramuscular injections are painful. The drug can be given IV, but the risk-to-benefit ratio of starting an IV line must also be examined.

22 Patients with a penicillin allergy can be treated with several alternative antibiotics. If the reaction is not type I hypersensitivity, cefdinir, cefpodoxime, or cefuroxime can be used. If the reaction is type I, a macrolide such as azithromycin or clarithromycin may be used. Traditional recommendations call for 10 days of antibiotic therapy; however, some experts have speculated that patients can be treated for as little as 3 to 5 days. Short-course treatment is not recommended in children younger than 2 years of age. N.B

23 In children at least 6 years old who have mild to moderate acute otitis media, a 5- to 7-day course may be used. Recurrent acute otitis media is defined as at least three episodes in 6 months or at least four episodes in 12 months. Recurrent infections are of concern because patients younger than 3 years are at high risk for hearing loss and language and learning disabilities. N.B

24 Treatment can be delayed until the onset of symptoms of an upper respiratory tract infection or antibiotic prophylaxis can be limited to 6 months’ duration during the winter months. Surgical insertion of tympanostomy tubes (T tubes) is an effective method for the prevention of recurrent otitis media. These small tubes are placed through the inferior portion of the tympanic membrane under general anesthesia and aerate the middle ear. Children with recurrent acute otitis media should be considered for T-tube placement. N.B

25 Prevention Vaccinations may prevent AOM in certain patients. Influenza vaccine is more effective in children older than 2 years because of impaired immune responses and immature host defenses in infants and toddlers. Antibiotic prophylaxis is not recommended because of antibiotic resistance trends. Exclusive breast-feeding for the first 6 months of life and avoidance of tobacco smoke are advised, but the effects of these interventions remain unproven. N.B

26 Acute otitis media: Update 2015
N.B Acute otitis media: Update 2015

27 Case example 1 A 13-month-old boy presents to the pediatric clinic with 2 days of fever (maximum temperature of 39.3°C [102.7°F]), rhinorrhea, and fussiness. His mother reports that he was rubbing his left ear throughout the day yesterday. She states that he is irritable and he was crying intermittently throughout the night last night. He has not eaten much today. He attends daycare 3 days a week and has a 5-year-old sister who recently had a cold. Meds: Acetaminophen drops 120 mg orally every 4 to 6 hours as needed for fever ROS: (+) rhinorrhea and fever, (–) vomiting, diarrhea, or cough N.B

28 Gen: Irritable child but consolable
PE: Gen: Irritable child but consolable VS: BP 100/64 mm Hg, P 130 beats/min, RR 22 breaths/min, T 39.1°C (102.4°F) HEENT: Erythema and severe bulging of the left tympanic membrane with the presence of middle ear fluid; the right tympanic membrane is obscured with cerumen. Patient has type 1 allergy to penicillin What information is suggestive of acute otitis media (AOM)? What risk factors does this child have for AOM? Given this information, what nonpharmacologic and pharmacologic therapy do you recommend? N.B

