Midterm Therapy 2 PDF

Respiratory Diseases ventilation Clinical Pharmacy 2 - Air in CO2) - -Airout (102) function in bronchi...

Respiratory Diseases ventilation Clinical Pharmacy 2 - Air in CO2) - -Airout (102) function in bronchi gas exchange I [diffusion] Asthma Part one - in alveoli have we airways in College of Pharmacy / Petra University bronchi - broncho constriction ↓ Pharmacology & Biomedical Sciences Department & 91(3)? 1;1) , 5 -? Prof. Salim Hamadi - breathlessness (SOB dyspnea) 2022-2023 ,  Asthma: A) Definition 1) GINA 2019 Definition of asthma ♣E Asthma is a heterogeneous disease, usually characterized by chronic airway inflammation. - - ⑭ ♣ It is defined by the history of respiratory symptoms such as wheeze, ⑤ / ② SOP ③ ⑭ shortness of breath, chest tightness and cough that vary over time and in - late night or early intensity, together with variable expiratory airflow limitation. morning - Every common)  " Asthma: A) Definition - -I Asthma is a disease characterized by: lablas 5 - 1) Symptoms: variable & recurring => 5. - 59295 2) Airway obstruction (that is at least partially reversible spontaneously or with treatment) ↳ bronchodilators 3) Airway inflammation (chronic) -> need anti-inflammatory. - 4) Airway hyperresponsivness to a variety of stimuli 6 I j > (BHR) -> Bronchial Hyper Responsivness. BHR = the tendency of airways to narrow excessively in response to triggers that have little or no effect in normal individuals.) ► Reversibility of airflow limitation may be incomplete in some patients with asthma  Asthma: B) Epidemiology ►Asthma is the most prevalent chronic disease of childhood, and it causes significant *dis s osd morbidity and mortality in both adults and children. ►About 235 million adults and children worldwide have asthma. ►In the United States, asthma affects 8% of adults (18.7 million) and 9.3% of children (6.8 million). ►Asthma is the primary diagnosis for 14.2 million physician office visits, 1.8 million emergency department visits, and 3345 deaths annually. ►Prevalence of asthma in children diagnosed by a physician between the Amman city group and Bedouins (8.8% versus 9.5%). ►Asthma is also a significant economic burden in the United States, with costs totaling nearly $60 billion annually. ►Prescription medications are the single largest direct medical expenditure and account for 71% of direct medical costs.  Asthma: C) Etiology >Cause - risk factor Asthma is a partially heritable complex syndrome that results from a complex interaction of genetic and environmental factors. 1) Genetic factors account for 60% to 80% of the susceptibility. &3 >59 8 ↑. j. Atopy &  Links between Atopy (genetically determined state of hypersensitivity to. environmental allergens manifested as the presence of positive skin-prick tests or the clinical response to common environmental allergens = genetically mediated predisposition to an excessive IgE reaction) ) and asthma. More recent: Atopy linked with genes for metalloproteinase (ADAM33) 2) Environmental risk factors: Trigger factors of acute asthma may include The following: (see next slide) ♣ Although genetic predisposition to Atopy is a significant risk factor developing asthma, not all atopic individuals develop asthma, nor do all patients with asthma exhibit senvironment), Asthma 5) % => genetic 5) j = 115 Atopy Atopy &- 19) - ↓ non-selective BB Allergic Atopic Rhinitis Eczema  risk & 1961 15 X - Asthma: C) Etiology: Trigger factors Respiratory infection RSV, rhinovirus, influenza, parainfluenza, Mycoplasma pneumonia Allergens Airborne pollens (grass, trees, weeds), house-dust mites, animal danders, cockroaches, fungal spores Environment Cold air, fog, ozone, sulfur dioxide, nitrogen dioxide, tobacco smoke, wood smoke Emotions Anxiety, stress, laughter Exercise Particularly in cold, dry environments Drugs / preservatives Aspirin, NSAIDs (COX-I), sulfites, benzalkonium chloride, nonselective β- blockers 255. ♣ General: Asthma is a disease of exacerbation and remission (Recurring) , so the patient may not have any signs or symptoms at the time of examination. ♣ Symptoms: The patient may complain of episodes of dyspnea (SOB), chest tightness, coughing (particularly at night), wheezing, (depending upon severity of asthma). ♣ Signs: Expiratory wheezing on auscultation, dry hacking cough, or signs of atopy (allergic rhinitis and/or eczema) may occur. ·i ! -- sig 2) Acute Severe Asthma (also referred to as status asthmatics) (Exacerbation) Is an acute (exacerbation) of asthma that does not respond to standard treatments of bronchodilator & corticosteroid (inhalers) -ss6l · - -I : - Es , ♣ Symptoms: The patient is anxious in acute distress and complains of severe dyspnea, SOB, chest tightness. The patient is only able to say a few words with each breath. Symptoms are unresponsive to usual measures (short-acting inhaled β2agonist administration). HR , BP, temperature ↓ ♣ Signs: expiratory and inspiratory wheezing on auscultation, dry hacking cough,Vital signs may reflect 2 i 361 tachypnea, tachycardia, and hypoxemia, pale or cyanotic skin, and hyperinflated chest.  Asthma: H) Diagnosis:  The diagnosis of asthma should be based on A) Patient Medical history: nature of symptoms, precipitating factors, profile of asthmatic attack. Symptoms : variable & recurring, wheeze, SOB, chest tightness, cough B) Presence of risk or precipitating factors, profile of asthmatic attacks. ! "I C) Pulmonary function tests: (PFTs): to demonstrate:- partially reve. 51551 A) Obstructive , B) Assess reversibility, C) Variability ♥ Respiratory disease can alter: 1) the mechanism of airflow to & from alveoli (ventilation), 2) gas exchange between alveoli and blood stream (diffusion). = : 15 - ! ♥ Abnormalities in airway function (Airflow or ventilation) are measured by:- A) Spirometry or B) peak expiratory flow (PEF) more accurate. / -14 I A) Spirometry: & ,3 It measures the abnormality in ventilation. It is useful as an index of the degree of obstruction and the amount of reversibility. It is a diagnostic as well as assessment of progress. de ⑤ ↳ · E st  Asthma: H) Diagnosis 1) Degree of obstruction  Most useful test for abnormality in airway function by Spirometry are: - Is g s 14 a) FEV1: Forced Expiratory Volume in the first second of exhalation. It is usually expressed as the percentage of the total volume of air exhaled b) FVC: Forced vital capacity : The total volume that the patient can forcibly exhale in one breath. c) FEV1/FVC ratio: useful, reproducible measure of the capabilities of lung in moving air. Normal person can exhale at least 75%-80% of their vital capacity in one second and all bronchconstriction of it in three second. - · 5/s , FEV1 normally is 80%of the FVC T 0 - - 31 -> Fobstruction In asthmatic patient: FEV1/FVC < 0.7 Normal FVC = 4-5 L, FEV1 = 3.2-4 L Measured FEV1 compared against “predicted normal” values for patients with similar physiologic characteristic (age, race, height, weight, gender)  Asthma: H) Diagnosis Is 5%)1 ; 2) Reversibility =) ex : COPD C irreversable reversable Reversible pulmonary function is a ≥12% increase FEV1 or PEFR after inhaling a #>⑧@°@° short-acting bronchodilator (SABA) (using Spirometry or peak flow meter) Confirming the diagnosis of asthma 3) Diurnal variability (day to day variation) -3 Variability of > 20% is highly suggestive of asthma. 5% in good control - 5 B) Peak flow meter: to measure peak expiratory flow rate (PEFR): Patient can test PEFR at home with a hand peak flow meter. ►Peak flow meters are helpful for assessing both the severity of airway obstruction and the response to bronchodilator therapy Normal adult, young PEFR = 550-700 l/min. Normal children PEFR = 150-200 L/min.  