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MOHD3: Exam 2 > Anti-inflammatory Drugs (Quelle) > Flashcards

Anti-inflammatory Drugs (Quelle) Flashcards

1
Q

inflammatory cytokines released by phagocytes that provoke a fever response from the hypothalamus and activation of complement in the liver

A

IL-1 (hypothalamus)

IL-6 and TNF-alpha (liver)

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2
Q

cytokine that activates bystander neutrophils, causing them to produce proteases that increase tissue destruction

A

IL-6

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3
Q

activity of this type of cell and its secretion of cytokines is stimulated by T-cell cytokine release, antibody/antigen complexes and PAMPs

A

macrophage

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4
Q

in addition to secreting cytokines, fibroblasts, endothelial, and epithelial cells secrete these chemical attractants to draw nearby responsive cells to the site of infection

A

chemokines

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5
Q

drugs which commonly target the cytokines that promote/amplify inflammatory activity

A

disease-modifying antirheumatic drugs (DMARDs)

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6
Q

Which of the following is NOT a characteristic associated with Infliximab?

A. Increases risk of respiratory and urinary infections
B. Must be administered parenterally
C. Is a humanized antibody that prevents TNF-alpha association with its receptor
D. Works best when administered on its own
E. Is used to treat RA and Chron’s disease

A

D.
On the contrary, infliximab is usually administered with methotrexate for the treatment of RA and with azathioprine in the treatment of Chron’s disease.

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7
Q

TNF-alpha antibody whose mechanism, usage and complications are similar to infliximab

A

adalimumab

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8
Q

TNF-alpha antibody that has long lasting effects, because it is a fusion protein, containing the ligand binding domain of the TNF-alpha receptor and the Fc domain of human IgG

A

etanercept

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9
Q

competitive IL-1 receptor antagonist with a short half life that must be administered via daily injection; useful in treating RA but increases risk of infection

A

anakinra

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10
Q

more than 60 known cytokines utilize this receptor signaling complex, which plays an important role in stimulating the adaptive immune response

A

JAK/STAT signaling complex

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11
Q

the two cytokines discussed that do NOT use the JAK/STAT signaling pathway

A

IL-1 and TNF-alpha

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12
Q

Which of these is NOT a characteristic of the JAK kinase inhibitor Tofacitinib?

A. It’s the second line therapy for those failing on methotrexate therapy
B. It inhibits all cytokines required for adaptive immune response
C. It’s only approved use is currently Chron’s disease, though indication is likely to expand
D. adverse effects include neutropenia, myelosuppression and increased risk herpes zoster
E. long-term safety is currently unknown

A

C.

Currently, the only approved use for tofacitinib is rheumatoid arthritis (RA) though there are other JAK kinase inhibitors in development and clinical trials, and their use is likely to expand beyond this.

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13
Q

lipid mediators of inflammation are produced and released from leukocytes in response to signals that activate what enzyme?

A

phospholipase A2 (PLA2)

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14
Q

what important physiologic role does activated PLA2 have?

A

it hydrolyzes phosphotidylcholine in the plasma membrane to free arachidonic acid (AA), and then AA is used for the synthesis of lipid mediators

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15
Q

name the 2 types of lipid mediators discussed in class, the enzymes that produce them, and the drugs that inhibit their production

A

prostaglandins - produced by cyclooxygenase - inhibited by NSAIDs

leukotrienes - produced by lipoxygenase - inhibited by zileuton

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16
Q

STORED mediators are released in response to signals that activate this enzyme

A

phospholipase C (PLC)

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17
Q

what important physiologic role does activated PLC have?

A

PLC activates signaling pathways that increase intracellular Ca2+ mobilization and promote degranulation of lipid storing vesicles

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18
Q

what 2 drugs (mechanism unknown) inhibit the PLC pathway and degranulation of lipid storing vesicles?

A

cromolyn and nedocromil

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19
Q

glucocorticoids increase the expression of this protein, which inhibits phospholipase A2 (PLA2)

A

annexin (lipocortin)

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20
Q

Which of these is NOT a mechanism by which glucocorticoids exert their effect?

A. reduced production of inflammatory cytokines
B. reduced production of B cell antibodies
C. decreased synthesis of lipid mediators
D. increased expression of annexin
E. direct blocking of cyclooxygenase

A

E.

glucocorticoids do not act directly on cyclooxygenase, as NSAIDs do, but act further up the chain to decrease the synthesis of arachidonic acid, which cyclooxygenase uses as a substrate for prostaglandin synthesis. They also work at a transcriptional level to decrease the synthesis of enzymes needed for prostaglandin production (e.g., COX, PLA2 and NO synthase).

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21
Q

histamine intolerance results from deficiency or reduced activity of what enzyme?

A

diamine oxidase

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22
Q

what is the enzyme that converts histidine to histamine?

A

histidine decarboxylase

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23
Q

what are the main sites of production of histamine, and what function does it serve in these two locations?

A
  1. tissues. particularly those with a higher chance of injury (e.g., mouth, nose, hands/feet, blood vessels at bifurcations, GI mucosa). histamine is released from mast cells in response to IgE, and increases the permeability of the capillaries to allow leukocytes better access to pathogens in infected tissues.
  2. central nervous system. acts as neurotransmitter, released from neurons in the hypothalamus. main purpose is to promote wakefulness.
24
Q

Which of these histamine receptors is NOT matched with its corresponding site of action?

A. H1 - Smooth/cardiac muscle
B. H2 - Gastric parietal cells
C. H3 - Mast cells
D. H4 - CD4 T cells

A

C.

H3 receptors are found on pre-synaptic terminals in the CNS.

Additionally:
H1 - found on smooth/cardiac muscle, endothelium, sensory nerve terminals, post-synaptic CNS
H2 - found on gastric parietal cells, mast cells, cardiac muscle, post-synaptic CNS
H4 - found on CD4 T cells, eosinophils and neutrophils

25
Q

Which histamine receptor is not found in the CNS?

A

only H4

26
Q

Histamine is mostly a muscle constrictor, but in smooth muscle it promotes relaxation and vasodilation. Why is this?

A

this is due to the secondary effect of histamine induced NO release

27
Q

what is the effect of histamine on endothelium?

A

induces muscle contraction and separation of endothelial cells –> edema

28
Q

how does epinephrine work to combat anaphylaxis?

A

antagonizes the effect of histamine - causes dilation of the airways to aid breathing and constriction of vessels, raising blood pressure

29
Q

topically absorbed drug that is used prophylactically to treat asthma by inhibiting degranulation of mast cells

A

cromolyn (or nedocromil)

30
Q

class of drugs that act as inverse agonists, reducing basal level of activity at the receptors they bind and blocking response

A

H1 antagonists

31
Q

this class of drugs are first line choice for allergic rhinitis and uticaria, though their clinical effectiveness varies by individual and may diminish with continued use

A

H1 antagonists

32
Q

name 3 H1 blockers that are 1st generation antihistamines that also have anticholinergic effects, and are useful in the treatment of motion sickness

A

promethazine
cyclizine
diphenhydramine (dimenhydrinate is a salt of this)

33
Q

Which of these is NOT an adverse effect associated with H1 antagonists?

A. Sedation
B. Dry mouth
C. Bradycardia
D. Orthostatic hypotension
E. Increased appetite
F. Block sodium channels
A

C.

H1 antagonists have many anticholinergic effects, including dry mouth, urinary retention, and tachycardia .

34
Q

these 2nd generation antihistamines have a high selectivity for H1 but penetrate poorly in the CNS, reducing their sedative effect (name 3)

A

loratadine
cetirizine
fexofenadine

35
Q

20-carbon fatty acid that is a common precursor in the prostanoid and leukotriene synthesis pathways

A

arachidonic acid (AA)

36
Q

Which of these is NOT a characteristic of prostanoids?

A. They are stored in vesicles for quick release in response to inflammatory cytokine signaling
B. Prostanoid membranes are permeable, facilitating their passive release from cells
C. They have both paracrine and autocrine function
D. Thrombaxanes are synthesized in platelets while PGI2 is made in vascular smooth muscle
E. Only TXA2 has a vasoconstriction effect on blood vessels

A

A.

Because prostanoids have short half lives (30 seconds - 3 minutes) and are not stored, their activity is synthesis-dependent.

37
Q

Which of these statements regarding the inflammatory effects of prostanoids is false?

A. PGE2 and PGI2 both signal through the Gs receptor and have a dilation/relaxation effect on vessels and muscles
B. PGE2 has no effect on platelet aggregation
C. Thrombaxanes have a vasoconstrictive effect
D. PGI2 inhibits platelet aggregation while PGE2 has no effect
E. Thromboxanes and PGI2 tend to raise core body temperature.

