Introduction to Pharmacology Corticosteroids

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

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

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).

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

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.

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!!

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

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

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

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

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

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

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”

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

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

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

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

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.

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

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

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

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

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

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

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

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

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

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