Asthma: H) Diagnosis D) Blood analysis: Typically shows a slight increased WBCs count during an acute exacerbation, eosinophil also may present. IgE level may increases (Allergy). Other test include: sputum eosinophil count & fraction exhale of nitric oxide (FENO) E) Pulse oximetry Another means of assessing the patient's ability to oxygenate tissues adequately is to measure oxygen saturation. ♣ It is a noninvasive means of the degree of hypoxemia during an acute exacerbation. It measure oxygen saturation in arterial blood (Sao2) & pulse. i artery /1. - - W F) Blood Gas Measurements:IArterialS blood gas measurements (ABG) (Gas diffusion) gauge the severity of the asthma exacerbation I ♣ ABG is the indicators of overall lung function (ventilation and diffusion). It may be required to help.. &.. I Des ABG include measurement of PaO2, PaCO2, and pH. Respiratory acidosis is a poor prognostic sign. It develops if hypoxemias worsen & the patient's respiratory rate is not maintained owing to respiratory fatigue. This results in a rising PaCO2 level. Hypercapnia. G) An ECG may show sinus tachycardia, especially in older patients.  Case study 1 - Case study 2 A 20- year- old man have FVC of 4.8 and FEV1 A 65-year-old smoker has a predicted normal FEV1 of 3.8L, but of 4 L when not experiencing asthma because of chronic bronchitis and asthma, his FEV1 chronically symptoms. During an acute exacerbation, the runs as 0.8L. Bronchodilator raise his FEV1 to 1L. FEV1 in the same patient falls to 3L. After Although his FEV1 has increased by 0.2L ( a 25% change), this bronchodilator therapy, FEV1⑧ rises to 3.5L patient remains severely obstructed Is asthma in this patient reversible?? Clinically significant improvement is considered either an increase Si-> Change of 0.5L or 17% % so 12 it's reversable of > 0.2L in FEV1 and/or subjective improvement in symptoms N FEV1. , 591() fEvis - 0. I 5/3 = 16 6. % 1) Degree of obstruction 2) Reversibility 3) Diurnal variability (day to day variation) Overview of asthma therapy Asthma lecture Part two College of Pharmacy / Petra University Pharmacology & Biomedical Sciences Department Prof. Salim Hamadi 2022-2023 Since asthma consists of both  1) bronchoconstriction &  2) inflammation, therefore, therapy should be directed to control of these two cardinal features of asthma: Brochodilator Antiinflammatory.  Clinical Overview of asthma therapy prevental [5-s gigdis- daily uses - - for chronic asthma 3 - X acute & 51 - [rescue] when - acute -> releive the needed - asthma Symptoms · only.. 1) Controller medications: Long-term control 61 : St 1 - -SI I - medications ♥ Used to achieve and maintain control of persistent asthma. ♥ Preventers & controller: Daily, long-term control of 3 2 asthma, prevents further attacks local I -> 351 -551 is side effect -.. > systemic/ -1s-1 * absorption is zero (no side effect] & Inhaler + LABA 3 Clukast) y (crom) 2) Add-on Controller Medication I inhibit Ach -> ↳ antimuscarinic sympathetica z I interlukein -> oral , injection 3 SABA : short acting LAMA : Long acting muscarinic antagonist Reliever Medication ?: Used to treat acute ↓ short symptoms and exacerbations. acting ♥ As needed: relievers (Rescue) * (SAMAS I 2 3 - I 3 ⑱ ⑦ ⑤5 =°@°@°->  - ⑤@°@④I ⑤°@⑧ Surgery]  / Bronchodilators: A) Short-acting bronchodilators: 1) Short- acting bronchodilators (SABA) 2) Short acting muscarinic bronchodilators (SAMA) B) Long –acting bronchodilators: 1) LABA 2) LAMA  Overview of asthma therapy Quick-relief medications "Relievers" 1) -agonists: Sympathomimetic agents: A) Selective B2-agonist most widely used (Albuterol,{Salbutamol outside USA], terbutaline, pirbuterol, Rimiterol, salmeterol, formoterol. (end with ole) · ►Selective B2-agonist are safe and replace non-selective adrenergic agents that was used in the past. ► They are potent bronchodilator & their clinical effects include:- a) Bronchodilation: relax airway smooth muscle by directly stimulating B2-adrenergic ****** ⑰- ⑭*** ⑦.5 ↳°@° !.I -. ⑤@}@ receptors in the airway, activate adenyl cyclase, which increase intracellular production @°@° of cyclic adenosine monophosphate (c AMP) b) Improve mucocilary clearance, stabilize mast cell membranes c) Reduced inflammatory cell mediators release.  Overview of asthma therapy ►Inhaled B2-agonist are classified as rather short- or long-acting based on their duration of action * 1) Short-acting B2-agonist (SABA) : bronchodilator, They have no anti-inflammatory effect. Indication of inhaled SABAs ►Are the most effective bronchodilators and are the drugs of choice for treating: A) acute asthma (Rescue), treatment of acute exacerbation and not for regular use B) Symptoms of chronic asthma C) Preventing exercise-induced bronchospasm: The early- phase response to antigen in asthma exacerbation is blocked by pretreatment with inhaled SABAs. short acting. ►Inhaled SABAs have an onset of action< 5 minutes and a duration of action of 4-6 hours. ) >]a)> · > ♦ Albuterol : the most commonly used inhaled SABA, is available as an MDI and solution for nebulization. ♦ Levalbuterol:- )>)$@x the pure R-enantiomer of albuterol, is available as an MDI and solution for nebulization. =°@°@°@°π@⑦ =@°@°@π ⑤@⑤°@°@π@- ►Levalbuterol has similar efficacy to albuterol and is purported to have fewer side effects; however, clinical trials have not demonstrated this benefit.  Overview of asthma therapy * 2) Long-acting B2-agonist (LABA) ►Salmeterol and formoterol are LABA provide up to 12 hrs. of bronchodilation after a single dose, but slow onset of action, so they used in prophylactic (controller, preventer) duration : in chronic asthma, daily uses, but not in the treatment of acute asthma long + ex : LABA * I eX : SABA short -> ►Formoterol - is a full agonist that has an onset of action similar to that of albuterol, but it is not currently approved for the treatment of acute bronchospasm in the United States, but it is approved for this use in Europe. Formoterol: immediate relief (as fast as :i - Salbutamol), with long duration? releiver' j ►Salmeterol - is a partial agonist with an onset of action of approximately 30 minutes. Indication for long-acting -agonists (LABAs) 1)are Maintenance treatment of moderate & severe persistent asthma in combination with - I inhaled corticosteroids (especially for patients with frequent symptoms) - 2) Prophylaxis of EIB  Overview of asthma therapy 3) Patients with COPD. * 4) Because of the long duration of bronchodilation, these agents are useful for patients experiencing nocturnal symptoms. -> ↳> LABA gly g ♣ LABAs should not be used as monotherapy for chronic asthma. There may be an increased risk of severe asthma exacerbations and asthma-related deaths when LABAs are used alone. Therefore, LABA should be used with ICS ♣ LABA should not be used as sole therapy for an acute asthma exacerbation ♣ LABAs are indicated for chronic treatment of asthma as add-on therapy for patients not controlled on low to medium doses of ICS. ♣ Adding an LABA to ICS is at least as effective in improving symptoms and decreasing asthma ) ⑧ ⑦· ⑤°@°@° ⑱... >@S - exacerbations as doubling the dose of an ICS or adding an LTRA to ICS., in addition to reduce the amount of ICS. LABAs may be used alone (monotherapy) if they used to prevent EIB or nocturnal asthma ex ♣ ►Example on combination of LABA should be used with ICS: Salmeterol and formoterol are available : - as single-ingredient products and as fixed-ratio combination products containing an ICS (fluticasone /salmeterol, budesonide/formoterol, or mometasone/formoterol). ♣  ~> 0. 