Inflammation - Pharmacology - Eicosanoids; NSAIDS & Acetaminophen; Corticosteroids; Antihistamines; Arthritis & Gout Flashcards
What are the three enzyme classes that produce eicosanoids from arachidonic acid?
- Cyclooxygenases
- Lipooxygenases
- Epoxygenases (CP450)
Name main eicosanoid classes produced by the following enzymes.
1. Cyclooxygenases
2. Lipooxygenases
3. Epoxygenases (CP450)
- Cyclooxygenases (Prostaglandins, thromboxanes)
- Lipooxygenases (leukotrienes, lipoxins, HETEs)
- Epoxygenases (CP450) (epoxyeicosatrienoic acids (EETs))
COX-___ must be induced (is not constitutively expressed).
COX-2 must be induced (is not constitutively expressed).
After cyclooxygenases form PGG2, what enzyme does the rest?
Endoperoxidase (POX)
NSAIDs target _____.
Acetaminophen targets _____.
NSAIDs target COX.
Acetaminophen targets POX.
What role do epoxyeicosatrienoic acids (EETs) mediate in the body?
Smooth muscle relaxation
Eicosanoids have a variety of effects in the body, including:
- Enhanced _____ signaling (GPCR decreases in _______ thresholds)
- Vaso________ and _________ permeability
- _________ body temperature (vasodilation + _________ effects)
Eicosanoids have a variety of effects in the body, including:
- Enhanced pain signaling (GPCR decreases in neuronal thresholds)
- Vasodilation and increased permeability
- Increased body temperature (vasodilation + hypothalamic effects)
COX-2 is constitutive in _________ _________ (antiplatelet and vasodilatory effects).
COX-2 inhibitors increase _________.
COX-2 is constitutive in vascular endothelium (antiplatelet and vasodilatory effects).
COX-2 inhibitors increase thrombogenicity.
Ulcers are a common effect of COX inhibition by _________.
Ulcers are a common effect of COX inhibition by NSAIDs.
NSAIDs are contraindicated in what population in particular?
Those with acute renal failure
NSAIDs excaberate renal dysfunction by decreasing production of _____.
NSAIDs excaberate renal dysfunction by decreasing production of PGE2.
Omega-__s are especially protective towards cardiovascular health.
Omega-3s are especially protective towards cardiovascular health.
D. Phospholipase A2
A. Cyclooxygenase-1
Prostaglandins cause an increase in body temperature via the following mechanism:
Increased ____ –> _________ neuronal firing in the anterior hypothalamus –> increased body temp.
Prostaglandins cause an increase in body temperature via the following mechanism:
Increased PGE –> decreased neuronal firing in the anterior hypothalamus –> increased body temp.
What is celecoxib?
A selective COX-2 inhibitor
True/False.
Aspirin (not technically an NSAID) is a ‘CNS-selective’ COX-inhibitor; hence, why it has analgesic and antipyretic effects without anti-inflammatory effects (inflammation is mostly a peripheral occurrence).
False.
Acetaminophen (not technically an NSAID) is a ‘CNS-selective’ COX-inhibitor; hence, why it has analgesic and antipyretic effects without anti-inflammatory effects (inflammation is mostly a peripheral occurrence).
An overdose of acetaminophen can cause acute ________ damage.
What is the antidote? What is it replacing?
An overdose of acetaminophen can cause acute hepatic damage.
N-acetylcysteine; reduced glutathione
Which NSAID has a relatively long half-life of about 15 hours?
Naproxen
Describe some of the following NSAIDs (and acetaminophen) according to how selective they are for either COX-1 or COX-2:
Acetaminophen (not an NSAID)
Ibuprofen
Naproxen
Celecoxib
Ketorolac
Describe ibuprofen’s mechanism of action.
Is it reversible?
Yes, it is reversible.
Describe aspirin’s mechanism of action.
Is it reversible?
Irreversible acetylation of the catalytic site
B. Aspirin
Due to the irreversible action of aspirin at the COX catalytic site, doses given over a relatively short period of time have a __________ effect.
Due to the irreversible action of aspirin at the COX catalytic site, doses given over a relatively short period of time have a cumulative effect.
Aspirin is slightly more selective for COX-1 than COX-2.
It preferentially targets COX-1 in __________, thus decreasing _____.
