1. Introduction to Pharmacology
Corticosteroids

2. Indications for inhaled corticosteroids
Maintenance for chronic asthmatics in the step 2 category or higher per the NAEPP
Used in conjunction with inhaled agents can help “control” asthma symptoms
NOT indicated for COPD maintenance per the ATS, may be considered if the patient has responded to oral steroids
American Thoracic Society, oral steroids are recommended by the ATS for acute exacerbations
PG 281 Lines based on pts condition
National Asthma Education Prevention Program

3. Nasal steroids
Used to manage seasonal and perennial allergic and nonallergic rhinitis
Act by decreasing inflammation

4. Endogenous Corticosteriod
Corticosteriods are a group of chemicals secreted by the adrenal cortex and referred to as adrenal cortical hormones.
There are actually three types of corticosteriods: glucocorticoids (cortisol), mineral corticoids (aldosterone), and sex hormones (androgens and estrogens).

5. Pulmonary steroids
The steroids that we use for inhalation come from Cortisol, better known as hydrocortisone
Cortisone may have been known to help asthma in the 1950’s
In the 1970’s we started using inhaled steroids to help combat inflammation for maintenance asthma therapy

6. Hypothalamic-Pituitary-Adrenal Axis HPA - Axis
Stimulation of the hypothalamus causes impulses to be sent to the median eminence. The median eminence releases CRF (corticotropin releasing factor), which circulates through the portal vessel to the anterior pituitary. The anterior pituitary release ACTH (adrenocorticotropine hormone), which stimulates the adrenal cortex to secrete glucocorticoids, such as cortisol.

7. Glucocorticoids
Glucocorticoids regulate the metabolism of carbohydrates, fats, and proteins to generally increase levels of glucose for energy.
The diurnal cycle or circadian rhythm regulate the HPA axis to produce glucocorticoids. The average individual produces more in the morning and production backs off in the evening.
Lipolysis, redistribution of fat stores, break down of tissue protein stores. Hence many of the S/E seen due to steroid use, hunch back moon face
Breaking down proteins for the amino acids to use (gluconeogenesis) causes muscle wasting and can cause increased blood sugar levels Steroid diabetes (LUCAS)
Diurnal jet lag noc shift set to be higher in the morning to handle the day!!

8. HPA Suppression
As patients take systemic steroids the HPA axis acknowledges that there are plenty of these steroids (glucocorticoids) in the blood. Therefore, the HPA axis decreases if not completely stops the production of endogenous glucocorticoids.
Inhalation is noted to decrease the incidence of adrenal suppression!
Body is not able to differentiate between endogenous and exogenous
Inhalation again minimizes dose and local treatment to the inflamed lung

9. TAPERING HPA went on strike Slowly weaning steroids down
Allows the body to start to sense decreased levels and start to work again
Inhaled agents do not replace what the HPA axis is missing

10. Inflammation 1920’s, Lewis Thomas described the triple response.
Redness – the local dilation of blood vessels, occurring in seconds.
Flare- a reddish color several centimeters form the site, occurring 15 to 30 seconds after injury.
Wheal- local swelling, occurring in minutes.
Hydrocortisone is an anti-inflammatory, asthma is inflammatory

11. Inflammation (cont)
The process of inflammation was described by Celsus, Thomas and others placing the process into four categories:
Increased vascular permeability
Leukocyte infiltration
Phagocytosis
Mediator Cascade
Exudate into surrounding tissues
WBC flood in to help
WBC’s and macrophages ingest and kill bacteria
Histamine and inflammatory mediators

12. Airway Inflammation
Causes: Direct trauma, indirect trauma, inhalation of toxic gases, respiratory infections, systemic infections, allergic and nonallergic stimulation of asthma.
Mast Cells release mediators such as Histamine, ECF-A, NCF, Bradykinin, Lymphokines. These mediators cause bronchospasm and capillaries to begin to leak.
Note card

