o Drug: Theophylline, the Methylxanthine. It has 100% oral bioavailability, and numerous side effects. It is an old agent that is nearly obsolete. Indication: COPD, Asthma

Mast Cell Stabilizers Anti-Inflammatory Drugs - General MoA: Intracellular calcium is required for the fusion of Histamine vesicles to the cell membrane and

subsequent degranulation. These medications stabilize mast cells by blocking the calcium channels essential for degranulation. By inhibiting degranulation, this prevents the release of Histamine and related mediators, thereby helping to control the extent of allergic disorders.

- Drugs: Nedocromil. There are inhalers available for the Indications of asthma. Human Immunoglobulin Antibody Anti-Inflammatory Drugs

- Omalizumab (Xolair): Recombinant DNA-derived humanized IgG1k mAb. Injected SubQ q2-4weeks o MoA: Selectively binds IgE, preventing the cross-linking of immune effector cells with Ag (which

normally would end in the release of mediators). T1/2 = 26 days o Indication: Patients with severe, persistent asthma, not controlled with high doses of corticosteroids o AE: Carries the risk of anaphylactic shock

(10/23) Goliak Lecture: Allergic Rhinitis What are allergies? – A Hypersensitivity reaction mediated by IgE, affecting 50million Americans. 5th most common chronic illness, with genetics as an influence on its development. Asthma is common comorbidity. Risks include:

- Socioeconomic status, nonwhite race, urban living, mama smokes cigs Allergic Rhinitis: Hypersensitivity reaction mediated by IgE

- Sx: Sneezing, Profuse and clear rhinorrhea, Nasal congestion, pruritus, postnasal drip, ocular sx o Seasonal allergens: Tree, grass, pollen, mold spores, ragweed – aka Hayfever o Perennial allergens: Dust mites, indoor molds, pet dander, cockroaches, occupational allergens

- Presentation, and mediated by… o Early-Phase (Minutes): Mediated by Histamine, Prostaglandin, Bradykinin, Leukotrienes o Late-Phase (Up to 24h): Mediated by Leukotrienes, Histamine, IL-5

- Dx: To adequately treat our patient, we must accurately diagnose them o Patient Hx: Timing and severity of symptoms, what makes it worse (triggers) o Physical Exam: Check nasal mucosa for engorgement or discoloration. Allergic shiners (dark by eyes)

§ Allergic Salute – rubbing the tip of nose with palm of hand § Mouth breathing--------------------------------------------------->

o Skin Testing: Can be expensive - Tx: Accept it, Allergic Rhinitis cannot be cured. And the best treatment is avoidance of the allergen. Drugs? - Environmental Controls – The primary non-pharmacological options

o Effort: Avoid pollen, Wash your clothes after being outside, take a shower every now and then o Setting: Low Humidity (<45%), Vacuum often with HEPA filter, no indoor plants, no stuffed animals

unless they’re allergen free, remodel your entire house and remove the carpets J? o Exercise: Increases sympathetic tone. Known to improve many disease states, including Allergic Rhinitis.

–Must sweat for at ³15-30 minutes though! (someone must have done a strange study) o Saline Irrigation/Nasal Wetting: Soothes nasal tissues, 2 sprays/drops QID PRN

§ Product: Ocean Nasal Spray, Simply Saline --- Low cost OTC - Antihistamines: Compete with Histamine for H1 receptor – Especially effective prophylactically

o Oral 1st Generation: Prevent and relieve wet symptoms (sneezing, itching, rhinorrhea), but does not relieve nasal congestion

§ Crosses the BBB easily, causing sedation in 40% of pt. Ethanolamines are MORE sedating

• Counsel pt: Don’t booze or drive with meds § AE: Anticholinergic- dry mouth, constipation, drowsiness § Dosing: Chronic Daily dosing > PRN § Efficacy: May switch to different product within same class

and find better results o Oral 2nd Generation: Do not cross the BBB as readily, thus less sedation. Added benefit- they lack

anticholinergic activity, so we don’t have those AE to worry about § Dosing: Once daily dosing § Pregnancy: B. Avoid in 3rd trimester – but always as MD first, especially about nursing

