7_Respiratory Pharmacology_KA.pdf

Drugs used in Respiratory Disorders Khalid Ansari 1 Adrenergic (Sympathomimetic/Agonists) Bronchodilators Definition: Adrenergic drugs are medications that stimulate certain nerves in your body. Some of them specifically allows relaxation of smooth muscle...

Drugs used in Respiratory Disorders Khalid Ansari 1 Adrenergic (Sympathomimetic/Agonists) Bronchodilators Definition: Adrenergic drugs are medications that stimulate certain nerves in your body. Some of them specifically allows relaxation of smooth muscle in the airway. Also known as Sympathomimetic bronchodilator or B2 agonists. These drugs are used in many life- threatening conditions, including cardiac arrest, shock, asthma attack, or allergic reaction. Types: 1. Ultra Short-Acting (Bronchodilators) e.g: Epinephrine, recemic epi, Isoetharine 2. Short-Acting (Bronchodilators) e.g: Albuterol, Pirbuterol 3. Long-Acting (Bronchodilators) e.g: Salmeterol and Formoterol https://quizlet.com/122662223/chapter-6-adrenergic- sympathomimetic-bronchodilators-flash-cards/ 2  Short Acting Bronchodilators (Adrenergic, Sympathomimetic, Agonists) Ultra-short-acting/Short-Acting Drugs Brand Name Receptor Dose Time Course(Onset, s peak Duraion) Epinephrine Adrenalin ª, β SVN: 1% Sol,. 2.5-5mg Onset: 3-5min, Peak: Chloride q.i.d. 5-20min MDI: 0.22mg/puff Duration: 1-3 hr (for Epi) Racemic Epi Micronefrin ª, β SVN 2.25% sol. 0.25- Onset: 3-5min, Peak: , S-2 0.5ml,5-11mg qid 5-20min Duration: 0.5-2 hr Metoproterenol Alupent Β2 SVN: 0.4-0.6% sol, Onset: 1-5min, Peak: tid,qid, Tabs 10-20mg 60 min tid,qid, syp: 10mg/5ml Duration: 2-6 hr Albuterol Proventil,V Β2 SVN: 0.5% sol Onset: 15min, Peak: entolin HFA 1.25 or 2.5mg tid,qid. 30-60 min MDI 90mcg/puff, 2puffs Duration: 5-8 hr tid,qid, tab 2,4,8mg bid, tid,qid. MDI: 200mcg/puff, 2puffs q4h. Pirbuterol Maxair Β2 MDI: 200mcg/puff, Onset: 5min, Peak: 30 autohaler 2puffs q4h. min 3 Duration: 5 hr Long Acting Bronchodilators (Adrenergic, Sympathomimetic, Agonists) Long acting Bronchodilator Agents Drugs Brand Recp Dose Time Name Course(Onset, peak Duration) Salmeterol Serevent Β2 DPI: Onset: 20 min, Peak 3-5 hr Diskus 50mcg/bister bid Duration: 12 hr Formeterol Foradil Β2 SVN: 20mcg/2ml, Onset: 15min, Peak 3-6 hr Certihale bid Duration: 12 hr r DPI: 8.5- 12mcg/inhalation , bid Arformeter Brovana Β2 SVN: 15mcg/2ml, Onset: 15min, Peak 3-6 hr ol bid Duration: 12 hr 4  Adrenergic (Sympathomimetic/Agonists) Bronchodilators Mechanism of Actions Beta 1 receptor stimulation: Causes increased myocardial conductivity, increased heart rate as well as contracting force of heart muscles. The bronchodilating action of the adrenergic drug is due to stimulation of B2 receptors to relax the smooth muscles in the bronchioles of the lungs. Also cause stimulation of mucocilliary clearance and release of inflammatory mediators. Alpha Receptor stimulation: it causes vasoconstrictor or vasopressor effect. It also inhibits histamine release from the mast cells. These are present in human lung tissue, pulmonary epithelium, and free in the bronchial lumen, inhibit secretions in the upper airway (nasal passages), this can provide decongestion. 5  Adrenergic (Sympathomimetic/Agonists) Bronchodilators Indications Ultra short –acting Bronchodilators (Racemic Epinephrine) 1. Reduce Airway swelling after extubating or epiglottitis, bronchiolitis, croup 2. Control bleeding during endoscopy or bronchoscopy. Short Acting Bronchodilators Agents (Albutereol) 1. Also known as rescue meds or relievers 2. Relief of acute reversible airflow obstruction Long Acting Bronchodilators Agents (Salmeterol) 1. Also known as controllers, since their slow time to peak effect, they consider as poor rescue drugs. 2. In asthma, these drugs are combined with anti- inflammatory drugs. 3. Maintenance of bronchodilation 4. Control of bronchospasm 5. Although Formeterol has rapid onset of action (similar to albutereol), its slower peak effect and prolonged activity make it a better maintanance drug than an acute reliever or rescue agent. 6  Adrenergic (Sympathomimetic/Agonists) Bronchodilators Adverse/ Side Effects Tremor (very common) Headache Insomnia Bronchospasm (with MDI use) Palpitations Some tolerance Nervousness Dizziness 7 Anticholinergic (Parasympatholytic/Antagonists) Bronchodilators Definition: Agents that block parasympathetic nerve fibers which allow relaxation of smooth muscle in the airway Types: 1. Tertiary Anticholinergic e.g. Atropine 2. Quaternary Anticholinergic e.g. Ipratropium Br and Tiotropium bromide 8 Pharmacologic Effects of Tertiary and Quaternary Anticholinergic Agents given as Inhaled Aerosol Tertiary Quaternary (Atropine) (Ipratropium and tiotropium) Respiratory Bronchodilation, decreased mucociliary Bronchodilation, little or clearance, blockage of mucus secretion minor decrease in mucociliary clearance, blockage of nasal secretion. Cardiac Small dose: minor bradycardia No effect Large dose: increased heart rate CNS Altered CNS function, mydriasis, No effect Eye cycloplegia (paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation) Gastrointestinal Dry mouth, dysphagia, slows motility of GI Dry mouth tract. Genitourinary Urinary retention No effect 9  Inhaled Anticholinergic Bronchodilators (Parasympatholytic) Drugs Recp Dose Time Course(Onset, peak Duration) Iprotropium M1, M2 and M3 HFA MDI: 17mcg/puff, 2 Onset: 15min, Peak: Bromide receptors.(less puffs qid SVN: 0.02% Sol 1-2 hr selective) or 500mcg tid, qid Duration: 4-6 hr Nasal spray: 21-42mcg 2- 4 times daily Iprotropium br Muscuranic MDI: 18mcg/puff and Onset: 15min, Peak: and Albuterol (Ipratopium) and B2 albuterol 90mcg/puff, 2 1-2 hr (Albuterol ) puffs qid Duration: 4-6 hr Tiotropium Br Highly selective M3 SVN: Ipratropium 0.5mg Onset: 30 min, Peak: and albuterol 2.5mg. 1-3 hr DPI: 18mcg/inhalation, 1 Duration: 24 hr inhalation daily (one cap) 10 Anticholinergic (Parasympatholytic/Antagonists) Bronchodilators Mechanism of Actions The bronchodilating action of the anticholinergic drug is due to the blockade of acetylcholine at the cholinergic (muscuranic) receptors at bronchial smooth muscles. It also reduce mucus production. Bronchoconstriction and mucus Drying of upper airway and secretion inhibition of constriction 11 Anticholinergic (Parasympatholytic/Antagonists) Bronchodilators Indications Indication for anticholinergic bronchodilators Ipratropium and tiotropium are indicated as bronchodilators for maintenance treatment in COPD, including chronic bronchitis and emphysema. Ipratropium is used and may be indicated in some individuals with asthma in addition to β agonists, especially bronchoconstriction that does not respond well to β- agonist therapy. Indication for combined anticholinergic and β-agonist bronchodilators A combination anticholinergic and β agonist, such as ipratropium and albuterol (Combivent, DuoNeb), is indicated for use in patients receiving regular treatment for COPD who require additional bronchodilation for relief of airflow obstruction. 12 Anticholinergic nasal spray Anticholinergic (Parasympatholytic/Antagonists) Bronchodilators Adverse/ Side Effects The main side effects of anticholinergics like ipratropium include: Dry mouth Constipation Cough Headaches Less common side effects include: Nausea, heartburn, difficulty swallowing (dysphagia), palpitations, throat irritation Difficulty urinating Glaucoma may worsen if the medication gets in the eyes when using an inhaler or a nebuliser. 13  Xanthines Bronchodilators Definition: Xanthine, is a purine base found in most human body tissues and fluids and in other organisms. A number of stimulants are derived from xanthine, including caffeine and theobromine. Xanthine is a product on the pathway of purine degradation. Xanthine Derivatives: 1. Theophylline 2. Oxytriphyline 3. Aminophylline 4. Dyphyline 14  Xanthines/Mehylxanthines/Theophylline Bronchodilators Mechanism of Actions Although, theophylline is usually classified as bronchodilator, it has relatively weak bronchodilating effect compared with B2 agonists. The primary effect of methylxanthines are stimulation of the CNS and bronchodilation. It also cause cardiac stimulation vasodilation and diuresis. The mechanism of action is not fully understood. Pulmonary effects of seven xanthine, exhibiting a range of potencies as cyclic nucleotide phosphodiesterase (PDE) inhibitors and as adenosine antagonists which in turn stimulate ventilatory drive or strengthen diaphragm. They relax bronchial smooth muscles and 15 16  Xanthines Bronchodilators Indications Asthma and COPD as second line drug. Also used as prophylaxis and treatment for bronchospasm in emphysema and chronic bronchitis. Apnoea of Prematurity in neonates 17 Xanthines Bronchodilators Adverse/ Side Effects 18  MUCUS CONTROLLING DRUGS (Mucolytics/Mucokinetics) Definition: These are a class of drugs which aid in the clearance of mucus from the airways, lungs, bronchi, and trachea. Healthy people produce 100ml/day/ 10 ml (expelled or swallowed), rest reabsorbed) Mucoactive/Mucolytics Agents (available as Aerosol) 1. N-Acetylcysteine (NAC-Mucomyst): very foul smelling: us ein lung disease not proven, approved use is only for acetaminophen overdose 2. Dornase Alpha (Pulmozyme) for cystic fibrosis 3. Aqueous aerosol, water, saline for sputum induction, secretion and mobilisation 4. Hyperosmolar (7%) saline (hypersal): Airway clearance (mucokinetics for cystic fibrosis Mucokinetics (Expectorants) 19 Sodium Citrate  MUCUS CONTROLLING DRUGS (MUCOLYTICS) Mechanism of Actions Mucolytic: It causes the disruption of chemical bonds between mucoprotein molecules of respiratory secretions. This leads to liquefaction of the mucus.(liquefy thick secretions). Mucokinetics (Expectorant): They increase secretions and decrease mucus viscosity, this makes sputum easily removable from chest. Which results in coughing become less tiring 20  MUCUS CONTROLLING DRUGS (MUCOLYTICS) Indications N-Acetylcysteine (NAC-Mucomyst): very foul smelling: use in lung disease not proven, approved use is only for acetaminophen overdose Dornase Alpha (Pulmozyme) for cystic fibrosis Aqueous aerosol, water, saline for sputum induction, secretion and mobilisation Hyperosmolar (7%) saline (hypersal): 21  MUCUS CONTROLLING DRUGS (MUCOLYTICS) Adverse/ Side Effects Nausea Vomiting Hypersensitivity Stomatitis Rhinorrhea Rash Fever Drowsiness Chest tightness Bronchoconstriction Likelihood of bronchospasm in asthmatics 22  Corticosteroids (Anti-inflammatories) Definition: Corticosteroids (cortisone-like medicines) are used to provide relief for inflamed areas of the body. They lessen swelling, redness, itching, and allergic reactions. They are often used to treat severe allergies or skin problems, asthma, and arthritis etc. Corticosteroids are naturally produced in the body (Endogenous). If body does not produce enough cortisone, doctor may need to prescribed (Exogenous). Corticosteroids are very strong medicines. In addition to their helpful effects in treating medical problems, they have side effects that can be very serious. Corticosteroids are multi-effect drug. 23  Corticosteroids (Anti-inflammatories) Mechanism of Actions Inhibit inflammatory response Increase number and sensitivity of b2 receptors and promote dilation Reduce mucus production and edema Corticosteroids may regulate gene expression Cytokines released from one cell affect the actions of other cells by binding to receptors on their surface. You can 24 think of these receptors as mailboxes. They receive the cytokine's chemical message, and then the receiving cell performs activities Pharmacokinetics of inhaled glucocorticoids. GI = gastrointestinal 25  Corticosteroids (Anti-inflammatories) Some examples of ICS Fluticasone prop/Salmeterol DPI/MDI DPI: 200Flu/100 Sal (Advair) mcg MDI: 45, 115.230,cg Flu/21mcg sal Budenoside/Formoterol MDI MDI: 80 or 160 bud/4.5 (Symbicort) form mcg 115.230,cg Flu/21mcg sal CFC: Contains chlorofluorocarbon (CFC- HFA: Hydro Flouro Alkaine 12), a substance which harms public health and the environment by destroying 26 ozone in the upper  Corticosteroids (Anti-inflammatories) Indications There is no doubt that the early use of ICS has revolutionized the management of asthma- first line for mild to moderate asthma, with marked reductions in asthma morbidity and improvement in health status. ICS are now recommended as first-line therapy for all patients with persistent asthma An optional dug in COPD. Reduce exacerbations and improve health related quality of life including reduction in hospitalisation. Prevention of irreversible changes in asthma and reduction in mortality. 27 Corticosteroids (Anti-inflammatories) General Adverse Effects 28  Corticosteroids (Anti-inflammatories) Specific Adverse Effects Systemic Steroids Aerosolized Hypo-pituitary gland suppression Steroids Immunosuppression Systemic (A-Age) Psychiatric reactions Adrenal insufficiency Cataract Extra pulmonary allergy Myopathy Acute asthma Osteoporosis Growth reduction (dose Peptic ulcer related) Fluid retention Hypertension Local: Increased WBCs Fungal infections Skin rash Dysphonia Growth reduction Cough Increased glucose levels Bronchoconstriction Incorrect use of MDI (inadequate dose) 29  Non Steroidal Anti-inflammatory Antiasthma Drugs (Anti-inflammatories) Definition: Nonsteroidal anti-inflammatory drugs are a drug class that groups drugs together that reduce pain, decrease fever, and, in higher doses, decrease inflammation. Types: Cromolyn Like Agents (Mast Cell Stablizers) e.g: Cromolyn Sodium or ketotifein, Gastrocrom. Antileukotrenes e.g: Montelukast (Singulair) Monoclonal Antibody e.g: Omalizumab (xolair) Mast cells: A type of white blood cell. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuroimmune systems and contains many granules rich in histamine and heparin. 30 An allergy is a local inflammatory response to an environmental substance that is not capable of causing disease (an allergen). When a B cell first encounters the allergen (initial exposure) it differentiates into a plasma cell and makes large amounts of antigen-specific IgE. The IgE molecules attach to mast cells. Upon re-exposure, the IgE-primed mast cells release large amounts of histamine and other inflammatory chemicals, leading to swelling and redness These reactions tend to be localised to the region of exposure - often the airways and 31 throat. A severe systemic allergic reaction is called anaphylaxis and can be fatal  Non Steroidal Anti-inflammatory Antiasthma Drugs Mechanism of Actions Cromolyn Sodium (mast Cell Stablizers): They inhibit degranulation of mast cells by trigger stimuli and prevent the release of histamine, LTs, PAFs, interleukins from mast cells. The agent achieve their action by blocking the calcium influx into the mast cells. Antileukotrienes: Relatively new class of anti-asthma drugs that either block leukotriene synthesis (5-lipoxygenase inhibitors) like zileuton, or inhibit the most relevant of their receptors (the cysteinyl leukotriene 1 receptor [CysLT1]) like montelukast and zafirlukast Monoclonal Antibody e.g: Omalizumab (xolair) It binds free IgE antibodies thereby decrease allergic Reaction severity. 32  Non Steroidal Anti-inflammatory Antiasthma Drugs Indications Cromolyn Sodium (mast Cell Stablizers): Prophylactic agent for asthma which means it is used to prevent asthma attacks in people with bronchial asthma. Cough due to the use of ACE inhibitors (lisinopril) Use after tapered withdrawal of corticosteroids Antileukotrienes: Only for prophylaxis and management of Chronic asthma (moderate to severe persistant) for adults and children >12 years (montelukast can be given to children < 6years) Monoclonal Antibody: Only for prophylaxis and management of Chronic asthma (moderate to severe persistant) for adults and children >12 years Allow reduction in high dose ICS or prevent increase in ICS dose. It also allow reduction of asthmatic rescue agents. 33  Non Steroidal Anti-inflammatory Antiasthma Drugs General Adverse Effects Cromolyn Sodium: Antileukotrienes Monoclonal Antibodies Nasocrom/Gastrocom (zileuton/Zyflo) Anaphylaxis (severe Transient Body pain Hypersensitivity) burning/stinging Body Weakness Pharyngitis upon instillation Dyspepsia Malignancies Dryness around the Abdominal pain Injection site eyes Headache reactions Puffy eyes Hepatotoxic infections Eye irritation (Zafirlukast/Accolate URTIs Watery eyes ) Rash Infection Styes (EYELID Nausea INFECTIONS) Abdominal pain Itchy eyes Headache Dyspnea Hepatotoxic Variable response (Montelucast/Singulai Can only be given r) in addition to Hypersensitivity other Pharyngitis bronchodilators Diarrhea and not alone Laryngitis 34 Otitis  Tasks 1 1.__________ is the long acting b agonist (bronchodilator) 2._________ is an example of short acting B agonist 3.Relievers (B2 Agonists group) are used to treat _________________ 1.Anticholinergics have which of the following respiratory effects a.Prevent bronchodilation b.Decreased respiratory secretion c.Increase bronchoconstriction d.All of the above e.None of the above (Choose from here: Diabetes, Cardiovascular disorder, Albuterol, Acute bronchospasm, MOI, Antidepressants, salmeterol, Epinephrine) 35 Tasks 2 1.__________ is contraindicated in under 12 children 2._________ is an example of tertiary anticholinergic 3.Large dose of atropine causes __________ in heart rate. 4.Combivent is the combination of which two agents: __________ and __________. 5.The bronchodilating action of the anticholinergic drug is due to the blockade of acetylcholine at ______________ receptors. (Choose from here: Increase, Decrease, tiotropium, atropine, ipratropium, Ipratropium br and Albuterol, Muscarinic, Beta1 and 2, Ipratropium br and salmeterol) 36 Tasks 3 1.The common adverse effects of xanthine derivatives are nervousness, _________ and tachycardia 2.__________ is also indicated to treat Apnoea of Prematurity in neonates. 3.The therapeutic theophylline plasma level is _________________ 4.____________ is contraindicated for patients with coronary artery disease and renal and liver disease. (Choose from here: Oxtriphylline, B agonists, corticosteroids,