Anti-inflammatory Questions (without DMARDS and Anti-gout Drugs)

A 55-year-old male is suffering from the diarrhea and vomiting takes a drug that non-selectively inhibits prostaglandin production to treat his aches and pains for the last three days. He finally goes to his primary care physician who performs a history and physical. Findings are significant for an increase in creatinine plasma concentration, negative for hematuria, and proteinuria. Urine sediment contains casts. What is the most likely underlying physiologic cause for his acute kidney injury? A Decrease in PGE2 produced afferent renal tubule dilation B Increase in activity of COX 2 C Increase in glomerular filtration D His advanced age E Increase in thromboxane A2 production

A Decrease in PGE2 produced afferent renal tubule dilation Prostaglandins PGE2 and PGI2 produced by both cox 1 and 2 enzymes serve as protectant roles in renal function to counterbalance vasoconstrictive induced decreases in renal blood flow. 1) Prostaglandins keep renal perfusion pressure at a sufficiently level during loss of blood pressure or via vasoconstriction. 2) Appose vassopressin actions (AVP (arginine vasopressin or anti-diuretic hormone) is released to adjust hypertonicity of the vascular system. It binds to vasopressin GPCR receptors to increase aquaporin-2 expression in the renal tubules allowing more water to be absorbed and the concentration of the urine. It also binds to peripheral vasopressin receptors on blood vessels to produce vasoconstriction.)

A 2 year old girl is suffering from symptoms of an influenza infection and presents to the emergency department with a fever of 104 C. Which of the following drugs would you most likely administer to this patient to reduce her fever? A. Acetaminophen B. Amoxicillin C. Aspirin D. Ciprofloxacin E. Indomethacin

A. Acetaminophen has antipyretic effects by inhibiting COX enzymes in the brain . Prostaglandin production in the hypothalamus is associated with increased body temperature. Aspirin use especially in children with influenza or varicella is associated with Reye Syndrome. This is a condition associated with progressive encephalopathy and hepatic dysfunction. Characteristics of this syndrome include vomiting and confusion that can evolve into seizures and coma.

Which is INNCORRECT regarding adverse or toxic effects of aspirin? A. GI intolerance or bleeding is only found in patients who take doses higher than recommended B. Aspirin use may increase bleeding time C. Toxic doses may lead to metabolic acidosis and respiratory depression D. Aspirin can cause tinnitus, vertigo and decreased hearing E. Aspirin may inhibit normal renal regulation of water and electrolytes

A. GI intolerance and bleeding are associated with aspirin use even at relatively low doses.

A common toxicity of ibuprofen use is which of the following? A. Gastroduodenal ulceration & bleeding B. Platelet aggregation C. Thrombocytopenia D. Reyes Syndrome E. Respiratory failure

A. GI ulcers and bleeding

Which of the following represents a drug that can be given every 2-4 weeks and is an immunoconjugate of IgG1 linked to human CTLA-4 which blocks CD28-CD80/86 activity on T-cells? A. Gemtuzumab ozogamicin (Mylotarg) B. Etanercept (Enbrel) C. Levamisole (Ergamisole) D. Alefacept (Amevive) E. Abatacept (Orencia)

Abatacept (Orencia)

Which of the following enzymes is expressed in endothelial cells and whose products can reduce platelet aggregation and serious cardiovascular events? A Cyclooxygenase 1 B Cyclooxygenase 2 C Thromboxane A2 synthase D 5' lipooxygenase E Epoxygenase CP450

B Cyclooxygenase 2 The products of Cox 1 and Cox 2 differ depending on the location. An important example is the balance created between Cox1 production of pro-coagulant TXA2 in platelets and the anti-platelet effects of Cox2 derived prostacyclin

Inflammation is a complex tissue reaction that includes the release of cytokines, leukotrienes, prostaglandins, and peptides. Prostaglandins involved in inflammatory processes are produced from arachidonic acid by A Cyclooxygenase 1 B Cyclooxygenase 2 C Glutathione-S-transferase D 5' Lipooxygenase E Phospholipase A2

