Anti-cholinergics Steroids

1. Anti-cholinergics & Steroids By Jim Clarke

2. Anticholinergic Bronchodilators Indications Used for the treatment of bronchoconstriction in COPD Is also available for the treatment of allergic rhinitis (nasal spray formulation)

3. How Anticholinergics Work

4. Vagal Triggers Irritant Aerosols Cold dry air Cigarette smoke Noxious fumes Histamines High airflow (in exercise) Persistent cough (upper airway inflammation)

5. Vagally-Mediated Bronchospasm

6. Anticholinergic Agents Ipratroprium Bromide (Atrovent) Atropine Sulfate Glycopyrrolate (Robinul) Oxitroprium bromide*

7. Effects of Atrovent

8. Affects of Atropine

9. Available Forms & Characteristics

10. Anticholinergic Use in COPD Appear to work better than Beta agonists for patient with emphysema-chronic bronchitis Also appears to be of some help in patients with severe long term asthma Acts mainly on larger, more central airways Has fewer side effects than beta agonists

11. Anticholinergic Use in Asthma Not as widely used for tx of asthma Useful in tx of; Nocturnal asthma Psychogenic asthma

12. Combination Drugs New preparations mix albuterol and ipratroprium for maximum bronchdilation effect Combivent (MDI) Frequently - unit dose preparations of the above medications are given during the same nebulizer treatment

13. Advantages of Combivent Patients can receive the benefits of taking two drugs at once Better bronchodilation with improved airflow Compliance is better since there is only 1 MDI vs 2 separate MDI�s

14. Corticosteroids

15. Physiology of Corticosteroids Secreted by the Adrenal gland �inner� zone or medulla produces epinephrine �outer� zone or cortex produces corticosteroids

16. Products of Adrenal Cortex Mineral corticoids aldosterone Sex hormones Estrogens & Androgens Glucocorticoids related to natural �cortisol� Referred to as corticosteroids or �steroids�

17. General Action of Steroids Defined as �anti-inflammatory� agents used in the treatment and prevention of asthma and other conditions causing an exaggerated inflammatory response in the lung. Inflammation is defined as �the response of vascularized tissue to injury�

18. Inflammation in Asthma New understanding of asthma defines it as a disease in which there is chronic inflammation of the airway wall, causing airflow limitation and hyperresponsiveness to a variety of stimuli Process is �mediated� by a variety of agents Mast cells; eosinophils; T lymphocytes; macrophages

19. Hallmark Signs of Inflammation Redness Local dilation of blood vessels Flare Reddish color several centimeters around the original injury site Wheal Local swelling, occurring in minutes

20. Events at the Cellular Level Increased vascular permeability Exudate in surrounding tissues Leukocytic infiltration White cells are attracted to area Phagocytosis White cells and macrophages ingest foreign material

21. Events at the Cellular Level Mediator Cascade Histamine & other chemicals are released at injury site Inflammatory mediators are produced leukotrienes

22. Early Phase Response After initial triggering event, there is mast c cell degranulation with release of variety of chemical mediators (histamine; prostaglandin D2; leukotrine C4) Early phase response is bronchospasm There is a resulting decrease in expiratory flows from the lungs

23. Late Phase Response After 1-2 hours, mast cells mediators recruit eosinophils, basophils, etc. to the lung After 6-8 hours, inflammatory cells have migrated into the airway walls Mediators stimulate other vasoactive and bronchoactive agents that last up to 24 hours longer Primary agent is arachidonic acid

24. Late Phase Culmination Increased mucus production Increased permeability of vessels causing mucosal edema of the airway Shedding of airway wall cells (desquamation) Goblet cell hypertrophy Thickening of epithelial basement membrane

25. Primary Actions of Steroids Inhibits recruitment & migration of inflammatory cells Act by inhibiting the production of arachidonic acid Induces gene expression for anti-inflammatory proteins and receptors Suppresses gene expression for pro-inflammatory proteins

26. Other Steroidal Effects Improve responsiveness to Beta 2 agents Decreases the white cell response to �chemotaxis� This causes eosinophil counts to fall

27. Corticosterods for Oral Inhalation Dexamethasone (Decradron) Beclomethasone (Vanceril; Beclovent) Triamcinlone (Azmacort) Flunisolide (AeroBid) Fluticasone (Flovent) Budesonide (not yet available in U.S.)

28. Side Effects Oral Candiasis or �Thrush� Rinse mouth after use to prevent Hoarseness Cough and actual bronchoconstriction Poor use leading to inadequate dosing

29. Systemic Steroids Given orally (p.o.); I.V. or I.M. Oral forms reach peak action in as short as 1 hour Some forms may remain available for up to 1-4 weeks (I.M. & I.V.)

30. Examples of Systemic Steroids Hydrocortisone (Solu-Cortef) Methylprednisolone (Medrol; Solu-Medrol; Depo-Medrol) Prednisolone (Delta-Cortef) Dexamethasone (Decadron)

31. Side Effects of Systemic Steroids Hypothalmic-Pituitary-Adrenal Suppression Immuno-suppression Psychiatric reactions (psychosis) Cataract formation Osteoporosis Fluid retention Hypertension

32. More Side Effects! Peptic ulcer formation Dermatologic changes Thinning of skin �Cushingoid� appearance Retardation of growth (in children) Slowing of healing in adults Incrased glucose levels � steroids diabetes Myopathy of skeletal muscle

33. Nasal Sprays Nasalide (flunisolide) Beconase; Vancenase (beclomethasone) Nasacort (triamcinolone) Rhinocort (budesonide) Flonase (fluticasone) Doses are typically 1-2 sprays/nostril 1-4 times/day

34. Indications for Steroid Use Control of Asthma It is NOT a rescue drug when given via MDI Treatment of other bronchospastic conditions not controlled by other therapy Control of seasonal allergic or non-allergic rhinitis Steroids have been widely used in COPD It is less clear if they actually help patients

35. End of Week 5 - Monday