Lecture 4: Respiratory Medications PDF

LECTURE 3 1. Definitions 2. Disease States and Symptoms 3. Mechanisms of Action Chemical Mediator: Substances released by cells Asthma: Chronic inflammatory disorder of the to influence immune and inflammatory resp...

LECTURE 3 1. Definitions 2. Disease States and Symptoms 3. Mechanisms of Action Chemical Mediator: Substances released by cells Asthma: Chronic inflammatory disorder of the to influence immune and inflammatory responses. airways causing wheezing, shortness of breath, Sympathomimetic Bronchodilators: Prostaglandins: Lipid compounds involved in and chest tightness. Stimulate beta-adrenergic receptors, inflammation, pain, and fever regulation. relaxing bronchial muscles and opening COPD (Chronic Obstructive Pulmonary airways. Histamine: A compound involved in allergic Disease): A progressive lung disease reactions and regulation of gastric acid. characterized by persistent respiratory Xanthine Derivative Bronchodilators: ECF-A (Eosinophil Chemotactic Factor of symptoms and airflow limitation. Inhibit phosphodiesterase, leading to Anaphylaxis): A mediator attracting eosinophils to bronchodilation and improved airflow. inflamed areas, especially in allergic reactions. Chronic Bronchitis: A type of COPD marked by SRS-A (Slow Reacting Substance of Anaphylaxis): chronic productive cough and inflammation of A group of leukotrienes involved in prolonged the bronchial tubes. allergic responses, causing bronchoconstriction. Leukotrienes: Lipid mediators involved in Emphysema: A form of COPD where alveoli are inflammation, particularly in asthma. damaged, causing shortness of breath and Bronchoconstriction: Narrowing of the airways, difficulty breathing. making breathing difficult. Bronchodilator: A drug that relaxes airway muscles, opening the airways. Xanthines: A class of drugs that act as bronchodilators and stimulants, commonly used in respiratory conditions. Mucolytic: Medications that thin mucus to make it easier to expel. Corticosteroids: Anti-inflammatory drugs used to reduce inflammation in conditions like asthma. Expectorants: Drugs that help clear mucus from the airway 4. Sympathomimetic Bronchodilators 5. Xanthine Derivative Bronchodilators 6. Anticholinergic Bronchodilators Subclasses Drugs: Theophylline (Theo-Dur) Drugs: Ipratropium (Atrovent), Alpha- and Beta-Adrenergic Agonists Dosage Forms: Tablet, injection Tiotropium (Spiriva) Drugs: Epinephrine (Adrenalin) Adverse Effects: Nausea, tachycardia Dosage Forms: Inhaler, injection Indications: Asthma, COPD Mechanism of Action: Block Indications: Acute asthma, anaphylaxis acetylcholine receptors, reducing Adverse Effects: Tachycardia, anxiety bronchoconstriction Beta Adrenergic Agonists, Non-Selective Drugs: Isoproterenol (Isuprel) Dosage Forms: Inhaler Dosage Forms: Inhaler, injection Adverse Effects: Palpitations, dizziness Adverse Effects: Dry mouth, urinary Beta-2 Adrenergic Agonist, Selective retention Drugs: Albuterol (Ventolin), Salmeterol Indications: COPD (Serevent) Dosage Forms: Inhaler, tablet Adverse Effects: Tremors, increased heart rate 7. Leukotriene Receptor Antagonists 8. Other Products in Asthma and COPD 9. Combination Products Drugs: Montelukast (Singulair), Zafirlukast (Accolate) Therapy Fluticasone/Salmeterol (Advair): Mechanism of Action: Block leukotriene receptors, Inhaled Corticosteroids: Reduce inflammation Inhaler for asthma and COPD reducing inflammation and bronchoconstriction (e.g., Fluticasone) (Rinse Mouth After Use) Dosage Forms: Tablet Mast Cell Stabilizers: Prevent release of Budesonide/Formoterol (Symbicort): Adverse Effects: Headache, gastrointestinal upset mediators (e.g., Cromolyn) Inhaler for asthma and COPD Indications: Asthma management Long-Acting Beta Agonists: Improve breathing (Rinse Mouth After Use) (e.g., Salmeterol) Asthma caused by ▪ An inflammatory condition of the respiratory system In susceptible patients, asthma attacks can be caused by: characterized by shortness of breath and wheezing ✓ Irritants (dust, pollutants, noxious chemicals) caused by bronchiolar constriction ✓ Exercise (particularly in cold weather) ▪ May also include mucosal edema, increased ✓ Respiratory tract infections production of bronchial mucus, and depression of ✓ Aspirin and related drugs ciliary activity in respiratory tract ✓ Allergy to foreign proteins (pollen and animal dander) Asthma Therapy Classes of drugs most commonly used: Goals: 1. Bronchodilators ✓ Maintain normal activity levels 2. Corticosteroids ✓ Prevent symptoms (cough, wheezing, dyspnea) 3. Anti-allergies ✓ Maintain normal spirometry 4. Leukotriene receptor antagonists ✓ Prevent exacerbations ✓ Avoid side effects of therapy The Role of Chemical Mediators in Asthma The Role of Chemical Mediators in Asthma ▪ In asthma, inflammatory response releases chemical Prostaglandins: mediators in the respiratory tract. o Widely distributed in body tissues. ▪ Mediators include histamine, ECF-A (Eosinophilic o Released by cell membranes in response to injury or Chemotactic Factor of Anaphylaxis), and SRS-A (Slow irritation, causing swelling. Reacting Substance of Anaphylaxis). In the Lungs (Asthma): ▪ Released from injured tissue, mast cells, and o Prostaglandin complex SRS-A (Slow Reacting Substance leukocytes. of Anaphylaxis) is released. Histamine: o SRS-A is made up of three leukotrienes (a type of Causes bronchoconstriction (airway narrowing). prostaglandin). Leads to mucosal edema (swelling). SRS-A Effects: Attracts eosinophils (white blood cells involved in o Potent bronchoconstrictor with long-lasting effect. inflammation). o Promotes mucosal edema (swelling). ECF-A: o Increases mucus secretion. Released by mast cells. o Leads to leukocyte infiltration (white blood cell Attracts eosinophils to the injury site, increasing accumulation). inflammation. Therefore…want to stop or slow down these chemical mediators to These mediators contribute to asthma symptoms and treat symptoms of asthma complications. This is the basis of most treatment options! Chronic Obstructive Pulmonary Disease COPD Therapy  Progressive respiratory condition caused by Goals: emphysema and chronic bronchitis. Both  Drug therapy provides some relief but not able to reverse physical conditions cause irreversible changes to the damage to the respiratory lining respiratory system.  Decrease or abolish dyspnea  Symptoms include :chronic cough, SOB, increased  Reduce impairment, disability & physical limitations susceptibility to infection and restriction of physical  Reduce frequency & severity of exacerbations activity.  Improve quality of life  Palliative at end stages  Chronic Bronchitis Emphysema ALSO KNOWN AS “Blue Bloaters” “Pink Puffers”  Chronic irritation and inflammation of the  Permanent enlargement of alveoli and destruction of alveolar respiratory tract walls caused by smoking and hereditary factors ✓ Cigarette smoking and other environmental pollutants ✓ Lungs lose their elasticity making the expiration of air very difficult increase secretions and thicken mucus which ✓ Irreversible lung damage forces patients to decrease daily activities interferes with gas exchange (when severe may cause ✓ Those with emphysema are exhausted since they expend 15-20% of cyanosis) total energy just to breathe ✓ Secretions over time cause fibrotic changes (degeneration of respiratory cells) in the respiratory ✓ Treatment includes respiratory exercises, O2 therapy, and lining medications (bronchodilators and mucolytics) ✓ Treatment usually palliative, help them breathe, but cannot reverse the changes in the fibrotic lining MOA of Bronchodilators Sympathomimetic Bronchodilators Xanthine Derivative Bronchodilators  Bronchiole smooth muscle tone and Sympathetic activation by ▪ Xanthine drugs inhibit the enzyme mucous production are under the control stimulation of adrenergic receptors phosphodiesterase that normally of the autonomic nervous system which increases the intracellular inactivates cyclic AMP  Sympathetic activation – concentration of the nucleotide ▪ Thus, increasing the activity of cyclic bronchodilation “cyclic AMP” AMP which results in bronchodilation  Parasympathetic (rest) activation – bronchoconstriction and increased Cyclic AMP causes bronchodilation ▪ Activity of these drugs has only been secretion of mucus by inhibiting the release of the demonstrated at very high doses and Therefore, -want drugs that increase chemical mediators from mast cells absorption/metabolism is patient sympathetic tone and/or decrease dependent parasympathetic tone AKA: B2 Agonists Bronchodilators Example: Albuterol (Salbutamol) Levalbuterol – (Xopenex) Sympathomimetic Bronchodilators Adrenergic Receptors ▪ Generally speaking, sympathetic activation occurs by stimulation of adrenergic receptors. ▪ There are four adrenergic receptors that you have learned about, Beta 1, Beta 2, Alpha 1, and Alpha 2. Beta 1 receptors - increases heart rate and strength of heart contraction Beta 2 receptors - dilation of blood vessels, bronchodilation, relaxation of smooth muscle walls in digestive and urinary visceral organs, stimulates secretion of resin, which in turn increases blood pressure and blood volume. Alpha 1 receptors - constrict blood vessels and visceral organ sphincters Alpha 2 receptors - inhibits release of norepinephrine from adrenergic terminals Alpha- and Beta-Adrenergic Agonists Beta Adrenergic Agonists (non-selective) EPINEPHRINE (EPIPEN OR adrenaline) ORCIPRENALINE (Alupent) ▪ stimulates all beta and alpha receptors ▪ nonselective beta agonist, both beta 1 and beta 2 receptors ▪ onset is immediate and duration is short acting ▪ ratio of bronchodilating effects to cardiac stimulation is favorable ▪ since not selective for lungs, must watch out for at usual doses systemic adverse effects ▪ onset is less than 5 minutes if inhaled, duration is 3-4 hours ▪ tachycardia, CNS stimulation, and renin secretion ▪ adverse effects include vasodilation, tachycardia, CNS ▪ used usually only in emergency situations stimulation, metabolic alterations (increase blood sugar) (anaphylaxis) ▪ recently discontinued as single ingredient product ▪ Dosage Forms: injection, inhalation, Ophthalmic Solution Beta-2 Adrenergic Agonists (selective) Beta-2 Adrenergic Agonists (selective) Longer acting (Controller or Maintenance) Shorter acting (Rescue or Reliever) FORMOTEROL SALBUTAMOL (Ventolin) ▪ used in treatment and prevention of symptoms of reversible TERBUTALINE (Bricanyl Turbuhaler) obstructive airway disease in patients 6 or older ▪ indication is for symptomatic relief and prevention ▪ onset under 5 minutes, duration for 12 hours of acute bronchospasm due to asthma or COPD ▪ adverse effects include headache, tremor, palpitation and prevention of exercise induced bronchospasm ▪ onset is under 15 minutes, duration 4-8 hours, SALMETEROL depending on drug ▪ used for maintenance treatment for patients with breakthrough ▪ adverse effects include vasodilation, tremor, symptoms not controlled by corticosteroids and requiring regular tachycardia use of short acting bronchodilator ▪ Dosage Forms: ▪ onset 10-20 minutes, duration for 12 hours ▪ adverse effects include headache, tremor, palpitation IDACATEROL (Onbrez Breezhaler) newest on market, longer lasting, dosed once daily Dosage Forms? Inhalation powder Anticholinergic Bronchodilators Anticholinergic Bronchodilator Anticholinergic Bronchodilators ▪ Block the action of acetylcholine Short Acting: ▪ Alternative for patients experiencing resulting in decreased levels of IPRATROPIUM tremors or tachycardia from B2-agonists intracellular cyclic GMP Long Acting: ▪ Adjunct in therapy for two methods of ▪ Decreased cyclic GMP results in TIOTROPIM bronchodilation blocking the release of chemical UMECLIDINIUM ▪ Delayed onset of action compared to mediators from mast cells and thus GLYCOPYRRONIUM B2-agonists no bronchoconstriction ACLIDINIUM ▪ Longer effect than B2-agonists ▪ Not widely used to treat asthma, ▪ derived from atropine focused on adult COPD ▪ used for maintenance treatment of ▪ Act by decreasing the intracellular bronchospasms in COPD concentration on “cyclic GMP” which ▪ adverse effects: include drying of is a parasympathetic mediator that mouth and upper respiratory passage, causes mucous production and headache, blurred vision, tremor, bronchoconstriction (glaucoma, mydriasis): if not use properly ▪ Dosage Forms:  Leukotriene Receptor Antagonists Mechanism of Action Leukotriene Receptor Antagonists MONTELUKAST (Singulair) ▪ Interferes with the prostaglandins known as leukotrienes ▪ block the receptors where leukotrienes bind & cause effect ▪ Leukotrienes cause bronchoconstriction, stopping them, stops bronchoconstriction ▪ Used for prophylaxis and chronic treatment of asthma (and allergies) ▪ also indicated for use in prevention of exercise induced bronchoconstriction ▪ generally, well tolerated ▪ Dosage Form: Tablets, Chewable Tablets, Oral Granules Other Therapies Mucolytics Expectorants N-ACETYLCYSTEINE GUAIFENESIN (Robitussin) given by inhalation Encourages the production of respiratory tract secretions while breaks down mucous lining bronchioles reducing their viscosity allowing secretions to be expelled more adjunctive therapy in COPD with bronchodilator as easily by cilia and cough tends to be irritating to respiratory tract and may No primary role in treatment of Asthma/COPD cause bronchospasm More commonly used in cough and cold preparations reserved for in hospital use, not commonly used for Dosage Form: Tablets, Liquid Syrup, Granules and Effervescent Tablets ambulatory patients “Bronchodilators Overview” “Bronchodilators Overview” Two most common classes: Beta-adrenergic Drugs (SABA) Anti-cholinergic Agents (SAMA)  Short-acting  Short-acting 1. Beta-Adrenergic Sympathomimetic Drugs = B2  salbutamol  Ipratropium Bromide (Atrovent) Agonists  Terbutaline  Long acting (LAMA)  Short Acting Beta 2 Agonists (SABA)  Long- acting (LABA)  Spiriva  Long-Acting Beta 2 Agonists (LABA)  salmeterol  Incruse Ellipta (umeclidinium) 2. Anti-cholinergic Drugs = Muscarinic  Symbicort  Seebri Breezhaler(glycopyrronium) Antagonists  Formoterol  Tudorza Genuair (Aclidinium)  Short Acting Muscarinic Antagonists  Xanthine Compounds Leukotriene Receptor Antagonists(LTRA) (SAMA)  theotha  Montelukast (singular)  Long-Acting Muscarinic Antagonists Mainly used for long-term control of  Accolate® (Zafirlukast) (AstraZeneca), (LAMA) asthma and COPD symptoms. Less commonly used today due to side effects and the need for blood level monitoring.  Combination Therapies Combivent Active Ingredients: Ipratropium bromide (anticholinergic) and albuterol (salbutamol) (beta-2 agonist). Classes: Anticholinergic and Beta-2 adrenergic agonist. Purpose: Combined to provide bronchodilation by two different mechanisms, which improves breathing in COPD patients Duaklir Active Ingredients: Aclidinium bromide (anticholinergic) and formoterol (beta-2 agonist). Classes: Anticholinergic and Beta-2 adrenergic agonist. Purpose: Combined to achieve long-lasting bronchodilation through different pathways, used in COPD treatment. Ultibro Active Ingredients: Indacaterol (long-acting beta-2 agonist) and glycopyrronium (long-acting anticholinergic). Classes: Long-acting Beta-2 agonist (LABA) and Long-acting muscarinic antagonist (LAMA). Purpose: Provides extended bronchodilation for COPD patients, improving airflow and reducing symptoms. Symbicort Active Ingredients: Budesonide (inhaled corticosteroid) and formoterol (long-acting beta-2 agonist). Classes: Corticosteroid and Long-acting beta-2 agonist (LABA). Purpose: Used for asthma and COPD to reduce inflammation (budesonide) and provide bronchodilation (formoterol). Advair Active Ingredients: Fluticasone propionate (inhaled corticosteroid) and salmeterol (long-acting beta-2 agonist). Classes: Corticosteroid and Long-acting beta-2 agonist (LABA). Purpose: Used in asthma and COPD to reduce airway inflammation (fluticasone) and maintain bronchodilation (salmeterol). Auxiliary Labels Bronchodilator MDI (Metered Dose Inhaler): Shake well before use. Rinse mouth after use (to prevent oral irritation and residue). Bronchodilator DPI (Dry Powder Inhaler): Do not shake. Rinse mouth after use (to prevent irritation). Combination Inhaler with Bronchodilator and Steroid: Shake well before use (if MDI). Rinse mouth after use (important for steroid component to reduce risk of oral thrush). Classification Drug Brand Name Bronchodilators Salbutamol Ventolin Xanthine’s Theophylline Uniphyl Mucolytics Acetylcysteine Mucomyst Corticosteroids Fluticasone Flovent Expectorants Guaifenesin Robitussin Anticholinergics Tiotropium Spiriva Antiallergics Cromolyn Sodium Nalcrom REFER TO MY CANVAS OR PDF FOR A CLEARER IMAGE  LECTURE 4 Steroids for Oral Inhalation Indications: 1. Treatment of acute bronchitis 2. Prophylactic management of steroid responsive bronchial asthma Cornerstone in infants and children as reduces and controls symptoms, and prevents airway remodeling 3. Adjunct when bronchodilators fail to provide relief or maintain control Asthma and Chronic Bronchitis Allows for reduction in the dosage of bronchodilator drugs Steroids - Mechanism Of Action Directly target site of inflammation and inhibit the inflammatory response by: Modulating & inhibiting action of chemical mediators Inhibition of eosinophils and other leukocyte cells to accumulate in lung tissue Increase sensitivity of B2 receptors and therefore make B2 receptor agonist drugs more effective No direct effect on relaxing airway smooth muscles Little effect on acute bronchoconstriction as sole agent Dosing and Effect In general, inhaled corticosteroid dosing is once or twice daily Use lowest effective dose, but depends on: Severity of disease Particular steroid used (equivalence) Device used to deliver drug (MDI>DPI) Side Effects of Oral Inhalation Steroid Significantly less side effects than systemic corticosteroids Side effects are dose dependent Hoarseness and vocal cord disturbances Susceptibility to fungal infections in oral cavity Others Side Effects: Osteoporosis? Reduction in child’s height? Glaucoma? Oral Inhalation Steroids GENERIC NAME BRAND NAME TYPES Beclomethasone Qvar Inhaled corticosteroid Budesonide Pulmicort Inhaled corticosteroid Fluticasone Propionate Flovent Inhaled corticosteroid Fluticasone Furoate Arnuity Ellipta Inhaled corticosteroid Ciclesonide Alvesco Inhaled corticosteroid Mometasone Asmanex Inhaled corticosteroid  Combination Inhalers BRAND NAMES Fluticasone/Salmeterol Advair Budesonide/Formoterol Symbicort Mometasone/Formoterol Dulera Fluticasone/Vilanterol Breo Ellipta What do we instruct patients to do to prevent or combat these above side effects? - RINSE MOUTH What auxiliary labels are often used for this class of inhaler? Do not use more than the recommended dose in 24 hours and rinse mouth Technician’s Role w/ Inhalers Technician’s Role w/ Inhalers ✓ Dispense, label, aux labels, priming, etc. 1. Recommend to phmt/MD better device based on ✓ Train patient on delivery device patient factors/performance* ✓ Recommend to phmt/MD better device based on patient 2. Recommend to patient use of aerochamber* factors/performance* 3. Flag to phmt the need of combination inhaler if ✓ Recommend to patient use of aerochamber* identified using two separately consistently* ✓ Flag to phmt the need of combination inhaler if identified 4. Flag to phmt the need for long acting +/or steroid if using two separately consistently* rescue inhaler dispensed too often or used too much** ✓ Flag to phmt the need for long acting +/or steroid if rescue inhaler dispensed too often or used too much* ✓ Knowledge of what is covered by ODB and drug plans ✓ Assess patient’s technique/compliance/SEs over time and re-teach as needed and/or referral to MD/Phmt Indication for “Intranasal Steroid” Use Side Effects with Intranasal Steroids Mainstay of therapy for moderate to severe rhinitis symptoms Headache Treatment of seasonal allergic rhinitis and perennial rhinitis not Burning or stinging responsive to conventional treatment (which is?) Epistaxis (nosebleed) Used prn or regularly Pink colour to mucous and membranes Bad taste in mouth/throat Rhinitis Steroids for Intranasal Inhalation GENERIC BRAND NAMES Beclomethasone Beconase AQ Flunisolide Nasarel Budesonide Rhinocort NEW ORAL INHALERS Fluticasone Propionate Flonase Ellipta, Twisthaler, Breezhaler, Respimat, Genuair, Handihaler. Fluticasone Furoate Breo Ellipta Triamcinolone Nasacort AQ Mometasone Nasonex Ciclesonide Omnaris