29 Case example 2 C.D. is a 7-month-old, 8-kg infant , stays in day care, who during the last 2 days has developed cough and rhinorrhea, became irritable and at times inconsolable, and now has a temperature of 102.4◦F (39.1◦C). Physical examination shows bulging, dark, yellow opaque tympanic membranes bilaterally. This is the first time he has had these symptoms What signs and symptoms does C.D. exhibit that are consistent with acute otitis media How should AOM be diagnosed? What are the risk factors for AOM in the case? What is the appropriate treatment for the case? N.B resistance rates ranging from 30% to 70%, initial therapy in most children with nonsevere disease should still be amoxicillin at a dose of 80 to 90 mg/kg/day.87,88 Amoxicillin is still effective against susceptible and intermediately resistant pneumococcus, it is affordable and palatable, and it has a narrow spectrum of activity.87 However, because C.D. has severe disease, he should receive amoxicillin/clavulanate at a dose of 360 mg by mouth twice daily (90 mg/kg/day), using the ES or XR formulation. Oral cephalosporins, including cefdinir, cefuroxime, or cefpodoxime, are options in patients with a non–type I allergy to penicillin, and macrolides such as azithromycin or clarithromycin may be used in those with type I allergies to penicillin. It is important to recognize that although the oral cephalosporins generally provide good activity against H. influenzae, M. catarrhalis, and penicillin-susceptible S. pneumoniae, they are not effective against penicillin-nonsusceptible pneumococcal isolates.94–98 Additionally, penicillin resistance does not necessarily confer resistance to amoxicillin.99 Macrolides have also been shown to be less effective than amoxicillin/clavulanate. Ear pain is a common feature of AOM, and it should be addressed regardless of the decision to use antibiotics or not. Acetaminophen 120 mg (15 mg/kg) or ibuprofen 80 mg (10 mg/kg) can provide adequate relief, and are first-line agents in the management of otalgia.90 Topical agents such as benzocaine can provide benefit as well, particularly in older children. Home remedies such as the application of heat or cold may also be helpful.90 For example, a washcloth can be soaked with very warm water, wrung out, and placed over the ear for comfort for 15 minutes several times per day. Whichever treatment course is taken in a patient (observation or antibiotic therapy withamoxicillin oramoxicillin/clavulanate), effectiveness is assessed for 48 to 72 hours. If the treatment is effective, the patient should defervesce, irritability should decrease, and normal activity should resume (e.g., eating, sleeping). If observation is ineffective, treatment with amoxicillin or amoxicillin/clavulanate is recommended. If amoxicillin or amoxicillin/ clavulanate is ineffective for C.D., ceftriaxone 400 mg (50mg/kg) intramuscularly for 1 or 3 days is recommended.Tympanocentesis may be useful if ceftriaxone fails, and clindamycin can be used if pneumococcus is strongly suspected or proven to be the pathogen.96

30 Acute Pharyngitis Pharyngitis is an acute infection of the oropharynx or nasopharynx. viral causes are most common… rhinovirus group A β-hemolytic streptococci (GABHS; also known as S. pyogenes), is the primary bacterial cause. Complications include acute rheumatic fever, acute glomerulonephritis, reactive arthritis, peritonsillar abscess, retropharyngeal abscess, cervical lymphadenitis, mastoiditis, otitis media, rhinosinusitis N.B

31 Children 5 to 15 years of age are most susceptible
Pharyngitis in a child younger than 3 years of age is rarely caused by GABHS. Seasonal outbreaks occur, and the incidence of GABHS is highest in winter and early spring. The incubation period is 2 to 5 days. N.B

32 Clinical Presentation
Pathophysiology Asymptomatic pharyngeal carriers of the organism may have an alteration in host immunity (e.g., a breach in the pharyngeal mucosa) and the bacteria of the oropharynx may migrate to cause an infection. Pathogenic factors associated with the organism itself may also play a role. These include pyrogenic toxins, hemolysins,streptokinase, and proteinase. N.B Clinical Presentation There are several options to test for GABHS. A throat swab can be sent for culture or used for the rapid antigen-detection test (RADT). Cultures are the gold standard, but they require 24 to 48 hours for results. The RADT is more practical in that it provides results quickly, it can be performed at the bedside, and it is less expensive than culture. If RADT is positive, it does not require a follow-up throat culture (strong, high).47 If RADT yields negative test results, it is generally recommended to follow up with a throat culture to confirm the results for children and adolescents but not necessary in adults (strong, Sore throat ( pain) is the most common symptom of pharyngitis Laboratory tests should not be performed unless the patient has symptoms consistent with GABHS pharyngitis.