13. Inflammation Culprits
Mast cells- major player in inflammation
Eosinophils- major player in inflammation
T-lymphocytes-release proinflammatory cytokines
Macrophages
Results in bronchospasm, leakage, swelling, and secretions
LONG TERM = remodeling of the AW
Sub mucosal glands produce the majority of secretions

14. Asthma
Steroids act as anti-inflammatory agents to help reduce the hyper responsiveness of the airway
Should decrease the severity and frequency of asthma “attacks”

15. Early phase of asthma Early- immediate reaction to irritant
Result is bronchospasm peaking at 5 minutes and starts to decline

16. Late phase of asthma
Recruitment of inflammatory cells has occurred, an adhesion molecule (ICAM) has been activated these all release inflammatory mediators
Occurs 6-8 hours after initial insult, can last 24 hours
ICAM intracellular adhesion molecule

17. Airway Inflammation (cont)
Phopholipid is also released from the Mast cell which converts to phospholipase A2 then to Arachidonic Acid.
Arachidonic acid then goes through two metabolic pathways: cylcooxygenas and lipoxygenase.
Both pathways cause airways and vessels to continue the late phase of inflammation.
Smooth muscle constriction
Mucus secretions
Mucosal swelling due to increased permeability
Shedding
Goblet cell hypergenesis (proliferation) The result is excessive mucus

18. Indications Control of moderate to severe asthma.
Treatment of related corticosteroid-responsive bronchospastic states not controlled by other therapy
Control of seasonal allergic or nonallergic rhinitis
Control of moderate to severe COPD if oral steroids showed a benefit

19. Mode of Action
First, steroids diffuse into the cell and bind to glucocoticoid receptor (GR). The general action of this binding is to upregulate the transcription of antiinflammatory genes for substances such as lipocortin.
The second general action is the suppression of factors which cause the transcription of genes involved in inflammation.

20. Mode of Action (cont)
The third general action is to suppress gene expression for proinflammatory proteins such as cytokines.
In other words, the action is to induce gene expression for anti-inflammatory proteins and receptors, and to suppress gene expression for proinflammatory proteins.
Glucocorticoids also reduce the number of mast cells found within the airways

21. Side Effects Systemic Administration HPA Axis suppression
Immunosuppression
Psychiatric reactions
Cataract formation
Myopathy of skeletal
muscle
Osteoporosis
Peptic Ulcer
Fluid retention
Hypertension
Increased WBC
Dermatologic changes
Growth retardation
Increased glucose levels

22. Systemic Steroids
Prednisone (oral form)
Solumedrol (IV form)

23. Inhaled Corticosteroids side effects
Oropharyngeal fungal infections or aspergillosis
Throat irritation, dry mouth
Cough, bronchoconstriction
Incorrect use of MDI
If give β 1st then steroid, gargle with alcohol based mouth wash

24. Inhaled Steroids Dexamethasone sodium phosphate
(Decadron) - 84μg/ inh, 3 puffs adults/2 puffs peds, 3-4/day
Beclomethasone dipropionate
(Beclovent/Vanceril) - 42μg/inh, 2 puffs adults,
1-2 puffs for kids (6-12yrs), 3-4/ day

25. Inhaled Steroids (cont)
Flunisolide (Aerobid)- 250 μg/inh
2 puffs adults and peds BID
Fluticasone propionate (Flovent)- 44, 110, 220 μg/inh
starts at 2 puffs BID,
max dose is 220 μg BID

26. Inhaled Steroids (cont)
Triamcinolone acetonide
(Azmacort)- 100μg/inh, 2 puffs adult/1-2 puffs peds, 3-4/day

27. Budesonide
0.25 mg and 0.5 mg via pari HHN
200 m / actuation

28. Minimizing side effects
Use lowest effective dose
Always use a reservoir device
Rinse mouth after treatment
Newest info to rinse with alcohol based mouthwash

29. Summary
Use corticosteroids to reduce airway inflammation for COPD and asthma patients
Has been upgrades to a first-line therapy for asthma
Long term continuous use
Potentiates β adrenergics