A

E.

Thrombaxanes and PGI2 have no effect on the hypothalamus and the raising of core temperature

38
Q

______ is constitutively expressed in most tissues of the body (not RBCs) and uses arachidonic acid almost exclusively as its substrate.

A

COX-1

39
Q

_____ is highly inducible by cytokines and LPS at sites of inflammation and is present in all cells except RBCs and platelets

A

COX-2

40
Q

elevated prostaglandin production associated with inflammation is mostly due to the activity of COX-1 or COX-2?

A

COX-2

41
Q

Which of these is NOT a characteristic of NSAIDs?

A. Analgesic
B. Reduces platelet aggregation (aspirin)
C. First line choice for severe inflammation
D. Effective pain reliever for rheumatoid arthritis and osteoarthritis
E. Antipyretic

A

C.

Though NSAIDs may have an anti-inflammatory effect on mild to moderate inflammation, they are not known for this and are certainly not a first line choice.

42
Q

Biochemically, what makes aspirin different from other NSAIDs?

A

it is a mixed COX1/2 inhibitor with an active acetyl group, and irreversibly inhibits COX-1 and COX-2

43
Q

name 3 mixed COX1/2 inhibitors. what is their primary target?

A

Naproxen (Rx anti-inflammatory), Ibuprofen (analgesic/antipyretic), Aspirin (CV prophylaxis)

Primary target: COX2

44
Q

why should aspirin, for CV prophylaxis, be taken either before administration of other NSAIDs or after they’ve been cleared?

A

because other NSAIDs antagonize the irreversible anti-platelet activity of aspirin

45
Q

what drug can be given to protect against the GI epithelium lysis that may occur with long term use of COX-1 inhibitors?

A

misoprostol (PGE2 analog that promotes mucus formation and decreases acid production)

46
Q

what sort of kidney problems can long term use of COX inhibitors cause?

A

they vasoconstrict the renal vessels, leading to edema, hypertension and eventual kidney failure

47
Q

why are NSAIDs used in the prevention of preterm labor or dysmenorrhea (menstrual cramps)?

A

because they interfere with the production of PGE2, which increases contractility in the uterine muscles

48
Q

hypersensitivity to aspirin is knowns as ______ and is characterized by hyperventilation, tinnitus, vertigo, emesis and sweating

A

salicylism

49
Q

syndrome in children caused by the use of aspirin or other salicylates, and is characterized by acute encephalopathy, viral disease, and fatty liver degeneration

A

Reye’s syndrome

50
Q

this drug has analgesic and anipyretic effects similar to aspirin but its activity is substantially reduced in the presence of peroxides (e.g, in inflammatory environments)

A

acetaminophen

51
Q

what is the major adverse effect of acetaminophen overdose?

A

hepatoxicity

52
Q

what is the main disadvantage of COX-2 specific inhibitors over non-selective NSAIDs?

A

they are associated with higher incidences of cardiovascular events - most have been removed from market

53
Q

this drug is a COX2 inhibitor used for the treatment of rheumatoid arthritis

A

celecoxib (also Parecoxib only in Europe - other COX2 inhibitors have been pulled from the market due to increased incidence of CV events)

54
Q

All NSAIDs, except ____, appear to be associated with an increased risk of all cause mortality. By what mechanism is this thought to occur?

A

ASA - aspirin. Thought to occur by the loss of COX2 inhibition of platelet aggregation, leading to CV events like MI and stroke

(Naproxen appears to maybe have a safer profile)

55
Q

5-10% of asthmatics exhibit severe sensitivity to Aspirin and other NSAIDs. Why is this thought to occur?

A

thought to occur from the sudden shift of arachidnoic acid metabolism from prostaglandin to leukotriene synthesis

56
Q

Which of these statements regarding leukotrienes is FALSE?

A. LTD4 produced by mast cells is a primary mediator of bronchical constriction in asthmatic airways
B. LTB4 is chemotactic for eosinophils, while LTD4 attracts neutrophils
C. Zileuton inibits leukotriene synthesis and is used in asthma therapy
D. Zafirlukast and Montelukast are receptor antagonists that are generally well-tolerated in asthma treatment
E. Zileuton is associated with liver toxicity and inhibition of cytochrome p450, decreasing the metabolism of other drugs

A

B. The opposite is true.

MOHD3: Exam 2 (22 decks)

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