33 Signs and Symptoms of GABHS Pharyngitis Sore throat Pain on swallowing
Fever Headache, nausea, vomiting, and abdominal pain (especially in children) Erythema/inflammation of the tonsils and pharynx with or without patchy exudates Enlarged, tender lymph nodes Red swollen uvula, petechiae on the soft palate, and a scarlatiniform rash N.B

34 Nonpharmacologic Therapy:
Signs Suggestive of Viral Origin for Pharyngitis • Conjunctivitis • Coryza • Cough Nonpharmacologic Therapy: antipyretic medications, analgesics( NSAIDs, acetaminophen) nonprescription lozenges sprays containing menthol and topical anesthetics for temporary relief of pain use of corticosteroids …..is not recommended N.B

35 N.B

36 Amoxicillin suspension is more palatable than penicillin and has the advantage of a once-daily dosing regimen. In patients with a type I hypersensitivity to penicillins, azithromycin, clarithromycin, or clindamycin may be used. In those with a non–type I allergy to penicillin, a first-generation cephalosporin may be considered. Newer macrolides such as azithromycin and clarithromycin are equally effective as erythromycin and cause fewer GI adverse effects. N.B

37 GABHS resistance rates to tetracyclines are high
GABHS resistance rates to tetracyclines are high. Sulfonamides and trimethoprim– sulfamethoxazole have poor eradication rates for GABHS. The newer fluoroquinolones have activity against GABHS but are expensive and have a broad spectrum of activity. The impact of appropriate antibiotic therapy is limited to decreasing the duration of signs and symptoms by 1 or 2 days. The duration of therapy for GABHS pharyngitis is 10 days…except for azithromycin N.B

38 Cephalosporins may be more effective than penicillin for relapse prevention and nasopharyngeal eradication, particularly in asymptomatic carriers. Usual duration of therapy is 10 days, but 5-day courses of some cephalosporins are as effective for streptococcal eradication as 10 days of penicillin N.B

39 Case example P.J., a 6-year-old boy weighing 23.4 kg, presents to the pediatrician’s office complaining of fever, sore throat, and headache. His mother reports that he initially complained of sore throat about 12 hours ago. His temperature this morning was 102◦F. He has had no other symptoms. He takes no medications and has no known drug allergies. Physical examination reveals erythematous tonsils and throat, as well as an enlarged anterior cervical lymph node. Are P.J.’s symptoms more consistent with GAS or viral pharyngitis? What is the appropriate treatment for this case? N.B As clinical and physical findings are not definitive forGASpharyngitis, confirmatory testing is important to determine the need for antibiotic therapy. A rapid antigen test is recommended and, if positive, treatment is initiated. If negative, a throat culture should also be obtained and treatment initiated if the culture grows GAS. Rheumatic fever can be effectively prevented if treatment is started within 9 days from the start of the illness. P.J. should receive amoxicillin (400 mg/5 mL), 12.5 mL (1,000 mg) every 24 hours for 10 days. For pain relief, he may also receive as-needed doses of acetaminophen (160 mg/5 mL), 10 mL every 6 hours, or ibuprofen (100 mg/5 mL), 10 mL every 6 hours.

40 ACUTE BACTERIAL RHINOSINUSITIS
Sinusitis is an inflammation and/or infection of the paranasal sinuses, or membrane-lined air spaces, around the nose. The term rhinosinusitis is now preferred because sinusitis typically also involves the nasal mucosa. Majority of rhinosinusitis infections are viral One in five antibiotics prescribed for adults in the United States is for rhinosinusitis Acute rhinosinusitis is characterized by symptoms that persist for up to 4 weeks, whereas chronic rhinosinusitis lasts for more than 12 weeks. N.B

41 Etiology Acute bacterial rhinosinusitis is caused, most often, by the same bacteria implicated in acute otitis media: S. pneumoniae and H. influenzae. These organisms are responsible for ~50% to 70% of bacterial causes of acute bacterial rhinosinusitis in both adults and children. N.B