It leaves the COX-2 constitutively expressed in __________ __________ alone, thus leaving _____ production unaffected.
Aspirin is slightly more selective for COX-1 than COX-2.
It preferentially targets COX-1 in platelets, thus decreasing TXA2.
It leaves the COX-2 constitutively expressed in vascular endothelium alone, thus leaving PGI2 production unaffected.
How long does it take for the effects of aspirin to fully wear off?
8 - 10 days
(platelet lifespan)
What medication, if taken shortly before aspirin, can negate the effect of aspirin at cyclooxygenase?
Ibuprofen or another NSAID
(competition for catalytic site; aspirin degraded quickly)
Low-dose aspirin has what effects?
High-dose aspirin has what effects?
Low-dose aspirin has analgesic, antipyretic, and antiplatelet effects.
High-dose aspirin has anti-inflammatory effects.
Which of the following is not an NSAID? Why?
Ibuprofen
Aspirin
Acetaminophen
Ketorolac
Naproxen
Celecoxib
Acetaminophen;
it has no anti-inflammatory effects
Listed are the complications of aspirin in increasing dosage order: impaired hemostasis,
________ upset,
(now out of therapeutic range)
________, _____ (oxidative phosphorylation uncoupling),
hyperventilation and _______ alkalosis,
________ acidosis (response to above),
coma, renal/respiratory failure
Listed are the complications of aspirin in increasing dosage order: impaired hemostasis,
gastric upset,
(now out of therapeutic range)
tinitus, fever (oxidative phosphorylation uncoupling),
hyperventilation and respiratory alkalosis,
metabolic acidosis (response to above),
coma, renal/respiratory failure
Those under ____ should not receive aspirin. Why?
18;
Reye’s syndrome (encephalopathy; hepatic dysfunction –> 50% mortality unless treated early)
What are the major effects of Reye’s syndrome?
Encephalopathy;
hepatic dysfunction
- Acetaminophen
NSAIDS can mainly damage the ________ and ________ tract.
Acetaminophen can mainly damage the ________.
NSAIDS can mainly damage the kidneys and GI tract.
Acetaminophen can mainly damage the liver.
NSAIDs inhibit the _____ enzyme class.
Acetaminophen inhibits the _____ enzyme class.
NSAIDs inhibit the COX enzyme class.
Acetaminophen inhibits the POX enzyme class.
Acetaminophen does not have any anti-inflammatory effects because ________ reverse its effects at the ________ enzyme, thus preventing its effects in ________ conditions.
Acetaminophen does not have any anti-inflammatory effects because hydroperoxides reverse its effects at the POX enzyme, thus preventing its effects in inflammatory conditions.
A. Acetaminophen
What drug is the most common sold in the U.S. and is found in an abundance of medication combos?
Acetaminophen
50% of cases of acute liver failure are caused by ____________.
50% of cases of acute liver failure are caused by acetaminophen (overdose; usually > 15 g).
What organs function to inactivate cortisol by converting it to cortisone?
Via what enzyme?
Kidney, placenta (to protect the fetus);
11-β-hydroxysteroid dehydrogenase-2
What organ functions to activate cortisone by converting it to cortisol?
Via what enzyme?
Liver;
11-β-hydroxysteroid dehydrogenase-1
What medication is not inactivated by 11-β-hydroxysteroid dehydrogenase-2 and thus can be used to send glucocorticoids across the placenta to the fetus?
Dexamethasone
Describe the anti-inflammatory effects of glucocorticoids.
Which steroid hormone is NOT bound by a plasma protein while it travels through the bloodstream?
Aldosterone
Besides its more classic signs and symptoms, Cushing’s syndrome can also cause the following:
__________ (eye complication)
__________ (GI complication)
necrosis of the ___________
Besides its more classic signs and symptoms, Cushing’s syndrome can also cause the following:
Cataracts
Ulcers
necrosis of the femoral head
After taking glucocorticoids for an extended period of time, how can one prevent adrenal insufficiency?