10. Administration & dosage of B2-agonist: oralsiss Sigo s [1- Inhalation is preferred to minimize adverse effects. Inhaled versus oral: inhaled is preferred due to: 1) dose in 1/10 oral, therefore less SE. 2) Direct delivery to bronchi, caused rapid onset. Problem with inhaler: patient should use inhaler properly. S2-Systemic administration: tablet or syrup ⑧ (onset: ↳ 1/2-1 hr, duration 4-8hrs). @°@|⑧⑦@> The limiting side effect of orally B2-agonist is-tremor Side effects of B2-agonist -) oral si.s gl.. )ree)s ♣ Cardiac effects: Albuterol, terbutaline, and all other β–agonists are cardiac stimulants that may cause tachycardia. Because they are relatively β2-specific, the * cardiac effects are more prominent with systemic - ↳ administration °π@- - =°x - (as opposed to inhalation) and at higher dosages. I. I°@-> @ =°@ - ⑦- ♣ Hypokalemia:⑱.. ⑧ ⑮. ⑰ β2-adrenergic result in activation of the Na+-K+ pump and subsequent transport of > potassium intracellularly. However, at usual doses, aerosolized albuterol and terbutaline cause relatively little effect on serum potassium. The effects may be more noticeable with systemic (oral or injectable) administration. A β2-adrenergic–mediated increase in glucose and insulin secretion also can contribute to the intracellular shift of potassium ♣ Shakiness (tremors) (Skeletal muscles stimulation), due to stimulate B2 receptors in skeletal muscle ♣ β-Adrenergic Agonist Subsensitivity (Tachyphylaxis): (type of tolerance) (decreases the duration but not onset of bronchodilation ⑮ provided > ! > ⑦ by>>>>> the SABA) which may be due to:- ! 1) !°@π-@π@°@°@°@°@°@°@ Scheduled SABA use, down regulation of receptors, disease progression, or true drug tolerance, or * ⑱④* $@π receptor polymorphism  Overview of asthma therapy - -113 2- Corticosteroids (CTS) : (symptoms controllers) : cornerstone of chronic asthma therapy ►Corticosteroids are the most potent anti-inflammatory agents available for the treatment of asthma and are available in inhaled, oral, and injectable dosage forms. Clinical effects: 1) Reduced production of inflammatory mediators (decrease airway inflammation). 2) Mast cell stabilization effects ⑧@②= ⑦* @_ $⑤°@ I ⑳ ⑤$ > -> that decrease airway hyperresponsivness & the inflammatory response 3) Decreased * - - ⑦ ⑦@= mucus * production, * *4) Prevention of endothelial & vascular leakage, =@π@°@°π⑦= 5) Partial reversal of tissue remodeling. 6) Enhanced -adrenergic receptor expression (thus making the 2-agonist work better, improve the response to B2 agonist) ↳$ A) Inhaled Corticosteroids (ICS) ♥ ICS are the preferred - ⑧ - ⑮ ⑳ ↳ ↳ @ therapy for all forms of persistent asthma ⑦°@ - in all age groups ♥ ♥ The primary advantage of using ICS compared with systemic corticosteroids is the targeted drug - delivery to the lungs, which decreases the risk of systemic adverse effects.  Overview of asthma therapy ♥ All ICS are equally effective if given in equipotent doses. pharmacokinatic ! 5 * ♣ Cigarette smoking decreases the response to ICS, and smokers require higher doses of ICS than nonsmokers. ♥ Although some beneficial effect is seen within 12 hours of administration of an ICS, 2 weeks of therapy A is necessary to see significant clinical effects. Longer treatment may be necessary to realize the full effects on airway inflammation. " - 0 ♣ Local adverse effects of ICS include oral candidiasis, cough, and dysphonia. The incidence of local ·Sit adverse effects can be reduced by using an MDI with a VHC and by having the patient rinse the mouth with water and expectorate after using the ICS. -Is  Overview of asthma therapy B) Systemic Corticosteroids: They are effective as both long-term control and rescue [releiver] medications. ♣ Prednisone, prednisolone, and methylprednisolone are the cornerstone of treatment for acute asthma not responding to an SABA. ♣ The duration of therapy usually ranges from 3-10 days. Tapering the corticosteroid dose in patients receiving short bursts (up to 10 days) is usually not necessary because any adrenal suppression is transient and rapidly reversible. ♣ Because of serious potential adverse effects, systemic corticosteroids are avoided as long-term controller medication for asthma, if possible. se :  Systemic SE of Corticosteroids Cushing-like syndrome (redistribution of body fat) , puffy face , increase body hair growth , acne , insomnia ,aincrease appetite , impaired wound healing (increased risk of infection),- adrenal suppression, decreased ↓ bone mineral density, skin thinning, cataract , osteoporosis, worsening of diabetes, hypertension, stomach - irritation, nervousness, restlessness and easy - bruising. - 11 & ↓ & , Is 951554S  Overview of asthma therapy Administration & dosing of corticosteroids A) Systemic corticosteroids ♥ Oral systemic corticosteroids are used for moderate and severe exacerbations as adjunct to SABAs to speed recovery and prevent recurrence of exacerbations ♥ They are used for rapid response during an exacerbation.(♥ For treatment of asthma acute exacerbation in adults) 8 ↳ëÓ ►Oral Prednisolone ⑤)> 2mg/kg (Max: 60mg/day), IV- treatment: methylprednisolone 120-180mg/day in 3-4 ↳ divided doses for 48hr. The dosage is then reduced to 60-80mg/day until PEFR reach 70%. ④· =@π@°@ ) >. >. ►For outpatient burst therapy, the dosage of Prednisolone is 1-2mg/kg/day (max: 60mg/day). in 1-2 divided doses for 3-10 days. -C is drug of choice B) Inhaled corticosteroid ♥ ICS is DOC in patient with moderate to severe asthma ⑤@°@⑦@ who requires inhalation of B2-agonist > twice daily.(Chronic asthma) ⑤) > => - Examples: beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, mometasone furoate, triamcinolone acetonide, ciclesonide  Overview of asthma therapy 3) Anticholinergic (Antimuscarinic agents) Work => on parasympathetic. ♣ They inhibit the effects of acetylcholine on muscarinic receptors in the airways smooth muscles and protect against cholinergic-mediated bronchoconstriction. ♣ The bronchodilating effects of anticholinergic agents are not as pronounced as SABAs in asthma (less). Response to anticholinergic is most pronounced in patients with fixed airway obstruction (e.g.,- COPD) Anticholinergic (Antimuscarinic agents) are of two types (end with ium) A) Short-acting Antimuscarinic Agents (SAMA)  Atropine: SE limited its use (due to systemic absorption). => not used anymore =>9615 - ↓ modification  Ipratropium bromide (Atrovent®) is available as an MDI and solution for nebulization & useful ↳ 24 hours. ♣ It used (off-label) 5min 5 as a long-term controller medication in patients ≥18 years with uncontrolled asthma. - i i -> effective - less SABA+LAMA , : LAMA SAMA already taking an ICS or an ICS andaction LABA combination. S , onset of - less Cantagonist) - ↓55 ♣ It decreases severe I exacerbations, SABA LABAimproves lung function, and isused 11 > , steroid sparing. in ♣ The sympathetic acute newer anticholinergics (B2-agonist) aclidinium bromide and Umeclidinium bromide have less clinical evidence - supporting their use in asthma.  Overview of asthma therapy 4) Anti-allergic drugs: Cromolyn sodium (Intal) and nedocromil sodium (Tilade) => slow onset. They are non-steroidal drugs with anti-inflammatory properties, no bronchodilatory effect. They stabilize mast cell membrane. They are used as prophylactic & should be used for maintenance therapy of persistent asthma or for prevention of EIB. They are not effective during acute asthma exacerbation. They are less effective than inhaled corticosteroids, however, because of their safety profile, they are sometime used in children. They are effective in both antigen & exercise induces asthma & chronic asthma.  Patients may notice improvement in 1 to 2 weeks, but maximal benefit may not be seen for 4 to 6 weeks. Available in only inhalation dosage form: MDI Nedocromil is approved for 12 years and older and is more effective than cromolyn sodium (which is used in all ages)  Both agents are well tolerated with adverse effects limited to cough and wheezing. Bad taste and headache have also been reported with nedocromil  Overview of asthma therapy 5- Leukotrienes Modifiers: we do modification : we don't give it to asthma patient because it inhibits 1) inhibit Lox cox only and Lox will eX zilenton They are non- :. cause inflamation. 