010 Respiratory Disorders.pdf

respiratory disorders Hany A. Omar, Ph.D Professor College of Pharmacy, UoS Office: M23-140 Office hours: Mon & Wed 11:00-12:00 email: [email protected]  Respiratory structures such as the airways, alveoli and pleura...

respiratory disorders Hany A. Omar, Ph.D Professor College of Pharmacy, UoS Office: M23-140 Office hours: Mon & Wed 11:00-12:00 email: [email protected]  Respiratory structures such as the airways, alveoli and pleural membranes may all be affected by various disease processes Influenza : Suddenly , Higherfever stronger common cold : These respiratory diseases include: Gradually 1. Infections such as pneumonia. 2. Obstructive disorders that obstruct airflow into and out of the lungs such as asthma, bronchitis and emphysema. 3. Restrictive disorders are conditions that limit normal expansion of the lungs such as pneumothorax, respiratory distress syndrome and cystic fibrosis. 4. Cancers or exposure to Inhaled particles alter the pulmonary function.  General symptoms of respiratory disease Hypoxia : Decreased levels of oxygen in the tissues Hypoxemia : Decreased levels of oxygen in arterial blood Hypercapnia : Increased levels of CO2 in the blood Hypocapnia : Decreased levels of CO2 in the blood Dyspnea : Difficulty breathing Tachypnea : Rapid rate of breathing Cyanosis : Bluish discoloration of skin and mucous membranes due to poor oxygenation of the blood Hemoptysis : Blood in the sputum  Respiratory infections Infections of the respiratory tract can occur in: 1. The upper respiratory tract or 2. The lower respiratory tract, or 3. Both. Organisms capable of infecting respiratory structures include: 1. bacteria. 2. viruses: the majority of upper respiratory tract infections are caused by viruses as rhinovirus and parainfluenza virus. 3. fungi. Depending on the organism and extent of infection, the manifestations can range from mild to severe and even life threatening. Upper respiratory tract Infections The Common Cold The most common viral pathogens for the “common cold” are rhinovirus, parainfluenza virus, respiratory syncytial virus, adenovirus and coronavirus. These viruses tend to have seasonal variations in their peak incidence. They gain entry to the body through the nasal mucosa and the surfaces of the eye. They are readily spread from person to person via respiratory secretions. Manifestations of the common cold include: Rhinitis: Inflammation of the nasal mucosa Sinusitis :Inflammation of the sinus mucosa Pharyngitis : Inflammation of the pharynx and throat Headache Nasal discharge and congestion Upper respiratory tract Infections Influenza Influenza is a viral infection that can affect the upper or lower respiratory tract. Three distinct forms of influenza virus have been identified: A, B and C, of these three variants, type A is the most common and causes the most serious illness. The influenza virus is a highly transmissible respiratory pathogen. Because the organism has a high tendency for genetic mutation, new variant of the virus are constantly arising in different places around the world. Serious pandemics (spread of infection across a large region) of influenza are seen every 8 to 10 years as a result of this genetic mutation. Upper respiratory tract Infections Influenza Symptoms of influenza infection: causes ->  Headache Fever, chills Tripers cytokines Muscle aches Nasal discharge AUnproductive cough Sore throat Influenza infection can cause marked inflammation of the respiratory epithelium leading to acute tissue damage and a loss of ciliated cells that protect the respiratory passages from other organisms. As a result, influenza infection may lead to co-infection of the respiratory passages with bacteria. It is also possible for the influenza virus to infect the tissues of the lung itself to cause a viral pneumonia. Upper respiratory tract Infections Influenza Treatment of influenza:  Bed rest, fluids, warmth  Antiviral drugs  Influenza vaccine : Provides protection against certain A and B influenza strains that are expected to be prevalent in a certain year. The vaccine must be updated and