1 / 28

Steroidal Anti-inflammatory Drugs (SAIDs)

Steroidal Anti-inflammatory Drugs (SAIDs). Hypothalamic-Pituitary Adrenal (HPA) Axis. Negative Feedback control of ACTH Production. Suppression of HPA STRESS: Overrides the neg. feedback mechanism . Adrenal cortex Produces 30 steroid hormones Major divisions include:

urian
Télécharger la présentation

Steroidal Anti-inflammatory Drugs (SAIDs)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Steroidal Anti-inflammatory Drugs (SAIDs)

  2. Hypothalamic-Pituitary Adrenal (HPA) Axis Negative Feedback control of ACTH Production. Suppression of HPA STRESS: Overrides the neg. feedback mechanism. Adrenal cortex Produces 30 steroid hormones Major divisions include: Glucocorticoids Mineralocorticoids Adrenal Sex steroids

  3. Biosynthesis of Glucocorticoids (GCs) Glucocorticoids Cortisol (95%) Corticostrone Cortisone 90% bound to plasma proteins Circadian release Of GCs; highest in the early morning and lowest in the evening.

  4. Steroid Receptor Activation

  5. Corticosteroid Effects

  6. Mechanism of Action for Anti-Inflammatory Steroids

  7. Mechanism of Action for Anti-Inflammatory Steroids • Suppress T-cell activation and cytokine production. • Suppress mast cell degranulation. • Decrease capillary permeability indirectly by inhibiting mast cells and basophils. • Reduce the expression of cyclooxygenase II and prostaglandin synthesis. • Reduce prostaglandin, leukotriene and platelet activating factor levels by altering phospholipase A2 activity.

  8. Routes of Administration for GC • Local(Preferred) • Intra-articular, IA • Intrabursal, IB • Intralesional, IL • Intrasynovial, IS • Soft tissue, ST • Intrarectal, IR • Topical • Nasal • Inhaled • Systemic • Oral, PO • Intramuscular, IM • Intravenous, IV • Subcutaneous, SC

  9. Pharmacokinetics of GC • Daily administration of corticosteroids at physiological concentrations for at least 2 weeks suppresses the HPA resulting in decreased production of endogenous hormones. Recovery may take up to 9-12 months. • Hepatic Metabolism: • The liver is the primary site of GC inactivation. GCs are metabolized by cytochrome P450 3A4 enzymes • 25% of GCs are excreted in bile and feces. • Renal Clearance • 75 % of GC metabolites are excreted in the urine.

  10. Differences in Individual Corticosteroids • Biological Half life • Mineralocorticoid potency • Glucocorticoid (anti-inflammatory) potency

  11. Mineralocorticoid actvity Corticosteroids control symptoms and DO NOT stop progression (cure) of the disease

  12. Short Acting Corticosteroid(8-12 hrs)

  13. Hydrocortisone • Prototype corticosteroid for anti-inflammatory activit • Short acting GC • Clinical uses: Localized inflammatory conditions, i.e. Ulcerative colitis & dermatitis • Relative anti-inflammatory potency is 1 • Plasma half-life is 30 min • Biological half-life is 8-12 hrs. • Administration: Oral, injectable, topical (creams and ointments) and IR (foam). • Contraindications (IR): Systemic fungal infection, recent ileocolostomy, intestinal anatomoses and abscess. • Cortisone

  14. Intermediate Acting Corticosteroid(18-36 hrs)

  15. Prednisone • Intermediate acting GC • Clinical uses: Adjunct therapy for arthritis (short term admin), asthma, COPD; Ulcerative colitis and Crohn’s disease.; Rheumatic and dermatologic disorders. • Relative anti-inflammatory potency is 4; It is 4x more potent than cortisol. • Inactive on its own. It must be metabolized in the liver to an active metabolite. • Plasma half-life is 60 min • Biological half-life is 18-36 hrs • Administration: Oral only.