B Cyclooxygenase 2 Concepts to focus on: There are two types of cyclooxygenase enzymes with significant clinical implications. The COX 1 enzyme is constitutively regulated and found in most. In the GI tract it is important for producing prostaglandins involved in gut cytoprotection. In platelets it promotes platelet aggregation. In theory inhibiting this enzyme would have less affects on inflammation and is likely to underlie the GI toxicity observed with NSAID use (more on this later). The COX II isotype is transcriptionally up regulated by inflammatory cytokines. In the number of enzymes is greatly increased upon stimulation. It is found in inflammatory cells, bone, kidneys, and female GU. The COX II isotype produces pro-inflammatory prostaglandins and in endothelial cells produces prostacyclin which inhibits platelet aggregation.

A 17-year-old patient complains that he gets severe shortness of breath whenever he takes aspirin for headache. Increased levels of which of the following may be responsible, in part, for some cases of aspiring hypersensitivity? A Alprostadil B Leukotriene LTC4 C Misoprostal D Prednisone E Prostacyclin

B Leukotriene LTC4 The lipoxygenase and cyclooxygenase pathways share the common precursor of arachidonic acid. NSAIDS inhibit the cyclooxygenase side thus creating a situation in some patients with asthma of excess AA which then fuels more production into the leukotriene pathway that is pro-bronchoconstrictive.

Recognized clinical indications for eicosanoid or their inhibitors include all of the following EXCEPT A Induce Abortion B Treat Primary Hypertension C Keep open Patent Ductus Arteriousus D Treat Primary dymenorrhea E Treat glaucoma

B Treat Primary Hypertension

Which of the following statements is correct? A. The conversion of arachidonic acid to leukotrienes is carried out by cyclooxygenase I B. PGE1 (alprostadil) is used to treat male impotence via smooth muscle relaxation C. Leukotrienes have prominent anti-inflammatory and bronchodilatory effects D. Prostaglandin production in the gut often leads to gastric ulcers E. Thromboxane stimulates receptor-mediated conversion of intracellular ATP into cAMP

B. Alprostadil can be injected into the corpus cavernous or placed as a pill transurethral. This is a less sought after alternative to phosphodiesterase inhibitors like sildenafil (Viagra), etc. Leukotrienes are the products of conversion of arachidonic acid by lipooxygenase. C and D are opposite to what these compounds do.

A 46-year-old male suffering from ischemic heart disease is put on a medication that irreversibly inhibits both cyclooxygenase 1 and 2. Which drug is this patient taking? A. Allopurinol B. Aspirin C. Ibuprofen D. Naprosyn E. Methotrexate

B. Aspirin

Which of the following should not be used on children because it is associated with Reyes Syndrome? A. Acetaminophen B. Aspirin C. Ibuprofen D. Prednisone E. Celecoxib

B. Aspirin, aspirin use especially in children with influenza or varicella is associated with Reye Syndrome. This is a condition associated with progressive encephalopathy and hepatic dysfunction. Characteristics of this syndrome include vomiting and confusion that can evolve into seizures and coma.

Which of the following is a potent, long-duration, glucocorticoid? A. Cortisone B. Betamethasone C. Hydrocortisone D. Piroxicam E. Prednisone

B. Betamethasone

Which of the following statements best describes an advantage of celecoxib over naproxen to treat arthritic symptoms in a patient with a history of ulcers? A. Celecoxib is a more effective anti-inflammatory and analgesic agent than naproxen B. Celecoxib inhibits more specifically the COX enzyme isotype that is inducible by cytokines and growth factors C. Celecoxib is a specific COX 1 inhibitor D. Celecoxib use can increase prostaglandin synthesis in the gastrointestinal tract E. Celecoxib use inhibits the constitutively regulated COX enzyme isotype found in the gastrointestinal tract

B. Celecoxib is more selective for COX 2 (pro-inflammatory), which is the inducible isotype of the COX enzymes.

A 32 year old woman complains to her family doctor of mild to moderate pain in all of her joints, a swollen right knee, and stiffness every morning. These symptoms have been occurring with increasing severity for the past week. She has swelling in 3,4,5 proximal interphalangeal joints bilaterally. Joint deformity 3, 4 bilaterally is visible with ulnar deviation bilaterally. She has decreased grip strength, L>R. She also has decreased range of motion in her shoulders, hips and knees. Blood tests are positive for serum rheumatoid factor. Her personal medical history indicates a history of GI bleeding from peptic ulcer disease and has no significant cardiovascular issues. The most appropriate drug to treat this woman's pain with the least amount gastrointestinal side effects is which of the following? A. Aspirin B. Celecoxib C. Dexamethasone D. Ibuprofen E. Indomethacin

