Nonsteroidal antiasthma agents Pharmacology Anti inflammatory different mechanism of action that corticosteroids

What do they do? Prophylactic management of mild persistent asthma So they can get on with life!!

Antigen-antibody reaction Asthmatics essentially have an allergic response to triggers Components to reaction Increased capillary permeability Increased mucus production Inflammation and edema Bronchospasm Mast cells are the keepers of Histamine. When antigen-antibody reactions happen the mast cells degranulates and release histamine

Nonsteroidals Control, never relieve symptoms for asthmatics that benefit from anti-inflammatory agents If a patient uses a β2-agonist more than 2/week they need a controller in their regime

Extrinsic Asthma Extrinsic asthma is an allergic asthma that involves mast cells and immunoglobin E (IgE), as well as an antigen antibody complex. Younger subjects

Extrinsic Asthma (cont) Activation of T-lymphocytes stimulates the production of IgE by B-lymphocytes. This antibody binds to the antigen which attaches to the mast cell. The mast cell releases mediators of inflammation Preventing the allergic reaction from happening

Intrinsic Asthma Non-allergic Adults and usually has a late onset Associated with asthma progressing and releasing cytokines Cromolyn good prophylactic Nonallergic asthma attack- cold air, infections, stress, exercise, emotional stimuli and some things we DO NOT know Something in the body stimulates the mast cells to degranulate and release histamine

Mediator Antagonists Mediator antagonists came around to control inflammation without exposing the patient to all the side effects from systemic steroid use. Cromolyn Sodium, Nedocromil, Zafirlukast, and Zileuton are examples of mediator antagonists.

Cromolyn Sodium Brand name – Intal Indications – Prophylactic management bronchial asthma, prevention of exercised induced asthma, and allergic rhinitis. Not to be used during acute bronchospasm. Mode of action – Stabilizes the mast cell. Dosage – DPI 20 mg capsule, MDI 800 μg/inh 2 puffs, solution for SVN 20mg/2 ml vial, frequency QID Side effects – very few, DPI/MDI throat irritation, hoarseness, dry mouth, cough, chest tightness SVN cough nasal congestion, wheezing, sneezing, nasal itching, epitaxis, or nose burning Why not used in acute bronchospasm?? DOES NOT OPERATE ON cAMP therefore no alpha or beta receptor site stimulation Intal is protective. And protection is does dependant start @ 80mg/day. MAY get to reduce to 40-60 mg/day. If stimulus increases may need more rescue agent use. Use DPI 60 min prior to exercise. Or 2 puffs MDI. Cromolyn can help with the late phase bronchoconstrtiction Effectiveness like theophylline, without S/E and narrow therapeutic margin If attempting to replace oral steroids what things should be taken into consideration? Still must taper steroids. Intal cannot help HPA suppression This drug can cause bronchospasm. So it goes without saying that in that case administer what prior to Intal.

Nedocromil Brand name – TiladeR Indications – Prophylactic for mild to moderate asthma. Mode of action – Inhibits activation and activity of numerous inflammatory cells, including mast cells, eosinophils, airway epithelial cells, and sensory neurons. No bronchodilating effect Dose – MDI 2mg/inh 2 puffs QID Side effects – unpleasant taste, headache, nausea, vomiting, dizziness. 1992 Prophylactic aerosols to prevent the inflammatory response in asthma Mast cell stabilizer “Cromolyn like”, with anti-inflammatory. Very useful in extrinsic (allergic) Management chronic bronchitis and asthma NO bronchodilating ability “Controller” Neither pass into CNS actually come out of the body in the same form they went in! Yeah less S/E Absorbed well by the lungs but has LOW bioavailability to the systemic system

Zafirlukast Brand name – AccolateR Indications – Prophylactic treatment of asthma caused by exercise, cold air, allergens or aspirin Mode of Action – Leukotriene inhibitor. Dose – 20 mg tablet BID Side effects – headache, infection, diarrhea, generalized and abdominal pain. Leukotrienes lipid mediators for inflammation, potent bronchoconstrictors and bully other cells, causing edema and mucus secretions and inhibiting cilliary beat and recruit other inflammatory cells . Leukotriene receptor antagonist

Montelukast Brand name- Singulair Indications- prophylaxis and control for asthma (approved for kids) Mode of action- Leukotriene inhibitor. Dose-10 mg tablet and 4 and 5 mg chewable cherry flavored tablet. To be taken in the evening Side effects-diarrhea, laryngitis, pharyngitis, nausea, otitis, sinusitis,

Zileuton Brand name – Zyflo Indications – Prophylactic treatment of asthma Mode of action - Leukotriene inhibitor Dose – 600mg tablet QID Side effects – headache, general pain, abdominal pain, loss of strength, and dyspepsia.

Anti-leukotriene Controlling asthma from triggers Exercise induced Aspirin induced Allergen induced Exercise induced- cooling and drying of AW’s=leukotrienes-= bronchoconstriction Increased leukotriene resulting from aspirin Block early phase and attenuate late phase

Why do steroids still exist? Anitleukotrienes – limited pathway action Steroids- broader anti-inflammatory response Used together results in the most improvement and decreases steroid doses necessary. Less S/E

Anti leukotrienes Never acute treatment Alternative to corticosteroids Decreases corticosteroid doses

Getting back to fun!!