Basic Pharmacology Deck 3

Question 1

What metabolic pathway to corticosteroids block?

Answer 1

cleaving of membrane phospholipid to arachidonic acid

Question 2

What product of the Eicosanoid pathway is produced in platelets?

Answer 2

TXA2, which is prothrombotic. (arachidonic acid first converted to prostaglandin precursor by COX)

Question 3

What product of the Eicosanoid pathway is produced in endothelial cells?

Answer 3

PGI2, which is antithrombotic (arachidonic acid first converted to prostaglandin precursor by COX)

Question 4

What is dexamethazone and what does it do?

Answer 4

anti-inflammatory that blocks COX-2.

Question 5

What is PGE2, and what does it do?

Answer 5

most common prostaglandin product, plays a critical role in fever production and neuropathic pain. (mPGES1 is a potentially good enzyme target for therapy).

Question 6

What is LTA4, and what does it do?

Answer 6

Important product of arachidonic acid (5-lipoxygenase product) that plays a critical role in neutrophil function.

Question 7

What is LTC4 and LTD4 and what do they do?

Answer 7

Important product of arachidonic acid (lipoxygenase product) play a prominent role in asthma and allergic responses, direct effect on vasculature.

Question 8

What is LTB4, and what does it do?

Answer 8

Important product of arachidonic acid (lipoxygenase product) that plays a critical role in neutrophil chemotaxis (released by neutrophils, recruits more neutrophils to cite of inflammation), contributes to edema.

Question 9

What are PGE2 effects on the gastric mucosa?

Answer 9

1) inhibits acid secretion
2) increases mucus secretion
3) increases perfusion.

Question 10

What is the primary target of non-steroidal anti-inflammatory drugs?

Answer 10

cyclooxygenase.

Question 11

What are the major toxicities of NSAIDs?

Answer 11

1) GI bleeding
2) renal toxicity
3) aspirin sensitivity (allergy-like response)

Question 12

What is celecoxib, and what is its effect?

Answer 12

brand name = celebrex, COX-2 inhibitor. Because it does not block COX-1, decreases GI toxicity associated with nonspecific COX inhibitors.

Question 13

What is rofecoxib, and what is its effect?

Answer 13

brand name = Viox, COX-2 inhibitor. Because it does not block COX-1, decreases GI toxicity associated with nonspecific COX inhibitors. Pulled from the market because of thrombotic effects.

Question 14

What is misoprostol and what is its effect?

Answer 14

EP agonist, the receptor which triggers COX-1 in the gut. Given with nonspecific COX-inhibitor this medication reduces GI toxicity. Because it is non-selective EP agonist, can cause cramping and diarrhea. Useful therapy for some people.

Question 15

What is role of prostaglandin role in kidney?

Answer 15

Causes vasodilation in response to low blood flow. Inhibition in prostaglandins in elderly can cause renal failure.

Question 16

What is low-dose aspirin a useful treatment to prevent MI?

Answer 16

irreversibly inhibits COX enzymes, particularly in blood, so prevents production of thromboxane from platelets. Endothelial cells respond to COX inhibition by synthesizing new COX very quickly, while new COX in platelets only materializes with new platelets (takes 14 days).

Question 17

Why do COX-2 inhibitors increase risk of thrombosis vs nonspecific COX inhibitors?

Answer 17

COX-2 decreases PG but does not decrease thromboxane, so balance gets shifted towards pro-thrombotic agent. non-specific COX inhibitors knock down both PG and TXA, so no thrombosis and no inflammation (but GI issues from low PG).

Question 18

What are the three muscarinic agonist drugs we need to know and what are their targets?

Answer 18

1) Bethanechol - increases tone in GI and bladder.
2) Muscarine - treatment for glaucoma (maybe).
3) pilocarpine - treatment for dry mouth, glaucoma.

Question 19

What are the two anti cholinesterase drugs we need to know and what are their targets?

Answer 19

1) physostigmine - used for atropine overdoes.

2) neostigmine - increase tone in GI, bladder and used to increase transmission at NMJ in myasthenia graves.

Question 20

What are the two muscarinic antagonists we need to know and what are their targets?

Answer 20

1) atropine - used to treat bradycardia, anti cholinesterase overdose.
2) scopolamine - used to treat motion sickness

Question 21

What happens if you block all autonomic nervous system functioning in the following systems (block nicotinic receptors in the ganglia:

1) arterioles / veins
2) sweat glands
3) heart
4) iris?

Answer 21

1) vasodilation / hypotension
2) anhidrosis (no sweating)
3) tachycardia
4) pupils dilate

Question 22

What happens if you block all autonomic nervous system functioning in the following systems (block nicotinic receptors in the ganglia:

1) salivary glands
2) bladder
3) GI tract

Answer 22

1) dry mouth
2) urine retention
3) constipation, reduced tone

Question 23

What Arachidonic acid derivative is a potent vasodilator and induces hypotension?

Answer 23

PGI2

Question 24

What arachidonic acid derivative is a potent vasoconstrictor?

Answer 24

TXA2, LTC4, LTD4 (LTs particularly in the coronary and pulmonary circulations)

Question 25

What arachidonic acid derivative induces plasma leakage, playing an important role in edema formation?

Answer 25

LTC4, LTD4, LTB4 (vasoconstrictive properties of LTC4 and LTD4 can overcome leakage effect)

Question 26

Why does cyclooxygenase inhibition increase risk of renal failure in patients with compromised renal function?

Answer 26

prostaglandins dilate renal blood vessels, counteracting vasoconstrictive effects of angiotensin II. W/o PG, decreased blood flow can lead to renal failure.

Question 27

Who do some COX inhibitors cause gastric ulcers?

Answer 27

PGs are necessary to inhibit gastric acid formation and increase gastric blood flow, which protects gastric mucosa.

Question 28

How do NSAIDs cause analgesic effect?

Answer 28

PGE2, PGI2 and LTB4 lower threshold of nociceptors, causing hyperalgesia.

Question 29

What is zileuton and why is it beneficial?

Answer 29

5-lipoxygenase inhibitor, beneficial in human allergic rhinitis and in asthma.

Question 30

What is misoprostol and why is it beneficial?

Answer 30

Oral PGE1 analog, reduces incidence of NSAID-induced gastric ulceration. Associated with diarrhea in up to 30% of patients, limiting its clinical utility.

Question 31

What arachidonic acid derivative inhibits fever and how does it work?

Answer 31

PGE2, released in regions of pre optic hypothalamus, producing febrile state. Inhibition prevents fever (does not drop temp in normothermic state).

Question 32

What is Bartter’s Syndrome and how do you treat it?

Answer 32

Disorder due to overproduction of renal prostaglandins. NSAIDs other than aspirin are effective.

Question 33

How does one treat patent ductus arteriosus?

Answer 33

Gps involved in maintaining potency of ductus. NSAIDs such as indomethacin, ibuprofen, given to neonates to effect closure.

Question 34

What does acetaminophen do and what is its mode of action?

Answer 34

analgesic and antipyretic - not anti-inflammatory. Very weak inhibitor of COX-1 and COX-2 but appears to inhibit COX in the brain. No adverse effects on GI and platelets.