Gradual tapering
Describe some of the potential adverse effects of glucocorticoid use on the following systems:
Skin
Muscle
Immune function
Bone
Describe some of the potential adverse effects of glucocorticoid use on the following systems:
CNS / Adrenal
Metabolic function
Eyes
Cardiovascular / Renal
Give the ratio of potencies at the glucocorticoid and mineralocorticoid receptors (GR:MR) for the following short-acting steroids:
Cortisol
Prednisone
Methylprednisone
Triamcinolone
1: 1
4: 1
5: 0.5
5: 0
Give the ratio of potencies at the glucocorticoid and mineralocorticoid receptors (GR:MR) for the following long-acting steroids:
Dexamethsone
Betamethasone
25: 0
25: 0
Give the ratio of potencies at the glucocorticoid and mineralocorticoid receptors (GR:MR) for the following short-acting steroid:
Fludrocortisone
10:125
Which medication blocks 11β-hydroxylase?
Metyrapone
Which medication blocks glucocorticoid and progesterone receptors?
What is it used for?
Mifepristone;
medical abortion (in conjunction with misoprostol)
What two medications are mineralocorticoid receptor antagonists?
Spironolactone;
eplerenone
Name a few 1st generation H1-blockers.
Brompheniramine;
chlorpheniramine;
diphenhydramine
Name a few 2nd generation H1-blockers.
Fexofenadine (Allegra);
loratadine (Claratin);
desloratadine;
cetirizine (Zyrtec)
Name a few indications for 1st generation H1-blockers.
Inflammation, urticaria, rhinitis, allergy;
antiemetic / motion sickness;
sleep aid
Name a few indications for 2nd generation H1-blockers.
Inflammation, urticaria, rhinitis, allergy
A patient presents with severe motion sickness.
Would loratadine help?
No;
2nd generation H1-blockers do not cross the BBB
___ generation H1-blockers can cross the blood-brain barrier.
1st generation H1-blockers can cross cross the blood-brain barrier.
1st generation H1-blockers can have anti_________ and anti_________ effects.
1st generation H1-blockers can have anticholinergic and antimuscarinic effects.
How does morphine cause itching?
Increases histamine release from mast cells
How does histamine cause itchiness?
Nerve stimulation
H1 and H2 are ___________________ receptors.
H1 and H2 are G-protein coupled receptors.
Name a few major H2-blockers.
Cimetidine;
ranitidine
Which is has a faster onset of action, H2-blockers or proton pump inhibitors?
H2-blockers
What is the main antagonist used to reverse anaphylaxis?
Epinephrine
What are cimetidine and ranitidine used to treat?
Which is not currently available on the U.S. market?
GERD, peptic ulcers;
ranitidine
C. Cimetidine
(H2-blockers are faster than proton pump inhibitors)
(ranitidine is not currently on the U.S. market)
What effects of epinephrine at α1 help to mitigate anaphylaxis?
Vasoconstriction;
decreased upper airway edema
What effects of epinephrine at β2 help to mitigate anaphylaxis?
Bronchodilation;
decreased mast cell degranulation
Adverse effects of cimetidine include:
inhibition of multiple ________ enzymes;
inhibits DHT and inhibits breakdown of estradiol, leading to _________ in males.
Adverse effects of cimetidine include:
inhibition of multiple CP450 enzymes;
inhibits DHT and inhibits breakdown of estradiol, leading to gynecomastia in males.
Name the effect had by histamine in each of the following roles:
1. Local immune responses
2. GI neurotransmitter
3. CNS neurotransmitter
- Vasodilation; chemotaxis
- Acid secretion
- Increased wakefulness
Histamine causes bronchial smooth muscle _________.
Histamine causes nasal mucus _________.
Histamine causes _________ cardiac output.
Histamine causes vascular smooth muscle _________.
Histamine causes bronchial smooth muscle contraction.
Histamine causes nasal mucus secretion.
Histamine causes increased cardiac output.
Histamine causes vascular smooth muscle dilation.
The H3 receptor mediates __________.
The H4 receptor mediates __________.
The H3 receptor mediates wakefulness.
The H4 receptor mediates chemotaxis.
Name two anti-inflammatory drug classes commonly used to treat rheumatoid arthritis.
NSAIDs;
corticosteroids
Name a few nonbiologic DMARDs (disease-modifying antirheumatologic drugs) used to treat rheumatoid arthritis.
Methotrexate, hydroxychloroquine, leflunomide, sulfasalazine
Name a few TNF-α blockers (biologic DMARDs) used to treat rheumatoid arthritis.