B. Celecoxib is the selective COX 2 inhibitor in this list.

A 43-year-old female patient with a history of gastrointestinal bleeding suffers an orthopedic injury and requires a minimum of a 4-week course of NSAID therapy to treat some of the symptoms associated with her injury. Which of the following NSAIDS would you most likely advise this woman to use? A. Aspirin B. Celecoxib C. Diclofenac D. Indomethacin E. Ketorolac

B. Celecoxib of this list is the most selective for COX 2.

Which of the following is a potentially significant advantage of celecoxib over aspirin? A. Aspirin inhibits COX 1 only B. Celecoxib has less corrosive effects on gastrointestinal lining C. Celecoxib inhibits both COX 1 and COX 2 D. Celecoxib is a more efficacious anti-inflammatory agent E. Celecoxib is an irreversible inhibitor of COX 1 and COX 2

B. In theory, because celocoxib is more selective for COX 2 (pro-inflammatory) than COX 1(pro-cytoprotection in the gut) it should have less corrosive effects on GI lining.

A 44 year old male is seen by his physician for severe pain in his left great toe. His toe is swollen, hot, tender, with normal joint space and erythematous. His serum uric acid level is 11.5 mg/dl (normal is 3.5-8.0 mg/dl). Synovial fluid aspirate demonstrates PMNs and monosodium urate crystals. A. Aspirin B. Allopurinol C. Indomethacin D. Probenecid E. Sulfinpyrazone Which drug listed above would most likely be used to treat this patient's acute gouty attack?

C Indomethacin is the NSAID of choice to treat acute inflammatory episodes associated with gout. Aspirin is avoided because it can prevent excretion of uric acid in the renal tubules.

A 60-year-old woman has glaucoma after cataract surgery. Which of the following can be used to reduce intra-ocular pressure? A Leukotriene LTD4 or its analogs B Prostaglandin PGE2 or its analogs C Prostaglandin PGF2a or its analogs D Slow-reacting substance of anaphylaxis (SRS-A) D Thromboxane TXA2 or its analog

C Prostaglandin PGF2a or its analogs

Which of the drug is correctly matched to its therapeutic use? Drug treatment : Disease treated A. PGF2α (Latanoprost) : asthma B. Thromboxane A2 : pulmonary hypertension C. PGE1 (Alprostadil) : erectile dysfunction D. Leukotriene B4 : Rheumatoid Arthritis E. PGE2 (Dinoprostone) : Unwanted Premature labor

C. Alprostadil can be injected into the corpus cavernous or placed as a pill transurethral. This is a less sought after alternative to phosphodiesterase inhibitors like sildenafil (Viagra), etc.

Which effect of aspirin requires the highest dose of the drug? A. Analgesic B. Antipyretic C. Anti-inflammatory D. Anti-thrombotic E. All effects need about the same dose

C. Anti-inflammatory dose. Gram quantities are used per dose vs mg quantities for the rest.

A 43-year-old man is suffering from muscle pain and mild joint inflammation associated that developed acutely after playing basketball. He decides to take ibuprofen to relieve the symptoms associated with this pain and inflammation. Which statement is true regarding the use of ibuprofen? A. After cessation of ibuprofen use the Antiplatelet effects can last 8-10 days B. Ibuprofen is a selective COX 2 inhibitor C. Ibuprofen can have similar effects to aspirin in patients with bronchospastic reactivity to aspirin D. Ibuprofen use is not associated with gastrointestinal irritation E. The Antiplatelet effects of ibuprofen and aspirin are synergistic

C. Both aspirin and ibuprofen are non-selective inhibitors of the COX enzymes. Arachidonic acid can shift over to the leukotriene pathway if these enzymes are inhibited. Asthmatics (especially with nasal polyps) can be sensitive to this shift.