2) Leukotriene & corticosteroid with anti- receptor antagonist. inflammatory effect ex : Mon, Zafir. CAspirin) They are use in asthma as prophylactic (controller). ►Leukotrienes: potent COX inflammatory mediators S LOX most potent Si A Block * 21 ⑧ >inflamation. & I ⑪  ↓ corticosteroid (5561) 2 3 - lenkotrein anti-allergic (201) Overview of asthma therapy ITherapeutic effects of- - Leukotrienes Modifiers 1- They have anti-inflammatory & bronchodilator activity, they may allow reduction in corticosteroids doses in some patients. 2- They considered second line agents since they are less effective anti-inflammatory than inhaled corticosteroids. IS = 1. 3- In children, inhaled drugs is challenging, therefore, oral leukotriene receptor antagonist mat be useful. 4- They may be useful in patients with concurrent allergic rhinitis & asthma. 5- They are the agent of choice in aspirin –induced asthma, or exercise-induced bronchospasm. ♣ Although these agents offer the convenience of oral administration, they are significantly less effective than low ICS doses. ♣ Combining an LTRA with an ICS is not as effective as an ICS plus an LABA but is considered steroid sparing.  Overview of asthma therapy ♣ Two types of Leukotrienes Modifiers ↑ A) Leukotrienes receptor antagonist (LRA): B) Lipooxygenase inhibitor (LOX-inhibitor) (Montelukast & Zafirlukast) ♥ Zileuton: is the only one approved by FDA is. It They are selective LRA; therefore, they prevents the formation of leukotrienes, by blocking 5- prevent leukotriene from interacting with their receptors. lipoxygenase. -I ♣ Zileuton is less commonly used because the need for Montelukast advantages over Zafirlukast: dosing four times daily, potential drug interactions, and ♣ Montelukast is generally well tolerated potential hepatotoxicity with the resulting need for with minimal need for monitoring and few frequent monitoring of hepatic enzymes drug interactions. ♥ For patients ≥12 years of age; liver function monitoring ♥ Single daily dose, ♥ lower age indication (used in children six year old), ♥ Lack of food is essential effect on absorption, ♥ lower drug ♣ ♣ Zileuton and Zafirlukast are metabolized through interaction. (Zafirlukast (twice daily, the CYP 2C9 hepatic pathway and have significant drug hepatotoxicity…drug interaction) interactions.  Overview of asthma therapy Adverse effects of Leukotrienes Modifiers : ♥ Headache, dyspepsia, diarrhea, abdominal pain. Elevation of liver enzymes occur with all three agents (Zileuton > Zafirlukast > Montelukast). ♥They are competitive inhibitor of the CYP2C9 hepatic isoenzyme (drug interaction with warfarin ). ♥ Churg–Strauss syndrome, a form of eosinophilic vasculitis, has rarely been associated with Zafirlukast, Montelukast. ♣ All three agents have reports of neuropsychiatric events, such as sleep disorders, aggressive behavior, and suicidal thoughts. 6- Xanthenes Derivatives: Theophylline, Aminophylline. ♣ They are PDE-Inhibitor & adenosine receptor antagonist which lead to bronchodilation. ↳ CAMPS1$lgs- A) They produce bronchodilation to a lesser extent than -agonist. I B) They may also have some degree of anti-inflammatory activity. 1) Be-agonist (5501) 2) anti-muscarinic 3) Xanthenes (201)  Overview of asthma therapy Clinical Indication: 1) They indicated if -agonist & corticosteroids fail to control an acute asthma exacerbation. 2) They are alternative to long-acting -agonist in treatment of persistent asthma. 3) They are most beneficial as an adjuvant to inhaled corticosteroids in patient with nocturnal or early morning symptoms. Theophylline: its use is limited because of : A) Inferior efficacy as a long-term controller medication compared with ICS, B) A narrow therapeutic index with potentially life-threatening toxicity (required monitoring) C) Multiple clinically important drug interactions. D) Poorly tolerated (side effects)  Overview of asthma therapy 7) Immunotherapy A) Anti-IgE monoclonal antibodies: Omalizumab (Xolair®) ♣ It is a recombinant humanized monoclonal anti-IgE antibody that inhibits binding of IgE to receptors on mast cells and basophils, resulting in inhibition of inflammatory mediator release and attenuation of the early- and late-phase allergic response. ►It is indicated for treatment of patients with moderate to severe persistent asthma whose asthma is not controlled by ICS and who have a positive skin test or (documented allergy) ►It significantly decreases ICS use, reduces the number and length of exacerbations, and increases asthma-related quality of life. not at home -> > anaphylactic shock ►It is given as a SC every 2-4 weeks in the office or clinic. The initial dose is based on the patient’s weight and baseline& total serum IgE concentration. ►The most common adverse effects are injection site reactions and include bruising, redness, pain, subcutaneous stinging, itching, and burning. Anaphylactic reactions are rare but may occur at any time after medication administration. ►It has been associated with an increased risk of cardiovascular and cerebrovascular events (eg, and perhaps cancer, but the magnitude of the increased risk is unclear.  Overview of asthma therapy B) Monoclonal Antibodies against cytokines (Interleukin 5) 1) Mepolizumab ♣ Mepolizumab is a humanized IgG1 kappa monoclonal antibody specific for interleukin 5. ♣ Mepolizumab binds to IL-5 and therefore stops IL-5 from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding to eosinophils reduces blood, tissue, and sputum eosinophil levels. ♣ It is indicated for add-on maintenance treatment of patients with severe asthma aged ≥ 12 years and with an eosinophilic phenotype. ♣ It has a significant improvement in decreasing asthma exacerbations and emergency department visits or hospitalization. 2) Reslizumab ♣ It is an IgG kappa monoclonal antibody that inhibits IL-5. It was approved by the FDA 2016 and is indicated for add-on maintenance treatment of patients with severe asthma aged ≥ 18 years with an eosinophilic phenotype. & ♣ It is administered as an IV every 4 weeks. ♣ It had a significant reduction in the frequency of asthma exacerbations of up to 59%  Overview of asthma therapy Other agents: -> not for Asthma ♣ Antihistamines are useful for patients with coexisting allergic rhinitis; however, their role in the treatment of asthma remains unclear. Antihistamines compete with histamine for H1-receptor sites on effector cells and thus help prevent the histamine-mediated responses that influence asthma. tyma -> not for ♣ Antibiotics are generally not used for the treatment of asthma, unless other signs of infection are present. until (bacterial) ♣ Magnesium sulfate, administered intravenously, may be useful in some patients because of its modest ability to cause bronchodilation. When administered intravenously, it also improves respiratory muscle strength in hypomagnesemic patients. Research has suggested that magnesium may reduce admission rate and improve FEV1 in severe, acute asthma exacerbations and in stable, chronic asthma.  Asthma lecture part three Asthma GINA GUIDLINE - College of Pharmacy / Petra University Pharmacology & Biomedical Sciences Department Prof. Salim Hamadi 2022-2023  Asthma GINA Guidline In asthma lecture part one, Definition, characteristics of asthma, pathophysiology , diagnosis , and clinical presentation of asthma were presented as in GINA guideline 2022 In asthma lecture two, An overview of asthma medications Asthma lecture part three: management of asthma will be presented based on GINA guideline : 1961 I's ! git Before stating management , the *= 51 I's I following should be reviewed W X X  I ↓1 /s & · : 515 -> -59 I 3 feedback no drug fit - ↓D SID all patient ~$1 ↳. 