Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacotherapy I > Exam 4 Inflammation, NSAIDs, and DMARDS > Flashcards

Exam 4 Inflammation, NSAIDs, and DMARDS Flashcards

1
Q

Heat, redness, ___, pain, and loss of function are all characteristic of inflammation.

A

Swelling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Are TNF, IL-1, and chemokines all cytokines for acute or chronic inflammation?

A

Acute

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What cytokines are characteristic of chronic inflammation?

A

IFN-y (T cells) and IL-12 (macrophages)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What kind of cells start off the inflammation process?

A

Phagocytes, which consume offending agents and release inflammatory mediators

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What cells diffuse to the site of injury and aid with phagoyctosis, then produce signaling molecules that suppress inflammation that helps with tissue repair?

A

Leukocytes – WBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which molecules help with leukocyte adhesion to blood vessel walls–selectins or integrins?

A

Integrins help with adhesion; selectins help with loose attachment.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q 
For the following, say whether they are associated more with acute or chronic inflammation:
Exudation of fluid and plasma proteins
Fibrosis
Lymphocytes and macrophages
Neutrophils
A

Exudation and neutrophils are acute; fibrosis, lymphocytes, and macrophages are chronic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What two ways can leukocytes injure tissue in acute inflammation?

A

Lysosomal enzymes (elastase), ROS and nitrogen species

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How is arachidonic acid (eicosanoid precursor) produced?

A

It is cleaved from membrane phospholipids by phospholipase A2 (PLA2) (enzyme production suppressed by corticosteroids)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What effect does the eicosanoid PGE2 have on blood vessels, bronchi, and uterus?

A

Dilation for all three

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What effect does the eicosanoid PGF2a have on blood vessels, bronchi, and uterus?

A

Constriction of all three

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What effect does PGI2 have on blood vessels and platelets?

A

Dilates blood vessels; inhibits platelet aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What effect does TXA2 have on blood vessels and platelets?

A

Constricts blood vessels; promotes platelet aggregation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Arachidonic acid is oxygenated in four different pathways. Which enzyme pathway produces prostaglandins and thromboxanes?

A

The COX pathway

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Arachidonic acid is oxygenated in four different pathways. What does the lipoxygenase pathway produce?

A

Leukotrienes, lipoxins, HPETEs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

TXA2, PGI2, PGE2, and PGF2a are all produced from what molecule?

A

PGH2 (which is produced from PGG2 by hydroperoxidase)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What enzyme converts arachidonic acid to PGG2?

A

Cyclooxygenase (COX) or PGH synthase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What physiological functions is COX-1 responsible for?

A

Housekeeping functions in various tisses such as gastric cytoprotection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What tissues especially is COX-2 located in?

A

Inflammatory and immune cells–stimulated by growth factors, tumor promoters, and cytokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

In what tissue is PGH2 converted into TXA2, a potent vasoconstrictor and platelet aggregator?

A

Within the platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

In what tissues is PGI2 (vasodilator, platelet inhibitor) produced?

A

Healthy, undamaged vascular endothelia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

From LTA4, LTB4, LTC4 and LTD4 are produced which two are bronchoconstrictors and involved in anaphylaxis? (The one remaining is chemotactic)

A

LTC4 and LTD4 are bronchoconstrictors and anaphylactic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Which pathways of eicosanoid synthesis do corticosteroids block?

A

ALL, because they stimulate the synthesis of lipocortins, which inhibit PLA2, therefore decreasing the amount of arachidonic acid released.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Of prostaglandins, thromboxane, and leukotrienes, which two do NSAIDs inhibit through the COX pathway?

A

Prostaglandins and thromboxanes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Name one drug that inhibits the lipoxygenase pathway and one that antagonizes the leukotriene receptor

A

Zileuton blocks the lipoxygenase enzyme; montelukast and zafirlukast antagonize the receptor

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What eicosanoid drug relaxes smooth muscles and expands blood vessels, so is used for erectile dysfunction?

A

Alprostadil – synthetic PGE1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What cytoprotective eicosanoid drug prevents peptic ulcer and terminates early pregnancy in combination with mifepristone?

A

Misoprostol – a PGE1 derivative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What eicosanoid drug constricts blood vessels, is topically active, and is used to treat glaucoma?

A

Latanoprost – PGF2a prodrug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

What eicosanoid drug is a powerful vasodilator and inhibitor of platelet aggregation and is used to treat pulmonary arterial hypertension?

A

Prostacyclin (epoprostenol) – PGI2

Do NOT use with anticoagulants

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Which type of arthritis is caused by CD4+ T cells recognizing self antigens, activating phagocytes by TNF, IL-1, and IL-6, and formation of IgM autoantibodies that form immune complexes with IgG?

A

Rheumatoid arthritis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

What does DMARD stand for?

A

Disease-modifying anti-rheumatic drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How do prostaglandins induce fever?

A

Prostaglandin production in the hypothalamus increase the body’s temperature set point, so the hypothalamus caused increased heat production

33
Q

How do prostaglandins potentiate pain?

A

They produce hyperalgesia and potentiate the stimulation of nerve endings by histamine or bradykinin

34
Q

What three actions do NSAIDs have?

A

Anti-inflammation, anti-pyretic, analgesic

35
Q

What is the difference between aryl propionic and aryl acetic acids?

A

Aryl propionic acids have a methyl group off the alpha carbon that enhances activity and reduces side effects that aryl acetic acids lack.

36
Q

What three ways to NSAIDs cause GI side effects such as dyspepsia, N/V, ulcers, hemorrhage, and blood loss?

A
  1. Acidity hurts lining
  2. Inhibition of cytoprotective PGEs in mucosa
  3. Inhibition of platelet aggregation – increased bleeding tendency
    Take with food!
37
Q

What NSAID irreversibly inhibits COX enzymes?

A

Aspirin

38
Q

What major organ can be affected by NSAIDs?

A

The kidneys – renal failure, especially in pts with CV, hepatic, or renal diseases

39
Q

What patient population is much more likely to have a hypersensitivity to NSAIDS?

A

Asthma patients – more arachidonic acid available to become pro-bronchoconstriction leukotrienes

40
Q

What class of NSAIDS carries the risk of Reye’s syndrome?

A

The salicylates, including aspirin, salsalate and diflunisal.

41
Q

What symptoms are characteristic of Reye’s? What can we do to prevent this?

A

Vomiting, delirium, and coma in children who have had the flu or chicken pox. Do not give aspirin to anyone under the age of 12.

42
Q

What CNS effects can NSAIDs cause?

A

Tinnitus, dizziness, HA

43
Q

What drugs can we use to prevent GI side effects?

A

Misoprostol (PGE1 analog), proton pump inhibitors, combination products.

44
Q

What is a major mechanism of drug interaction with NSAIDs?

A

Competition for binding sites on serum albumin because NSAIDS are highly bound.
Ex: NSAIDs increase the plasma concentration of anticoagulants

45
Q

What is the NSAID originally discovered in willow and poplar bark that also suppresses COX 2 expression?

A

Salicylic acid

46
Q

True or false: Salicylic acid and acetylsalicylic acid (aspirin) have about the same potency.

A

False – ASA actually irreversibly inhibits COX and is 2x more potent

47
Q

What cardiovasular effect does aspirin have?

A

Increased risk of bleeding but reduced risk of MI and CVA

48
Q

What is salsalate?

A

A salicylic acid dimer that is hydrolyzed in the small intestine before absorption and does not cause GI bleeding.

49
Q

What salicylate is a more potent and longer-lasting analgesic than aspirin with fewer side effects and less antipyretic activity?

A

Diflunisal

50
Q

What two arylacetic acid NSAIDs are the most potent NSAIDs in use? Of these two, which one has a high incidence of side effects so is not suitable for long term use?

A

Indomethacin and diclofenac (which is also the most widely used in the world).
Indomethacin is not suitable for long-term use due to high SE profile.

51
Q

Which arylacetic acid is a prodrug that has less side effects and is good for long term use for chronic inflammation?

A

Sulindac

52
Q

Which arylacetic acid NSAID is somewhat selective for COX-2?

A

Diclofenac (also one of the most potent and widely-used NSAIDS in the world)

53
Q

What arylpropionic acid has analgesic activity similar to centrally-acting narcotics?

A

Ketorolac – great for short-term management of moderate-severe pain

54
Q

Of ibuprofen and naproxen, which is more potent and has a longer half-life? Which is sold as a racemic mixture?

A

Naproxen is more potent and longer-lasting. Ibuprofen is a racemic mixture (naproxen is pure S enantiomer)

55
Q

What non-carboxylate NSAID belongs to the oxicam class, only requires a single daily dose, is as potent as indomethacin, and is somewhat COX-2 selective?

A

Meloxicam

56
Q

What non-carboxylate NSAID is a prodrug with potent anti-inflammatory activity and minimum side effects but weak analgesic activity?

A

Nabumetone

57
Q

What are some consequences of COX-1 inhibition?

A

Stomach irritation and ulceration, blockade of platelet aggregation, inhibition of uterine motility, inhibition of some renal functions, hypersensitivity reactions

58
Q

How do selective COX-2 inhibitors increase the risk of heart attack and stroke?

A

They selectively reduce the production of PGI2 (prostacyclin) but do not alter TXA2. The imbalance leads to a heightened thrombotic response. They also elevate BP and accelerate atherogenesis.

59
Q

What is structurally different in COX-2 selective NSAIDs?

A

Larger and more rigid substituents that fit well into COX-2 but not into COX-1.

60
Q

Of our two selective COX-2 inhibitors, celecoxib and acetaminophen, which one all around more potent?

A

Celecoxib

61
Q

What is the odd mechanism of action for acetaminophen?

A

It scavenges peroxynitrite, which is required for COX (PGHS) activity. However, in inflammation, acetaminophen is overwhelmed by the amount of peroxynitrite present so it has minimal anti-inflammatory properties.

62
Q

In general, what is acetaminophen’s side effect like compared to aspirin?

A

Much better–lower GI SEs, well tolerated in coagulation disorders, no Teye’s, low hypersensitivity.
However, hepatotoxicity at high doses associated with overloading glutathione.

63
Q

What is the common mechanism for DMARDs?

A

Immunosuppression

64
Q

How does methotrexate suppress the immune system?

A

It looks like folic acid and inhibits two enzymes required for purine and pyrimidine synthesis, leading to a anti-proliferative, pro-apoptotic effect on inflammatory cells.
First line treatment! Predictable benefit.

65
Q

What side effects do we worry about with methotrexate? How can we improve these side effects?

A

GI, stomatitis, rash, alopecia, myelosuppression, hepatotoxicity, rare but serious pulmonary toxicity. Contraindicated in pregnancy.
Administer with folic acid.

66
Q

What prodrug DMARD inhibits pyrimidine synthesis (inhibits T cell proliferation) and undergoes extensive enterohepatic recirculation?

A

Leflunomide (Arava)

67
Q

What side effects are associated with leflunomide?

A

Hepatotoxicity, diarrhea, alopecia, rash. Monitor liver damage. Never in pregnant women.

68
Q

What DMARD inhibits protein secretion and can cause retinal toxicity?

A

Hydroxychloroquine

69
Q

What side effects are associated with hydroxychloroquine?

A

Generally well tolerated but monitor for retinal toxicity.

Use in combo with MTX, but reduces MTX clearance

70
Q

What DMARD prodrug, cleaved in the colon by bacteria, suppresses cytokine release from macrophages?

A

Sulfasalazine – in combo with MTX, monitor for myelosuppression

71
Q

What three biologic TNF blockers can we use for rheumatoid arthritis?

A

Infliximab (Remicade), adalimumab (Humira), and etanercept (Enbrel)

72
Q

Which of the three TNF blockers is human and given SC every 2 weeks?

A

Adalimumab (Humira) - antibody to TNFa (in combo with MTX)

73
Q

Which TNF blocker is chimeric and given every 8 weeks?

A

Infliximab (Remicade) - antibody to TNFa

74
Q

Which TNF blocker is a TNFa receptor/Fc antibody fragment chimera that competitively inhibits TNFa binding?

A

Etanercept (Enbrel) - use with MTX

75
Q

What DMARD is a recombinant version of human IL-1 receptor antagonist and cannot be combined with TNF blockers?

A

Anakinra (Kineret)

76
Q

How does rituximab work?

A

This humanized monoclonal antibody induces apoptosis of CD20+ cells (B cells), reducing antibody production and activation of T cells
+MTX
Risk of serious infection

77
Q

What DMARD inhibits co-stimulation of T cells by APCs?

A

Abatacept (Orencia) – fusion of CTLA-4 and Fc region of antibody binds CD80/86 on APCs

78
Q

What side effects do we worry about with abatacept?

A

Risk of serious infection and increased risk of lymphomas. Can be used with other DMARDS but NOT TNF-a blockers.

Pharmacotherapy I (15 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions