Objec9ves. Drug Classes with Indications to Treat AR. Allergic Rhinitis. Allergic Rhinitis. Action Statements

Transcription

1 Sneezes, Wheezes, and espiratory Diseases: An update on Asthma, Allergic hini5s, and COPD Amelie Hollier, DNP, FNP-BC, FAANP Advanced Practice Education Associates Objec9ves Evalua9on of the latest allergic rhini9s guidelines and medica9ons (10 mins) Evalua9on of the medica9ons used to treat asthma and COPD (25 mins) Develop strategies for management of pa9ents who have combina9ons of these diseases (25 mins) Allergic hinitis 5 th most common chronic disease in US Affects 1 in 6 people Treatment costs: $2-5 Billion annually Allergic hinitis an inflammatory response of the nasal mucous membranes after inhaling an allergen, such as grass pollen, dust mites, pet dander,. Symptoms include runny nose, congestion, sneezing, itching Otolaryngol Head Neck Surg Feb;152(1 Suppl):S1-43. Otolaryngol Head Neck Surg Feb;152(1 Suppl):S1-43. Action Statements Strong ecommendation: Intranasal steroids first line Second generation oral antihistamines for sneezing and itching Drug Classes with Indications to Treat A Intranasal glucocorticoids (INGCs) Oral antihistamines Antihistamine sprays Mast cell stabilizers Leukotriene modifiers Otolaryngol Head Neck Surg Feb;152(1 Suppl):S

2 Intranasal Glucocorticoids INGCs THE single most effective therapy for nasal symptoms Downregulate the inflammatory response Fewest side effects Best use in nasal congestion Superior efficacy compared to antihistamines Why do they work? Inhibit allergic inflammation in nose Downregulate inflammatory responses by binding to the glucocorticoid receptors in the cytoplasm of the inflammatory cells Intranasal Glucocorticoids Divided into Generations 1st Generations INGCs First Generation (unknown bioavailability): Beclomethasone (Beconase) Equal efficacy as other INGCs Higher risk of systemic effects because of greater bioavailability 2nd Generations INGCs 2nd Generation (10-34% bioavailability): Budesonide Equal efficacy as other INGCs Potentially fewer systemic effects compared to 1 st generation 3rd Generations INGCs 3rd Generation INGCs: Fluticasone proprionate (<2% bioavailability) Mometasone (undetectable) Fluticasone furoate (<1%) Ciclesonide (minimal) No or limited effect of HPA axis and growth in children 2

3 NAME Generic? Brand Name Fluticasone proprionate Yes Flonase Mometasone Yes Nasonex Budesonide Yes hinocort AQ Beclomethasone No Qnasl Triamcinolone Yes Nasacort AQ Beclomethasone No Beconase AQ Fluticasone furoate No Veramyst Ciclesonide AQ No Omnaris Ciclesonide (dry spray) No Zetonna Comparisons between INGCs Comparative studies between INGCs have not demonstrated significant differences in efficacy Berger, Kaiser, Gawchik, Tillinghast, Woodworth, Dupclay, Georges. Otolaryngol Head Neck Surg. 2003; 129(1):16. Prescribers Letter, March 2015; Vol:31. Allergic hinitis. Determination of Efficacy First pass metabolism: decreases drug bioavailability Fluticasone furoate (Veramyst) June, 2007 Me too drugs Contains fluticasone furoate instead of fluticasone propionate No evidence that furoate is more efficacious than propionate Lipophilicity: ability of GC to penetrate the cell Fluticasone furoate Fluticasone furoate is unscented, no bad taste or smell Improves nasal symptoms, improves eye symptoms $ (27.5 mcg/spray) Ciclesonide Nasal (Omnaris) New steroid Hypotonic solution Hypothesized to increase retention and local absorption at the nasal mucosa $94.49 June,

4 Beclomethasone Nasal (Qnasal) Uses HFA propellant like asthma inhalers Non-aqueous Less PND than with aq sprays 44% systemic absorption Once daily $130/month May, 2012 Get the Drug Where it Needs to Work! Drug must remain in the nose (not down the back of the throat) If nose is crusted or contains mucus, get it out!!! Use saline PN Look at your Toes and Spray your Nose! Best way to instill Direct away from the nasal septum Sniff to pull into upper parts of nose If it drains down the throat, sniff was too hard! eassurance for Long Term Use No increased rate of fractures, glaucoma, or cataracts No detrimental effects on bone density or intraocular pressure Ann Allergy, Asthma, Immunol 2006; 96:1. Quiz When to Use INGCs? When is the best time of day (or night) to use a nasal INGC? Evening/PM Nasal inflammation is greater at night than during the day Ann Allergy, Asthma, Immunol 2006; 96:1. 4