2  GINA Stepwise treatment GINA developed stepwise Assessing treatment based on age: asthma severity 1) Adult & adolescent ⑩ Five steps for treatment 1) Mild asthma 12 + years 95 46 1 I Step1 & step 2 2) Children 6-11 years 2) Moderate asthma Step 3 3) Children 5 years and 3) Severe asthma younger Step 4 & 5  The GINA treatment figure for adults and adolescents For clarity, the GINA treatment figure now shows two ‘tracks’, based on evidence about outcomes with the two reliever choices across asthma severity Track 1, Track 2, ♣ With low dose ICS-formoterol as the reliever, ♣ With SABA as the reliever, is an alternative is the preferred approach approach SABA+ICS. ♣ Using ICS-formoterol as reliever reduces the ♣ Use this, if Track 1 is not possible, or is not risk of exacerbations compared with using a preferred by a patient with no exacerbations on SABA reliever, with similar symptom control their current controller therapy and similar lung function ♣ Before considering a regimen with SABA reliever, consider whether the patient is likely to be adherent with daily controller – if not, they will be exposed to the risks of SABA-only treatment Treatment may be stepped up or down within a track using the same reliever at each step, or switched between tracks, according to the patient’s needs and preferences  Adults & adolescents 12+ years Sever Moderate Mild 1 "S reliever 2 GINA 2023 Adults & Adolescents Track 1 GINA 2023 Adults & Adolescents Track 2 Anti-inflammatory Maintenance and reliever Maintenance and reliever reliever (AIR) therapy (MART) therapy (MART) Therapy alone: steps 1-2 Step 3 Step 4-5 Budesenide-formetrol * Budesenide-formetrol 200/6, 1 inhalation twice daily or 200/6, 1 inhalation for once as maintenance treatment, plus one inhalation as symptom relief needed for symptoms relief  Asthma medications are categorized as controllers, relievers, and add-on therapies: 1) Controllers (SMART) contain ICS, which reduce airway 2) Relievers (AIR) air (low-dose ICS– formoterol or SABA) contain rapid-onset inflammation, control symptoms, and reduce the risks of exacerbations , bronchodilators. They are used “as even in mild asthma, and of asthma death. “Maintenance” therapies are needed” (i.e., for quick relief of symptoms, including during controllers that are prescribed for daily use. exacerbations). ♣ Single Maintenance and Reliever Therapy: (SMART)(MART): ♣ Using ICS–formoterol as a reliever (often called an “anti-Inflammatory Combination of with ICS/ formoterol (budesonide and formoterol) as reliever” or “AIR”) also reduces the risk both maintenance and quick-relief therapy. of severe exacerbations, compared with a SABA reliever, both with or without ♣ double-blind trials show that budesonide/formoterol delivered as maintenance controller treatment. SMART achieves better asthma outcomes than budesonide monotherapy ♣ SABA or ICS–formoterol is also recommended before exercise if needed to or lower doses of budesonide/formoterol delivered in separate prevent exercise-induced formulations. bronchoconstriction. ♣ SMART strong recommendation on supporting SMART with ICS/ formoterol in both step 3 and step 4 3) Add-on therapies are mainly for patients with difficult-to-treat or severe asthma.  The risks of SABA-only treatment is :**B I 1) Regular use of SABA, (even for 1–2 weeks), is associated with adverse effects - A) B-receptor downregulation, B) Decreased bronchoprotection, C) Rebound hyperresponsiveness, * D) Decreased bronchodilator response; D) Increased allergic response, and E) Increased eosinophilic airway inflammation 2) Higher use of SABA is associated with adverse clinical outcomes -Is S :1 ♠ Dispensing of ≥3 canisters per year (i.e. daily use) is associated with higher risk of severe exacerbations ♠ Dispensing of ≥12 canisters per year is associated with much higher risk of death ►Inhaled corticosteroids reduce the risk of asthma deaths, hospitalization and exacerbations requiring oral corticosteroids (OCS), BUT adherence is poor, particularly in patients with mild or infrequent symptoms  ;j.-1D Treatment of acute asthma -53615 1961 - : - 50 ►In acute asthma, the severity of an exacerbation does not depend on the classification of the patient’s chronic asthma because even patients with intermittent asthma can have life- threatening acute exacerbations. Severity at the time of evaluation can be estimated by signs and symptoms or presenting PEF or FEV1. Acute asthma (exacerbation) is considered: ♥ Mild if the patient is only having dyspnea with activity and the PEF is at least 70% of the personal best value, ♥ Moderate if the dyspnea limits activity and the PEF is 40% to 69% of the personal best. ♥ Severe with PEF less than 40% and dyspnea interferes with conversation or occurs at rest. When the patient is not able to speak or the personal best PEF is ˂ 25% of the personal best predicted value, it is a life-threatening exacerbation.  2) Management of acute asthma Management of acute severe asthma in adults in hospital: SABA ►Immediate treatment: Chigh dose because of ►Oxygen ►Salbutamol 5mg via an oxygen-driven nebulizer. symptoms) · ►Ipratropium bromide 0.5mg via nebulizer, ►Prednisolone tablets 40-60mg or IV hydrocortisone 100mg or both if very ill, ►No sedatives of any kinds (C/I) ↳ contraindicated. systemic S ►Subsequent management S - ►If patient is improving continue: ►40-60% oxygen, ►Prednisolone 40-50mg daily or IV-hydrocortisone 100mg 6 hourly. ►Nebulized B2-agonist & Ipratropium 4-6 hourly. ►If patient not improving after 15-30 minutes: ►Continue oxygen & steroid ►Give Nebulized B2-agonist more frequently (salbutamol 5mg every 15-30min or 100mg hydrocortisone every hour. ►Continue Ipratropium 0.5mg 4-6 hours until patient improving. ►If patient is still not improving; ►Discus patient with senior clinician & ICU team. ►IV-magnesium sulfate 1.22gm over 20min) ►May consider use of IV-B2-agonist or IV-aminophylline  Exercise-Induced Bronchospasm (EIB) ♣ EIB is defined as a drop in FEV1 of ≥15% from baseline (pre-exercise value). ♣ Patients with persistent asthma may experience EIB. ♣ The exact pathogenesis of EIB is unknown, but heat loss and /or water loss from the central airways appears to play an important role. ♣ EIB is provoked more easily in cold, dry air; Alternatively, warm, humid air can blunt or block it. ♣ Studies have demonstrated increased plasma histamine, cysteinyl LTs, prostaglandins levels during EIB, suggesting a role for mast cell degranulation. EIB can usually be prevented with one of the following options: (1) SABA (albuterol) should be administered 5-15 min. before exercise (< 3hrs). These are considered the drug of choice for EIB. (2) LABA (Salmeterol) Because of its rapid onset, formoterol may be dosed 15 min. before exercise. But generally, SABA are preferred over LABA. (3) Nedocromil may be used to prevent EIB and exacerbations related to exposure to other asthma triggers. Nedocromil should be administered no more than 1 hr before exercise or exposure. (4) Leukotriene modifiers given daily help with EIB but should not be used on an as-needed basis just before exercise.  Special Populations A) Pregnancy ►Since uncontrolled asthma is a greater risk to the fetus than asthma medication use, it is safer for pregnant women to have asthma treated with medications than to experience worsening asthma. ►Consequently, asthma exacerbations should be managed aggressively with pharmacotherapy. ► The stepwise approach to asthma therapy in pregnancy is similar to that for the general population. ►Budesonide has the most safety data in humans and is the preferred ICS; it is the only ICS classified as pregnancy category B. ►Albuterol is the drug of choice for the treatment of asthma symptoms and exacerbations in pregnancy.  Special Populations B) Young Children ► Although asthma is the most common disease in children, diagnosing and monitoring it in this population is challenging. Treatment in children 0 to 4 years of age is extrapolated from studies completed in adults and older children. ►Albuterol and ICS are the treatments of choice in this group. However, use of montelukast is common because of the drug formulation. ►Route of delivery is an important issue. Nebulization treatment is commonly used, and MDI with VHC is becoming more popular due to its decreased time of administration compared with nebulization. ►Budesonide is the only corticosteroid available in nebulization form and is approved for use in this age group.  