  16. Anti-inflammatory Drugs • Glucocorticoids • Inhaled • Beclomethasone • Budesonide • Flunisolide • Fluticasone propionate • Triamcinoloneacetonide • Oral (Quick relief of asthmatic symptoms) • Prednisone • Prednisolone • * Unresponsive to 2 agonists Metered Dose Inhaler Also, Dry-powder inhalers and Nebulizers

  17. Prednisolone • Intermediate acting GC • Prenisolone acetate/sodium phosphate • Clinical uses: Opthalmic disorders, respiratory diseases. • Plasma half-life is 60 min • Biological half-life is 18-36 hrs. • Administration: Oral, Injectable (systemic and local).

  18. Methylprednisolone • Intermediate acting GC • Methylprenisolone acetate/sodium succinate • Clinical uses: Rheumatoid arthritis Intra-articular injections • , UC,severe alcoholic hepatitis. • Plasma half-life is 60 min • Biological half-life is 18-36 hrs. • Administration: Oral, Injectable (systemic and local). • Adverse effects: vertigo, headache, weight gain, sodium/water retention and impaired wound healing.

  19. Triamcinolone • Intermediate acting GC • Triamcinoloneacetonide/diacetate/hexacetonide • Clinical uses: Similar to prednisone: Opthalmic disorders, respiratory diseases. • Plasma half-life is 60 min • Biological half-life is 18-36 hrs. • Administration: Oral, Injectable (systemic and local).

  20. Inhaled Glucocorticoids: “Long-term control” of Chronic Asthmatic Symptoms Taken Daily, over a long period of time SE: oropharyngeal candidiasis (Thrush), dysphonia (hoarseness), adrenal suppression, bone loss, in children, retarded growth Reduced risk of toxicity with inhaled preparations Beclomethasone Budesonide Flunisolide Fluticasone propionate Triamcinoloneacetonide Mechanisms of Action: • Reduce bronchial hyperreactivity • Decreased synthesis and release of inflammatory mediators, e.g, leukotrienes, prostaglandins and histamine • Decreased infiltration and activity of inflammatory cells, e.g. eosinophils, leukocytes) • Decreased edema of the airway mucosa and mucus production • Increase responsiveness to 2 agonists

  21. Long Acting Corticosteroid(36-54 hrs)

  22. Betamethasone • Long acting GC • Betamethasone acetate/sodium phosphate • Clinical uses: Respiratory diseases, Respiratory distress syndrome, local inflammatory conditions (similar to prednisone). Life threatening or disabling condition. • Relative anti-inflammatory potency is 25. • Plasma half-life is 300+ min • Biological half-life is 36-54 hrs. • Administration: Oral, topical, Injectable (systemic and local).

  23. Dexamethasone • Long acting GC • Dexamethasone acetate/sodium phosphate • Clinical uses: Lupus and Rheumatoid arthritis.; Life threatening or disabling conditions. • Maximal anti-inflammatory action. • Relative anti-inflammatory potency is 25. • Plasma half-life is 110-210 min • Biological half-life is 36-54 hrs. • Administration: Oral, topical, Injectable (systemic and local).

  24. Adverse Effects • Adrenocortical insufficiency: Suppression of HPA • Adrenocortical excess (Cushing’s disease): “Moon face”, “buffalo hump” • Diabetes Mellitus • CNS effects: psychological and behavioral changes; aggravation of pre-existing psychiatric disorders. • Impaired wound healing • Musculoskeletal effects: osteoporosis (brittle bones), muscle weakness and atrophy • Cardiovascular effects: fluid retention, edema, hypertension. Glucocorticoid Withdrawal: Should be performed slowly Withdrawal syndrome: hypotension, hypoglycemia, myalgia and fatigue

  25. Cushing Syndrome (Hypercorticism)

  26. Drug Interactions • Drugs that Enhance Corticosteroid Effects • Estrogens • Oral contraceptives • Antifungal agents • Antibiotics • *all of these agents inhibit cytochrome P450 enyzymes • Drugs that Reduce Corticisteroid Effects • Antacids • Cholestyramine • *these drugs decrease the absorption of corticosteroids • Phenytoin: inhibits cytochrome P450 enyzymes

More Related