Bronchial Asthma2

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BRONCHIAL ASTHMA :

BRONCHIAL ASTHMA Respiratory Disease

PowerPoint Presentation:

2 Epidemiology Asthma is a problem worldwide, with an estimated 300 million affected individuals Prevalence increasing in many countries, especially in children A cause of a significant number of preventable deaths A major cause of school/work absence

Asthma:

Asthma Asthma is characterized clinically by recurrent bouts of coughing, shortness of breath, chest tightness, and wheezing; physiologically by widespread, reversible narrowing of the bronchial airways and a marked increase in bronchial responsiveness to inhaled stimuli; and pathologically by lymphocytic, eosinophilic inflammation of the bronchial mucosa

Asthma:

Asthma More severe forms of asthma are associated with frequent attacks of wheezing dyspnea, especially at night, and may be associated with chronic airway narrowing, causing chronic respiratory impairment .

Mechanisms Underlying the Definition of Asthma:

Mechanisms Underlying the Definition of Asthma Risk Factors (for development of asthma) INFLAMMATION Airway Hyperresponsiveness Airflow Obstruction Risk Factors (for exacerbations) Symptoms

Etiology:

Etiology As a sthma is a respiratory allergic disease, the influence of allergens permeated into the organism through airways is essential for the disease development. The allergens are divided into : communal, industrial, occupational, natural pharmacological

PowerPoint Presentation:

Сommunal allergens are contained in the air of apartment houses. They are: house-dust mites which live in carpets, mattresses and upholstered furniture; spittle, excrements, desquamated epidermis, hair and fur of domestic animals; vital products of domestic insects (e.g., cockroach); mycelial yeast-like fungi ( molds); tobacco smoke during active or passive smoking; various communal aerosols and synthetic detergents.

PowerPoint Presentation:

industrial allergens nitric, carbonic, sulfuric oxides, formaldehyde, ozone and emissions of biotechnological industry - main components of industrial and photochemical smog - must be mentioned. The most important occupational allergens are dust of stock buildings, mills, weaving-mills, book depositories etc. Natural allergens are represented by plant pollen (especially ambrosia, wormwood and goose-foot pollen) and different respiratory, particularly viral, infections.

Some allergens which may cause asthma:

Some allergens which may cause asthma H ouse-dust mites which live in carpets, mattresses and upholstered furniture S pittle, excrements, hair and fur of domestic animals P lant pollen Pharmacological a gents ( enzymes, antibiotics, vaccines, serums ) F ood components ( stabilizers, genetically modified products ) D ust of book depo - sitories

Some allergens which may cause asthma:

Some allergens which may cause asthma P lant pollen

PATHOGENESIS OF ASTHMA:

PATHOGENESIS OF ASTHMA Foreign materials that provoke IgE production are described as "allergens"; the most common are proteins from house dust mite, cockroach, cat dander, molds, and pollens. Once produced, IgE antibodies bind to mast cells in the airway mucosa. On reexposure to a specific allergen, antigen-antibody interaction on the surface of the mast cells triggers both the release of mediators stored in the cells' granules and the synthesis and release of other mediators .

PowerPoint Presentation:

The histamine, tryptase, leukotrienes C 4 and D 4 , and prostaglandin D 2 , when released, diffuse through the airway mucosa triggering the muscle contraction and vascular leakage responsible for the acute bronchoconstriction of the " early asthmatic response." " late asthmatic response ," which is associated with an influx of inflammatory cells into the bronchial mucosa and with an increase in bronchial responsiveness that may last for several weeks after a single inhalation of allergen .

PATHOGENESIS OF ASTHMA:

PATHOGENESIS OF ASTHMA The mediators responsible for this late response are thought to be cytokines characteristically produced by TH2 lymphocytes, especially interleukins 5, 9, and 13. The cytokines attract and activate eosinophils, stimulate IgE production by B lymphocytes, and directly stimulate mucus production by bronchial epithelial cells.

Principles of the Allergic Response:

Principles of the Allergic Response Sensitized individual, sufficient exposure, end organ responses.

Pathophysiology of Allergic Inflammation: Sensitization:

Pathophysiology of Allergic Inflammation: Sensitization Antigen-presenting cell (eg, dendritic cell) CD4 T cell B cell IgE antibodies Allergens Processed allergens B lymphocyte (Plasma cell)

Pathophysiology of Allergic Inflammation: Clinical Disease:

Early Inflammation Allergens Sneezing Rhinorrhea Congestion Mast cell IgE antibodies Mediator release Blood vessels Nerves Glands Late Inflammation Cellular infiltration Eosinophils Basophils Monocytes Lymphocytes Resolution Complications Irreversible disease? Late-phase reaction Priming Hyper- responsiveness Pathophysiology of Allergic Inflammation: Clinical Disease

Pathophysiology:

Pathophysiology As a result of antigen-antibody reaction the peculiar “explosion” occurs. The membranes of mast cells, basophils and eosinophils of bronchial mucous wreck with output of biologically active substances (histamine, serotonin, chemotaxis factors, heparin, proteases, thromboxane, leukotrienes, prostaglandins), which induce hyperergic inflammation, mucous edema, spasm of smooth myocytes, glands hypersecretion, viscous exudate formation in bronchial lumen. Airway fill with mucus Muscles contract Airways swell

Pathologic anatomy:

Pathologic anatomy Macroscopic changes: viscous mucous/ mucopurulent phlegm airway dyskinesia with zones of spastic contraction and paralytic expansion of bronchi obstruction of airway lumen lung emphysema, pneumosclerosis RV and RA hypertrophy and dilation

Pathophysiology:

Pathophysiology Hallmark of Asthma -Bronchial wall Hyperresponsiveness Early Phase Asthma Reaction Bronchoconstriction Antigenic Stimulation of bronchial wall Mast Cell Degranulation releases Histamine Chemotactics Proteolytics Heparin Smooth Muscle Bronchoconstriction

Drug therapy:

Drug therapy Antiinflammatory drugs (basic) Bronchodilators 2 drug categories are used: Are divided into: hormone-containing (corticosteroids) nonhormone-containing (cromones, leukotriene receptor antagonists) 3 groups : anticholinergic drugs b 2-agonists methylxanthines

Asthma Medications:

Asthma Medications Bronchodilators (Sympathomimetics) Bronchodilators (Anticholinergics) Inhaled Corticosteroids Biologic Response Modifiers (Monoclonal Antibodies) Leukotriene Receptor Antagonists Mast Cell Stabilizers Methylxanthene Derivatives

Bronchodilators:

Bronchodilators b 2-agonists Anticholinergic drugs Smooth muscle relaxation Stimulates b 2-adrenergic receptors of bronchi reduce tonus of vagus Methylxanthines inhibit phosphodiesterase

PowerPoint Presentation:

Table 36-3 Mechanisms of anti-asthmatic drug action

Bronchodilators and Respiratory Agents:

Bronchodilators and Respiratory Agents Bronchodilators Xanthine derivatives Beta-adrenergic agonists Anticholinergics Antileukotrienes Corticosteroids Mast cell stabilizers

Bronchodilators: Xanthine Derivatives:

Bronchodilators: Xanthine Derivatives Plant alkaloids: caffeine, theobromine, and theophylline Only theophylline is used as a bronchodilator Examples: aminophylline Theophylline Slo-Bid® Uniphyl®

Xanthine Derivatives: Drug Effects:

Xanthine Derivatives: Drug Effects Cause bronchodilation by relaxing smooth muscles of the airways Result: relief of bronchospasm and greater airflow into and out of the lungs Also cause CNS stimulation Slow onset action and are mostly used for prevention Aminophylline(Status asthmaticus)

Xanthine Derivatives: Drug Effects (cont’d):

Xanthine Derivatives: Drug Effects (cont’d) Also cause cardiovascular stimulation: increased force of contraction and increased HR, resulting in increased cardiac output and increased blood flow to the kidneys (diuretic effect)

Bronchodilators: Beta-Agonists (cont’d):

Bronchodilators: Beta-Agonists (cont’d) Three types Nonselective adrenergics Stimulate alpha-, beta 1 - (cardiac), and beta 2 - (respiratory) receptors Example: epinephrine Nonselective beta-adrenergics Stimulate both beta 1 - and beta 2 -receptors Example: isoproterenol Selective beta 2 drugs Stimulate only beta 2 -receptors Example: salbutamol

Anticholinergics: Mechanism of Action:

Anticholinergics: Mechanism of Action Acetylcholine (ACh) causes bronchial constriction and narrowing of the airways Anticholinergics bind to the ACh receptors, preventing ACh from binding Result: bronchoconstriction is prevented, airways dilate

Muscarinic antagonists:

Muscarinic antagonists Muscarinic antagonists competitively inhibit the effect of acetylcholine at muscarinic receptors (see Chapter 8). In the airways, acetylcholine is released from efferent endings of the vagus nerves, and muscarinic antagonists block the contraction of airway smooth muscle and the increase in secretion of mucus that occurs in response to vagal activity

Anticholinergics (cont’d):

Anticholinergics (cont’d) Side effects: Dry mouth or throat Gastrointestinal distress Headache Coughing Anxiety No known drug interactions

Antileukotrienes:

Antileukotrienes Also called leukotriene receptor antagonists (LRTAs) Newer class of asthma medications Three subcategories of agents

Antileukotrienes (cont’d):

Antileukotrienes (cont’d) Currently available agents: Montelukast (sold as Singulair®) Zafirlukast (sold as Accolate®)

Leukotriene Pathway Inhibitors :

Leukotriene Pathway Inhibitors Because of the evidence of leukotriene involvement in many inflammatory diseases and in anaphylaxis, considerable effort has been expended on the development of drugs that block the synthesis of these arachidonic acid derivatives or their receptors. Leukotrienes result from the action of 5-lipoxygenase on arachidonic acid and are synthesized by a variety of inflammatory cells in the airways, including eosinophils, mast cells, macrophages, and basophils.

Leukotriene Inhibitors:

Leukotriene Inhibitors Leukotriene B 4 (LTB 4 ) is a potent neutrophil chemoattractant, and LTC 4 and LTD 4 exert many effects known to occur in asthma, including bronchoconstriction, increased bronchial reactivity, mucosal edema, and mucus hypersecretion

Inhaled Corticosteroids:

Inhaled Corticosteroids Budesonide (Pulmicort®) Fluticasone (Flovent®)

Corticosteroids:

Corticosteroids Corticosteroids have been used to treat asthma since 1950 and are presumed to act by their broad anti-inflammatory efficacy, mediated in part by inhibition of production of inflammatory cytokines but their most important action is inhibition of the lymphocytic, eosinophilic mucosal inflammation of asthmatic airways.

Inhaled Corticosteroids: Side Effects:

Inhaled Corticosteroids: Side Effects Pharyngeal irritation Coughing Dry mouth Oral fungal infections Systemic effects are rare because of the low doses used for inhalation therapy

PO corticosteroids:

PO corticosteroids Prednisolone (sold as Pediapred®) Prednisone (sold as Deltasone®)

Mast Cell Stabilizers:

Mast Cell Stabilizers Cromoglycate (sold as Intal®) Nedocromil (sold as Tilade®) Ketotifen fumarate (sold as Zaditen®)

Signal Transduction Pathway for Bronchodilation:

Signal Transduction Pathway for Bronchodilation Bronchodiliation PDE3

Bronchodilators (Sympathomimetics):

Bronchodilators (Sympathomimetics) Albuterol Salmeterol Terbutaline

Bronchodilators (Anticholinergics):

Bronchodilators (Anticholinergics) Ipratropium

Inhaled Corticosteroids:

Inhaled Corticosteroids Beclamethasone Flunisolide Triamcinalone

Mast Cell Stabilizers:

Mast Cell Stabilizers Cromolyn Nedocromil

Methylxanthene Derivatives:

Methylxanthene Derivatives Theophylline

Albuterol:

Albuterol Actions Agonist for Beta 2 adrenergic receptors; relaxing bronchial smooth muscle which results in bronchodilation Minimal cardiac side effects

Albuterol:

Albuterol Indications: Treatment of bronchospasm associated with asthma, chronic bronchitis and emphysema Prevention of exercise-induced bronchospasm

Albuterol:

Albuterol Contraindications: Hypersensitivity to sympathomimetics Cardiac dysrhythmia Tachycardia and tachydysrhythmias

Albuterol:

Albuterol Adverse Reactions: Excessive use may cause paradoxical bronchospasm and arrhythmias Tachycardia, palpitations, angina, PVCs, hypotension, and hypertension Tremors Hyperglycemia Peripheral vasodilation Nervousness Nausea/Vomiting

Albuterol:

Albuterol Precautions: Diabetes Hyperthyroidism Cerebrovascular disease Seizure disorders

Albuterol:

Albuterol Dose: 2 inhalations with metered-dose inhaler, q 4-6 hours 2. 3 ml premixed bullet in nebulizer

Albuterol:

Albuterol Incompatible/Reactions: Tricyclic antidepressants/monoamine oxidase inhibitors (MAOIs), may increase the effect of this drug Other sympathomimetics Beta blockers inhibit the effects

Albuterol:

Albuterol Notes: Onset: 5-15 minutes Peak: 30 minutes – 2 hours Duration: 3-4 hours Can be delivered by inhaler and nebulizer Metabolized in the liver and excreted in the urine

Respiratory Pharmacology:

Respiratory Pharmacology GENERIC: Epinephrine BRAND: Adrenalin CLASS: Sympathomimetic/Catecholamine

Epinephrine:

Epinephrine Action: Direct effect on alpha and beta adrenergic receptor sites Effects include: Alpha: bronchial, cutaneous, renal and visceral arteriolar constriction Beta 1: positive inotropic and chronotropic actions, increases automaticity Beta 2: bronchial smooth muscle relaxation and dilation of skeletal vasculature 3. Inhibits the release of histamine

Epinephrine:

Epinephrine Indications: Cardiac arrest in general Ventricular fibrillation Asystole Pulseless electrical activity Infusion for profound hypotension associated with bradycardias, in combination with other pressors Bronchospasm and bronchoconstriction of bronchial asthma and some forms of COPD Anaphylaxis

Epinephrine:

Epinephrine Contraindications: Uncorrected tachydysrhythmias Underlying cardiovascular disease or hypertension Glaucoma Hypersensitivity to catecholamines Hypothermia

Epinephrine/Adverse Reactions:

Epinephrine/Adverse Reactions Hypertension Ventricular arrhythmias Pulmonary edema Tachycardia Palpitations Anxiety Psychomotor agitation Nausea/Vomiting Pupil dilation Angina Nervousness Headache Dizziness Tremors Hallucinations Cerebral hemorrhage Anorexia

Epinephrine:

Epinephrine Precautions: Due to the possibility of cardiovascular disease, epinephrine should be administered with caution in patients over 35 years of age (with respiratory problems or if they are conscious) The patient should be carefully monitored for changes in pulse, blood pressure, and ECG after administration of epinephrine. Because of its strong inotropic and chronotropic effects, epinephrine causes an increased myocardial O2 demand

Epinephrine:

Epinephrine Precautions: Hypovolemia (replenish volume first) Diabetes mellitus Hyperthyroidism Prostatic hypertrophy Must be protected from light Tends to be deactivated by alkaline solutions (sodium bicarbonate) Do not use with MAOIs or tricyclic antidepressants due to the danger of hypertensive crisis

Epinephrine:

Epinephrine Dose: Cardiac dosage: 1:10,000 a. 1 mg q 3-5 minutes (until the heart restarts) b. Intermediate: 2-5 mg q 3-5 minutes c. Escalating: 1 mg – 3 mg – 5 mg; 3 minutes apart d. High: 0.1 mg/kg q 3-5 minutes Infusion: Mix 1 mg in 250 ml and run at 2-10 mcg/min Anaphylaxis and Asthma: .1-.5 mg (1:1,000) SQ or IM

Epinephrine:

Epinephrine Incompatible/Reactions: Potentiates other sympathomimetics Patients on MAOIs, antihistamines, and tricyclic antidepressants may have heightened effects Sodium bicarbonate – deactivates epinephrine Nitrates Lidocaine Aminophylline Don’t mix the above drugs in the same syringe with epi; but can use in the same IV line – just flush between meds

Epinephrine:

Epinephrine Notes: ONSET: Immediate PEAK: Minutes DURATION: Several minutes

Respiratory Pharmacology:

Respiratory Pharmacology GENERIC: Isoetharine BRAND: Bronkosol, Bronkometer CLASS: Sympathomimetic

Isoetharine:

Isoetharine Actions: 1. Beta 2 agonist (slight specificity); relaxes smooth muscle of bronchioles, vasculature, uterus

Isoetharine:

Isoetharine Indications: 1. Relieve bronchospasm associated with asthma, chronic bronchitis, and emphysema

Isoetharine:

Isoetharine Contraindications: Hypersensitivity to sympathomimetics Cardiac dysrhythmias Tachycardia and tachydysrhythmias

Isoetharine:

Isoetharine Adverse Reactions: Dose-related tachycardia, palpitations, tremors, nervousness, peripheral vasodilation, nausea/vomiting, transient hyperglycemia, life-threatening arrhythmias; multiple excessive doses can cause paradoxical bronchoconstriction Angina Hypertension Headache, dizziness, anxiety, restlessness, hallucinations

Isoetharine:

Isoetharine Precautions: Use with caution in patients with diabetes, hyperthyroidism, cardiovascular and cerebrovascular disease Seizure disorders Isoetharine contains acetone sodium bisulfite; a sulfite that may cause allergic-type reactions, including anaphylactic symptoms in certain susceptible individuals

Isoetharine:

Isoetharine Dose: ADULT 1-2 inhalations with metered-dose inhaler 3-7 inhalations, via hand nebulizer q 4 hours PEDIATRIC Not recommended in children less than 12 years

Isoetharine:

Isoetharine Incompatible/Reactions: 1. Additive adverse effects with other beta agonists

Isoetharine:

Isoetharine Notes: ONSET: Immediate PEAK: 5-15 minutes DURATION: 1-4 hours

Respiratory Pharmacology:

Respiratory Pharmacology GENERIC: Metaproterenol Sulfate BRAND: Alupent, Metaprel CLASS: Sympathomimetic

Metaproterenol Sulfate:

Metaproterenol Sulfate Actions: 1. Agonist for Beta 2 adrenergic receptors – acts directly on smooth muscle

Metaproterenol Sulfate:

Metaproterenol Sulfate Indications: 1. Relieve bronchospasm of COPD and Asthma

Metaproterenol Sulfate:

Metaproterenol Sulfate Contraindications: Hypersensitivity to sympathomimetics Hyperthyroidism Cerebrovascular or cardiovascular disorders Tachycardia and tachydysrhythmias

Metaproterenol Sulfate Adverse Reactions:

Metaproterenol Sulfate Adverse Reactions Dose-related tachycardia Palpitations Nervousness Peripheral vasodilation Excessive use – lethal arrhythmias, paradoxical bronchospasm Hypertension Tremors, headache, dizziness, anxiety, hallucinations Nausea/vomiting

Metaproterenol Sulfate:

Metaproterenol Sulfate Precautions: History of cardiovascular disease or hypertension Seizures

Metaproterenol Sulfate:

Metaproterenol Sulfate Dose: ADULT: 2-3 inhalations, q 3-4 hours Metered-dose inhaler or nebulizer PEDIATRICS: Not recommended in children under 12 years

Metaproterenol Sulfate:

Metaproterenol Sulfate Incompatible/Reactions: Beta blockers MAOIs, tricyclic antidepressants Potentiates other beta agonists

Metaproterenol Sulfate:

Metaproterenol Sulfate Notes: ONSET: 1 minute PEAK: 1 hour DURATION: 1-5 hours with single dose 2-5 hours with repeated dose

Respiratory Pharmacology:

Respiratory Pharmacology GENERIC: Terbutaline Sulfate BRAND: Bricanyl, Brethine CLASS: Sympathomimetic

Terbutaline Sulfate:

Terbutaline Sulfate Actions: Beta 2 agonist – has an affinity for beta 2 receptors of bronchial, vascular, and uterine smooth muscle At increased doses, beta 1 effects may occur

Terbutaline Sulfate:

Terbutaline Sulfate Indications: Relieve bronchospasm associated with asthma, chronic bronchitis and emphysema (prevalent in patients over the age of 40 or with coronary artery disease) Used in-hospital to stop pre-term labor

Terbutaline Sulfate:

Terbutaline Sulfate Contraindications: Hypersensitivity to sympathomimetics Cardiac dysrhythmias Tachycardia and tachydysrhythmias Glaucoma

Terbutaline Sulfate:

Terbutaline Sulfate Adverse Reactions: Tachycardia, tremors, palpitations, nervousness and dizziness Angina, PVCs, hypotension, and hypertension Headache, anxiety, hallucinations Nausea, vomiting Bronchospasm

Terbutaline Sulfate:

Terbutaline Sulfate Precautions: Used with caution to patients with a history of cardiovascular disease or hypertension Seizure disorders Thyroid disease Diabetes

Terbutaline Sulfate:

Terbutaline Sulfate Dose: ADULT: 0.25 mg SQ; repeat in 15-20 minutes 2 inhalations separated by a 60 second interval with a metered dose inhaler 4mg/7ml nebulizer mix

Terbutaline Sulfate:

Terbutaline Sulfate Incompatible/Reactions: Alkaline solutions Degrades when exposed to light for long periods of time

Terbutaline Sulfate:

Terbutaline Sulfate Notes: ONSET: 15 minutes PEAK: 30-60 minutes DURATION: 90 minutes – 4 hours

Respiratory Pharmacology:

Respiratory Pharmacology GENERIC: Theophylline Ethylenediamine BRAND: Aminophylline CLASS: Methylxanthine Spasmolytic

Theophylline:

Theophylline Actions: Beta 2 agonist; directly relaxes bronchial smooth muscle Dilates pulmonary and coronary arterioles, decreasing pulmonary hypertension and increasing coronary blood flow Slight positive chronotropic and inotropic effects Strengthens diaphragmatic contractions by affecting intracellular calcium Mild diuretic

Theophylline:

Theophylline Actions: Stimulates CNS vomiting centers Respiratory center stimulant Stimulates vagal and vasomotor centers in the brain – can lead to decreased heart rate, vasoconstriction in the brain – depends on CNS or peripheral predominance

Theophylline:

Theophylline Indications: Relieve bronchospasm associated with asthma, chronic bronchitis, emphysema, and pulmonary edema Management of CHF and pulmonary edema

Theophylline:

Theophylline Contraindications: Hypersensitivity to xanthene compounds (e.g. caffeine) Cardiac dysrhythmias Tachycardia and tachydysrhythmias

Theophylline Adverse Reactions:

Theophylline Adverse Reactions Nausea/vomiting Hypotension Irritability Tachycardia Angina Flushing Diarrhea Increased respiratory rate Cardiac arrhythmias Tremors Seizures Palpitations Hypertension Anorexia

Theophylline:

Theophylline Precautions: Caution if patient is already taking theophylline-containing medications Caution to patients with a history of cardiovascular disease or hypertension Thyroid disease Active peptic ulcer Hypotension may occur following rapid administration May oppose the effects of beta blockers

Theophylline:

Theophylline Dose: ADULT: Loading dose of 6 mg/kg IV infusion over 20 minutes Loading dose of 1 mg/kg IV infusion over 20 minutes if the patient has had theophylline products in the last 35 hours

Theophylline:

Theophylline Incompatible/Reactions: Incompatible with most drugs Simetidine, propranolol, erythromycin, and troleandomycin may increase the effects of the drug Barbiturates, phenytoin, and smoking may decrease blood levels May increase the effects of anticoagulants

Theophylline:

Theophylline Notes: ONSET: 15 minutes: PEAK: 30 minutes – 1 hour DURATION: Averages 5 hours Common forms or oral aminophylline include: * Marax * Primatene * Quibron * Slo-Phyllin * Slobid * Somophyllin * Tedral * Theo-Dur

Respiratory Pharmacology:

Respiratory Pharmacology Respiratory meds are used for several purposes, the most obvious is the treatment of asthma. Class includes: Cough suppressants Nasal decongestants Antihistamines

Antiasthmatic Medications:

Antiasthmatic Medications Asthma has two basic pathophysiologies: Bronchoconstriction Inflammation Treatment is aimed to relieve bronchospasm and decrease inflammation. Specific approaches are categorized as beta 2 selective sympathomimetics, nonselective sympathomimetics, methylxanthines, anticholinergics, glucocorticoids and leukotriene antagonists.

Beta 2 Specific Agents:

Beta 2 Specific Agents Albuterol (Proventil, Ventolin) is the prototype of this class. These agents relax bronchial smooth muscle, resulting in bronchodilation and relief from bronchospasm. These agents are first line therapy for acute shortness of breath. Administered via metered dose inhaler or nebulizer. Overall, these agents are very safe.

Nonselective Sympathomimetics:

Nonselective Sympathomimetics Stimulate both beta 1 and beta 2 receptors, as well as alpha receptors. Rarely used to treat asthma because they have the undesired effects of increased peripheral vascular resistance and increased risks for tachycardias and other dysrhythmias. Agents include: epinephrine, ephedrine, and isoproterenol Epinephrine is the only nonselective sympathomimetic in common use today.

Methylxanthines:

Methylxanthines CNS stimulants that have additional bronchodilatory properties. Used only when other drugs such as beta 2 specific agents are ineffective. Possibly block adenosine receptors. Prototype is theophylline, taken orally. Aminophylline, an IV medication, is rapidly metabolized into theophylline and, therefore, has identical effects. Chief side effects: nausea/vomiting, insomnia, restlessness, and dysrhythmias

Anticholinergics:

Anticholinergics Ipratropium (Atrovent) is an atropine derivative given by nebulizer. Because stimulating the muscarinic receptors in the lungs results in constriction of bronchial smooth muscle, ipratropium, a muscarinic antagonist, causes bronchodilation. Ipratropium is inhaled, and has no systemic effects. Has an additive effect when used with beta 2 agonists. Most common side effect is dry mouth

Glucocorticoids:

Glucocorticoids Anti-inflammatory properties. Lower the production and release of inflammatory substances such as histamine, prostaglandins, and leukotrienes, and reduce mucus and edema secondary to decreasing vascular permeability. May be inhaled or taken orally, as well as IV. Prototype of inhaled glucocorticoid is beclomethasone. Prototype of oral glucocorticoid is prednisone. Administered as preventative care.

Glucocorticoids:

Glucocorticoids When inhaled they cause few side effects. Side effects are due mostly to direct exposure on the oropharynx, and gargling after taking the drug can decrease the side effects. Side effects from the IV administrations of methylprednisolone in emergencies are not likely Long periods of administration can lead to adrenal suppression and hyperglycemia. Another anti-inflammatory agent used is cromolyn (Intal), an inhaled powder.

Glucocorticoids:

Glucocorticoids Cromolyn is the safest of all antiasthma agents. Only side effects are coughing or wheezing due to local irritation caused by the powder. Often used for preventing asthma in adults and children.

Leukotriene Antagonists:

Leukotriene Antagonists Leukotrienes are mediators released from mast cells upon contact with allergens. Contribute powerfully to both inflammation and bronchoconstriction Can either block the synthesis of leukotrienes or block their receptors. Zileuton (Zyflo) is the prototype of those that block the synthesis of leukotrienes Zafirlukast (Accolate) is the prototype of those that block their receptors

DRUGS USED FOR RHINITIS AND COUGH:

DRUGS USED FOR RHINITIS AND COUGH Rhinitis: (inflammation of the nasal lining) comprises a group of symptoms including nasal congestion, itching, redness, sneezing, and rhinorrhea (runny nose). Allergic reactions or viral infections may cause it Drugs that treat the symptoms of rhinitis and cold are commonly found in over-the-counter remedies. Nasal decongestants, antihistamines, and cough suppressants are available in prescription medications.