5 OTC Meds for Allergic hini9s FDAs non- x Drugs Advisory CommiPee Triamcinolone acetonide (Nasacort Allergy 24H) for OTC status: (available Spring 2014) Flu9casone propionate (Flonase Allergy elief): available early 2015 Allergic hini9s Hhhhmmmm.Insurance issues with x topical nasal steroids? $ $27.99 OTC Generic cost to you? Action Statements Strong ecommendation: Intranasal steroids first line Second generation oral antihistamines for sneezing and itching Anti-histamines (AH) Why Not First Genera9on An9- histamines? Otolaryngol Head Neck Surg Feb;152(1 Suppl):S st Generation AH Diphenhydramine Chlorpheniramine Hydroxyzine Brompheniramine Cyproheptadine Others 1st Generation AH Cause significant sedation They are lipophilic and cross the blood brain barrier 5

6 1st Generation AH Intellectual and motor function impairment are present even when there is no subjective awareness of sedation 1st Generation AH Prohibited by the FAA for working pilots Prohibited in many states for any person who works in public transportation Older patients more susceptible to anticholinergic effects (dry eyes and mouth, urinary hesitancy, and confusion) 2nd Generation AH Oral Agents Loratadine, desloratadine, cetirizine, levocetirizine, fexofenadine (orals) Mostly non-sedating Lipophobic (so don t cross BB barrier as the 1st gens do) Less impact on nasal congestion 2nd Generation AH Fexofenadine (metabolite of terfenadine) Desloratadine (loratadine) Levocetirizine (purified isomer of cetirizine) Adverse Effects: Sedation Cetirizine, levocetirizine and azelastine are sedating for many patients Loratadine mostly non-sedating Adverse Effects Fexofenadine is non-sedating even at higher than recommended doses 6

7 2 nd Generations Less effective than topical nasal steroids for allergic rhinitis All oral 2nd generation agents have similar efficacies Options Clinicians may offer: Intranasal antihistamines seasonal, perennial, or episodic allergic rhinitis Otolaryngol Head Neck Surg Feb;152(1 Suppl):S nd Generation AH Sprays Azelastine (generic) (Astelin), olopatadine (Patanase) Can be sedating apid onset of action (< 15 minutes) Some anti inflammatory effects Improve nasal congestion PN use Bitter taste Watch out for Medication Errors with Olopatadine! Patanase 0.6%: Nasal spray Patanol 0.1% and Pataday 0.2%: Ophthalmic drops Can be sedating if swallowed Azelastine/ fluticasone(dymista) Jan, 2012 Combines 2 generic meds Steroid plus antihistamine 1 spray each nostril BID Action Statements ecommendation: Clinicians should offer, or refer to a clinician who can offer, immunotherapy (sublingual or subcutaneous) for patients with A who have inadequate response to symptoms with pharm therapy. Otolaryngol Head Neck Surg Feb;152(1 Suppl):S

8 Grass Pollen Extracts Grastek: grass pollen allergen extract Oralair: grass pollen allergen extract Sublingual immunotherapy for allergic rhini9s > $200/month Allergic hini9s agwitek: ragweed pollen allergen extract Sublingual immunotherapy for rhini9s Must have documented allergies before prescribing (Companies that will do this for primary care) Action Statements ecommended Against: Oral leukotriene receptor antagonists as primary therapy for patients with allergic rhinitis. Chronic Obstructive Pulmonary 2014 Global Ini9a9ve for Chronic Obstruc9ve Lung Disease (GOLD) A report by NHLBI and WHO to define, diagnose, treat COPD Otolaryngol Head Neck Surg Feb;152(1 Suppl):S GOLD Staging System The Global Initiative for COPD COPD Medications Most Commonly Used: Inhaled Beta 2 -agonists: short and long Inhaled Anticholinergics (AC): short and long Combo: short Beta 2 and short AC Combo: long Beta 2 and long AC 8

