Basic Pharmacology Deck 3 Flashcards
What metabolic pathway to corticosteroids block?
cleaving of membrane phospholipid to arachidonic acid
What product of the Eicosanoid pathway is produced in platelets?
TXA2, which is prothrombotic. (arachidonic acid first converted to prostaglandin precursor by COX)
What product of the Eicosanoid pathway is produced in endothelial cells?
PGI2, which is antithrombotic (arachidonic acid first converted to prostaglandin precursor by COX)
What is dexamethazone and what does it do?
anti-inflammatory that blocks COX-2.
What is PGE2, and what does it do?
most common prostaglandin product, plays a critical role in fever production and neuropathic pain. (mPGES1 is a potentially good enzyme target for therapy).
What is LTA4, and what does it do?
Important product of arachidonic acid (5-lipoxygenase product) that plays a critical role in neutrophil function.
What is LTC4 and LTD4 and what do they do?
Important product of arachidonic acid (lipoxygenase product) play a prominent role in asthma and allergic responses, direct effect on vasculature.
What is LTB4, and what does it do?
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.
What are PGE2 effects on the gastric mucosa?
1) inhibits acid secretion
2) increases mucus secretion
3) increases perfusion.
What is the primary target of non-steroidal anti-inflammatory drugs?
cyclooxygenase.
What are the major toxicities of NSAIDs?
1) GI bleeding
2) renal toxicity
3) aspirin sensitivity (allergy-like response)
What is celecoxib, and what is its effect?
brand name = celebrex, COX-2 inhibitor. Because it does not block COX-1, decreases GI toxicity associated with nonspecific COX inhibitors.
What is rofecoxib, and what is its effect?
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.
What is misoprostol and what is its effect?
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.
What is role of prostaglandin role in kidney?
Causes vasodilation in response to low blood flow. Inhibition in prostaglandins in elderly can cause renal failure.
What is low-dose aspirin a useful treatment to prevent MI?
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).
Why do COX-2 inhibitors increase risk of thrombosis vs nonspecific COX inhibitors?
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).
What are the three muscarinic agonist drugs we need to know and what are their targets?
1) Bethanechol - increases tone in GI and bladder.
2) Muscarine - treatment for glaucoma (maybe).
3) pilocarpine - treatment for dry mouth, glaucoma.
What are the two anti cholinesterase drugs we need to know and what are their targets?
1) physostigmine - used for atropine overdoes.
2) neostigmine - increase tone in GI, bladder and used to increase transmission at NMJ in myasthenia graves.
What are the two muscarinic antagonists we need to know and what are their targets?
1) atropine - used to treat bradycardia, anti cholinesterase overdose.
2) scopolamine - used to treat motion sickness
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?
1) vasodilation / hypotension
2) anhidrosis (no sweating)
3) tachycardia
4) pupils dilate
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
1) dry mouth
2) urine retention
3) constipation, reduced tone
What Arachidonic acid derivative is a potent vasodilator and induces hypotension?
PGI2
What arachidonic acid derivative is a potent vasoconstrictor?
TXA2, LTC4, LTD4 (LTs particularly in the coronary and pulmonary circulations)