• Anticholinergic effect may prevent lactation

Alkylamines Less sedating

Ethanolamines MORE sedating

Brompheniramine Clemastine

Chlorpheniramine Diphenhydramine

Dexbromphen-iramine

§ Loratadine (Claritin): 2yo+. Adults (6yo+) = 10mg Qdaily. AE: HA, Dry mouth • Indicated for (1) seasonal rhinitis

§ Cetirizine (Zyrtec): 2yo+. Adults (6yo+) = 10mg Qdaily. AE: Drowsiness warning! • Indicated for (1) Seasonal (2) and Perennial Rhinitis- • Indicated for Infants 6mo of age, but require Rx (‘suggested’)

§ Levocetirizine (Xyzal): 2yo+. Adults (12yo+) = 5mg QPM. AE: Fatigue, D, Epistaxis • Indicated for (1) Seasonal (2) and Perennial Rhinitis. Just went OTC March 2017

§ Desloratadine (Clarinex): Rx only, 6mo+. Adult (12yo+) 5mg Qdaily. • Indicated for (1) Seasonal (2) and Perennial Rhinitis

§ Fexofenadine (Allegra): 2yo+. Adult (12yo+) 180mg Qdaily (traditionally 60mg BID) • Indicated for (1) Seasonal Rhinitis

o Intranasal Antihistamines: Both of the ones we discuss are pregnancy category C – caution § Azelastine (Astepro): 12yo+. 2 sprays Qdaily. AE: Bitter taste (20%), Sedation, Epistaxis

• Indicated for (1) Seasonal (2) Perennial Rhinitis Rx § Olopatadine (Patanase): 6yo+. 2 sprays BID. AE: Bitter taste, sedation

• Indicated for (1) Seasonal Rhinitis - Decongestants: Stimulate a-adrenergic receptors to reduce nasal congestion and tissue edema. Important to note

that- these do not improve pruritus, rhinitis, or rhinorrhea o Dosing: PRN is preferred over chronic daily use. Chronic daily use for 3-5 days is associated with

rhinitis medicamentosa – rebound congestion o AE: - --- ‘contraX’ in HT, Hyperthyroidism, and Glaucoma patients

§ CNS Stimulation: Restless, Insomnia, Anxiety § Cardiovascular Stimulation: Heart palpitations, HRÝ § Local Side effects (intranasal): Burning, stinging, dryness

o Oral Decongestants: Pseudoephedrine, Phenylephrine. AE: BPÝ, HRÝ, IntraocularÝ § Pseudoephedrine (2yo+). Max 120mg ER BID § Phenylephrine (12yo+). Max 10mg Q4h à 60mg. Not as effective. Requires hella dosing

o Intranasal Decongestants: Naphazoline, Oxymetazoline, PE, Tetrahydrozoline, Xylometazoline § Very effective at shrinking the nasal mucosa, Use at onset for a couple of days along with

intranasal corticosteroid – improves its penetration ability. Beware rhinitis medicamentosa § AE: Nasal irritation, dryness, sneezing, rhinitis medicamentosa

- Anticholinergics: Safe in pregnancy, these help decrease nasal mucus secretion AE: HA, Epistaxis o Ipratropium Bromide (Atrovent)- Indicated for Seasonal Rhinitis. o ContraX: Angle-closure glaucoma, prostatic hypertrophy

- Mast Cell Stabilizers: Best if used 1-2 weeks before symptoms occur – predicting the time of year we have our worst allergic responses. In general, mast cell stabilizers prevent and relieve sneezing, rhinorrhea, and itching

o Cromolyn Sodium (NasalCrom) 1 spray each nostril 3-4x daily o Safe in the elderly, safe in preggers…. But overall these are not the most effective agents.

- Corticosteroids: Used to prevent and relieve symptoms. They produce mild vasoconstriction, decrease leukotrienes and prostaglandins. \, they are effective in relieving sneezing, itching, rhinorrhea, and congestion.

o Therapy Initiation: Best if used before high risk season – full response in 2 weeks o Dosing: Daily! This is much better than as needed. Begin on maximum dose, titrate down. o AE: Local irritation, sneezing, mucosal erosion, epistaxis, HA o STEP 1: BLOW YOUR NOSE BEFORE YOU USE INTRANASAL CORTICOSTEROIDS o Triamcinolone (Nasacort): 2yo+, Scent and Alcohol free. 12yo+: 2 sprays EN daily, once controlled,à1 o Fluticasone (Flonase): 4yo+. Has a light floral scent and booze. Additional Indication: Itchy/water eyes o Fluticasone (Sensimist): Alcohol-free, scent-free. But lower dose. Just another classic marketing scam. o Budesonide (Rhiocort): Scent Free, Alcohol-free. “lower spray volume than Flonase”