Nasal Decongestants:

Nasal Decongestants Nasal congestion is caused by dilated and engorged nasal capillaries. Drugs that constrict these capillaries are effective nasal decongestants. Main pharmacologic classification in this functional category is alpha 1 agonists Alpha 1 agonists may be given either topically or orally Examples of agents: phenylephrine, pseudoephedrine, and phenylpropanolamine, (administered in drops or mist)

Antihistamines:

Antihistamines Arrest the effects of histamine by blocking its receptors. Histamine is an endogenous substance that affects a wide variety of organs systems. Noted for its role in allergic reaction. Histamine binds with H1 receptors to cause vasodilation and increased capillary permeability (vasculature) In the lungs, H1 receptors cause bronchoconstriction In the gut, H2 receptors cause an increase in gastric acid release Histamine also acts as a neurotransmitter in the CNS.

Antihistamines:

Antihistamines Histamine is synthesized and stored in two types of granulocytes; tissue-bound mast cells and plasma-bound basophils Both types are full of secretory granules, which are vesicles containing inflammatory mediators such as histamine, leukotrienes, and prostaglandins, among others. When cells are exposed to allergens, they develop antibodies on their surfaces. On subsequent exposures, the antibodies bind with their specific allergen.

Antihistamines:

Antihistamines Secretory granules then migrate towards the cell’s exterior and fuse with the cell membrane. Causing them to release their contents. Histamines are useful in our immune systems. When our immune systems overreact do allergies such as hay fever or cedar fever send us running for the antihistamines Typical symptoms of allergic reaction include most of those associated with rhinitis. Severe allergic reactions (anaphylaxis) may cause hypotension

Antihistamines:

Antihistamines Antihistamines are at best only a secondary drug for treating anaphylaxis. Just as there are H1 and H2 histamine receptors, there are H1 and H2 histamine receptor antagonists. Most old antihistamines were H1 receptor antagonists, newer antihistamines are H2 receptor antagonists. Chief side effect is sedation (H1), newer generation do not cause this sedation effect (H2). First generation medications: alkylamines (chlorpheniramine [Chlor-Trimeton]), ethanolamines (diphenhydramine [Benadryl])

Antihistamines:

Antihistamines Other first generation antihistamines: clemastine (Tavist), and phenothiazines (promethazine [Phenergan]). Some antihistamines also have significant anticholinergic properties: promethazine and dimenhydrinate (Dramamine), used for motion sickness. Second generation antihistamines include: terfenadine (Seldane), loratadine (Claritine), cetirizine (Zyrtec, and fexofenadine (Allegra). These agents do not cross the blood-brain barrier and therefore do not cause sedation.

Cough Suppressants:

Cough Suppressants Coughing is a complex reflex that depends on functions in the CNS, the PNS, and the respiratory muscles. It is a defense mechanism that aids the removal of foreign particles like smoke and dust. In general, treating a productive cough is not appropriate, as it is performing a useful function. An unproductive cough, usually results from an irritated oropharynx and can be troublesome. The three classifications of cough suppressants include one that is supported by evidence and two that are not.

Cough Suppressants:

Cough Suppressants Antitussives Suppress the stimulus to cough in the CNS. This functional class includes two specific pharmacologic types: a. Opioids b. Nonopioids Two most common opioid antitussives are codeine and hydrocodone Both inhibit the stimulus for coughing in the brain but also produce varying degrees of euphoria

Cough Suppressants:

Cough Suppressants The nonopioid antitussives do not have the potential for abuse. a. Dextromethoraphan b. Diphenhydramine c. Benzonatate (Tessalon) Expectorants: intended to increase the productivity of cough Mucolytics: make mucus more watery and easier to cough up Little data supports the effectiveness of either of these approaches to cough suppression

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