Adalimumab, certolizumab, etanercept, golimumab, infliximab
Name an IL-1 blocker (biologic DMARD) used to treat rheumatoid arthritis.
Name an IL-6 blocker (biologic DMARD) used to treat rheumatoid arthritis.
Anakinra;
tocilizumab
Name a JAK inhibitor (biologic DMARD) used to treat rheumatoid arthritis.
Tofacitinib
Name the respective mechanisms of action of the following drugs that allow them to be used as treatments for rheumatoid arthritis:
Methotrexate
Adalimumab
Etanercept
Methotrexate - indirectly inhibits adenosine deaminase
Adalimumab - inhibits TNF-α receptor
Etanercept - binds TNF-α
Name the respective mechanisms of action of the following drugs that allow them to be used as treatments for rheumatoid arthritis:
Anakinra
Tofacitinib
Infliximab
Anakinra - inhibits IL-1 receptor
Tofacitinib - inhibits certain JAKs
infliximab - binds TNF-α
Disease-Modifying AntiRheumatic Drugs (DMARDs) should be used in the ______ stages of treatment to preserve joint integrity and function (DMARDs can be subdivided into “non-biologic” & “biologic” DMARDs).
Antiinflammatory drugs such as NSAIDs & glucocorticoids should be used as ______ to therapy.
Disease-Modifying AntiRheumatic Drugs (DMARDs) should be used in the early stages of treatment to preserve joint integrity and function (DMARDs can be subdivided into “non-biologic” & “biologic” DMARDs).
Antiinflammatory drugs such as NSAIDs & glucocorticoids should be used as adjuncts to therapy.
IL-6 antagonists and JAK inhibitors are _____-line treatments for rheumatoid arthritis.
Methotrexate and TNF-α inhibitors are _____-line treatments for rheumatoid arthritis.
IL-6 antagonists and JAK inhibitors are second-line treatments for rheumatoid arthritis.
Methotrexate and TNF-α inhibitors are first-line treatments for rheumatoid arthritis.
In treating malignancies, methotrexate inhibits ___________ ___________.
In treating autoimmune disorders, methotrexate inhibits ___________ ___________.
In treating malignancies, methotrexate inhibits dihydrofolate reductase.
In treating autoimmune disorders, methotrexate inhibits adenosine deaminase.
Why is inhibiting adenosine deaminase useful in treating autoimmune disorders?
Adenosine is potently anti-inflammatory
(inhibiting T cell proliferation and TNF-α production)
What NSAIDs are used in treating gout?
What other anti-inflammatory medications can be used?
Ibuprofen, naproxen, indomethacin, ketorolac;
corticosteroids, colchicine
Cochicine binds to ________ in ________.
Colchicine binds to microtubules in neutrophils (inhibiting their chemotactic responses).
What medications are used to treat gout by lowering plasma urate?
(And how do they work?)
Allopurinol (inhibits xanthine oxidase)
Febuxostat (inhibits xanthine oxidase)
Probenecid (inhibits PCT anionic reuptake)
Pegloticase (solublizes urate for excretion)
Describe the multi-pronged treatment approach used for gout.
What is the main treatment course for cases of acute gout?
Anti-inflammatory
(NSAIDs, colchicine, steroids)
What is the main treatment course for cases of chronic gout?
Xanthine oxidase inhibitors (allopurinol, febuxostat);
uricosurics (probenecid);
uricoslytics (pegloticase)
Histamine plays an important role in initiating the body’s immune response to the presence of foreign antigens and pathogens. A primary source of histamine released during inflammatory conditions are:
A. B cells
B. Enterochromaffin-like cells
C. Presynaptic nerve terminals
D. Mast cells
E. T lymphocytes
D. Mast cells
Use of this class of over-the-counter drugs has been associated with poor academic performance in children, an increased incidence of automobile accidents, increased work injuries and a significant decline in cognitive function in the elderly. A commonly used member of this drug class is:
A. diphenhydramine
B. fexofenadine
C. loratadine
D. nizatidine
A. diphenhydramine
Histamine can be released by different “triggers” including tissue injury and immune activation caused by the detection of foreign antigens. However, a few drugs are also capable of directly causing histamine release by displacing the bound form of histamine stored within mast cells. An example of a drug producing this type of histamine reaction is:
A. cephalexin
B. cimetidine
C. epinephrine
D. morphine
E. penicillin G
D. morphine
A 24 year old patient presents on a bright sunny Spring morning with a constellation of signs & symptoms that include a stuffy runny nose, sneezing, and red, itchy, watery eyes, and a cough related to postnasal drip. A diagnosis of allergic rhinitis is made. In addition to a decongestant or corticosteroid spray, what other medication could you recommend that would counteract the effects related to histamine release, but have the least impact on mental status?