42 Signs and Symptoms Purulent anterior nasal discharge, purulent or discolored posterior nasal discharge Nasal congestion or obstruction, facial congestion or fullness, facial pain or pressure Fever, headache Ear pain/pressure/fullness Dental pain, cough, and fatigue Children: Persistent nasal or postnasal drainage, nasal congestion, mouth breathing, persistent cough (particularly at night), morning periorbital edema or facial swelling, fatigue, facial or tooth pain N.B

43 Onset with persistent signs or symptoms compatible with acute rhinosinusitis, lasting for ≥10 days without any evidence of clinical improvement. Onset with severe signs or symptoms of high fever (≥39°C [102°F]) and purulent nasal discharge or facial pain lasting for at least 3 to 4 consecutive days at the beginning of illness Onset with worsening signs or symptoms characterized by new-onset fever, headache, or increase in nasal discharge following a typical viral URI that lasted 5 to 6 days and were initially improving N.B

44 N.B

45 General Approach to Treatment
The first step is to delineate viral and bacterial rhinosinusitis Viral rhinosinusitis typically improves in 7 to 10 days; therefore, a diagnosis of acute bacterial rhinosinusitis requires persistent symptoms (10 days or greater) or a worsening of symptoms after 5 to 6 days. Potential reasons for referral include mental status changes, visual disturbances, immunosuppressive illness, nosocomial infections, anatomic defects causing obstruction and possibly requiring surgery, unusually severe symptoms, multiple recurrent episodes (3 to 4/y), unilateral findings, risk factors for unusual or resistant pathogens, and history of antibiotic failure. N.B

46 pharmacologic Therapy
nasal decongestant sprays that reduce inflammation by vasoconstriction, such as phenylephrine and oxymetazoline. Use should be limited to no more than 3 days to prevent the development of tolerance and/or rebound congestion. Oral decongestants also may aid in nasal/sinus patency. Irrigation of the nasal cavity with saline and steam inhalation may be used to increase mucosal moisture N.B

47 mucolytics (e.g., guaifenesin) may be used to decrease the viscosity of nasal secretions.
if a patient is suspected of having acute bacterial rhinosinusitis, then decongestants and antihistamines are not recommended. These can dry mucosa and disturb clearance of mucosal secretions. Intranasal corticosteroids are now recommended for patients with a history of allergic rhinitis N.B

48 Moderate infection N.B

49 N.B list amoxicillin as the first-line treatment option due to its safety, narrow spectrum of activity, good tolerability, and favorable cost.

50 For adults, the recommended duration is only 5 to 7 days
cephalosporins are no longer recommended as monotherapy due to variable rates of resistance against S. pneumoniae. Macrolides are no longer recommended because of high rates of S. pneumoniae resistance Trimethoprim–sulfamethoxazole has not been recommended for some time due to resistance among S. pneumoniae and H. influenzae. For adults, the recommended duration is only 5 to 7 days N.B

51 Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults, 2016
Nasal congestion, purulent nasal discharge, maxillary tooth pain, facial pain or pressure, fever, fatigue, cough, hyposmia or anosmia, ear pressure or fullness, headache, and halitosis Symptoms have a variable duration (1 to 33 d) and sometimes take longer to resolve completely. Most cases are caused by viruses, allergies, or irritants. Nonviral causes occur in <2% of cases and include Streptococcus pneumoniae, Haemophilus influenzae. Antibiotics may be prescribed if symptoms last >10 d, severe symptoms last for >3 consecutive days, or worsening symptoms last after 3 consecutive days N.B

52 Oral amoxicillin, 500 mg 3 times daily for 5 to 7 d If Allergy:
Oral amoxicillin, 500 mg, and clavulanate, 125 mg, 3 times daily for 5 to 7 d Oral amoxicillin, 875 mg, and clavulanate, 125 mg, twice daily for 5 to 7 d Oral amoxicillin, 500 mg 3 times daily for 5 to 7 d If Allergy: Oral levofloxacin, 500 mg once daily for 5 to 7 d Oral moxifloxacin, 400 mg once daily for 5 to 7 d American collage of physicians,2016 N.B

