Bronchial Asthma

25
1 . Defining Asthma . 3 . Cause . 4 . Pathophysiolo . 5 . Diagnosis . 6 . Treatment . 6.1 Medical . 6.2 Pharmaceutical . 6.3 Long-acting β2- agonist . 2 . Signs and Symptoms . 7 . Drugs of Treatment . 7.1 Short-acting, selective beta2 – adrenoceptor agonists . 7.1 Sablutmol (albuterol) . 8 . Emergency treatment . 9 . Prevention . 10 . prevention drugs . 10.1 Drugs on inhaled 10.1.1 Fluticasone . 11 . Trigger avoidance . Contents

description

wgjkgdjghdgjgdhgjsh

Transcript of Bronchial Asthma

  • Bronchial Asthma

    Awal Bachtera B.Dept. Penyakit Dalam RSUDAM

  • 1. Defining Asthma . 3. Cause .4.Pathophysiolo . 5.Diagnosis . 6.Treatment .6.1 Medical .6.2 Pharmaceutical .6.3 Long-acting 2-agonist .2. Signs and Symptoms . 7.Drugs of Treatment . 7.1 Short-acting, selective beta2 adrenoceptor agonists . 7.1.1 Sablutmol (albuterol) . 8. Emergency treatment .9.Prevention . 10.prevention drugs . 10.1 Drugs on inhaled 10.1.1 Fluticasone . 11. Trigger avoidance . Contents

  • 1. Defining Asthma .Asthma Is a chronic condition involving the respiratory system in which the airways occasionally constricts and are extra sensitive, becomes inflamed and swollen, and is lined with excessive amounts of mucus .this swelling and mucus make the airways narrower.

  • 2. Signs and Smptoms 2.1 Symptoms Some or all of the following symptoms may be present in those with asthma :wheezing : , Coughing : Not all people have these symptoms, and symptoms may vary from one asthma attack to another. Symptoms can differ in how severe they are: Sometimes symptoms can be mildly annoying, other times they can be serious enough` to make you stop what you are doing, and sometimes symptoms can be so serious that they are life threatening. Severe shortness of breath :Coughing from asthma is often worse at night or early in the morning, making it hard to sleep. Wheezing is a whistling or squeaky sound when you breathe. breathless or out of breath. You may feel like you can't get enough air in or out of your lungs.Some people say they can't catch their breath, or they feel

  • 2.2 signsSigns of an asthmatic episode include:Wheezing, rhonchous lung soundThe presence paradoxical of pulse and over-inflation of the chestDuring very severe attacks, an asthma sufferer: Can turn blue from lack of oxygen, and can experience chest bain or even loss of consciousness . Just before lss of consciousness, there is a chance that the patient will feel numbness in the limbs and palms may start to sweat.The person's feet may become icy cold. Severe asthma attacks, which may not be responsive to standard treatments, are life-threatening and may lead to respiratory arrest and death. a rapid heart rate,

  • 3.Causes

    Asthma is caused by a complex interaction of genetic and environmental factors, there are many genetic and environmental factors have been suggested ascauses of asthma3.1 Environmental causes Many environmental risk factors have been associated with asthma Poor air or high quality from traffic pollution ozone levels Environmental tabacco smoke, especially maternal cigarette smoking Viral respiratory infections at an early age may be protective against asthma Psychological stress on the part of a child's caregiver has been associated with asthma, * ***

  • Over 25 genes had been associated with asthma 3.2 Genetic causes:EX ADRB2 (-2 adrenergic receptor) 3.3 Gene-Environment Interactions causes EX The CD14 SNP C-159T and exposure are a well-replicated example of a gene-environment interaction that is associated with asthma. Endotoxin exposure varies from person to person and can come from several environmental sources, including environmental tobacco smoke, dogs, and farms. Research is now finding that some genetic variants may only causes asthma when they are combined with specific environmental exposures