A. brompheniramine
B. chlorpehniramine
C. diphenhydramine
D. fexofexadine
E. ranitidine
D. fexofexadine
Mr. Thibidoux arrives in your ER after suffering a gunshot wound in a bar fight. After taking a brief history and exam, you decide to rapidly reduce his severe pain by administering i.v. morphine. Shortly thereafter Mr Thibidoux complains of feeling nauseous and itchy, and you notice that the skin on his neck and chest have become severly pink, when they were previously pale white. Which of the following would best reduce all of these symptoms if administered?
A. adrenaline
B. cimetidine
C. cromolyn sodium
D. diphenhydramine
E. loratidine
D. diphenhydramine
(the only one that has CNS effects and works as an anti-emetic)
A neighbor calls you at 6 AM from a bait shop in Grand Isle, an hour before he is departing on a six hour fishing trip in the Gulf of Mexico. He wants advice on “anything” he could take to help prevent sea sickness. He reads off a short list of medications that the store has available. You realize that several of them would probably be effective if taken well before departure. However, amongst the medications mentioned, the least likely to be effective in preventing sea sickness would be:
A. dimenhydrinate
B. diphenydramine
C. loratidine
D. promethazine
C. loratidine
Susan is a 70 year-old woman who arrives for her regular medical appointment with a new complaint about recent episodes of heartburn (dyspepsia) that she has been experiencing once or twice a week. You discuss the effectiveness of proton pump inhibitors, but she indicates a strong reluctance to taking them due to concerns about an increased risk for hip fractures. You then recommend an alternative over-the-counter treatment that involves blocking the effect of histamine on acid secretion, and suggest that she try taking:
A. cimetidine
B. diphenhydramine
C. fexofenadine
D. loratidine
E. promethazine
A. cimetidine
A 35-year-old man with a history of duodenal ulcer arrives for his annual appointment and complains of bilateral tenderness and swelling of his breasts. Upon further examination, a diagnosis of gynecomastia is made. If his condition was drug-induced, which medication below was he most likely taking?
A. cimetidine
B. famotidine
C. nizatidine
D. rinitidine
A. cimetidine
John is a 60-year-old patient with a history of peptic ulcer, hyperlipidemia, atrial fibrillation and epilepsy. To treat his multiple medical conditions John has been on multi-drug therapy which includes omeprazole, atorvastatin, amiodarone and phenytoin. While this multi-drug regimen has been well tolerated for the past year, he now presents to your clinic with multiple simultaneously developed health complaints. Analysis of a blood sample indicates that ALL of his prescribed medications have accumulated to toxic plasma levels. When asked about any recent changes to his lifestyle, John admits to having taken an additional over-the-counter drug for the past two weeks to control heart burn. Which of the following did John most likely take?
A. calcium carbonate (Tums ®)
B. cimetidine
C. famotidine
D. nazatidine
E. sodium bicarbonate (Alka Seltzer ®)
B. cimetidine
Cimetidine is a relatively broad-spectrum inhibitor of many CP450 isoforms
A 19 year-old woman suffering from nausea and vomiting related to a migraine headache was given an i.v. infusion of “Drug X” in a local Emergency Department. During the infusion, she complained of extreme pain at the site where the i.v. line was inserted. Soon thereafter she developed circulatory problems at the site of injection, which then over several weeks progressed to gangrene, which required amputation of her arm in stages. What most likely was Drug X?
A. bromopheniramine
B. chlorpheniramine
C. diphenhydramine
D. promethazine
E. ranitidine
D. promethazine
(in its injectible form it is highly caustic to the intima of blood vessels & surrounding tissues)
Aspirin is a drug commonly used for the primary prevention of cardiovascular disease in patients with elevated risk factors (e.g. advanced age, diabetes, smoking, high blood pressure, and/or coronary artery disease). While aspirin has been found to be effective in reducing cardiovascular risk in such patients, it has also been found that other drugs can significantly interfere with aspirin’s beneficial effects if taken concomitantly. An example of the type of drug to be avoided in such patients is:
A. Colchicine
B. Ibuprofen
C. Methotrexate
D. Montelukast
E. Prednisone
B. Ibuprofen
Step 2
Your ten year old son is running a fever of 101°F after developing a cold. To help him feel better you go to the local pharmacy to purchase an a fever-lowering medication. However, as a good parent you recall that there are warnings about the risk of drug-induced Reye’s syndrome in children given the wrong type of NSAID. Which NSAID is associated with this potentially serious condition?
A. acetaminophen
B. aspirin
C. celecoxib
D. montelukast
B. aspirin
John is a 63 year old alcoholic with a 5 year history of ulcers. Recently when self-medicating for a back condition John consumed 5 times the recommended daily dose of an over-the-counter pain reliever. Soon afterwards John developed a severe episode of nausea and vomiting. Twleve hours later his wife brings him to the local Emergency Department. After quizzing John about the identity of his analgesic, the ER physician draws blood samples for drug analysis and administers N-acetylcysteine (Mucomyst) 140 mg/kg orally to prevent further toxicity. What analgesic did John most likely take to cause this problem?
A. acetaminophen
B. aspirin
C. ibuprofen
D. naproxen
E. prednisone
A. acetaminophen
Mikey is a twleve year old boy who has suffered from asthma for the past five years. His asthma has become worse after a recent episode of pneumonia, and now requires some form of chronic, preventative therapy. His parents express concern about the harmful effects associated with the long-term use of inhaled corticosteroids, and ask about possible therapeutic alternatives. After further discussion, it is decided to have Mikey try taking an oral formulation of montelukast for three months until his next regular appointment. The mechanism of action of this drug involves:
A. COX-1 inhibition
B. COX-2 inhibition
C. leukotriene receptor antagonism
D. lipoxygenase inhibition
C. leukotriene receptor antagonism
A premature newborn suffering from cyanosis is found to have a heart murmur upon auscultation. A 2D doppler echocardiogram indicates the presence of a patent ductus arteriosis. A drug is prescribed, and during the next followup exam, the murmur is gone. A new echocardiogram indicates a normal pattern of blood flow inside the heart. The drug prescribed was most likely:
A. ibuprofen
B. montelukast
C. PGE2
D. propranolol
A. ibuprofen
Highly selective COX-2 inhibitors are anti-inflammatory drugs with fewer GI side effects compared to traditional non-selective COX inhibitors, such as aspirin. What other effect do COX-2 inhibitors lack, in contrast to aspirin?
A. analgesic
B. antiinflammatory
C. antipyretic
D. antiplatelet
E. lipoxygenase inhibition
D. antiplatelet
During a daily visit with your 95-year-old grandmother (who is suffering from severe dementia and rheumatoid arthritis) you realize that half of the bottle of 100 aspirin tablets that you brought her yesterday are gone. She can’t recall what happen to the missing tablets. Worried that she may have taken an overdose of aspirin for her arthritis, you realize that she may have also fed them to her tropical fish (one of her quirky habits). Which of the following signs or symptoms would be most consistent with grandma having taken a drug overdose?
A. dead fish
B. fever
C. hypertension
D. shallow breathing
B. fever
(uncoupling effect)
A patient takes a drug that has analgesic and antipyretic effects, but is not antiinflammatory. It can cause potentially fatal hepatotoxicity when large doses (e.g. 15 grams) are consumed over a short time period, especially in alcoholic patients, or those with pre-existing liver disease. Which drug best fits this description?
A. acetaminophen
B. aspirin
C. colchicine
D. ibuprofen
E. methylprednisolone
A. acetaminophen
Cortisol is a naturally occurring glucocorticoid released by the adrenal gland in response to a wide variety of stressful events, including fear and other forms of psychological stress, vigorous exercise, acute trauma, surgery, or severe infection. The responses produced by cortisol can be divided into metabolic effects and anti-inflammatory effects that are mediated primarily by changes in gene expession. Which of the following is a metabolic effect produced by elevated levels of this hormone?
A. hyperglycemia
B. increased insulin sensitivity
C. reduced lipolysis
D. reduced muscle catabolism
A. hyperglycemia
Glucocorticoid-mediated suppression of the inflammatory response has important pharmacologic implications for the treatment of conditions such as organ transplantation, asthma, rheumatoid arthritis & other autoimmune disorders such as lupus. The anti-inflammatory effects of glucocorticoids are known to be mediated by multiple mechanisms. Which of the following is one such mechanism?
A. Decreased production of Annexin A1
B. Decreased release of cytokines by monocytes and macrophages
C. Increased COX-1 expression
D. Increased production of eicosanoids
E. Stimulation of phosopholipase A2
B. Decreased release of cytokines by monocytes and macrophages
(NOTE: annexin A1 is another name for lipocortin.)
Greg is a 14 year old patient who was started on a high dose of oral prednisone (40 mg qd) to control a severe asthma flair-up related to a severe head cold. After five weeks of prednisone therapy, his asthma symptoms begin to dissipate, and his pediatrician decides to change his medications from oral predisone to inhaled fluticasone to minimize the development of severe side effects. However, rather than abruptly switching Greg from one medication to another, his pediatrician decides to slowly taper the dose of oral prednisone (lowering its dose by 5 mg per week) over the next 2 months, while simultaneously initiating the use of inhaled fluticasone. What was the main reason why the pediatrician didn’t simply have Greg switch from one medication to the other, and have him stop taking prednisone “cold turkey”?
A. Because the onset of action of the inhaled drug is very slow
B. To allow the hypothalamic-pituitary axis time to regain full activity
C. To avoid a rebound of his asthma
D. To avoid causing a rebound surge in cortisol release by the adrenal gland
B. To allow the hypothalamic-pituitary axis time to regain full activity
Regina is a 56 year-old woman that has been on long term treatment for a chronic health condition. Her recent health check up indicated that compared to her baseline health status a few years ago, she has developed increased hypertension, hyperglycemia, and osteoporosis. Which of the following is MOST LIKELY responsible for causing her symptoms?
A. inhaled fluticasone for asthma
B. oral fludrocortisone for Addison’s disease
C. oral prednisone for SLE
D. hydrocortisone PO twice daily for Addison’s disease
C. oral prednisone for SLE
A 32 year old woman suffering from weight gain, hirsutism, fatigue, hypertension, diabetes and premature osteoporosis is found to have elevated plasma cortisol levels. To determine if her cortisol production is under pituitary control, you attempt to suppress pituitary ACTH production by administering a potent & long-acting synthetic glucocorticoid. Which glucocorticoid would you use for this purpose?
Dexamethasone
Patients who are on long-term therapy with glucocorticoids can experience a number of significant side effects. Most side effects are reversible when drug therapy is tapered to levels physiologically equivalent to normal corisol. Which effect, if it developed, would NOT be reversible?
A. avascular necrosis of femoral heads
B. fatigue & weakness
C. increased blood pressure
D. increased likelihood for infections
E. moon face appearance
A. avascular necrosis of femoral heads
Some drugs have multiple clinical indications that are unrelated because drugs can affect more than one type of receptor. One drug that fits this description is an antagonist of both progesterone and glucocorticoid steroid receptors. As a result it can be used for two completely different uses: 1) termination of pregnancy and 2) reducing hyperglycemia in patients with inoperable Cushing’s disease. The drug that fits this description is:
A. Fludocortisone
B. Methylpredisolone
C. Metyrapone
D. Mifepristone
E. Triamcinolone
D. Mifepristone
Normal physiological levels of circulating cortisol have a minimal effect on mineralocorticoid receptors expressed in the distal collecting duct of the kidney. If this were not the case, normal levels of cortisol would produce salt & water retention, leading to the development of hypertension. This insensitivity of cells in the collecting duct results from:
A. conversion of cortisol to cortisone by kidney cells
B. impermeability of kidney cells to cortisol
C. renal expression of a mineralocorticoid splice variant that is insensitive to cortisol
D. renal expression of a P-glycoprotein that effluxes cortisol
A. conversion of cortisol to cortisone by kidney cells
(kidney cells express 11-beta-hydroxysteroid dehydroxylase-2)
Rheumatoid arthritis is a relatively common autoimmune disease, with multiple treatment options. Which of the following is an example of a drug class that has been shown to halt or reverse the progression of this disease in most patients?