Special Populations C) Nocturnal asthma: ♣ Is a worsening of asthma during sleep. ♣ Patients with nocturnal asthma exhibit significant falls in pulmonary function between bedtime and awakening. ♣ Most experts consider nocturnal symptoms to be a sign of inadequately treated persistent asthma. Awakening from nocturnal asthma is a sensitive indicator of both severity and inadequate control. ♣ Factors contribute to nocturnal asthma (Although the pathogenesis of this phenomenon is unknown) 1) it has been associated with diurnal patterns of endogenous cortisol secretion and circulating epinephrine(lowest at midnight), 2) Increased release of inflammatory mediators, increased activity of parasympathetic nervous system 3) patient with GERD. ►Initial treatment is the same for other population. ►LABA is preferred over SABA as bedtime dose since LABA (duration 12hrs) ►Check the proper use of ICS since inflammatory process is essential to both asthma & nocturnal.  College of Pharmacy / Petra University Pharmacology & Basic Biomedical Sciences Department Prof. Salim Hamadi 2022  COPD: Definition & Introduction 5 - ►COPD is define as a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases.(GOLD 2023) ♦ The most common persistent respiratory symptoms include: ( dyspnea, chronic cough, and sputum production along with persistent airflow limitation that is not fully reversible. ►Airflow limitation is often progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases (rather than allergic substances as in asthma) ►COPD is primarily affect the lung, it also associated with systemic consequences (extra-pulmonary manifestations that may contribute to disease severity in individual patients) ►Chronic bronchitis & Emphysema and are two commonly used terms that reflect the spectrum of this disease and are often used as pathologic subtypes of COPD. 1) Chronic bronchitis: is clinically defines as a chronic cough with excessive mucus secretion that occurs on most days for at least 3 months for 2 consecutive years, Its pathologic hallmark involves inflammation & fibrosis of small airway. 2) Emphysema: is pathologically defined & characterized by alveolar wall destruction & air-space enlargement, without obvious fibrosis.  COPD: Epidemiology · Is Si heavy /. 8 I I smokers ♣ COPD is currently the fourth leading cause of death in the world. It is projected to be the 3rd leading cause of death by 2020. ♣ More than 3 million people died of COPD in 2012 accounting for 6% of all deaths ♣ Globally, the COPD burden is projected to increase in coming decades because of continued exposure to COPD risk factors and aging of the population. ♣ COPD exacerbations are the most significant contributor to the cost burden of the disease accounting for approximately 50% to 75% of all costs. ♣ COPD is also a leading cause of disability in the United States.  COPD is the leading cause of hospitalization in the older population. ♣ Prevalence of COPD was higher in smokers and ex-smokers compared to non-smokers ♣ In most patients, COPD is associated with significant concomitant chronic diseases, which increase its morbidity and mortality.  COPD: Etiology & Pathogenesis ♥ The exact mechanisms responsible for the pathogenesis of COPD are not entirely clear, but likely involve activation of the innate and adaptive immune system leading to chronic inflammation. The following are the proposed etiology of COPD: 1) In general, inhalation of noxious agents, such as cigarette smoke, leads to the activation of resident immune and parenchymal cells, which in turn recruit additional inflammatory cells from the systemic compartment into the resident tissue and airway ♣ The activation and recruitment of immune cells is largely mediated through the production and release of cytokines and chemokines. 2) Recent evidence also supports a role for oxidant stress as a disease mediator. The consequences of an oxidant-rich environment include the activation of inflammatory genes, inactivation of antiproteases, stimulation of mucus secretion, and increases in plasma exudate.  COPD: Etiology & Pathogenesis 3) The most well studied cause of COPD, and particularly emphysema, relates to protease–antiprotease imbalance. In this setting, inflammation promotes the production and release of proteases from inflammatory and parenchymal cells. When the local concentration of antiproteases becomes overwhelmed, proteases go unchecked and destroy the major connective tissue components in the lung, such as elastin, leading to the irreversible loss of alveoli. The classic example of this occurs in patients with α1-antitrypsin deficiency. jbX13 trypsin ↳ - an 4) Although the traditional idea of disease pathogenesis focuses on smoking-related lung injury, more recent hypotheses suggest that another important component of disease pathogenesis may involve inadequate lung repair. Indeed, there is evidence that normal lung homeostatic mechanisms are altered in COPD. This may involve inadequate production of growth factors as well as altered regulation of apoptosis, or programmed cell death. Summary of etiology of COPD 1) Inhalation of noxious agents, such as cigarette smoke 2) oxidant stress 3) protease–antiprotease imbalance 4) inadequate lung repair  COPD: Risk factors 1) Environmental factors (exposures) 2) Host factors A) Tobacco smoke exposure: A) Genetic factors  Direct smoking  1-antitrypsin deficiency is the strongest  Environmental (passive smoking) single genetic risk factors (1-2% of COPD) B) Other environmental exposure B) Airway responsiveness , allergy &  Occupational dust,  Chemicals (Vapors, respiratory infections fumes, irritants) when exposures are sufficiently intense or prolonged. Air pollution: Indoor & outdoor pollution C) Impaired lung growth D) Age: increasing age results in ventilator impairment (most frequently related to cumulative smoking) F) Gender G) Social, economic & hereditary factors.  COPD: Pathology ♣ The airflow obstruction caused by COPD is usually progressive and is attributed to pathologic changes in the lung. ♣ The major pathological changes in COPD affect four major different compartments of the lung & all are affected in most COPD patients to vary degree. 1) Central airways -⑤ - $ s chronic · Clarge) - cough 2) Peripheral airways ~ High mucus. (small) (important???) 3) Lung parenchyma (respiratory wSS - ~gas bronchioles, alveoli & capillaries) exchange - sever hypoxemia 4) Pulmonary vasculature:  COPD: Pathology & Physiology 4) Pulmonary vasculature ♣ In the later stages of COPD, chronic hypoxemia causes persistent vasoconstriction in the lung vascular õÓé ⑤@|ï bed, particularly the small pulmonary arteries. This can result in permanent structural alteration of the -> - blood vessels, causing intimal hyperplasia and smooth muscle hypertrophy. vasoconstriction of the pulmonary - arteries and promoting vessel wall remodeling. Hypoxemia plays the primary role in the development of pulmonary hypertension. - ⑯@ ⑭>))))>)>⑦④⑦ ♦ The loss of pulmonary capillaries in emphysema can also contribute to increased pulmonary · vascular - pressures. The cumulative impact of vascular changes can result * & in progressive pulmonary hypertension and, eventually, right-sided cardiac failure (cor pulmonale). Cor pulmonale is associated with venous stasis and thrombosis that may result in pulmonary embolism. - ♣ Pulmonary hypertension is the most common cardiovascular complication of COPD and can result in cor =°=> pulmonale, or right-sided heart failure.  