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USMLE - Pharm

Kaplan Section 6 - Inflammatory Drugs - Gout, Asthma, Steroids, DMARDs

What drugs used for the initial treatment of rheumatoid arthritis? NSAIDs (decrease pain and swelling)
For treatment of RA, why wouldn't you want to use NSAIDs long term? Marked adverse side effects, plus, they have no beneficial effects on the course of the dz or on bone deterioration
What are DMARDs Dz modifying anti-rheumatic drugs
What do DMARDs do? slow dz progression
What is DOC for mild arthritis? Hydroxychloroquine
What is DOC for moderate to severe RA? methotrexate
Which RA drug is associated with cinchonism? Hydroxychloroquine (GI distress and visual dyxfxn)
What happens when you prescribe hydroxychloroquine to person with G6PD deficiency? hemolysis
What is the mechanism of hydroxychloroquine? stabilizes lysosomes and dec chemotaxis
What is the mechanism of methotrexate? cytotoxic to lymphocytes
What is sulfasalazine? DMARD.
What is a special adverse side-effect of sulfaxalazine? can cause SLE-like syndrome
What is eternacept? a recombinant form of the TNF receptor -- binds TNF. Is a DMARD.
What is infliximab? monoclonal antibody to TNF. Is a DMARD.
What is anakinra? IL-1 receptor antagonist. DMARD.
Name the DMARDs HMS is A GIL PEG. Hydroxycloroquine, Methotrexate, Sulfasalazine, Anakinra, Glucocorticoids, Infliximab, Leflunomide, Penicillamine, Gold Salts, Eternacept
What are the three DMARDs that can cause injection-site reactions and infections? Eternacept, infliximab, and anakinra.
Name four drugs/drug classes commonly used for acute inflammatory episodes of gout 1. colchicine, 2. indomethacin, 3. other NSAIDs (naproxen, sulindac), 4.intra-articular steroids
What is the mechanism of colchicine Drug for gout. Binds tubulin --> dec microtubular polymerization, dec LTB4 (activation of integrins, PMNs and chemotaxis), dec leukocyte and granulocyte migration
Acute adverse effect of colchicine diarrhea, GI pain
Adverse effect of colchicine due to long term usage 1. hematuria, 2. alopecia, 3. myelosuppression, 4. gastritis, 5. peripheral neuropathy
What is the drug strategy in treating chronic gout? reduce the uric acid pool
What are the three drugs used in the treatment of chronic gout? 1. allopurinol, 2. probenecid, 3. sulfinpyrazone
What is the mechanism of allopurinol Treat chronic gout. Pro-drug --(xanthine oxidase)--> alloxanthine ----| purine metabolism --> dec uric acid production
What are the adverse effects of allopurinol? 1. GI distress, 2. peripheral neuropathy, 3. rash, 4. vasculitis, 5. stone formation
Talk about drug interactions of allopurinol. inhibits 6-mercaptopurine metabolism.
What is the mechanism of probenecid? inhibits proximal tubular reabsorption of urate --> more urate peed out --> less uric acid in body
What is the limitation of probenecid as a gout drug? ineffective in pts whose GFR is less than 50 mL/min
What is the mechanism of Sulfinpyrazone? inhibits proximal tubular reabsorption of urate --> more urate peed out --> less uric acid in body
What is the limitation of Sulfinpyrazone as a gout drug? ineffective in pts whose GFR is less than 50 mL/min
What are the adverse effects of probenecid and sulfinpyrazone 1. GI distress, 2. nephrotic syndrome, 3. rash, 4. crystallization if high excretion of uric acid
What does ASA do to the effects of probenecid and sulfinpyrazone? decreases its effects
Put in order of increasing duration of drug action: betabethasone, dexamethasone, cortisol, prednisone, triamcinolone cortisol < prednisone < tiamcinolone < dexamethasone/betamethasone
List three steroid effects on the cellular level antiinflammation: 1. dec leukocyte migration, 2. dec capillary permeability, 3. inc lysosomal membrane stability --> dec phagocytosis
List four steroid effects on the biochemical level antiinflammation: 1. inhibit phospholipase A2 --> dec synthesis of prostaglandins and leukotrienes, 2. dec expression of COX2, 3. dec platelet activating factor (causes platelet aggregation), 4. dec production of interleukins (e.g. IL-2)
How does steroids affect the production of ACTH? Steroids suppress ACTH --> cortical atrophy, malaise, myalgia, arthralgia and fever
Why should you not abruptly withdraw steroids? may result in shock state with abrupt withdrawal