9 Quiz Which long-acting medication class is preferred first line for a patient with COPD who complains of frequent SOB: Beta agonists or Anticholinergics? COPD Medications Others Methylxanthines Inhaled corticosteroids: solo and combo with Beta 2 Systemic steroids Phosphodiesterase-4 Inhibitors Bronchodilators 1. Beta agonists (cause bronchodilation): Short acting beta agonists (SABAs) Example: albuterol Suffix is terol escue med (works immediately and effects last for about 4 hours) Bronchodilators SABAs Albuterol ProAir HFA, Proventil HFA, Ventolin HFA, Levalabuterol (Xopenex), ProAir espiclick (inhalation powder) $42 - $56 per inhaler True or False Levalbuterol is more effective than albuterol. What s the difference between the ß-2s? Drug ß-2 potency Onset in minutes Duration in hrs Albuterol 2 Within Pirbuterol (MaxAir Autohaler) 5 Within 5 5 Levalbuterol??? Within 5 8 9

10 What s the relationship between levalbuterol (Xopenex ) and albuterol? isomer ===> bronchodilation S isomer ===> tachycardia,etc. Albuterol is a mixture of and S isomers Levalbuterol is -isomer of albuterol Albuterol is a mixture of and S isomers S S S S S S Albuterol Xopenex Levalbuterol (Xopenex ) -isomer of albuterol Albuterol is a mixture of and S isomers Levalbuterol (Xopenex ) Inconclusive whether there are fewer side effects for the degree of bronchodilation Older adults: inconclusive More expensive than albuterol Levalbuterol (Xopenex ) Studies of children who use levalbuterol have failed to demonstrate an advantage with levalbuterol More expensive than albuterol Long acting beta agonists (LABAs) Salmeterol (Serevent ), formoterol (Foradil ): Twice Daily Indacaterol (Arcapta Neohaler), Olodaterol (Striverdi espimat): Once Daily Suffix is terol Not a rescue med (takes mins to work) but works for hours 10

11 LABA Dosing Frequency Cost Formoterol (Foradil) Salmeterol (Serevent) Indacaterol (Arcapta Neohaler) Olodaterol (Striverdi espimat) BID $ BID $ Daily $ Daily $ LABAs More convenient and more effec9ve for symptom relief educe exacerba9ons and hospitaliza9ons Improve symptoms Improve health status Bronchodilators 2. Inhaled Anticholinergic Works by preventing bronchoconstriction (yeah, ok it bronchodilates a little) Examples: Ipratropium (Atrovent), tiotropium (Spiriva), aclidinium (Tudorza Pressair), Umeclidinium (Incruse Ellipta) Suffix is tropium Combos: with SABA, LABA, May cause constipation, increased IOP Long Ac9ng An9cholinergic (LAAC) Aclidinium (Turdoza Pressair) Tiotropium Spiriva Handihaler Spiriva espimat Umeclidinium (Incruse Ellipta) Dosing Frequency Cost BID $ Daily $ Daily $ An9cholinergic Medica9ons An5- cholinergic Side Effects Memory impairment, confusion, hallucina9ons, dry mouth, blurred vision, urinary reten9on, cons9pa9on, tachycardia, acute angle glaucoma An Ode to an An9cholinergic Med Oh this drug, it makes me pink, Some9mes, I can t think or even blink. I can t see, I can t pee, I can t spit, I can t (**it) ( defecate ). 11

12 Combo LABA and LAAC Combo Dosing Frequency Cost Olodaterol/ Tiotroprium (S9olto espimat) Vilanterol/ Umeclidinium (Anoro Ellipta) Daily $ Daily $ : 3. Inhaled Pharmacologic Steroids Management Best in COPDers with FEV1 <60% predicted Increases risk of pneumonia Withdrawal may lead to exacerbations Examples: fluticasone, mometasone, budesonide, others Suffix is one or ide Best in combo with bronchodilators Steroid Pharmacologic Combos Management 4. Steroid plus bronchodilators Combined mechanism as for steroid and bronchodilators Examples: fluticasone plus salmeterol (Advair), budesonide plus formoterol (Symbicort), mometasone plus salmeterol (Dulera) No generics, very expensive!!! Oral Steroids CHONIC use should be avoided!!! Unfavorable risk to benefit ratio Oral Steroids for Exacerbations Shorten recovery 9me Improve lung func9on (FEV 1 ) and arterial hypoxemia (PaO 2 ) educe the risk of early relapse, treatment failure, and length of hospital stay A dose of 40 mg prednisone per day for 5 days is recommended Prescribing Strategy for COPD 1. Short acting anticholinergic PN or SA Beta 2 PN, then 2. Long acting anticholinergic or LABA; plus rescue med, then 3. ICS + LABA or LA anticholinergic; plus rescue med, then 4. ICS + LABA and/or LA anticholinergic; plus rescue med *Theophylline is an alternate treatment but not preferred (relatively inexpensive) **PDE4: phosphodiesterase inhibitor (roflumilast, Daliresp) used to reduce exacerbations for patients with chronic bronchitis, severe airflow limitation and frequent exacerbations not controlled by LABAs