Which of the following drugs has the highest salt-retaining potency? A. Beclomethasone B. Dexamethasone C. Fludrocortisone D. Metyrapone E. Triamcinolone

C. Fludrocorisone in addition to activated glucocorticoid receptors can activate aldosterone receptors in the renal tubule which leads to sodium retention in the body.

A 45-year-old male who is suffering from multiple minor injuries is taking ibuprofen daily to treat his injuries. Unfortunately, his injuries occur often preventing him from terminating the current course of ibuprofen. He has been taking the drug for over a month. He now is suffering from gastro-intestinal (GI) ulcers. The principle mechanism that ibuprofen is producing these GI symptoms is mediated by which action? A. Irreversible inhibition of the cyclo-oxygenase one enzyme B. Irreversible inhibition of the cyclo-oxygenase two enzyme C. Reversible inhibition of the cyclo-oxygenase one enzyme D. Reversible inhibition of the cyclo-oxygenase two enzyme E. Reversible inhibition of lipoxygenase

C. Reversible inhibition of COX 1 preventing pro-cytoprotectant prostaglandins from being made in the GI tract.

This patient accidentally takes twice the amount of aspirin as was indicated by her physician. She now experiences symptoms of tinnitus, decreased hearing and vertigo. You administer sodium bicarbonate to alkalinize the urine. At what renal tubular pH would aspirin or its metabolites, which have a similar pKa, be most efficiently excreted in the urine? A. 5 B. 6 C. 7 D. 8

D. Aspirin is a weak acid. Weak acids H+ + A- = HA . Weak acids become disassociated when the hydrogen ion concentration is reduced. Therefore, the higher the pH (lower the hydrogen ion concentration) the more charged aspirin will be present. The charged form will not be reabsorbed and will be excreted.

A 43-year-old man routinely takes aspirin to control muscle and joint pain. He has his wisdom tooth extracted, and he experiences excessive bleeding. The most likely cause of the excessive bleeding is A. Hepatic damage caused by aspirin use B. Inhibition of leukotriene synthesis by aspirin C. Inhibition of thromboxane synthesis by aspirin D. Inhibition of prostacyclin synthesis by aspirin E. Metabolic acidosis caused by aspirin use

D. Inhibition of thromboxane synthesis by aspirin. Aspirin prevents the production of PGH2 in platelets by inhibiting COX1. TXA2 is made when PGH2 is converted to TXA2 by thromboxane synthase.

The anti-inflammatory mechanism of action of aspirin is produced by A. Competitive inhibition of cyclooxygenase (COX) one enzyme B. Competitive inhibition of cyclooxygenase (COX) two enzyme C. Irreversible inhibition of cyclooxygenase (COX) one enzyme D. Irreversible inhibition of cyclooxygenase (COX) two enzyme E. Irreversible inhibition of lipoxygenase enzyme

D. Irreversible inhibition of cyclooxygenase (COX) two enzyme. The COX 2 isotype is associated with inflammation.

What is the mechanism of action of aspirin? A. Selective reversible inhibitor of cyclooxygenase 1 B. Reversible inhibitor of both cyclooxygenase 1 and 2 C. Irreversible inhibitor of both cyclooxygenase and lipooxygenase D. Irreversible inhibitor of both cyclooxygenase 1 and 2 E. Irreversible inhibitor of lipoxygenase

D. Irreversible non-selective COX inhibitor

A 56-year-old woman was diagnosed rheumatoid arthritis 1 year ago. She has been taking non-steroidal-anti-inflammatory agents with adequate dosing and meticulous compliance. However, her inflammation and erosive bone changes are still evident and appear to be getting worse. Which of the following drugs can be administered orally to the above patient and has similar efficacy in treating rheumatoid arthritis as methotrexate? A. Aurothiomalate (parenteral Gold) B. Etanercept C. Indomethacin D. Leflunamide E. Naproxen

D. Leflunamide is a metabolite that inhibits dihydro orate dehydrogenase and de novo ribonucleotide synthesis,. This stops T cell proliferation and B cell function.

An economical, safe, and effective way to prevent NSAID-associated ulcers is the simultaneous use of A. Antacids B. Misoprostol C. Pepto-Bismol D. Proton pump inhibitors E. Sucralfate

D. Proton pump inhibitors. Many of the choices could be used to treat NSAID-associated GI irritation. Misoprostol could be used to replace cyto-protective prostaglandins not produced when COX one is inhibited but it is not economical and is associated with its own toxicities (Headache, constipation, dyspepsia,which are common (1-10%).

Which of the following is NOT typically involved in mediating the direct glucocorticoid effects in various cells? A. Glucocorticoid response elements on DNA B. Heat shock proteins C. Intracellular glucocorticoid receptor protein D. Seven-domain trans-membrane receptors E. Transcription factors

D. Seven-transmembrane receptors. Glucocorticoids pass through cell wall to activated a transcriptional regulator. When bound by glucocorticoids the intracellular receptor disassociates from the heat shock protein (HSP 90), moves into nucleus, where it activates or inhibits DNA transcription when it binds to the glucocorticoid response element in several genes.

Corticosteroids inhibit the following processes, EXCEPT A. Adhesion of leukocytes to the vascular endothelium B. Induction of cyclooxygenase II C. Release of ACTH from the pituitary D. Synthesis of pulmonary surfactant protein E. The effect of vitamin D on calcium absorption

D. Synthesis of pulmonary surfactant protein

Which of the following statements is most correct regarding the use of ibuprofen and aspirin? A. Aspirin is not used as an antipyretic B. Ibuprofen is more effective than aspirin at reducing inflammation C. Ibuprofen is not associated with any serious gastrointestinal effects D. The duration of action of aspirin on platelet function is longer than ibuprofen E. Ibuprofen does not have any analgesic properties

D. The duration of action of aspirin on platelet function is longer than ibuprofen. Aspirin is an irreversible inhibitor while ibuprofen in not. Platelets don't make new enzymes. Therefore, the effects of aspirin will last for the life of the platelet.

The main advantage of ketorolac over aspirin is that ketorolac A. Can be obtained as an over the counter agent B. Does not prolong the bleeding time C. Is not associated with gastro-intestinal toxicity D. Is available in a parenteral formulation E. Is less likely to cause acute renal failure

D. is available in a parenteral formulation

A 46-year-old male develops a skin rash after walking his dog through an area of poison oak. His rash consists of small liquid filled eruptions. His doctor prescribes prednisone, an oral glucocorticoid. Why was prednisone used in this patient? A. to increase gene expression of endogenous glucocorticoids B. to increase the gene expression of cyclooxygenase 2 C. to increase the enzyme activity of phospholipase A2 D. to reduce gene expression pro-inflammatory proteins E. to reduce the probability of opportunistic infections

D. to reduce gene expression pro-inflammatory proteins

Which of the following contraindicate the use of glucocorticoids? If all (A-D) do, answer E! A. Diabetes B. Heart disease C. Infection D. Peptic ulcer E. All of the above

E. All of the above. High doses for longer than two weeks can result in iatrogenic Cushing's syndrome. Symptoms include changes in fat redistribution (round-puffy "moon" face, truncal obesity , spindly limbs, hump on back) acne, insomnia, increased appetite, many metabolic effects (protein breakdown, glucose production, increased insulin requirement, weight gain), structural consequences (osteoporosis, muscle loss, skin thinning with striae and bruising). Other notable effects include peptic ulcers, increased infections, CNS changes (acute psychosis, depression), eye (cataracts and increased intraocular pressure—dangerous in patients with glaucoma), growth retardation in children, and adrenal suppression Contraindicated Peptic ulcer disease Hypertension with heart disease Certain infections Varicella TB Psychoses Diabetes Osteoporosis Glaucoma

A 60-year-old male with a history of gastric ulcers develops rheumatoid arthritis. His physician would like to begin therapy with aspirin. To avoid the recurrence of gastric ulcers in this patient, the physician should advise him to A. Take aspirin between meals B. Take aspirin at night with a glass of wine C. Take aspirin as a suppository D. Take ibuprofen instead E. Take misoprostol with aspirin

E. Aspirin, an irreversible-COX-1 and-2-inhibitor, can prevent the cytoprotective prostaglandins from being made. Misoprostol, a PGE1 analog can be used to augment the aspirin induced endogenous production of PGE1 in the gut. Proton pump inhibitors are now more favored as a mechanism to reduce gut erosion.

Which process can lead to toxic products of acetaminophen (Tylenol)? A. Conjugation with glucuronide B. Conjugation with sulfate C. Conjugation with glutathione D. Induction of CytP450 by acetaminophen E. Metabolism of acetaminophen by CytP450

E. CYP 2E1 metabolizes approximately 5% of ingested Tylenol and converts it into a free radical that if not rapidly conjugated to glutathione can bind to important enzymes and lead to liver cell death.

Which of the following NSAIDs (A-D) causes irreversible inhibition of platelet aggregation? (If none of them does, answer E!) A. Ibuprofen B. Celecoxib C. Naproxen D. Sodium salicylate E. None of the above

E. Only aspirin is the irreversible COX 1 and 2 inhibitor the rest are reversible. Celocoxib is reversible and selective for COX 2, which is not involved in TXA2 production.

A 65-year-old women is on a medication that decreases symptoms and slows the progression of erosive changes produced by her rheumatoid arthritis (RA). However, she is complaining of symptoms of diarrhea, stomatitis, dermatitis and her lab values indicate hematologic abnormalities. She no longer wishes to take the medication. Which drug is she currently using to treat her RA? A. Celecoxib B. Indomethacin C. Etanercept D. Infliximab E. Parenteral gold (aurothiomalate)

E. Parenteral gold is associated with all of these side effects.

Which of the following (A-D) constitutes a relative contraindication of corticosteroid treatment? If all of (A_D) are contraindications, answer E! A. Viral infection B. Osteoporosis C. Diabetes D. Glaucoma E. All of the above (A-D) are relative contraindications of glucocorticoid treatment

E. corticosteroids are an immunosuppressant that has many important metabolic effects and associated toxicities if used for extended periods.

Which of the following autocoids is produced in endothelial cells by cyclooxygenase 2 and functions in part to inhibit platelet aggregation and produces vasodilation? a Prostaglandin E2 (PGE2) b Prostacyclin (PGI2) c Leukotriene B4 (LTB4) d Resolvin (RVE1) e Thromoxane A2 (TXA2)

Prostacyclin (PGI2)

Which of the following autocoids is produced in activated platelets cells and causes immune cell chemo-attraction, T cell modulation, and increases platelet aggregation by upregulating expression of the glycoprotein complex GPIIb/IIIa on the cell membrane of platelets?\ a Prostaglandin E2 (PGE2) b Leukotriene B4 (LTB4) c Lipoxin d Resolvin (RVE1) e Thromboxane A2 (TXA2)

Thromboxane A2 (TXA2)

A 55-year-old man who has been practicing Shotokan Karate for 15 years is now suffering from severe osteoarthritis in digit three of his right metacarpophalangeal joint and requires an intra-articular injection of a glucocorticoid. Which one of the following would be the best choice based on anti-inflammatory potency and duration of action? a Betamethasone b Cortisone c Fludrocortisone d Prednisone

a Betamethasone and dexamethasone are both long-acting high potency anti-inflammatory glucocorticoids.

A 25-year-old female at gestation week 44. It is decided that an endocervical gel should be used to promote cervical ripening in order to promote labor. Which of the following medications was most likely used? a Alprostadil (PGE1 analog) b Dinoprostone (PGE2 analog) c Latanoprost (PGF2a analog) d Prednisone e Zafirlukast

b Dinoprostone (PGE2 analog)