What is iatrogenic cushingoid syndrome? result of steroid use --> fat deposition, muscle weakness/atrophy, bruising, acne
Why would steroids produce a hyperglycemic state? cortisol --> gluconeogenesis --> inc insulin demand and other adverse effects
How do steroids affect bone? Can cause osteoporosis --> vertebral fractures and aseptic hip necrosis (poor blood supply to bone --> bone death)
Why do steroids cause ulcers? increased GI acid and pepsin release --> ulcers and GI bleeding
Do steroids cause high vol or low vol state? Na/water retention --> edema and HTN
How do steroids affect K+ and Ca2+ levels? hypoK+ alkalosis, hypoCa2+
How do steroids affect skeletal growth in children? retards skeletal growth
How do steroids affect infections and wound healing? Increases chance for infection; slows wound healing
How do steroids affect the eye? increases glaucoma and cataracts
What are the three most common causes of toxicity in children under 3 yo? 1. ASA (Reye's), 2. Acetominophen, 3. supplementary Fe
T or F: Asthma is an inflammatory dz True. It's an inflammatory dz associated with bronchial hyperactivity, bronchospasm, inc mucus secretion, edema, and cellular infiltration
Early asthmatic responses 30 to 60 min. Histamine and leukotrienes --> bronchospasm
Late asthmatic responses infiltration of eosinophils and lymphocytes into airways --> bronchoconstriction and inflammation with mucus plugging
How to provide short term relief to asthmatics? broncohdilators (reduce bronchial hyperactivity) and anti-inflammatory agents (protect against cellular infiltration)
In asthma, what are B2-selective agonists used for? Albuterol, metaproterenol, terbutaline. Used for relief of acute bronchoconstriction. Also used for prophylaxis of exercise-induced asthma (like Annie and Pat).
What asthma medication can I use to decrease nighttime attacks prophylactically? Salmeterol (longer-acting drug)
Why would you want to use M receptor blockers for asthmatics who have CV disease? B2 agonists can cause CV toxicity if overused. M blockers like ipratropium are safter in pts with CV dz and still cause bronchodilation in acute asthma.
If an asthmatic pt had bronchospasm due to B-blockers, what is the DOC? Ipratropium or other M blockers (minor atropine-like effects)
What is theophylline and why would you use it in asthmatics? A bronchodilator. Inhibits phosphodiesterase --> inc cAMP --> bronchodilation; antagonize adenosine (a bronchoconstrictor)
Toxicity for thoephylline is increased by what drugs? erythromycin, cimetidine, and fluororquinolones
What is aminophylline? IV. Sometimes used in bronchospasm or status asthmaticus.
What do cromolyn and nedocromil do? Prevent degranulation of pulmonary mast cells
What do cromolyn and nedocromil release from mast cells? histamine, platelet activating factor, LTC4
Can cromolyn and nedocromil be used prophylactically? yes -- dec sx's and bronchial hyperactivity (esp responses to allergens)
What are the adverse effects of cromolyn and nedocromil? throat irritation and cough (relieved by B2 agonist)
Why would you use adrenal steroids for asthma? block mediator release; inhibit prostaglandins, leukotrienes, and interleukins --> dec bronchial hyperactivity.
What type of drugs are beclomethasone and flunisolide? Adrenal steroids. Surface-active drugs - can be inhaled. Used for acute attacks as well as prophylactically.
What happens with excessive use of adrenal steroids? 1. Oropharyngeal candidiasis, 2. dec long bone growth in children
What would you use for severe acute asthma attacks? Oral prednisone or IV steroids.
What type of drug is zafirlukast? antagonists at LTD4 receptors. Slow onset.
What are the adverse effects of zafirlukast? diarrhea, headache, increased infections
What is zileuton? selective inhibitor of lipo-oxygenases, decreasing formation of leukotrienes.
Which has faster onset? Zafirlukast or zileuton? Zileuton (1 to 3 hrs)
What are the adverse effects of zileuton? asthenia (feeling of weakness without actual loss of strength), headache, and inc LFTs
What would you use for acute asthma in the ER? 1. O2, 2. aerosolic B agonists, 3. IV steroids
Created by: christinapham
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