A. aspirin
B. azathioprine
C. everolimus
D. methotrexate
E. prednisone
D. methotrexate
a non-biologic Disease Modifying Anti-Rheumatic Drug (DMARD)
JQ is a professional 40 year old golfer who has developed a progressively more painful stiffness in her arms and legs over the past year that interferes with her ability to compete in golf tournaments. During her most recent medical checkup, her lab results reveal an elevated erythrocyte sedimentation rate (ESR), elevated CRP level and a high RF level. Xray imaging revealed the presence of bilateral erosion of several joints in her arms and legs. After being referred to a rheumatologist, she is prescribed methotrexate. Which of the following best describes the mechanism of action of this drug?
A. increases adenosine levels
B. inhibits dihydrofolate reductase
C. inhibits IL-6 signal transduction
D. small molecule kinase inhibitor
E. TNF-alpha receptor antagonist
A. increases adenosine levels
In a follow-up visit, a patient being treated for rheumatoid arthritis is still exhibiting significant signs and has not achieved her therapeutic goal. After some discussion about treatment options, adalimumab (s.c. every 2 weeks) is added to her treatment regimen. Major side effects with this class of medication include:
A. infections & malignancy
B. mucosal ulcers
C. osteoporosis
D. renal impairment
A. infections & malignancy
While TNF-alpha inhibitors are the most commonly used biologic DMARDs, an IL-6 receptor antagonist has also been found to be effective in treating arthritis. An example of this drug class is:
A. abatacept
B. ankinra
C. leflunomide
D. rituximab
E. tocilizumab
E. tocilizumab
Gout is a relatively common inflammatory condition affecting 4% of all adults, and has been estimated to account for ~4 million outpatient visits per year in the US. It is 3-4 times more common in men than women, and is typically observed in adults over 40 years of age. Which of the following variables is most closely associated with the development of this condition?
A. diet
B. endogenous metabolism of purines
C. kidney disease
D. TNF-alpha
B. endogenous metabolism of purines (2/3)
A. diet (1/3)
Mr Kingfish, a 67 year old man (5’4”, 280 lbs) complains of significant pain associated with the region immediately behind his left big toe. His toe appears red and swollen, consistent with podagra. When asked about his diet, he admits to eating shrimp several times a week, and drinking 3-4 beers with dinner most evenings. Recently he has been eating steak every other evening following a successful deer hunting trip. His blood tests indicate a moderately high level of uric acid (7 mg/dl). In addition to recommended weight loss and changes in diet, which of the following would be a treatment of first choice for Mr. Kingfish’s condition?
A. acetaminophen
B. allopurinol (high dose)
C. ibuprofen
D. methotrexate
E. pegloticase
C. ibuprofen
During a return visit several months later, Mr Kingfish states that the combination of NSAIDs, dietary restrictions and moderate weight loss have helped control his symptoms of gout. However taking ibuprofen has been causing him stomach pain, and he has been reluctant to take the higher doses needed to control his toe pain. What other anti-inflammatory drug could you recommend for acute therapy that doesn’t have similar side effects on the stomach?
A. allopurinol
B. colchicine
C. keterolac
D. methylprednisolone
B. colchicine
In a follow-up visit 6 months later Mr. Kingfish states that he is still having occassional flare-ups of podagra every few weeks, despite his best efforts at controlling his diet and losing 20 lbs. His recent lab tests indicate a serum urate level of 6.7 mg/dl (about the same as his lab values 6 months prior). What medication would you recommend that could reduce his rate of uric acid production, and consequently reduce his incidence of gout attacks?
A. allopurinol
B. etanercept
C. hydroxycholorquine
D. probenecid
A. allopurinol
Mr Kingfish’s gout continues to flare up occassionally, despite treatment, and his physician recommends that he try adding an additional “uricosuric” drug that can be taken along with his other medications for preventing gout flare-ups. This drug acts by inhibiting anionic transporters in the proximal tubule, which reduces the renal reabsorption of uric acid by by 30-40%. On the downside, it can also promote the formation of uric acid kidney stones in patients with high urinary uric acid levels, and is not very effective in patients with reduced renal function. Which drug best fits this description?
A. anakinra
B. azathioprine
C. colchicine
D. febuxostat
E. probenecid
E. probenecid
(inhibits URAT1)
