Term
| What is serotonin and where is it synthesized? What metabolizes it and to what? |
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Definition
-It is an autocoid; acts like a hormone, but locally
-It is synthesized in the GI cells, neurons, and platelets
-**MAOa metabolizes it to 5-hydroxyinolacetic acid (5HIAA) |
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Term
| What is 5HIAA a marker for? |
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Definition
| -it is a urinary marker for a carcinoid; slow-growing type of neuroendocrine tumor typically found in the terminal ilium or appendix |
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Term
| What is the proper name for serotonin anyway? What are its receptors? Which one is not G-protein linked? |
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Definition
-5-hydroxytryptamine (5HT)
-It has seven receptors (5HT1-7) with all but 5HT3 being G-protein coupled |
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Term
| What do the first three types of receptors do overall and where are they? |
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Definition
5HT1;
-In the CNS (inhibitory; i.e. Gi linked)
-In smooth muscle (excitatory or inhibitory)
5HT2;
-In the CNS (excitatory)
-**In periphery; vasodilation, visceral smooth muscle contraction, platelet aggregation
5HT3;
-In area postrema (medulla); controls **vomiting
-*Ion channel linked (not G-protein) |
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Term
| Note; skipping all the non-migraine info for now |
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Definition
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Term
| What are the two major migraine drug types that impact the serotonin system? What do they target exactly? |
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Definition
1. "-triptans"; such as *sumatriptan
-Agonist at 5HT(*1d*); *blocks pain signal
-Also get some *vasoconstriction
2. Ergots; such as *ergotamine and dihydroergotamine
-*Partial agonist at both **α and 5HT*2; causing vasoconstriction
-Maleque is saying it works at 5HT1d as well
-Interesting; Ergots are fungi that infect rye and eating infected breads caused Saint Anthony's Fire, or ergotism, which caused **gangrene and convulsions |
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Term
| What are the side effects of ergotamine and sumatriptans? When are they contraindicated? |
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Definition
-triptans; Asthenia (weakness), chest or neck tightness, paresthesia (tingling)
-Contraindicated in those with vascular diseases because of *coronary vasospasm risk and general vasoconstriction
Ergots; Mostly *GI distress from the 5HT2 action
-Also can get *prolonged vasoconstriction and gangrene, vasospasm, etc., from the α action
-Therefore contraindicated in those with *CV disease
-Also, can cause **abortion near term;
-A similar drug, ergonovine, is given post labor to stimulate uterine contraction
-Remember, ergots stimulate visceral smooth muscle contraction by stimulating 5HT2 receptors |
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Term
| How do we use ergotamine? What can we pair it with |
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Definition
-For **acute attacks, not chronically
-We also can pair it with things like aspirin, caffeine, other NSAIDs, antiemetics, and opioid-analgesics |
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Term
| What are the major prophylaxis drugs that we can use (4)? |
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Definition
1. *Propranolol; a β blocker (nonselective, partial agonist)
2. Verapamil; a Ca2+ channel blocker
3. *Amitriptyline; a TCA (tricyclic antidepressant)
4. Valproic; an anti-epileptic
-All of these are CNS depressants used for privation of severe migraines (starred ones for Maleque)
Maleque also has added in;
-Methysergide; *serotonin antagonist
-Phelzine; *MAOa inhibitor |
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Term
| What is the prodrome for migraines? |
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Definition
-Prodromes are just symptoms before the major disease symptoms set in
-Aura is a classic symptom before migraine onset |
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