Inflammation 3 PDF

Inflammation 3 H. Schaefer, MN all images are for educational purpose only, further dissemination subject to copyright H. Schaefer, MN 1 Glucocorticoids & when are they used?...

Inflammation 3 H. Schaefer, MN all images are for educational purpose only, further dissemination subject to copyright H. Schaefer, MN 1 Glucocorticoids & when are they used? Video: Dr. Mike 2 Allergy – reflecting back on allergies 3 Allergy tx overview: remember: allergens trigger allergies local allergy, contact dermatitis: Antihistamine, topical e.g. Benadryl (diphenhydramine) cream known allergen, systemic exposure: Antihistamine, non-drowsy preferred Reactin (cetirizine) , 1tablet qd eye symptoms: Antihistamine, topical to eye Patanol (olopatadine) eye drops If allergen exposure anticipated in high doses: prophylaxis with Leukotriene modifiers Drug: Singulair, 1 tablet x 2 days pre-exposure If allergic response becomes systemic: anaphylaxis Anaphylaxis: high histamine => systemic inflammatory response => severe inflammation & vasodilation s&s: evidence of allergy + bronchoconstriction & hypotension Main issues: bronchoconstriction & hypotension (d/t vasodilation) Tx focuses on ABCs: Epinephrine, IM; IV Dexamethasone, IV antihistamines, IV + IV fluids (for CO)  Epinephrine endogenous neurotransmitter & hormone non-selective adrenergic agonist (alpha, beta) antihistamine effect Drugs: epinephrine (Epipen, Adrenalin) Route: IV, IM Onset: rapid Duration 20 min: repeat doses 6 Glucocorticoids side effects, caution Cushing’s syndrome: overtreatment with systemic no or minimal side effects: glucocorticoids => exaggerated side acute treatment e.g. anaphylaxis effects leading to dysfunction of affected systems local route e.g. topical Voltaren PRN e.g. intranasal Avamys PRN increasing risk of systemic side effects: long term treatment systemic route e.g. PO note on negative feedback: decreases/stops adrenal glucocorticoid synthesis => no abrupt stoppage of tx slow titration of dose ‘weaning protocol’ (until 0 mg) H. Schaefer, MN 7 H. Schaefer, MN 8 Examples of diagnoses marked by inflammation, which is longterm: chronic Allergic rhinitis Dermatitis Psoriasis Arthritis IBD asthma COPD Glucocorticoids often used in the tx plan Evaluation: clinical efficacy, risk vs benefit, local vs systemic use, patient response H. Schaefer, MN 9 Chronic inflammation Acute inflammation < 10 days Chronic inflammation > 1st , acute inflammation occurs followed by proliferation of: lymphocytes, macrophages, fibroblasts, endothelial cells, collagen V, inflammatory mediators & tissue growth factors => Tissue destruction by repetitive inflammation Scar tissue formation Less vascular Less flexible Less strong cycle causes cellular tissue changes dysfunction of the tissue susceptibility to unusual growth & altered cellular division E.g. neoplasms H. Schaefer, MN 10  Allergic rhinitis High incidence Upto 40% of population Trigger: inhaled allergens => Tx: antihistamines pre/during hypersensitivity exposure, e.g. PO often seasonal (occasional) intranasal corticosteroids for nasal E.g. pollen, dust, dander mucosa inflammation tx S&S: rhinitis (nasal discharge, Drugs, intranasal: swelling) fluticasone (Flonase, Avamys) mometasone (Nasonex) conjunctivitis (eyes); sneezing, budenoside (Rhinocort) snoring, itching, headache from nasal-sinus congestion BW: high easinophils H. Schaefer, MN 11 Brainstorm You have never heard of this brand name medication: Dymista. You look at the generic names (active ingredients) and see this: ○ Fluticasone ○ Azelastine Based on this info, which drug class does Dymista belong to? What is the mechanism/s of action? When do you think it’s used? Video: Atopic dermatitis H. Schaefer, MN 13 Atopic dermatitis atopy = tendency to develop allergies/heightened immune response dermatitis=eczema atopic dermatitis – most common type of eczema allergy-triggered high plasma IgE autoimmune tendency (atopy) Chronic inflammation of the skin: pruritic (itchy) scar formation ‘lichenification’ => deficient innate skin barrier risk of super-infection bacterial, viral Tx: moisturize + topical glucocorticoids antihistamines antibiotics/antivirals if infection H. Schaefer, MN 14 15 Psoriasis chronic inflammatory skin disease Risk factors: family hx + trigger: skin trauma, climate, stress, medications Chronic inflammation of the skin: Hyperkeratosis Thinned stratum granulosum Dilated dermal papillae S&S: dry scaly skin patches, on extensor surfaces, often non-pruritic Tx: glucocorticoids local-> systemic in ‘flare-ups’ moisturizing creams other: DMARDs; UV light H. Schaefer, MN 16 17 H. Schaefer, MN 18 Rheumatoid arthritis (RA) arthritis=joint inflammation RA= chronic systemic rheumatic (inflammatory) disease, autoimmune Risk factors: Family hx, gender, trigger triggered by an antigen (e.g. pathogen/noxious stimulus) => chronic inflammation of connective tissue Affected tissues: joints; heart, lungs, kidneys; eyes In joints: => dysfunction of the synovial cavity: ’pannus’ => destruction of surrounding tissue (bone, cartilage) => deformity of the tissue => loss of normal fx => pain progressive & autoimmune destruction of healthy endogenous tissues H. Schaefer, MN 19 20  S&S: synovial joint inflammation hands, knees, cervical spine, … + systemic symptoms e.g. generalized fatigue, anorexia BW: high C-reactive protein Tx: NSAIDs, glucocorticoids (PO route) H. Schaefer, MN 21 Tx Drug class: BRMs (biologic response modifiers) Biologics; IV, SC inhibit pro-inflammatory cytokines (e.g. interleukins, integrins,…) => decrease T & B cell response Drugs: Infliximab, Adalimumab, Ustekinumab Drug class: DMARDs (disease modifying anti- rheumatic drugs) inhibits nucleotide synthesis inhibits WBC synthesis & fx Drugs: methotrexate H. Schaefer, MN 22 Osteoarthritis (OA) degenerative disorder of articular cartilage Risk factors: Mechanical stress, obesity, age, gender ‘Wear & tear’ arthritis fewer joints affected than in RA Cartilage changes occur: repetitive pro/inflammatory mediator release (cytokines, prostaglandins) => chronic inflammation => decreased proteoglycans => weakened collagen II network => cartilage tissue destruction => bone- bone in articulating surface! H. Schaefer, MN 23  Tx: NSAIDs, glucocorticoids local glucocorticoid administration useful H. Schaefer, MN 24 Glucocorticoid, intra-articular injection: drug: betamethasone (Celestone) H. Schaefer, MN 25 H. Schaefer, MN 26 27