UpToDate: Chronic glucocorticoid therapy is used in the treatment of a variety of disorders (e.g. rheumatoid arthritis, large- and small-vessel vasculitis, systemic lupus erythematosus, polymyalgia rheumatica, and sometimes inflammatory bowel disease. Despite its efficacy, steroid-induced side effects generally require tapering of the drug as soon as the disease being treated is under control. Why is tapering important? a To allow time for the steroid receptors to upregulate b To compensate for cortisol deficiency from feedback suppression of HPA c DNA transcriptional regulation occurs within the first day d The inflammatory cascade has a built in self-limiting mechanism e To allow for the upregulation of phospholipase A2

b To compensate for cortisol deficiency from feedback suppression of HPA Exogenous supplied glucocorticoids (like Prednisone, etc.) and endogenous cortisol have similar effects on the body (they both bind to the same receptor). Cortisol levels are under tight physiologic regulation and is released in a pulsatile fashion when you wake up, with meals, or when you are experiencing stress. Levels of endogenous cortisol go down rapidly do to its ability to feedback and inhibit its own production. When a patient takes prednisone on a continuous non-physiologic-regulatable fashion to treat inflammation there is no decrease in plasma glucocorticoid levels. The maintained elevated glucocorticoid plasma levels provides continuous suppression of endogenous cortisol production. Under these conditions the body now requires exogenous glucocorticoid to have any appreciable levels of any glucocorticoids in the plasma. The body will not make endogenous cortisol until the feedback regulation mechanism is adjusted and this can takes days to months depending on how long the suppression has occurred. During this period of time if the patient precipitously stops the exogenous glucocorticoid there will be a time period of no endogenous glucocorticoid production and this will manifest as withdrawal symptoms—usually in the opposite direction of what the drug does.

Which of the following eicosanoid/receptor/signal cascade is most likely to produce pulmonary vasodilation? a PGE2: EP1: Gq/IP3 b PGE2: EP3 : Gi c PGF2a: FP : Gs/cAMP d PG12: IP : Gs/cAMP

d PG12: IP : Gs/cAMP

Which of the following drugs bind to a receptor that can turn on and off DNA transcription? a Aspirin b Alprostadil c Dinoprostone d Progesterone e Zafirlukast

d Progesterone Aspirin: Non selective COX 1 and 2 inhibitor Alprostadil: PGE1 analog Dinoprostone: PGE2 analog Zafirlukast: leukotriene receptor antagonist

A 55-year-old man with suffering from several conditions including fatigue, myalgia, photosensitive rash, arthritis of peripheral joints visits his primary care physician. A complete history and physical is performed. Laboratory exams are significant for leukopenia, proteinuria, and high anti-double-stranded deoxyribonucleic acid (ANA) titers. It is decided to give him a short course of high dose methylprednisolone. Many of the patient's symptoms resolve. Why would his physician decide not to maintain therapy with methylprednisolone? a Glucocorticoids are contraindicated in renal failure b Glucocorticoids are contraindicated in patient with systemic lupus erythematosis c To avoid the development of tolerance d To avoid iatrogenic Cushing's syndrome e The physician doesn't want the patient to become addicted

d To avoid iatrogenic Cushing's syndrome Cushing syndrome is a condition observed in patients taking high levels of glucocorticoids for a long period of time. Cortisol is an important metabolic regulator under tight regulatory control. The symptoms of cushing syndrome are caused by continuous exposure of the body to cortisol like drugs. Many metabolic features are observed: weight gain, fatty tissue deposits (midsection, upper back between shoulders, moon face), skin effects (stretch marks thin fragile skin), hormonal changes, weakness, fatigue, depression, bone loss, etc.

The use of glucocorticoids should be used with caution in all of the following, except? a Diabetes b Glaucoma c Osteoporosis d Peptic ulcer disease e Prostatic cancer

e Prostatic cancer There are many disease related concerns when using systemic glucocorticoids. Duration of use and dose dependent effects can be achieved. For example see excerpt from UpToDate, GD use with cation in the following diseases: due to • Cardiovascular disease: increased fluid retention and hypertension. • Diabetes: altered glucose production and regulation • Gastrointestinal disease: increased perforation risk via decline in protective prostaglandin production • Hepatic impairment: Use with caution in patients with hepatic impairment, including cirrhosis; effects may be enhanced. • Myasthenia gravis: exacerbation of symptoms has occurred especially during initial treatment with corticosteroids. • Myocardial infarction (MI): corticosteroids have been associated with myocardial rupture. • Osteoporosis: high doses and/or long-term use of corticosteroids have been associated with increased bone loss and osteoporotic fractures. • Seizure disorders: seizures have been reported with adrenal crisis. • Thyroid disease: Changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones.