Brainscape's Knowledge GenomeTM

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


See full index

Foundations Exam 2 > Pharmacology of Inflammation > Flashcards

Pharmacology of Inflammation Flashcards

1
Q

function of bradykinin

A

vasodilation, increase permeability of blood vessels, lower blood pressure, stimulate pain receptors

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

_____ are released by macrophages and mast cells in injured tissue regions to enhance the action of bradykinin

A

prostaglandins (PGE2)

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

prostaglandins:
1. derived from _______
2. belong to _____ family
3. [short/long] lived
4. [systemic/local] acting

A
  1. derived from ARACHIDONIC ACID (a fatty acid)
  2. belong to EICOSANOID family (including prostaglandins, thromboxanes, leukotrienes)
  3. short lived (action is seconds to minutes)
  4. locally acting
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

prostaglandins, thromboxanes, and leukotrienes belong to the _______ family

A

eicosanoid family - 20C atom molecules

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

collectively, prostaglandins and thromboxanes are known as _______

A

prostanoids (because they are structurally similar)

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

describe the effects of the following prostanoids:
a. PGE2
b. PGI2 (prostacyclin)
c. TXA2 (thromboxane)

A

a. PGE2: gastric mucus secretion, inflammation

b. PGI2 (prostacyclin): gastric mucus secretion, inhibits blood clotting, promotes vasodilation

c. TXA2 (thromboxane): promotes platelet aggregation (clotting) and vasoconstriction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

which prostanoids promote gastric mucus secretion in the stomach?

A

PGE2 and PGI2 (prostacyclin)

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

which 2 prostanoids counterbalance each other to maintain cardiovascular homeostasis?

A

PGI2: inhibits platelet aggregation (clotting), promotes vasodilation

TXA2 (thromboxane): promotes platelet aggregation (clotting), vasoconstriction

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

the main prostanoid involved in inflammation is _____

what effects does it have? (5)

A

prostaglandin E2 (PGE2):
- vasodilation
- increase vascular permeability
- increased sensitivity of pain receptors to bradykinin
- pain neuromodulation in dorsal horn of spinal cord
- pyresis (fever)

appears at site of injury

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

mast cells and macrophages produce large amounts of PGE2 via what process? (name the enzyme)

A

catalysis of arachidonic acid by the enzyme Cyclo-OXygenase 2 (COX-2)

arachidonic acid -(COX2)-> PGE2

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

COX-1 vs COX-2

A

COX-1: produced constitutively in most cells; catalyzes arachidonic acid to biosynthesize “housekeeping” prostaglandins

COX-2: expression induced by inflammation (mast cells, macrophages) —> catalyzes arachidonic acid catalysis to PGE2

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

describe the steps and players of general prostaglandin synthesis (distinct from inflammatory prostaglandin synthesis)

A
  1. phospholipid in cell membrane converted to arachidonic acid via phospholipase A2
  2. arachidonic acid (omega 6 FA) converted to PGH2 via COX
  3. PGH2 converted to prostaglandins via prostaglandin synthases
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

describe the steps and players of inflammatory prostaglandin synthesis

A
  1. membrane phospholipid converted to arachidonic acid via phospholipase A2
  2. arachidonic acid (omega-6 FA) converted to prostaglandin H via COX-2
  3. prostaglandin H converted to prostaglandin PGE2 via PGE synthase

PGE2 produced at the site of injury

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

where do the processes for general vs inflammatory prostaglandin synthesis diverge

A

in general prostaglandin synthesis, arachidonic acid converted to PGH2 (via COX), which is then converted to prostaglandins

in inflammatory prostaglandin synthesis, arachidonic acid converted to prostaglandin H (via COX-2), which is then converted to prostaglandin PGE2 at the site of injury

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

NSAIDs reduce the production of ____

A

non-steroidal anti-inflammatory drugs

reduce production of PGE2 (inflammatory) via inhibiting COX-2

effects:
- reduce edema
- reduce bradykinin-induced pain
- reduce allodynia (skin tenderness)
- anti-pyretic (fever)

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

name 4 standard OTC NSAIDs

A
  1. aspirin (Bayer)
  2. ibuprofen (Advil)
  3. naproxen (Motrin, Aleve)
  4. diclofenac (Voltaren)

*non-steroidal

17
Q

Bayer, an OTC NSAID, is generically known as

A

aspirin

18
Q

Advil, an OTC NSAID, is generically known as

A

ibuprofen

19
Q

Motrin and Aleve, both OTC NSAIDs, are generically known as

A

naproxen

20
Q

describe what causes the side effects of NSAIDs

A

NSAIDs inhibit COX-2 to reduce PGE2 prostaglandin levels

COX-2 is similar in structure to COX-1

so non-inflammatory “housekeeping” prostaglandins produced by COX-1 are reduced…

such as PGE2 and PGI2 that are in the stomach to induce mucus secretion —> GI discomfort, bleeding caused by gastric acid

21
Q

NSAIDs are contraindicated for which patients?

A

those with peptic ulcers, aspirin hypersensitivity, coagulation defects, congestive heart failure, others

remember that NSAIDs inhibit COX-2 (inflammatory), which is structurally similar to COX-1 (housekeeping),

so side effects develop from COX-1 inhibition —> GI discomfort, stomach bleeding (PGE2 and PGI2 in the stomach promote mucus secretion)

22
Q

NSAIDs may induce asthma attacks

explain this phenomenon

A

after phospholipids are converted to arachidonic acid, 5-lipoxygenase may convert arachidonic acid to

5-HPETE, which becomes leukotrienes

this pathway is associated with inflammatory/immune response, allergic reactions, anaphylactic shock

*this happens in people taking too many NSAIDs - pathway is shunted

23
Q

what follows if 5-lipoxygenase acts on arachiodnic acid rather than COX-1 or COX-2

A

arachidonic acid -(5-lipoxygenase)-> 5-HPETE —> leukotrienes

—> inflammatory/immune response, allergic reactions, anaphylactic shock

NSAIDs may induce asthma attacks (if someone is taking way too many of them)

24
Q

how does aspirin (acetylsalicylic acid) work, and what is it used for?

A

aspirin covalently (irreversibly) binds COX-1 and COX-2 and inhibits TXA2 (thromboxane A2) production in platelets

used as anti-platelet anticoagulant drug (patients with coronary artery disease/CAD at risk of thrombosis)

lower doses (81-100mg) can be used to avoid GI problems

*do not prescribe to children because of Reye syndrome (brain swelling, liver damage)

25
Q

celecoxib (Celebrex) is the only _____ still available in the US

A

selective COX-2 inhibitor - does not disturb housekeeping prostaglandins, so stomach bleeding/GI issues is not a side effect… however…

*selective COX-2 inhibition enhances cardiovascular risk —> due to imbalance of TXA2 over PGI2

(celeCOXib is selective for COX-2)

26
Q

why are selective COX-2 inhibitors associated with cardiovascular risk?

A

leads to imbalance of thromboxane (TXA2 - promotes clotting/ vasoconstrictor) over PGI2 (inhibits clotting, vasodilator) —> increased risk of thrombosis

PGI2 and TXA2 counterbalance to maintain cardiovascular homeostasis

(remember that selective COX-2 inhibitors will reduce PGI2 production)

27
Q

why is aspirin used to prevent myocardial infarction and stroke?

A

aspirin covalently (irreversibly) binds COX-1 and COX-2, and inhibits thromboxane (TXA2) production in platelets

platelets lack a nucleus, so biosynthesis of TXA2 requires new platelet cells, which takes longer

so overall effect is slight excess of PGI2 (anti-coagulation, vasodilation) over TXA2 (coagulation, vasoconstriction)

28
Q

what does acetaminophen (paracetamol or APAP) do, and what does it specifically not do?

A

acetaminophen: anti-pyretic (reduces prostaglandin synthesis in hypothalamus), analgesic

NOT anti-inflammatory/NSAID

*short term uses has few side effects but therapeutic window is narrow

29
Q

the most common cause of acute liver failure

what is the antidote

A

acetaminophen (paracetamol or APAP) toxicity

toxic metabolite NAPQI accumulates in liver

antidote: N-Acetylcysteine (NAC) administered IV —> increases glutathione antioxidant in liver

30
Q

what enzyme is responsible for producing the minor yet toxic metabolite of acetaminophen (paracetamol or APAP)? what metabolite does it produce?

A

p450 (induced in alcoholics) —> produces NAPQI (toxic)

(remember that the antidote for acetaminophen toxicity is NAC, which induces glutathione - this metabolizes NAPQI to non-toxic molecules)

31
Q

what is the max recommended dose per day of acetaminophen and minimum toxic single dose in healthy adults

A

max dose per day: 4g (8 500mg tablets)

min toxic single dose: 7.5-10g (15-20 500mg tablets)

*severe liver injury in alcoholics reported to have take <4g

32
Q

what is the effect of synthetic glucocorticoids such as hydrocortisone, prednisolone, prednisone, dexamethasone, and betamethasone?

A

mimic action of cortisol and other endogenous glucocorticoids
steroidal anti-inflammatory drugs

—> anti-inflammatory (powerful): downregulate COX-2 production (and thereby PGE2)

—> immunosuppressive: reduced histamine production, inhibit mast cells (for treating autoimmunity and cytokine storm, but risk of infection)

33
Q

glucocorticoid therapy is indicated for disorders with a ______ component

A

inflammatory component

ex: allergy reactions, asthma, inflammatory bowel syndrome, SLE, arthritis, bursitis, cerebral edema, atopic dermatitis

minimal effective doses preferred - can have serious metabolic complications

34
Q

describe the potentially serious metabolic complications of glucocorticoid therapy

A

carbohydrates: stimulate gluconeogenesis and inhibit glucose uptake by cells —> hyperglycemia, weight gain, diabetes

lipids: stimulate lipolysis —> fat redistribution to face/back of neck

proteins: reduce protein synthesis —> muscle wasting, osteoporosis

Foundations Exam 2 (42 decks)

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