ب ه نام خد ا فارماکوویژیالنس و عوارض ناخواسته داروها آذر ماه 1396
Upper Respiratory Tract Infections Z. Sahraei Pharm. D., Ph.D. Infectious Disease Clinical Pharmacist
Rhinosinusitis
Definition Acute rhinosinusitis is defined as: Symptomatic inflammation of the nasal cavity and paranasal sinuses lasting up to 4 weeks. The term "rhinosinusitis" is preferred to "sinusitis" since inflammation of the sinuses rarely occurs without concurrent inflammation of the nasal mucosa.
Epidemiology Rhinosinusitis is an extremely common condition. Nearly 1 in 7 (13.4%) of adults aged 18 years were diagnosed with rhinosinusitis within the previous 12 months. Incidence rates among adults are higher for women than men (~1.9-fold).
Acute rhinosinusitis: symptoms for less than 4 weeks Subacute rhinosinusitis: symptoms for 4 to 12 weeks Chronic rhinosinusitis: persists greater than 12 weeks Recurrent acute rhinosinusitis: 4 or more episodes of ARS per year, with interim symptom resolution.
Etiology: Typically caused by a single pathogen. The vast majority of cases of acute rhinosinusitis (ARS) are due to viral infection (AVRS). Acute bacterial (ABRS) infection occurs in only 0.5 to 2.0 percent of episodes. The most common viruses: rhinovirus, influenza virus, and parainfluenza virus. The most common bacteria: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. ABRS due to dental root infection: microaerophilic and anaerobic bacteria
The prevalence of a bacterial infection during acute rhinosinusitis is estimated to be 2% 10%, whereas viral causes account for 90% 98%.
Nasal congestion and obstruction Purulent nasal discharge Maxillary tooth discomfort Facial pain or pressure that is worse when bending forward Fever Fatigue Cough Hyposmia or anosmia Ear pressure or fullness Headache
Diagnosis
Conventional Criteria for the Diagnosis of Sinusitis Based on the Presence of at Least 2 Major or 1 Major and 2 Minor Symptoms Diagnosis of ABRS in most RCTs of antimicrobial therapy is based on the presence of compatible symptoms and signs of acute rhinosinusitis.
The following two criteria as most highly predictive of acute sinusitis, whether viral or bacterial: Purulent rhinorrhea Nasal congestion and facial pain/pressure Distinguishing bacterial from viral infection!!!!!!
IDSA 2012 - ABRS Persistent symptoms or signs of ARS lasting 10 days without evidence of clinical improvement. Onset of severe symptoms or signs of high fever (>39 C) and purulent nasal discharge or facial pain for at least 3-4 consecutive days at the beginning of illness. Onset with worsening symptoms or signs: (new onset fever, headache, nasal discharge) that lasted 5-6 days and were initially improving.
Gold Standard The gold standard for the diagnosis of ABRS is the recovery of bacteria in high density ( 10 4 colony-forming units per milliliter) from the cavity of a paranasal sinus.
Imaging Studies Imaging studies such as plain radiographs or CT are frequently used by clinicians for the diagnosis of ABRS.
Complications Complications of ABRS: Rarely occur Related to local extension into the central nervous system and orbit of the eye.
Management of acute viral rhinosinusitis (AVRS) aims to relieve symptoms of nasal obstruction and rhinorrhea; treatment does not shorten the clinical course of the disease. Treatment for acute bacterial rhinosinusitis (ABRS) includes antibiotics to eliminate the infection and prevent complications. Studies suggest that 40 to 69 percent of patients with ABRS may clear their infection spontaneously.
SYMPTOMATIC THERAPY FOR ACUTE RHINOSINUSITIS Analgesics: NSAIDs and acetaminophen Topical glucocorticoids : decrease in mucosal inflammation primarily in patients with a history of allergic rhinitis Topical decongestants : no more than three consecutive days to avoid rebound congestion Oral decongestants:, pseudoephedrine, phenylephrine Antihistamines????: but over-drying of the mucosa may lead to further discomfort. Antihistamines have side effects (drowsiness), and their use for the treatment of acute sinusitis is not recommended
IS SALINE IRRIGATION OF THE NASAL SINUSES OF BENEfiT AS ADJUNCTIVE THERAPY IN PATIENTS WITH ABRS? Intranasal saline irrigation with either physiologic or hypertonic saline is recommended as an adjunctive treatment in adults with ABRS.
ANTIMICROBIALS Treatment is most often initiated empirically. Although culture-guided therapy is optimal, and is generally reserved for patients with complications.
Amoxicillin (500 mg three times a day) for its narrow spectrum, relatively low cost, and low sideeffect profile. Amoxicillin clavulanate is recommended as empiric therapy. The dose would be either 500 mg/125 mg orally three times daily or 875 mg/125 mg orally twice daily.
HIGH-DOSE AMOXICILLIN-CLAVULANATE High-dose (2 g orally BD or 90 mg/kg/day orally BD) : 1. Geographic regions with high endemic rates ( 10%) of penicillin-nonsusceptible S. pneumoniae. 2. Severe infection (evidence of systemic toxicity with fever of 39ºC or higher, and threat of suppurative complications) 3. Attendance at daycare 4. Age<2 or >65 years 5. Recent hospitalization 6. Antibiotic use within the past month 7. Immunocompromised
Doxycycline is a reasonable alternative for firstline therapy and can be used in patients with penicillin allergy. A respiratory fluoroquinolone (levofloxacin or moxifloxacin) is another option for penicillinallergic patients. Macrolides (clarithromycin or azithromycin), trimethoprim-sulfamethoxazole, and second- or third-generation cephalosporins are not recommended for empiric therapy because of high rates of resistance of S. pneumoniae.
SHOULD A RESPIRATORY FLUOROQUINOLONE VERSUS A B-LACTAM AGENT BE USED AS FIRST- LINE AGENTS FOR THE INITIAL EMPIRIC ANTIMICROBIAL THERAPY OF ABRS? A beta-lactam agent (amoxicillin- clavulanate) rather than a respiratory fluoroquinolone is recommended for initial empiric antimicrobial therapy of ABRS.
Duration for initial treatment The IDSA guidelines advise a 5 to 7 day course of antibiotics (rather than 10 to 14 days) in adults The recommended duration of therapy for uncomplicated ABRS in adults is 5 7 days. In children with ABRS, the longer treatment duration of 10 14 days is still recommended.
INFLUENZA
INTRODUCTION Influenza is an acute respiratory illness caused by influenza A or B viruses that occurs in outbreaks and epidemics worldwide, mainly during the winter season. Signs and symptoms of upper and/or lower respiratory tract involvement are present, along with indications of systemic illness such as fever, headache, myalgia, and weakness. Although acutely debilitating, influenza is a self-limited infection in the general population (uncomplicated influenza); however, it is associated with increased morbidity and mortality in certain high-risk populations (complicated influenza).
INFLUENZA VIRUSES A, B, AND C Influenza virus types A, B, and C are members of the Orthomyxoviridae family and affect many species, including humans, pigs, horses, and birds.
HEMAGGLUTININ AND NEURAMINIDASE Hemagglutinin allows the influenza virus to enter host cells by attaching to sialic acid receptors and is the major antigen to which antibodies are directed upon exposure. Neuraminidase allows the release of new viral particles from host cells by catalyzing the cleavage of linkages to sialic acid. Orthomyxovirus that contains the glycoproteins Haemagglutinin and Neuraminidase. For this reason, they are described as H1N1, H1N2 etc
PANDEMICS Spanish Flu of 1918 Asian Flu of 1957 Hong Kong Flu of 1968 Avian Influenza of 1997 Swine Flu of 2009
CLINICAL PRESENTATION AND DIAGNOSIS OF INFLUENZA The clinical diagnosis of influenza can be difficult because the presentation is similar to a number of other respiratory illnesses The clinical course and outcome are affected by age,immunocompetence, viral characteristics, smoking, comorbidities, pregnancy, and the degree of preexisting immunity. Complications of influenza may include exacerbation of underlying comorbidities, primary viral pneumonia, secondary bacterial pneumonia or other respiratory illnesses (e.g., sinusitis, bronchitis, otitis), encephalopathy, myocarditis, pericarditis,
SIGNS AND SYMPTOMS Classic signs and symptoms of influenza include rapid onset of fever, myalgia, headache, malaise, nonproductive cough, sore throat, and rhinitis. Nausea, vomiting, and otitis media are also commonly reported in children. Signs and symptoms typically resolve in approximately 3 to 7 days, although cough and malaise may persist for more than 2 weeks.
Complications Primary viral pneumonia: predominantly in pregnant women and in those with underlying cardiovascular disease, usually begins with fever and dry cough, which changes to a productive cough. This rapidly progresses to dyspnea, hypoxemia, and cyanosis with radiologic evidence of bilateral interstitial infiltrates. Secondary bacterial pneumonia: seen in individuals with underlying pulmonary disorders and presents during the early stages of defervescence from the influenza infection. These patients usually present with fever, productive cough, and radiologic evidence of consolidation.
DIAGNOSIS: LABORATORY TESTS Complete blood count and chemistry panels should be obtained to assess the overall status of the patient. The gold standard for diagnosis of influenza is viral culture, which can provide information on the specific strain and subtype. Tests such as polymerase chain reaction (RT- PCR) assay may be used for rapid detection of virus. Chest radiograph should be obtained if pneumonia is suspected.
GOALS OF THERAPY The four primary goals of therapy of influenza are as follows: 1. Control symptoms; 2. Prevent complications; 3. Decrease work and/or school absenteeism; 4. Prevent the spread of infection.
Medications Two classes of antiviral drugs are available for the treatment and prevention of influenza: The neuraminidase inhibitors, zanamivir and oseltamivir, which are active against both influenza A and B. The adamantanes, amantadine and rimantadine, which are only active against influenza A. Due to a marked increase in resistant isolates, the (ACIP) recommends that adamantanes not be used in the United States for the treatment of influenza.
NEURAMINIDASE INHIBITORS OSELTAMIVIR/ZANAMIVIR Oseltamivir and zanamivir are neuraminidase inhibitors that have activity against both influenza A and influenza B viruses. When administered within 48 hours of the onset of illness, oseltamivir and zanamivir may reduce the duration of illness by approximately one day versus placebo. The neuraminidase inhibitors also reduce the duration of shedding and viral titer.
OSELTAMIVIR TAMIFLU Prophylaxis: Oral: 75 mg once daily; initiate prophylaxis within 48 hours of contact with an infected individual; Duration of prophylaxis: 7-10 days Treatment: Oral: 75 mg twice daily initiated within 48 hours of onset of symptoms; Duration of treatment: 5 days Hospitalized patients with severe influenza infection may require longer (eg, 10 days) treatment courses Some experts have recommended empirically doubling the treatment dose (ie, 150 mg twice daily)
Note: Dose reduction recommended in those with creatinine clearance less than 30 ml/min. Treatment dosing of oseltamivir for children (> 7 years): 15 kg: 30 mg twice daily; 15 to 23 kg: 45 mg twice daily; 23 to 40 kg: 60 mg twice daily; >40 kg, the dose is 75 mg twice daily. The prophylactic dosing of oseltamivir for children (> 5 years ): Weight base mentioned doses once daily
ZANAMIVIR - RELENZA Prophylaxis: Household setting: Two inhalations (10 mg) once daily for 10 days. Begin within 36 hours following onset of signs or symptoms of index case. Community outbreak: Two inhalations (10 mg) once daily for 28 days. Begin within 5 days of outbreak. Treatment: Two inhalations (10 mg total) twice daily for 5 days. Doses on first day should be separated by at least 2 hours; on subsequent days, doses should be spaced by ~12 hours. Begin within 2 days of signs or symptoms. Longer treatment may be considered for patients who remain severely ill after 5 days. Children (>1 year): same as adult dose
Adverse effects of neuraminidase inhibitors Zanamivir can cause bronchospasm and a decline in respiratory function in patients with asthma and other chronic respiratory disorders. As a result, the manufacturer has issued a warning advising particular caution in patients with asthma or chronic obstructive pulmonary disease. Oseltamivir can also cause nausea and vomiting, but these side effects have not generally resulted in discontinuation of therapy.
ADAMANTANES AMANTADINE/RIMANTADINE The adamantanes, amantadine and rimantadine, are active only against influenza A viruses, but high rates of resistance have developed and these drugs are infrequently indicated. These drugs prevent viral replication by blocking the viral M2 protein ion channel, which prevents fusion of the virus and host-cell membranes.
Amantadine: ACIP: Due to issues of resistance, amantadine is no longer recommended for the treatment or prophylaxis of influenza A. Influenza A treatment: Oral: 200 mg once daily or 100 mg twice daily. Initiate within 24-48 hours after onset of symptoms; duration of therapy is generally 3-5 days. Influenza A prophylaxis: Oral: 200 mg once daily or 100 mg twice daily. Continue prophylaxis throughout the peak influenza activity in the community influenza season in patients who cannot be vaccinated. ADRa: CNS side effects including anxiety, insomnia, impaired thinking, confusion, lightheadedness, and hallucinations. Seizure in patients with a history of epilepsy, caution in such individuals. Anticholinergic effects that can cause dry mouth and mydriasis; as a result, it is contraindicated in patients with untreated angle closure glaucoma. These side effects appear to be related to peak drug concentrations and are more common in elderly patients
Rimantadine: Prophylaxis: 100 mg twice daily continue for 2 weeks and until ~10 days after illness onset in the last patient. Treatment: Oral: 100 mg twice daily ADRs: Similar CNS side effects have been described with rimantadine but at a considerably lower rate. May be associated with an increased rate of seizure activity in patients with a history of epilepsy, and should be used with caution in such individuals
TARGET POPULATIONS FOR TREATMENT Individuals with severe disease (requiring hospitalization or evidence of lower respiratory tract infection) Adults at high risk for complications for influenza include: 1. Residents of nursing homes and other chronic care facilities 2. Adults 65 years of age 3. Pregnant women and women up to two weeks postpartum 4. Individuals with chronic medical conditions including: Pulmonary disease, including asthma (particularly if systemic glucocorticoids have been required during the past year), Cardiovascular disease, except isolated hypertension, Active malignancy, Chronic renal insufficiency, Chronic liver disease, Diabetes mellitus, Hemoglobinopathies, such as sickle cell disease, 5. Immunosuppression, including HIV infection (particularly if CD4 <200 cells/microl), organ or hematopoietic cell transplantation, inflammatory disorders treated with immunosuppressants 6. Any neurologic condition that can compromise handling of respiratory secretions (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, neuromuscular disorders) 7. Individuals who are morbidly obese (body mass index [BMI] 40)
Those who present >48 hours after illness onset should not be treated with antivirals since they are unlikely to benefit Patients with mild uncomplicated influenza infections who do not have risk factors for severe or complicated illness are not likely to benefit from antiviral therapy if it is initiated more than 48 hours after symptom onset
Oseltamivir or Zanamivir are Pregnancy Category C drugs. No adverse events have been shown to be caused by oseltamivir or zanamivir among women who received these agents during pregnancy or among infants who were exposed while in utero, although there are limited data
VACCINATION The primary means of influenza prevention employed in the United States is annual vaccination. Vaccination can help prevent hospitalization and death among those at high risk, decrease influenza- like illness, decrease visits to physicians offices and emergency rooms, decrease otitis media in children, and prevent school and/or work absenteeism. New vaccines are produced each year to match circulating viruses.
INDICATION In 2010, (ACIP) expanded the recommendation for influenza vaccination to include all individuals six months of age and older. Annual vaccination is recommended for those at high risk for complications and severe disease, such as:
1. 6 months through 4 years (59 months) of age 2. Are 50 years 3. Have chronic disease 4. Immunosuppressed 5. Are or will be pregnant during the influenza season 6. Are 6 months through 18 years of age and receiving long-term aspirin therapy (and may be at risk for Reye syndrome after influenza virus infection) 7. Are residents of nursing homes and other chronic-care facilities 8. Morbidly obese (body mass index [BMI] 40 for adults 9. Healthcare personnel 10. Household contacts or caregivers of children <5 years and adults 50 years of age, with particular emphasis on contacts of children <6 months 11. Household contacts or caregivers of persons with medical conditions that put them at increased risk for severe complications of influenza
The ideal time for vaccination is during October or November to allow for the development and maintenance of immunity during the peak of the influenza season.
VACCINES TYPE In the United States, two different types of influenza vaccine are available, inactivated influenza vaccines (IIVs) and a live-attenuated vaccine (LAIV). Current influenza vaccines are trivalent or quadrivalent. The trivalent vaccine contains two influenza A virus antigens and one influenza B virus antigen, whereas the quadrivalent vaccine contains two influenza A antigens and two influenza B antigens
LAIV
PEDIATRIC VACCINATION (6 MONTH 8 YEARS) If they have never received seasonal influenza vaccine (ie, this is their first season of vaccination), or if their vaccination status cannot be determined, they should receive 2 doses separated by 4 weeks, in order to achieve satisfactory antibody response.
THE COMMON COLD
The most prevalent viral infection is the common cold. The frequency of the occurrence of a cold is greater in younger children and decreases with increasing age. Although the common cold is self-limiting, otitis media occurs in approximately 20% of children following infection. Many viruses have been isolated from patients with respiratory infections, but rhinovirus is the most common viral pathogen. Other pathogens include coronavirus, parainfluenza, RSV, adenovirus, and enterovirus. Because of the number of pathogens known to cause the common cold, development of an effective vaccine remains difficult.
TREATMENT Treatment for the common cold is directed at pharmacologic treatment of symptoms. NSAIDs, oral or intranasal decongestants, antihistamines, and antitussives may be used. However, these products provide minimal relief of symptoms and do not shorten the natural course of infection.
IN PEDIATRIC PATIENTS YOUNGER THAN 2 YEARS, THE USE OF COUGH AND COLD MEDICATIONS IS NOT RECOMMENDED BY THE FDA DUE TO THE DEATHS ASSOCIATED WITH THEIR USE.
PREVENTION Zinc, a dietary supplement, has been studied in both the prevention and treatment of the common cold. Echinacea is an herbal product extracted from the Echinacea plant. Echinacea is believed to stimulate the immune system, specifically phagocytosis.
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