administered yearly to be effective but will not be effective against influenza strains not included in the vaccine. The influenza vaccine is particularly indicated in elderly people, in individuals weakened by other disease and in health-care workers Upper respiratory tract Infections imp he will ask about effective Inhibit the releaseoen n Influenza Not very T &Drugs for Treating Influenza: Amantidine Used orally or by aerosol administration Effective only against type A influenza Inhibits viral fusion, assembly and release from the infected host cell inhibits the & attachment innailed orally Neuraminidase inhibitors (Zanamavir, Oseltamivir) New drugs that can be used by inhalation (Zanamavir) or orally (Oseltamivir) needed to other Effective against both type A and B influenza move Inhibits the activity of viral neuraminidase enzyme that is necessary for spread of the influenza virus  Lower respiratory tract Infections The respiratory tract is protected by a number of very effective defense mechanisms designed to keep infectious organisms and particulates from reaching the lungs. For an organism to reach the lower respiratory tract, the organism must be particularly virulent and present in very large number or the host defense barriers must be weakened. Factor that might weaken the respiratory defense barriers: Cigarette smoking, which can paralyze the cilia lining the cells of the respiratory passages and impair removal of secretions, particles and microorganisms. The presence of a respiratory pathogen such as the cold or influenza virus.  Lower respiratory tract Infections Defenses of the Respiratory System 1. Moist, mucus-covered surfaces : Trap particles and organisms 2. Cell surface IgA, lysosomes 3. Ciliated epithelium : Clears trapped particles and organisms from airway passages 4. Cough reflex and epiglottis : Prevents aspiration of particles and irritants into lower airways 5. Pulmonary macrophages : Phagocytize foreign particles and organisms in the alveolar spaces Lower respiratory tract Infections Pneumonia Pneumonia is a condition that involves inflammation of lower lung structures such as the alveoli or interstitial spaces. It may be caused by bacteria or viruses such as pneumocystis carinii. - The prevalence and severity of pneumonia have been heightened in recent years due to the emergence of HIV as well as antibiotic resistance. Pneumonia may be classified according to the pathogen that is responsible for the infection. There tend to be distinct organisms that cause pneumonia in the hospital setting vs. the community setting. Lower respiratory tract Infections Pneumonia Individuals Most at Risk for Pneumonia Elderly Those with viral infection Chronically ill AIDS or immunosuppressed patients Smokers Patients with chronic respiratory disease e.g. bronchial asthma. Lower respiratory tract Infections Pneumonia Community acquired pneumonia (CAP) Aspiration pneumonia Hospital Hospital acquired pneumonia (HAP) Ventilator associated pneumonia (VAP) Healthcare associated pneumonia (HCAP) Lower respiratory tract Infections Pneumonia Potential Pathogens Typical bacteria Streptococcus pneumoniae Hemophilus influenzae Mycobacterium catarrhalis Klebsiella pneumoniae Atypical Atypia ca Chlamydia pneumoniae Legionella pneumophila Mycoplasma pneumoniae. Viruses Fungi Lower respiratory tract Infections spectu regitated bacteria - Pneumonia A second classification scheme for pneumonia is based on the specific structures of the lung that the organisms infect and includes typical and atypical pneumonia. Typical pneumonia bacterial Usually bacterial in origin. Organisms replicate in the spaces of the alveoli. Manifestations: Inflammation and fluid accumulation are seen in the alveoli. White cell infiltration and exudation can be seen on chest radiographs. High fever, chest pain, chills, and malaise are present. L Purulent sputum is present. green Some degree of hypoxemia is present. Lower respiratory tract Infections Yellowish or transparent viral Pneumonia Atypical pneumonia viral Usually viral in origin. Organisms replicate in the spaces around the alveoli. Manifestations: Mildersymptoms than typical pneumonia. Lack of white cell infiltration in alveoli. Lack of fluid accumulation in the alveoli. Not usually evident on radiographs. May make the patient susceptible to bacterial pneumonia. Lower respiratory tract Infections Pneumonia Opportunistic organisms A number of organisms not commonly associated with respiratory illness in otherwise healthy individuals can cause severe respiratory infections and pneumonia in patients with HIV or those who are immunocompromised as a result of immune suppressive therapy. These organisms include mycobacteria, fungus (Histoplasma) and protozoa (Pneumocystis carinii). Treatment of these organisms requires specific drug therapy, and, in the case of protozoa and fungi, the organisms are very difficult to kill. Lower respiratory tract Infections Pneumonia Treatment of pneumonia: Antibiotics if bacterial in origin. The health-care provider should consider the possibility that antibiotic-resistant organisms are present. Oxygen therapy for hypoxemia. A vaccine for pneumococcal pneumonia is currently available and highly effective. This vaccine should be considered in high-risk individuals.  Respiratory Tract Drugs To treat acute & minor To treat chronic & conditions serious conditions 1. Nasal congestion 1. Bronchial Asthma 2. Cough 2. Chronic bronchitis 3. Seasonal allergies 3. Cystic fibrosis Genetic 4. Emphysema  Drugs used to treat respiratory tract irritation & control secretion These drugs are used to treat symptoms of cough & irritation that result from: – Common cold – Seasonal allergies – Upper respiratory tract infections. This group includes: preven ecough o > - 1. Antitussives 2. Decongestant 3. Antihistamines - - 4. Mucolytics & Expectorants ↓ More irretation lung in watery  1-Antitussives Jes The drugs used to suppress cough associated with common cold & minor throat irritation. They are usually prescribed only for short term use in relieving symptomatic coughing. Turns to Morphine1. Codeine ↓ cough stops bystopping it from medulla 2. Hydrocodone very / espective 3. Diphenhydramine - ② Anti ne · histamivery7 The reason for the cough The cililiated cells in the : Lessective not lung try to expel something from the lung "Defence" Common side effects are: Sedation, Dizziness, GIT upset  deadbacteria and dead viruses collection of dead cells and Spectur The : Greenish- > Bacteria yellowish virus Transparent- > if spectum that you have very sticky expel you can't use mucolytic ↓ sputum/mucous breakdown substances into more watery Antihistamine 2-Decongestants Congestion & mucosal discharge (runny nose) are features of many respiratory conditions like: 1. Allergies 2. Common cold 3. Respiratory Tract Infections Most of the used drugs are alpha-1 agonists to stimulate the alpha-1 receptors in the blood vessels of the nasal mucosa. They cause vasoconstriction & effectively drying up the mucosal vasculature & decreasing local congestion in the nasal passages. Can be given systemically or locally. Common side effects are: Headache, Dizziness, Nervousness, Nausea and CVS problems Drugs Used to Treat Chronic & Serious Conditions  Airway obstruction is a major problem in respiratory disorders such as o Bronchial asthma o Cystic fibrosis o Chronic bronchitis COPD o Emphysema The goal of drug therapy of these conditions is to prevent or reverse the bronchial constriction & obstruction of the airways by the use of o Bronchodilators o Anti-inflammatory agents. Bronchial Asthma  Bronchial Asthma Asthma is a chronic inflammatory disorder of the airway caused mostly by an immunologic reaction to known allergens. Disease of airways, characterized by episodes (attacks) of “reversible” bronchoconstriction due to increased responsiveness of bronchial tree to various stimuli in only - asthma Binding of allergens to IgE (on mast cells) results in release of histamine, LTs, PGs and ILs. Narrowing of air passages, causing breathlessness, cough and wheezing  Bronchial Asthma 10 % of adults 22 % of children 30% of all people at some time in their lives Most live normal lives, but several hundred deaths each year.  Bronchial Asthma Trigger factors – Allergens – Irritants – Respiratory infection – Aspirin & NSAIDs in some patients  Bronchial Asthma How NSAIDs may trigger bronchoconstriction? blocksa me inhibits > - stricti ↳ a inhibits  Bronchial Asthma Emotional stress may induce an attack, so have patient’s inhaler available for use during his visit to the dental clinic and try to minimize stress. Metered-dose (MDI) Disk Inhalers Turbuhaler Inhalers  Chronic Obstructive Pulmonary Disease - COPD is a chronic, slowly progressive disorder characterized by airflow obstruction, which does not change markedly over several months. It Chronicitationa includes bronchitis and emphysema. e Chronic bronchitis is characterized by chronic or recurrent cough with sputum production on most days in the absence of other diseases recognized to cause sputum production. Emphysema is characterized by gradual progressive loss of lung elastic tissues - Tobacco smoking is the most important and dominant risk factor for the development of COPD.  Drug Classes used in Respiratory Diseases Bronchodilators – ß2 adrenoreceptor agonists – Anticholinergic drugs – Xanthines (theophylline) Anti-inflammatory drugs – Corticosteroids Inhaled Systemic – Cromolyns – Leukotriene receptor antagonists Other – Omalizumab  ß2-Adrenoreceptor Agonists Act selectively on ß2 receptors in smooth muscle in airways to cause relaxation Also inhibit release of inflammatory mediators ATP β-agonist + Adenyl Cyclase - contraction in skeletal Bronchodilatation nhibitor I cAMP Vasodilatation - - Inhibit mediator release Theophylline - Phosphodiesterase rade des increasing Camp CAMD 5`AMP  ß2-Adrenoreceptor Agonists Short acting agents – For symptom relief Salbutamol Terbutaline Long acting agents – For prophylaxis Salmeterol It is also available combined with corticosteroids  ß2-Adrenoreceptor Agonists ↓ Usually given by inhalation Because of very high first pass clearance, systemic adverse effects minimised Short acting group – Rapid (5 -15 minutes) onset of action – 3 - 6 hours duration of action Long acting group – 10 - 30 minutes onset of action – 12 hours duration of action – Useful for nocturnal attacks and prophylaxis  ß2-Adrenoreceptor Agonists Adverse effects – Tremor, muscle cramps – Tachycardia (ß1 effect), palpitations – Headache – Agitation, especially in children – Hypokalemia  Corticosteroids Anti-inflammatory Reduce bronchial hyperreactivity Increase number of ß2 adrenoreceptors – Increase responsiveness to ß2 agonists One of the first line agents  Corticosteroids Delivered by inhalation o Beclomethasone o Fluticasone – Very potent agents - local effect High first pass clearance Few systemic adverse effects in adults if daily dose less than 200 µg (beclomethasone) Adverse effects: dysphonia; oropharyngeal candidiasis Hangvoire a Prednisolone: oral  physiologicalsor e an Corticosteroids Decemsense met Systemic adverse effects – Thin skin & hematoma – Impaired wound healing Ssoodgat etisisn'tone h – – Susceptibility to infection Adrenal impairment - Do t – Bone density loss, cataract, impaired growth enough s – Diabetes, hirsutism, acne, psychosis  will He ask Anti-inflammatory Preventers - Cromolyns Cromoglycate; nedocromil for prevention a meanne Inhibit release of inflammatory mediators from mast cells Useful in maintenance (preventive) treatment, especially in children Given by inhalation, almost none absorbable Adverse effects – Throat irritation – Cough  Theophylline Bronchodilator; by increasing cAMP level Useful in acute asthma and in prophylaxis in asthma and COPD Given orally, usually as slow-release form Hepatic clearance Narrow therapeutic index – Anorexia, nausea, vomiting – Epileptic seizures, cardiac arrhythmias – blood level monitoring is useful  Anticholinergic Bronchodilators (Ipratropium, Tiatropium) Inhibit cholinergic bronchial tone Useful in acute asthma and in maintenance treatment of COPD Given by inhalation - local action Few adverse effects when used by inhalation: – Dry mouth worsen – Rarely urinary retention and exacerbation of closed angle glaucoma  Leukotriene Modifiers - Act by suppressing effects of Leukotriene (LTs). - Members of this class include: o Zleuton (inhibits LTs synthesis) o Montelukast and Zafirlukast (block LTs receptors). - They are used orally - Effective in prevention of aspirin and exercise-induced asthma - Allow reduction or cessation of inhaled corticosteroids  Adverse effects - Headache, abdominal pain, diarrhoea - Angioedema, anaphylaxis  Omalizumab “Xolair” Monoclonal antibody against IgE in the blood and interstitial fluid. Used to control severe allergic asthma, which does not respond to high doses of corticosteroids Given by subcutaneous injection every 2-4 weeks May cause thrombocytopaenia Similar drugs: Reslizumab (Cinqair), Mepolizumab (Nucala), Benralizumab (Fasenra). Omalizumab treats severe asthma that’s triggered by allergies while others treat severe asthma that’s caused by a type of white blood cell (eosinophilic asthma).  Oxygen O2 therapy is sometimes indicated in hypoxic patients (Asthma in severe attacks). A maximum concentration of 24% oxygen is used as higher concentrations result in fall of ventilation, CO2 retention and respiratory acidosis. Must observe patient carefully, and measure his blood gases Chronic Obstructive Pulmonary Disease (COPD)  Chronic Obstructive Pulmonary Disease (COPD) Is persistent obstruction of the airways.  COPD Chronic Bronchitis Long-standing inflammation of the bronchial tree Characterized by production of sputum on most days for 3 months of 2 successive years. May cause obstruction and narrowing of the airway lumen with excess mucous.  COPD Emphysema A pathological condition in which there is dilatation of the air spaces by destruction of the alveolar walls. Obstruction results from the decrease of the lungs’ elasticity, which normally holds the airways open in expiration.  COPD 1. Smoking 2. Alpha-1 anti-trypsin deficiency  Smoking Cigarette smoking is the most important cause of COPD, although only about 15% of smokers develop the disease. Lung function improves only a little if people stop smoking. With aging, susceptible cigarette smokers lose lung function more rapidly than nonsmokers.  termain limite is a Alpha1-Antitrypsin (A1AT) Deficiency A1AT is an enzyme produced by the liver which inhibits the action of other enzymes called proteases. Proteases break down proteins as part of normal tissue repair. A1AT protects the lungs from the damaging effects of proteases. Genetic deficiency of A1AT or due to smoking causes Emphysema.  Features of COPD 1. Cough 2. Excessive Sputum 3. Dyspnoea 4. Wheezing 5. Hyperinflation 6. Cyanosis 7. Loss of weight  Treatment of COPD The aim of treatment is to maintain the airway open & prevent airflow restriction. 1. Bronchodilators (β-2 agonist , anticholinergic,theophylline) 2. Corticosteroids 3. Mucolytics & Expectorants 4. Chest physiotherapy Cystic Fibrosis  Cystic Fibrosis CF is an orphan (not common) genetic disease characterized by abnormal transport of chloride across an epithelium, leading to thick, viscous secretions. Caused by mutation in cystic fibrosis transmembrane conductance regulator (CFTR) gene Mucous plugging of the bronchioles may result in: 1. Pneumonia 2. Bronchitis 3. Pulmonary fibrosis  Cystic Fibrosis Treatment The aim of treatment is to maintain the airway patent as much as possible. 1. Bronchodilators 2. Mucolytics & Expectorants 3. Corticosteroids 4. Antibiotics to treat infections 5. Ivacaftor is a "potentiator" of CFTR. It forms cell-membrane pores allowing ion transport [similar to the antifungal agent amphotericin B (AmB)] https://www.nature.com/articles/d41586-019-00781-y SARS-CoV-2 SARS-CoV-2 SARS-CoV-2 Vaccines  - Management of mild/moderate COVID-19 patients: home-based care and community centres Case Management Team, WHE/WHO, HQ Geneva  Classification of severity of patients with COVID-19 infection See WHO website for most up-to-date case definition: https://www.who.int/emergencies/diseases/novel-coronavirus- 2019/technical-guidance  Non-severe COVID-19 infection MILD disease: Symptomatic patients meeting the case definition for COVID-19 without evidence of pneumonia or hypoxia MODERATE disease: Patients with clinical signs of pneumonia (fever, cough, dyspnoea, fast breathing) but no signs of severe pneumonia, including SpO2 ≥ 90% on room air. https://www.who.int/publications/m/item/covid-19- home-care-bundle-for-health-care-workers https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021-1 Risk factors for severe disease in patients with COVID-19 infection LOWER RISK: Children and young adults become infected but are less likely to become seriously ill. They can also transmit the disease. HIGHER RISK: Risk of severe disease increases with age and in those with underlying noncommunicable diseases. Risk factors for severe disease include: Older age (> 60 years), overweight/obesity, hypertension, diabetes, cardiac disease, chronic lung disease, cerebrovascular disease, dementia, mental disorders, chronic kidney disease, immunosuppression (including HIV), cancer, smoking. In pregnancy, increasing maternal age, high BMI, non-white ethnicity, pre-existing comorbidities and pregnancy-specific conditions such as gestational diabetes and pre-eclampsia. How to monitor a COVID-19 patient who is at risk of severe disease If a patient is at risk for severe disease*: Monitor oxygen saturation with pulse oximeter at least twice a day. If oxygen saturation is lower than 90% instruct patient and caregiver to call for emergency help immediately. Photo: WHO If oxygen saturation is between 90–94% instruct patient and caregiver to call for emergency help, as this range may be an early sign for deterioration. Oral corticosteroids may be described at this time by a clinician. Supplemental oxygen at home should be medically prescribed and supervised by a health worker.  Management of mild/moderate COVID-19 cases at home Vital signs and assessment measures: temperature, blood pressure, SpO2, AVPU  Management of MILD and MODERATE COVID-19 - Antibiotics should NOT be prescribed unless there is explicit clinical suspicion of a bacterial infection (in addition to COVID-19). Few patients with COVID-19 experience a secondary bacterial infection. - Treat symptoms – Give antipyretics (paracetamol) for fever – Ensure adequate nutrition – Ensure adequate hydration - Encourage the patient to take rest when needed but to try to resume activities at appropriate pace. - Support of patient’s psychosocial needs No specific medication has been approved and recommended against mild and moderate COVID-19 (https://www.who.int/publications/i/item/WHO-2019-nCoV-therapeutics-2021.1) https://www.bmj.com/content/370/bmj.m3379 Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis. https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30423-7/fulltext Empiric antibacterial therapy and community-onset bacterial coinfection in patients hospitalized with coronavirus disease 2019 (COVID-19): a multi-hospital cohort study. https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1239/5895253 Home-based care for COVID-19 patients: toolkit COVID-19 home care bundle for health care workers (who.int)  Referral to hospital or health care facility When to refer to hospital 1. Severe and critical cases 2. Moderate cases with risk factors 3. Mild or moderate cases that present worsening of symptoms: - Chest pain, - Difficulty breathing (at rest or while speaking), - Confusion or altered mental status, - Loss of speech or mobility. Any other emergency sign:  Conclusions - Screening and triage of patients with COVID-19 infection: identify the best plan for case management depending on severity and risk factors. - Monitoring and follow up of patients at home or in community facilities is crucial (measure vital signs: pulse oximeter). - Identification of emergency signs or clinical deterioration – to refer if necessary to the next level of care.  Thank you References  Lippincott Illustrated Reviews: Pharmacology 6th edition (Lippincott Illustrated Reviews Series), Ed. K. Whalen, 6th Edition, 2014, Pub. Lippincott Williams & Wilkins, Philadelphia, ISBN-13: 978-1451191776  Basic & Clinical Pharmacology. Ed. B.G. Katzung & A. J. Trevor, 14th Edition, 2017, Pub. McGraw-Hill, New York City, ISBN-13: 978-1259641152.