COPD: Pathology & Physiology: -512/ Significant Comorbid Illness ♣ Systemic consequences of COPD ►As COPD progresses, additional systemic consequences can arise, including cachexia, skeletal muscle dysfunction, osteoporosis, depression, and anemia. The cause of these additional systemic disease processes is not entirely clear but likely involves the dynamic interplay of progressive respiratory dysfunction, lung and systemic inflammation, side effects from medication use, and physical debilitation. ♣ In summary, although COPD is primarily a disease of the large and small airways and adjacent alveolar structures, it also includes important systemic consequences. The clinical consequences of the morphologic and pathophysiologic alterations include progressive dyspnea on exertion, chronic cough and sputum production, increased risk for respiratory infections, deconditioning, and an overall reduction in quality of life. ► Progressive loss of skeletal muscle mass in longstanding COPD contributes to exercise limitation and declining health status.( Another important systemic effect of COPD) ►These extra-pulmonary effects may contribute to disease severity and should not be overlooked.  ③ ⑩ ② - J  COPD: Clinical presentation ►Symptoms Symptom onset is variable and does not correlate well with severity of airflow limitation measured by FEV1. Initial symptoms include chronic cough (> 3 months), chronic sputum production, and dyspnea on exertion. Patients may complain of a sensation of heaviness in the chest. As COPD progresses, dyspnea at rest and/or orthopnea develop, and ability to perform activities of daily living declines. ►Signs Inspection may reveal use of accessory muscles of respiration (paradoxical movements of the chest and abdomen in a seesaw-type motion), pursed-lips breathing, and hyperinflation of the chest with increased anterior– posterior diameter (“barrel chest”). On lung auscultation, patients may have distant breath sounds, wheezing, a prolonged expiratory phase,  Diagnosis and Initial Assessment 1) COPD should be considered in and dyspnea, chronic cough or sputum production, and/or a history of exposure to risk factors. Symptoms of COPD 2) Spirometry is required to make the diagnosis Chronic and progressive dyspnea 3) Concomitant chronic diseases occur frequently in Cough COPD patients, including cardiovascular disease, Sputum production skeletal muscle dysfunction, metabolic syndrome, Wheezing and chest tightness osteoporosis, depression, anxiety, and lung cancer. Others – including fatigue, weight loss, anorexia, syncope, ♣ These comorbidities should be actively sought and rib fractures, ankle swelling, treated appropriately when present as they can depression, anxiety. influence mortality and hospitalizations independently. 2) Spirometry (gold standard diagnosis test) ♣ It should be performed when the patient‘s condition is 1) stable & 2) after dose of SABA (post bronchodilator): ♣ It is used to: A) Confirm the diagnosis of COPD, using FEV1) / FVC ratio :- ►A post-bronchodilator FEV1/FVC ratioa< 70%> (0.70) confirms airflow limitation that is not fully reversible. - ↳ (to define airflow limitation).>12 SABA ⑧ B) Further to classify severity of > airflow limitation in COPD ?????? ↳ irreversable.  COPD: Diagnosis B)The GOLD classification categories of severity based on post-bronchodilator FEV1 as follows: Four “grades” are used to classify the degree of airflow limitation using post- bronchodilator Spirometric results in patients with an FEV1/FVC 80% predicted >80% 50% A) Increased sputum purulence(Change color). :5 ·:181 - B) Either increased sputum volume(volume change) C) Or increased dyspnea(Increased breathlessness ) D) patients with all three of these symptoms, or patients who require mechanical ventilation. ►The most common bacterial pathogens isolated during COPD exacerbations are: Haemophilus influenzae, Streptococcus pneumonia, and Moraxella catarrhalis  Treatment of acute exacerbation of COPD ⑳ Summary of treatment of acute exacerbation of COPD Therapy Comments 1) Antibiotics Recommended if two or more of the following are present: r 1) Increased dyspnea, 2) Increased sputum production, 3) Increased sputum purulence 2) Corticosteroids Oral or intravenous therapy may be used. ~ If intravenous is used, it should be changed to oral after improvement in pulmonary status. If continued longer than 14 days, then the dose should be tapered to avoid hypothalamic–pituitary–adrenal axis suppression. 3) Bronchodilators - Nebulization. 4) Controlled oxygen therapy Titrate oxygen to desired oxygen saturation (>90%). ~ Monitor arterial blood gas for development of hypercapnia. 5)Noninvasive mechanical ventilation Consider for patients with acute respiratory failure. u  Asthma COPD Age at onset Usually < 30 Usually >40 Sudden onset of disease Often Almost never Family history Usually Uncommon History of atopy Often Uncommon Smoking history Variable Essentially always Allergy Often Sometimes Dyspnoea Often (i) Often Wheezing Often Sometimes Coughing Sometimes Often Sputum production > Seldom Often Crave)  Asthma COPD Chronic airflow limitation Seldom Almost always Variable airflow limitation Almost always Seldom Reversible airflow limitation Almost always Partial Airway hyperresponsiveness Almost always Sometimes Diurnal peak expiratory Almost always Sometimes Progressive deterioration Uncommon Typical (ideal) Anticholinergic responsivity B-agonist better Best first-line B-agonist responsivity Very good Anticholinergic better Steroid responsiveness Strong Usually weak  asthmas -8 55. , COPD LAMA LABA ICS Asthma SI -- -I - SABA UPPER RESPIRATORY TRACT INFECTIONS Dr. Derar H. Bal’awi Loading… - double sickening. Ss. S. ⑲s Loading… OTITIS MEDIA Eustachian tube  OTITIS MEDIA (OM) - DEFINITION Otitis Media: inflammation of the middle ear. There are three subtypes of otitis media: acute otitis media, otitis media with effusion, and chronic otitis media. The three are differentiated by onset, signs and symptoms of infection, and the presence of fluid in the middle ear Acute otitis media (AOM) symptomatic middle ear infection that occurs rapidly along with effusion, or presence of fluid. Otitis Otitis media Media with effusion (OME) inflammation sign of the middle ear with liquid collected in the middle ear; the signs and andsymptoms sympto of acute infection are absent. frequently precedes the development of AOM or follows its resolution. middle ear fluid is present, but signs and symptoms of infection are absent. Chronic suppurative OM is a chronic inflammation of the middle ear that persists at least 6 weeks and is associated with otorrhea through a perforated TM, an indwelling tympanostomy tube, or a surgical myringotomy.  OTITIS MEDIA – EPIDEMIOLOGY Otitis media is most common in: infants and children, 75% at least one episode by the age of 1 year. ~20% of otitis media cases occur in adults, particularly in those with a history of these infections as a child OM remains the most common condition for which antibacterial agents are prescribed for children in the UK and USA.  OTITIS MEDIA - AETIOLOGY Bacterial and viral cultures of middle ear fluid collected by tympanocentesis from children with AOM showed: 55% with bacteria only, 30% with viruses only, and 15% with bacteria and viruses. (in other studies: up to 85%-90% is bacterial). Common bacterial pathogens include: Streptococcus pneumoniae (25%-50%) gramtVe. nontypeable Haemophilus influenzae (15%-30%) Moraxella catarrhalis (3%-20%) more recent data indicated that Streptococcus pneumoniae and Haemophilus influenzae are now equal due to vaccination. The microbial aetiology may be changing as a result of the introduction and widespread use of the influenza vaccine and pneumococcal conjugate vaccines (PCV). Specifically, the proportion of S. pneumoniae cases may be declining, and the proportion of H. influenzae cases may be on the rise. Viruses: RSV and influenza viruses. Almost all of the episodes are preceded by upper respiratory viral infection. The risk factors for amoxicillin-resistant bacteria in acute otitis media are: attendance at child care centers, recent receipt of antibiotic treatment (within the past 90 days), age younger than 2 years. OTITIS MEDIA – PATHOGENESIS  Children tend to be more susceptible  Eustachian tubes are  shorter make them less functional for drainage and  more flaccid protection of the middle ear from bacterial  more horizontal entry  Young children, especially infants, are more likely to present with nonspecific Vertigo, tinnitus than specific (ear-related) symptoms when they have AOM, which is a dilemma in making the diagnosis. Nonspecific s×s include: fever, irritability, headache, apathy, anorexia, vomiting, and diarrhea.  3 2 4 1 Bullous Myringitis is an infection involving the ear drum. It usually begins with a common cold causing severe pain in the ear, hearing loss and fever. Examination of the ear may reveal the drum to have a clear or reddish blister on it. This condition can be very painful. Tympanocentesis is the trans-tympanic needle aspiration of middle ear contents. Aspiration of fluid reduces middle ear pressure and is very effective in relieving pain. If a culture and sensitivity is to be performed on the aspirate, the external ear canal should be thoroughly cleaned and isopropyl alcohol instilled into the external canal for one minute, then removed. Tympanocentesis can be performed on infants using restraints, local or mild sedation. Older children will be more comfortable if a local or general anesthesia is used. OTITIS MEDIA - COMPLICATIONS  Complications of otitis media  Most common: fluctuating/persistent hearing loss  Infrequent:  mastoiditis,  bacteraemia,  meningitis (most common intracranial complication)  Auditory sequelae.  longer the time spent with otitis media with effusion, the higher is the likelihood of poor linguistic performance. ** Perform hearing evaluation in 3-6 weeks in preschool children, and after 3 months for older children.  30 - 61 i sidt - -5S512.. -3515622 : 5- - - AAP 2013 35. 5 93 ! S ,si!" , ↳5! =9 , =. o macrolides - - - - s Because of the differences in the chemical structures, cefdinir, cefuroxime, Lazithromycin) for type I cefpodoxime, and ceftriaxone are highly unlikely to be associated with cross- : 1 cephalosporins non-type I : reactivity with penicillin. has not received amoxicillin in the past 30 days does not have concurrent purulent conjunctivitis ↳: antibiotic not allergic to 011 I penicillin if it's severe : Ceftriaxone 50mg/kg per day 34 PHARYNGITIS PHARYNGITIS - DEFINITION  Pharyngitis is an acute infection of the oropharynx or nasopharynx.  Other conditions, such as gastroesophageal reflux, postnasal drip, or allergies, also can cause sore throat and must be distinguished from infectious causes. ↳ cheif complaint 53  PHARYNGITIS - MICROBIOLOGY  Viral causes are most common:  Rhinovirus (20%),  Coronavirus (≥5%),  Adenovirus (5%),  Influenza virus (2%),  Parainfluenza virus (2%),  Epstein-Barr virus (>1%)  Primary bacterial causes  Group A β-hemolytic Streptococcus (S. pyogenes) – (GAS)  Pediatrics 20% - 30%  Adults 5% - 15%  Antibiotics should be used only in cases of lab-documented streptococcal pharyngitis with symptoms. Late treatment till 9 days can still prevent complications.  MODIFIED CENTOR CRITERIA FOR CLINICAL PREDICTION OF GABHS PHARYNGITIS 01 : -5- , 15. 95. - =s j8; 1 & / 61sg - ,S: - 66 ! J -Y Q1. is 539194 (91)15; )=5442 ~ i 191 ,j5-5103 5. 1958. Q5 - ⑧ 05 5 bacterial viral 55 &s PHARYNGITIS - TREATMENT  Non-pharmacological  rest,  fluids,  lozenges,  saltwater gargles.  Pain is often the primary reason for visiting a physician,  Acetaminophen or NSAID  Acetaminophen better option because NSAIDs may increase the risk for necrotizing fasciitis/toxic shock syndrome. Symptoms may resolve 1 to 2 days sooner with such interventions.  PHARYNGITIS - TREATMENT  Pharmacological Treatment  Based on their narrow spectrum of activity, infrequency of adverse events/reactions, and modest cost, penicillin or amoxicillin is the recommended drug of choice for those non-allergic to these agents (strong, high).  Penicillin-resistant GAS has never been documented.  Amoxicillin (duration: 10 days) 40mg/1kg  can be used in children because the suspension has a better taste than that of penicillin.  Gastrointestinal side effects and rash are more common.  In patients allergic to penicillin:  Macrolide (duration: 10 days)  First- & second-generation cephalosporin (for 10 days) may be considered first line therapy.  Clindamycin useful for recurrent infection  SINUSITIS Dr. Derar H. Bal’awi Consultant Pharmacotherapist – Infectious Diseases SINUSITIS - MICROBIOLOGY  Viruses are responsible for most cases of acute sinusitis;  Acute bacterial rhinosinusitis (ABRS) (10%)  same bacteria implicated in acute otitis media  70% of bacterial causes of acute sinusitis in both adults and children:  S. pneumoniae, H. influenzae.  M. catarrhalis - frequently implicated in children (25%).  less frequent  Streptococcus pyogenes,  Staphylococcus aureus,  fungi,  anaerobes  Chronic sinusitis  polymicrobial with an increased prevalence of anaerobes  less common pathogens,  gram-negative bacilli  Fungi SINUSITIS – EPIDEMIOLOGY & ETIOLOGY  diagnosed more frequently in children.  Risk factors for ABRS:  viral upper respiratory tract infections  Children  5%-13% complicated by bacterial sinusitis  Adults  0.5%-2% complicated by bacterial sinusitis.  allergic inflammation  less commonly  systemic diseases, cystic fibrosis or ciliary dyskinesia, asthma, immunodeficiency,  trauma: head injury, dental infections  environmental exposures: smoking, swimming, illicit drugs, intranasal medication, nasogastric tube  anatomic abnormalities: septal deviation, nasal polyps E majors55. - 157,3d Eminors A major gi 83  SINUSITIS – TREATMENT: SUPPORTIVE THERAPY 3 ↑ days to avoid rebound 1. Nasal decongestant sprays often used in sinusitis. Neither topical nor oral decongestants and/or antihistamines are recommended as adjunctive treatment in patients with ABRS (strong, low-moderate). 2. Irrigation of the nasal cavity with saline and steam (weak, low-moderate).... ⑤ 3. Mucolytics/expectorant (to decrease the viscosity of nasal secretions)  Guaifenesin. No evidence 1395 - 5619895, 4. Antihistamines / -- I -> - - - : es - Should not be used for ABRS. Have anticholinergic effects, so:  can dry mucosa  disturb clearance of mucosal secretions. Second-generation antihistamines may play a role in chronic sinusitis where allergy is a component. 5. Glucocorticoids intranasally may decrease inflammation causing headache, nasal congestion, and facial pain; however, there is little data in acute sinusitis.86 INCSs are recommended as an adjunct to antibiotics in the empiric treatment of ABRS, primarily in patients with a history of allergic rhinitis (weak, moderate).  - amoxiciling (1 295 51 > Quinolones /Sioxaci is moxi- levo - 400mg 95 = Doxycyclin. , tetracyclin 100mg 2= - CASE – OTITIS MEDIA 98 CASE - PHARYNGITIS CASE - SINUSITIS  Dr. Derar H. Bal’awi Consultant Pharmacotherapist – Infectious Diseases INTRODUCTION  LRTI: Tracheobronchial tree and lung parenchyma.  The most common infections involving the lower respiratory tract include bronchitis, bronchiolitis, and pneumonia.  The diagnosis of viral infections rests primarily on the recognition of a characteristic constellation of clinical signs and symptoms.  In contrast, because bacterial pneumonia usually necessitates expedient, effective, and specific antibiotic therapy, its management depends, in large part, on isolation of the etiologic agent by culture from lung tissue or secretions.  Bronchitis and bronchiolitis are inflammatory conditions of the large and small elements, respectively, of the tracheobronchial tree.  The inflammatory process does not extend to the alveoli.  Bronchitis frequently is classified as acute or chronic.  Acute bronchitis occurs in all ages, whereas chronic bronchitis primarily affects adults.  Bronchiol