  • 4. Pathophysiology4.1 Bronchoconstriction

    Inflamed airways and bronchoconstriction in asthma. During an asthma episode, inflamed airways react to environmental triggers such as smoke, dust, or pollen The airways narrow and produce excess mucus, making it difficult to breathe. In essence, asthma is the result of an immune response in the bronchial airways .The airways of asthmatics are "hypersensitive" to certain triggers,, the bronchi contract into spasm (an "asthma attack").Inflammation leading to a further narrowing of the airways and excessive mucus production, which leads to coughing and other breathing difficulties

  • 4.2 stimuliAllergens from nature:Indoor air pollution from volatil organic compounds: including Medications: including aspirin.

    such as thehouse dust mite,cockroach and. perfumed productesExamples soap, dishwashing liquidgrass pollen* * * * Food allergies:such asmilk,peanuts, and eggsUse of fossil fuel related allergnic air pollution such as ozone, smog* * * * Various industrial compounds and other chemicals:notably sulfitesEarly childhood infections, Hormonal changes* * Emotional stressCold weather

  • 4.4Asthma and sleep apnea 4.5 Asthma and gastro-esophageal reflux disease It is recognized with increasing frequency, that patients who have both obstructive sleep apnea (OSA) and bronchial asthma, often improve tremendously when the sleep apnea is diagnosed and treated If gastro-esophageal reflux disease is present, the patient may have repetitive episodes of acid aspiration, which results in airway inflammation and "irritant-induced" asthma. 4.3 Bronchial inflammation

    The mechanisms behind allergic asthma, asthma resulting from an immune response to inhaled allergens. In both asthmatics and non-asthmatics, inhaled allergens that find their way to the inner airways are ingested by a type of cell known as antigen presenting cells, or APCs. APCs then "present" pieces of the allergen to other immune system cells. In most people, these other immune cells (TH0 cells) "check" and usually ignore the allergen molecules. In asthmatics, however, these cells transform into a different type of cell (TH2), the resultant TH2 cells activate an important arm of the immune system, known as the humoral immune system. The humoral immune system produces antibodies against the inhaled allergen. Later, when an asthmatic inhales the same allergen, these antibodies "recognize" it and activate a humoral response. Inflammation results

  • 20% difference on at least three days in a week for at least two weeks20% improvement of peak flow following treatment, for example

    **10 minutes of inhaled -agonist (e.g.,salbutamol);

    20% decrease in peak flow following exposure to a trigger (e.g., exercise).

    Testing peak flow at rest and after exercise can be helpful, especially in young asthmatics In the Emergency Department doctors may use acapnography which measures the amount of exhaled carbon dioxide, along with pulse oximetry which shows the amount of oxygen dissolved in the blood Asthma is defined simply as reversible airway obstruction. Reversibility occurs either spontaneously or with treatment. The basic measurement is peak flow rates and the following diagnostic criteria are used by the British Thoracic society5.Diagnosis

  • 6.1 Medical The specific medical treatmen t recommended to patients with asthma depends on the severity of their illness and the frequency of their symptoms. Specific treatments for asthma are broadly classified as relievers, preventers and emergency treatment. For those who suffer daily attacks, a higher dose of glucocorticoid in conjunction with a long-acting inhaled -2 agonist may be prescribed; alternatively, a leukotriene modifier or theophylline may substitute for the -2 agonist. In severe asthmatics, oral glucocorticoids may be added to these treatments during severe attacks.6 Treatment

    The most effective treatment for asthma is identifying triggers, such as pets or aspirin, and limiting or eliminating exposure to them. Other forms of treatment include relief medication, prevention medication, long-acting 2-agonists, and emergency treatment.

  • A nebulizer which provides a larger, continuous dose can also be used that they are more effective than inhalers used with a spacer. Nebulizers may be helpful to some patients experiencing a severe attack. Such patients may not be able to inhale deeplyRelievers include:Short-acting, selective beta2- adrenoceptor agonists, such as salbutamol(albutero) Older, less selective adrenerigc agonists, such as inhaled epinephrine and ephedrine tablets, have also been used. Anticholinergic medications, such as ipratropium bromide may be used instead***an asthma spacer is used. The spacer is a plastic cylinder that mixes the medication with air in a simple tube making it easier for patients to receive a full dose .6.2 Pharmaceutical Symptomatic control of episodes of wheezing and shortness of breath is generally achieved with fast-acting bronchodilators. These are typically provided in pocket-sized, metered-dose inhalers (MDIs).

  • Currently available long acting beta2-adrenoceptor agonists include salbutamol formoterol,bambuterol , and sustained-release oral albuterol. Combinations of inhaled steroids and long-acting bronchodilators are becoming more widespread; the most common combination currently in use is fluticasone/salmeterol Found that long-acting beta-agonists increased the risk for asthma hospitalizations and asthma deaths 2- to 4-fold, compared with placebo which These agents can improve symptoms through bronchodilation at the same time as increasing underlying inflammation and bronchial hyper-responsiveness Three common asthma inhalers containing the drugs salmeterol or formoterol may be causing four out of five US asthma-related deaths per year and should be taken off the market" 6.3 Long-acting 2-agonists Are similar in structure to short-acting selective beta2-adrenoceptor agonists, but have much longer side chains resulting in a 12-hour effect, and are used to give a smoothed symptomatic relief

  • 7.Drugs of Treatment .Short-acting, selective (albuterol) C13 H21 NO3 Salbutamolchemical formula : Salbutamol or albuterol is a short-acting beta2-adrenoceptor receptor agonists used for the relief of bronchospasm in conditions such as asthmaClinical use

    Salbutamol is specifically indicated in the following conditions : 1. acute asthma 2. protection against exercise-induced asthma3. hyperkalaemia, especially in patients with renal failureAdverse effects

    Common adverse effects include:tremor,palpitations, low blood pressure, and headache. beta2-adrenoceptor agonistssalbutamoSystematic (IUPAC) name4-[2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol

  • Salbutamol synthesis It is prepared from 4-hydroxyacetophenon , the chloromethylation which gives 4-hydroxy-3-hydroxymethylacetophenone (1.1) this is acetylated into a diacetyl derivative (1.2) which is further brominated into the corresponding bromoacetophenone (1.3). Reacting this with N-benzyl-N-tert-butylamine gives a derivative of amino acatophenone (1.4) the acetyl group of which is hydrolyzed by hydrochloric acid , and the resulting product (1.5 ) undergoes a reduction - frist by sodium borohydride for transforming the keto groub into a hydroxy l group to give (1.6) ,and then by hydrogenation over a palladium catalyst for removing the benzyl- protectin group giving salbutamol (1.7) .

  • 8 . Emergency treatment

    When an asthma attack is unresponsive to a patient's usual medication, other treatments are available to the physician or hospital Oxygen to alleviate the hypoxia that results from extreme asthma attacks. ****Nebulized slbutamol or terbutline (short-acting beta-2-agonists), often combined with ipratropium (an anticholinergic). Systemic steroids, oral or intravenous (prednisone,prednisolone, methylprednisolone,dexamethasone, or hydrocortisone). Other bronchodilators that are occasionally effective when the usual drugs fail: Intravenous salbutamol

    - Nonspecific beta-agonists, injected or inhaled (epinephrine, isoetharine,isoproterenol, metaproterenol-Intravenous salbutamol

  • Inhalation anesthetics that have a bronchodilatory effect (isoflurane,halothane,enflurane) -The dissociative anaesthetic ketamine, often used in endotracheal tube induction --Magnesium sulfate, intravenous **Intubation and mechanical ventilation, for patients in or approaching respiratory arrest. Heliox, a mixture of helium and oxygen, may be used in a hospital setting. It has a more laminar flow than ambient air and moves more easily through constricted airways. Methylxanthines (theophylline,aminophylline)-

  • 9 . Prevention

    Current treatment protocols recommend prevention medications such as an inhaled corticosteroid, which helps to suppress inflammation and reduces the swelling of the lining of the airways, in anyone who has frequent need of relievers or who has severe symptoms. If symptoms persist, additional preventive drugs are added until the asthma is controlled. With the proper use of prevention drugs, asthmatics can avoid the complications that result from overuse of relief medications.Preventive agents include the following1.Inhaled glucocorticoids (corticosteroids) - are the most widely used of the prevention medications and normally come as inhaler devices (cicleronide, beclomethasone,,flunisolide,fluticasone, budesonide and mometasone) - Long-term use of corticosteroids can have many side effects including:A redistribution of fat, increased appetite, blood glucose problems and weight gain.*

  • Deposition of steroids in the mouth may cause a hoarse or oralthrush (due to decreased immunity). * 2. Leukotriene modifiers, (montelukast, zafirlukast, pranlukast, and zileuton) :Headshe, dizziness, heartburn, upset stomach, and tirednees - Leukotriene recceptor antagonists have very rare side affects such as:(cromoglicate (cromolyn), and nedocromil), (ipratropium,oxitropium, and tiotropium), which have a mixed reliever and preventer effect. (theophylline and aminophyllineThere are some side effects of methylxanthines such as: Diarrhea , nausea ,heartburn ,and loss of appetite And also headaches nervousness, rabid heart beat, and upset stomach

    often used to treat allergic symptoms that may underlie the chronic inflammation. 3. Mast cell stabilizers 6. Antihistamines5. Methylxanthines, 4. Antimuscarinics/anticholinergics

  • 10. Prevention Drugs

    Drugs on Inhaled glucocorticoids (corticosteroids)10.1.1 Fluticasone Fluticasone is a potent synthetic corticosteroid often prescribed astreatment for Asthma and allergic rhinitisS-(fluoromethyl)(6S,8S,9R,10S,11S,13S,14S,16R,17R)- 6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo- 6,7,8,11,12,14,15,16-octahydrocyclopenta[a] phenanthrene-17-carbothioate Systematic (IUPAC) name Fluticasone chemical Formula: C22H27F3O4SSide effect of fluticasone- Hoarseness and sore throat.Thrush or yeast infection (looks like a whitish layer on your tongue).

  • Fluticasone synthesis:The synthesis of fluticasone propionate utilizes commercially available flumethasone (2.1). by Oxidation of (2.1) with periodic acid gave the etianic acid (2.2) , whose imidazolide when treated with hydrogen sulphide gas gave the carbothioic acid (2.3) , treatment with excess propionyl cloride followed by aminolysis of the mixed anhydride with dimethyl amine gave (2.4) alkylation with bromochloromethane gave the chloromethyl carbothioate (2.5) which was converted to iodomethyl ester (2.6) by treatment with sodium iodide . Convertion to fluticasone was accomplished by treatment with silver fluoride in acetonitrile . Alternatively . fluticasone was also prepared directly from the potassium salt of carbothioic acid (2.4) using bromofluoromethane .

  • As is common with respiratory disease, smoking is believed to adversely affect asthmatics in several ways, including an increased severity of symptoms, a more rapid decline of lung function, and decreased response to preventive medications Automobile emission are considered an even more significant cause and aggravating factor. 10. Trigger avoidance

    Asthmatics who smoke or who live near trafice typically require additional medications to help control their disease. Furthermore, exposure of both non-smokers and smokers to wood smoke, gas stove fumes and second-hand smoke is detrimental, resulting in more severe asthma, more emergency room visits, and more asthma-related hospital admissions Smoking cessation and avoidance of second-hand smoke is strongly encouraged in asthmatics For those in whom exercise can trigger an asthma attack(exercise-induced asthma), higher levels of ventilation and cold, dry air tend to exacerbate attacks. For this reason, activities in which patients breathes large amounts of cold air, such as skiing and running, tend to be worse for asthmatics, whereas swimming in an indoor, heated pool, with warm, humid air, is less likely to provoke a response .

  • The End