- Leukotriene Modifiers: Improves daytime nasal symptoms, nasal congestion, itching, sneezing, and runny nose. o Montelukast (Singulair): Approved for 15yo+ allergic rhinitis. Beneficial in asthma patients

§ Tried to go OTC 3/2014, were rejected by FDA - Immunotherapy: Administration of very dilute solutions of allergen extracts to increase tolerance. This is

performed 1-2x per week. Efficacy is variable, some benefit some don’t. Takes 3-5 years. o Oral Immunotherapy: Latest thing, barely on the market yet. GRASTEK, Oralair, RAGWITEK, these

are the oral meds, for grass and ragweed allergies.

Therapeutic Goals of Tx Allergic Rhinitis: Minimize or prevent symptoms. Therapy is multimodal and should involve a sequence of allergen avoidance, pharmacotherapy, and immunotherapy. TARGET the most dominant symptom. Methamphetamine Control Act: Passed in 2006, affected cold and allergy products (Pseudoephedrine PSE)

- Purchase max 2 packages a month, show an ID – log your purchase. Must be 18yo+ (10/24) Stranges Lecture: Asthma Defining Asthma: A chronic obstructive airway disease best characterized by airway inflammation and airway hyporesponsiveness. Common key symptoms include Wheezing, SoB, and Cough

- Dx: While clinical features and history are utilized, confirmation with Spirometry is required. Furthermore, the diagnosis of asthma cannot be based on medical history alone

- Goals of Therapy: Reduce impairment, Reduce the risk of future exacerbations, “normal” pulmonary function o £ 2 Days a week of Daytime symptoms £ 2 nighttime awakenings per month

Treatment of Asthma - Non-Pharmacological Interventions -Self-Management Education- (How patients treat their disease at home)

o Asthma Action Plan: As part of self-management education, an Asthma action plan is an instructional document outlining the key methods for improving QoL and reducing exacerbations. It includes:

§ Recognizing Worsening Asthma: • Peak Flow-based (PEF): Measuring strength of expiration, ~ helps predict changes in

inflammation and lung capacity before symptoms occur • Symptom-based: Recognize common symptoms, after they occur, then address it

§ Recognizing and Avoiding Triggers: Viral Illness (Colds, URTI), Exercise (humidity in lungs), Allergies (Check with allergy specialist – Review often!), Stress/Emotions, Hormones, Meds

§ Understanding the role of comorbid conditions: Certain conditions predispose or exacerbate Asthma conditions, thus it is important to encourage patients to maintain their comorbid therapies

• Atopy (Trifecta: Rhinitis, Sinusitis, Nasal Polyps), GERD, Obesity, Depression, Allergies § Responding to worsening asthma: How to use their medications and what they are for

- Pharmacological Interventions There are two general classes of medications o Quick Relief (Rescue) Medications: All asthma patients should have them, used to treat symptoms

§ Short-acting b-agonist (SABA), Short-acting anticholinergics o Controller Medications: Used chronically to address he underlying problem/inflammation

§ Corticosteroids, Long-acting b-agonists, Long-acting anticholinergics, Leukotriene Modifiers, monoclonal antibodies, Xanthines, Mast cell stabilizers

Critical Components for determining Asthma Severity -For the classification and staging of Asthma - Daytime Sx - Frequency of rescue medication use - Nighttime Asthma Awakenings (Asthma

Sx are commonly worse at night) - Exacerbation history requiring ICU

stays/intubation to support breathing - Patient Experience and their limitations - Lung Function Assessment (FEV1,

FEV1/FVC) Assigning Severity Diagnosis and Step Therapy

- Initial Therapy will be based off the most severe category the patient is in

- Method: Over-treat at first, and pull back therapy later

- Steroid Burst: In cases of severe persistent asthma upon presentation, often a Steroid Burst is used

o 5 day supply of oral steroids - All diagnosed patients should have a

reliever – Low-dose ICS o Albuterol alone does not treat underlying

inflammation is asthma, and is not an appropriate controller medication