53 Case example 1 A 17 year old previously healthy female presents to her primary care physician with a 12 day history of persistent thick nasal discharge, nasal congestion, cough, and intermittent low grade fever,the cough is worse at night but there is no wheezing. temperature spike daily to about 38.2 C. She is not taking any medications. She denies any vomiting, headache, earache, or rashes. Her tympanic membranes are clear. She has nasal congestion with thick yellow purulent mucus in the posterior nasal pharynx. Her nasal turbinates are red and swollen. She has mild tenderness to palpation of her maxillary sinuses She has no obvious dental caries or pain on tapping of her teeth. Her lungs are clear. The rest of her exam is normal what are signs and symptoms of sinusitis? What is the appropriate therapy if you know that she has non type penicillin allergy and tried 2 courses of amoxicillin / clavanate with no use? N.B

54 Case example 2 A 43-year-old man presents to his primary care physician with purulent postnasal discharge, nasal congestion, headache, and fatigue. He reports that his symptoms began 6 days ago and have worsened over the past 2 days. He states that his “head hurts” when he bends forward and he noticed that his upper molars ache when he eats or brushes his teeth. He tried acetaminophen and phenylephrine but received no relief. He has sinus infections every few years. His last course of antibiotics was 8 months ago when he received penicillin for streptococcal pharyngitis. He has two daughters (9 years and 13 years of age). N.B

55 Allergies: Grass and tree pollens
Meds: Fexofenadine 60 mg orally twice daily during allergy season; intranasal fluticasone one spray each nostril twice daily; acetaminophen 500 mg orally as needed; phenylephrine 10 mg orally every 4 hours as needed PE: Gen: Tired-appearing, moderate distress, appears uncomfortable VS: BP 132/74 mm Hg, P 88 beats/min, RR 14 breaths/min, T 38.2°C (100.8°F), Wt 95.5 kg HEENT: Thick, purulent brown postnasal discharge; nasal mucosal edema; right maxillary facial pain and right upper molar hypersensitivity upon tapping; no oral lesions; erythematous pharynx with mild tonsillar hypertrophy What is the appropriate antibiotic for this case? N.B

56 Antibiotics should not be used.
Common Cold Mild upper respiratory viral illness with sneezing, rhinorrhea, sore throat, cough, low-grade fever, headache, and malaise that lasts up to 14 d. All causes are viral. Leading causes include rhinovirus (up to 50%); coronavirus (10% to 15%); influenza (5% to 15%); respiratory syncytial virus (5%); parainfluenza (5%). Antibiotics should not be used. N.B

57 symptomatic therapy is the appropriate management strategy
Patients seeking medical advice for the common cold should be advised that symptoms can last up to 2 weeks and should be advised to follow up with the clinician if symptoms worsen or exceed the expected time of recovery Antihistamines have more adverse effects than benefits when used alone, 1 out of 4 patients treated with combination antihistamine–analgesic– decongestant products has significant symptom relief N.B

58 Other symptomatic treatments that may offer relief include inhaled ipratropium bromide, inhaled cromolyn sodium, antitussives, and analgesics. Zinc supplements have been shown to reduce the duration of common cold symptoms in healthy persons if administered less than 24 hours after symptom onset; however, their potential benefits should be weighed against adverse reactions, such as nausea and bad taste. No evidence supports the use of vitamins and herbal remedies, such as vitamin C . N.B

59 References Pharmacotherapy, Principles & Practice, 4th ed,2016, chapter 72 Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of Physicians and the Centers for Disease Control and Prevention, American collage of physicians,2016 Acute otitis media: Update 2015 , By: Janet R Casey Pharmacotherapy, physiological approach, 2014, Chapter 86 Applied therapeutics, 2013, Chapters 25,99 Pharmacotherapy, principles and practice, 3th ed, 2013, chapter 72 N.B


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