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First Aid 2014 > MSK: 439 - 441 > Flashcards

MSK: 439 - 441 Flashcards

1
Q

What pathway produces leukotrienes?

A

Lipooxygenase

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2
Q

How is arachidonic acid formed?

A

From membrane lipids (e.g. phosphatidylinositol) via the action of phospholipase A2

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3
Q

What class of drugs inhibits phospholipase A2?

A

Corticosteroids

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4
Q

What are the 2 pathways that arachidonic acid can take?

A
  1. Lipoxygenase

2. Cyclooxygenase

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5
Q

What drug inhibits lipoxygenase?

A

Zileuton

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6
Q

What is the intermediate between arachidonic acid and leukotrienes?

A

Hydroperoxides (HPETEs)

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7
Q

What are the four leukotrienes produced in the lipoxygenase pathway?

A

LTB4, LTC4, LTD4, LTE4

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8
Q

Differentiate LTB4, C4, D4, E4 by their effects.

A

LTB4 - neutrophil chemotaxis

LTC4, LTD4, LTE4 - bronchoconstriction, vasoconstriction, contraction of smooth muscle, increased vascular permeability

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9
Q

What do zafirlukast and montelukast inhibit?

A

LTC4, LTD4, LTE4

Remember they are asthma drugs so it makes sense that you would want to inhibit the leukotrienes that are increasing bronchial tone

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10
Q

How many cyclooxygenases are there?

A

COX-1, COX-2

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11
Q

What are the three things produced in the cyclooxygenase pathway?

A
  1. Prostacyclin (PGI2)
  2. Prostaglandins (PGE2, PGF2)
  3. Thromboxane (TXA2)
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12
Q

What is the intermediate between arachidonic acid and the ultimate products of the cyclooxygenase pathway?

A

Endoperoxides (PGG2, PGH2)

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13
Q

Which drugs inhibit cyclooxygenase?

A
  1. NSAIDs
  2. Aspirin
  3. Acetaminophen
  4. COX-2 inhibitors
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14
Q

What are the effects of prostacyclin?

A

Decreased:

  1. Platelet aggregation
  2. Vascular tone
  3. Bronchial tone
  4. Uterine tone
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15
Q

What are the effects of prostaglandins?

A
  1. Increased uterine tone

2. Decreased bronchial tone

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16
Q

What are the effects of thromboxane?

A

Increased:

  1. Platelet aggregation
  2. Vascular tone
  3. Bronchial tone
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17
Q

Is aspirin a selective or non-selective COX inhibitor?

A

Non-selective; inhibits both 1 and 2

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18
Q

How does aspirin inhibit COX?

A

Covalent acetylation

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19
Q

How does aspirin affect bleeding time, PT, and PTT?

A

Increased bleeding time until new platelets are produced (around 7 days)

No effect on PT, PTT

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20
Q

What category of drug does aspirin fall in?

21
Q

What are the three clinical uses for aspirin and their doses?

A

Low dose (< 300 mg/day): decrease platelet aggregation

Intermediate dose (300 - 2400 mg/day): antipyretic and analgesic

High dose (2400 - 4000 mg/day): anti-inflammatory

22
Q

What are the two main side effects of aspirin use?

A
  1. Gastric ulceration

2. Tinnitus (CN VIII)

23
Q

What can chronic use of aspirin lead to (toxicities)?

A
  1. Acute renal failure
  2. Interstitial nephritis
  3. Upper GI bleeding
24
Q

When would you worry about Reye syndrome with aspirin?

A

In children treated with aspirin for viral infection

25
How can aspirin affect acid-base balance?
Can stimulate respiratory center and cause hyperventilation leading to a respiratory alkalosis
26
Name 5 NSAIDs that are not aspirin.
1. Ibuprofen 2. Naproxen 3. Indomethacin 4. Ketorolac 5. Diclofenac
27
Are NSAIDs selective or non-selective COX inhibitors?
Non-selective
28
What are the three clinical uses for NSAIDs?
1. Antipyretic 2. Analgesic 3. Anti-inflammatory
29
What can we use indomethacin for?
Close a PDA
30
What are 3 toxicities of NSAIDs?
1. Interstitial nephritis 2. Gastric ulcer 3. Renal ischemia
31
Why are gastric ulcers a potential toxicity for NSAIDs?
NSAIDs inhibit the production of prostaglandins which normally protect the gastric mucosa
32
Why is renal ischemia a potential toxicity for NSAIDs?
NSAIDs inhibit the production of prostaglandins which normally vasodilate the afferent arteriole
33
What is celecoxib?
Selective COX-2 inhibitor
34
Where do we find COX-2?
Inflammatory cells and vascular endothelium
35
What functions does celecoxib target/spare?
Targets functions of COX 2 - inflammation and pain Spares functions of COX 1 - maintenance of gastric mucosa, platelet function
36
Why is platelet function spared by celecoxib?
TXA2 production depends on COX 1
37
What are 3 clinical indications for celecoxib?
1. Rheumatoid arthritis 2. Osteoarthritis 3. Patients with gastritis or ulcers
38
What are the 2 major toxicities of celecoxib?
1. Increased risk of thrombosis | 2. Sulfa allergy
39
For aspirin, NSAIDs, celecoxib, acetaminophen, which are reversible inhibitors and which are irreversible?
Aspirin - irreversible NSAIDs, celecoxib, acetaminophen - reversible
40
Where does acetaminophen act?
Mostly in CNS; inactivated peripherally
41
What are the 2 clinical uses for acetaminophen?
1. Antipyretic 2. Analgesic NOT anti-inflammatory
42
When would you preferentially use acetaminophen over aspirin?
Children with viral infection - to avoid Reye syndrome
43
What does an overdose of acetaminophen cause and why?
Hepatic necrosis - acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue adducts in the liver
44
What is the antidote for acetaminophen overdose?
N-acetylcysteine (regenerates glutathione)
45
What are bisphosphonates?
Pyrophosphate analogs that bind hydroxyapatite in bone and inhibit osteoclast activity
46
Give an example of a bisphophonate.
Alendronate (+ other -dronates)
47
What are 3 clinical indications for bisphosphonates?
1. Osteoporosis 2. Hypercalcemia 3. Paget disease of bone
48
What are 2 toxicities of bisphosphonates?
1. Corrosive esophagitis | 2. Osteonecrosis of the jaw
49
How do you prevent corrosive esophagitis as a bisphosphonate toxicity?
Patients are advised to take the medication with water and to remain upright for 30 minutes

First Aid 2014 (24 decks)

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