13 COPD oflumilast (Daliresp) New class: oral tablet phosphodiesterase 4 inhibitors MOA: increases camp in lung cells educes lung inflammation eserve for severe or very severe COPD; to reduce recurrent exacerbations COPD oflumilast (Daliresp) Maximize other inhalers first $255.99/month Watch out for 3A4 drug interactions COPD oflumilast (Daliresp) Watch for insomnia, weight loss, depression, change in mood Global Strategy for Diagnosis, Management and Prevention of COPD Differential Diagnosis: COPD and Asthma COPD Onset in mid-life Symptoms slowly progressive Long smoking history ASTHMA Onset early in life (often childhood) Symptoms vary from day to day Symptoms worse at night/early morning Allergy, rhinitis, and/or eczema also present Family history of asthma 2015 Global IniKaKve for Chronic ObstrucKve Lung Disease NAEPP The National Asthma Education and Prevention Program: Expert Panel eport 3, Guidelines for the Diagnosis and Management of Asthma -- Full eport 2007 Effective Asthma Management Preventive approach egularly scheduled visits (assess symptoms, pulmonary function is monitored, medications adjusted, ongoing education) 13

14 Medications Bronchodilators Corticosteroids Leukotriene blockers Bronchodilators Every asthma patient NEEDS a short acting BD This is a safety issue!!! Short acting ß agonists elief of acute symptoms only emember the ule of 2s These do NOT relieve inflammation Never as monotherapy for any persistent asthma What s the difference between the ß-2s? Drug ß-2 potency Onset in minutes Duration in hrs Albuterol 2 Within Pirbuterol 5 Within 5 5 Levalbuterol??? Within 5 8 Overuse of short acting ß-2? Decreased sensitivity to beta agonists if used on a chronic basis Doesn t work as well Overuse of short acting ß-2? Downregulation of beta-2 adrenergic receptors (there is a decrease in the number of ß-2 receptors) Uh oh! 14

15 What about the long acting ß-2? It can and does happen, but it is not observed as often as it is hypothesized It IS observed in SA agents Take Away Points Changes in the cor9costeroid molecule produce significant differences in potency (binding affinity at the glucocor9coid receptor) Binding affinity = Potency; Many factors impact improvement in lung func9on: Steroid, delivery device (MDI, DPI, NEB), addi9on of a spacer, facemask; pa9ent technique Kelly,HW. The Annals of Pharmacotherapy. 2009;43(3): Comparison of Steroids Dose (mg) ela9ve An9- inflammatory Ac9vity Dura9on of Ac9on Hours Cor9sol Prednisone Prednisolone Methylprednisolone Dexamethasone Good Steroid Choices Asthma: prednisone or prednisolone (less mineralocor9coid ac9vity) COPD: Methylprednisolone, prednisone (men9oned in GOLD guidelines) Last Points Adrenal insufficiency: hydrocor9sone used to help retain retain sodium and water Give prednisone, methylprednisolone, prednisolone once daily to minimize HPA axis suppression Proper9es of Inhaled Steroids Drug eceptor Binding Affinity Lung Delivery % Beclomethasone dipropionate/17- monopropionate 0.4/ Budesonide Ciclesonide/ desciclesonide 0.12/ Flunisolide Flu9casone propionate Mometasone furoate Triamcinolone acetonide

16 Leukotriene Blockers (LTA) Montelukast (Singulair) Zafirlukast (Accolate) Take Home Point! LTA: consider for mild asthma IF a patient can t or won t use an inhaled steroid Steroids are preferred for ANY form of persistent asthma Prevent remodeling!!!! Moderate or Severe Persistent Pharmacologic Asthma Management 4. Steroid plus bronchodilators Combined mechanism as for steroid and bronchodilators Examples: fluticasone plus salmeterol (Advair), budesonide plus formoterol (Symbicort), mometasone plus salmeterol (Dulera) No generics, very expensive!!! Take Home Points! Allergic hinitis: STEOIDS, second gen antihistamines COPD: Bronchodilators Asthma: STEOIDS Take Home Points! Make Evidence Based treatment decisions! Thank you! For ques9ons or to contact me: Dr. Amelie Hollier amelie@apea.com Advanced Practice Education Associates Lafayette, LA 16