5-HT/Migraine Flashcards
- rapidly metabolized by MAO and stored, 90% found in enterochromaffin cells of GI treact
- stored in platelets and serotonergic nerve endings
- concentration in vesicles blocked by reserpine
serotonin (5-hydroxytryptamine)
-5-HT3 receptors in GI tract and medulla produce the ______ reflex
vomiting
5-HT2 stimulates platelet _______
activation
- serotonin receptor on GI tract that stimulates smooth muscle
- increased tone, facilitation of peristalsis
5-HT2
- serotonin receptor on GI tract that increases acetylcholine from nervous system
- prokinetic effect
5-HT4
carcinoid syndrome in GI tract produces ______
diarrhea
- 5HT1a partial agonist
- non benzodiazepine anxiolytic
buspirone
- 5-HT2c agonist
- appetite suppression
- withdrawn due to toxicity
dexfenfluramine
- inhibit release of vasodilating peptide CGRP
- constrict cerebral and meningeal vessels in treatment of acute migraine headaches
- adverse: tingling, warm sensations, muscle weakness, neck pain, chest discomfort
-triptans (5-HT1b/1d agonist)
-5HT4 agonist used for treatment of GERD and motility disorders
cisapride
-partial 5HT4 agonist, utilized for IBS with constipation
tegaserod
- long acting 5-HT2 antagonist
- also alpha adrenergic antagonist
phenoxybenzamine
- 5HT2 antagonist and H1 receptor antagonist
- useful for smooth muscle effects of carcinoid tumors
- serotonin syndrome treatment
cyprohepatidine
- 5HT3 receptor antagonists
- treatment of nausea and vomiting in cancer chemo
-setrons
ondansetron, granisetron, dolasetron
- HTN, hyperreflexia, tremor, clonus, hyperthermia, hyperactive bowel sounds, diarrhea, mydriasis, agitation, coma
- precipitating drugs: SSRIs, 2nd gen antidepressants, MAOIs, linezolid, tramadol, meperidine, fentanyl, ondansetron, sumatriptan, MDMA, LSD, St Johns Wort, ginseng
Serotonin syndrome
- catecholamine and serotonin like
- admin with caffeine increases absorptin
ergot alkaloids
- selectivity for dopamine receptors
- ergot alkaloids that suppress prolactin secretion, treat pituitary tumor
bromocriptine, cabergoline
ergot alkaloid that’s a potent vasoconstrictor in vascular smooth muscle
ergotamine
limited 5-HT effects, but preferred for treatment of migraine, an ergot alkaloid
dihydroergotamine
- most selective ergot alkaloid for the uterus, stimulate smooth muscle
- if oxytocin fails, is utilized to limit postpartum hemorrhage
ergonovine
- side effects: GI disturbances n/v/d due to increased GI motility resulting from activation of 5-HT receptors in CNS and GI
- prolonged vasospasm in arms and legs, may cause gangrene
- drowsiness and hallucinations occur infrequently
toxicity of ergot alkaloids
- episodic attacks of headache lasting 4-72 hours
- two of following: unilateral pain, pain moderate to severe, throbbing, aggravation on movement
- one or more: nausea, vomiting, photophobia, phonophobia
migraine
ergotamine, dihydroergotamine, triptans are _______ migraine drugs
specific
- which beta blockers used in preventive therapy of migraine?
- adverse: tiredness, postural, contra in asthma
propanolol (b1, b2)
metoprolol (b1)
antidepressant used in preventive migraine therapy? adverse - drowsiness
amitriptyline
- anticonvulsants used in preventive therapy of migraine
- adverse: drowsiness, weight gain, tremor, hair loss, liver abnormality
valproate, topiramate
calcium channel blockers used in preventive therapy of migraine?
-adverse: tiredness, weight gain, depression, parkinsonism
flunarizine, verapamil
- serotonin antagonist used in preventive therapy of migraine?
- drowsiness, leg cramps, hair loss, retroorbital fibrosis
methysergide
SSRI used in preventive therapy of migraine?
-adverse: anxiety, insomnia
fluoxetine
NSAIDS are non specific therapy for treatment of ______ migraine attacks
acute
analgesic overuse can _______ migraine, limit drug treatment to 2-3 days
transform
- meperidine, butophanol, oxycodone, hydromorphone
- relief for severe migraine, risk of dependence and tolerance
- rebound headaches, dizziniess, n/v, cognitive function
- risk of transforming migraine
opiate analgesics
- metoclopramide
- chlorpormazine
- prochlorperazine
antiemetics, treat acute migraines
- adjunctive therapy to combat n/v due to migraine and alkloid treatment
- centrally acting dopaming receptor antagonists
antiemetics - metoclopramide, chlorpromazine, prochlorperazine
- weak 5-HT3 receptor antagonist
- anti-emetic
metoclopramine
- migraine specific therapy
- vascoconstriction due to stimulation of alpha-adrenergic and 5-HT3 receptors
- cerebral vasoconstriction has been attributed to partial agonist effects on neuronal 5-HT1d receptors
ergotamine, dihydroergotamine
- effective, low cost
- adverse: complex, variable absorption, potent and sustained vasoconstrictive effect –> increased risk of vascular effects
ergot derivatives
- selective 5-HT1d and 1b receptor agonists
- distinctive advantages: selective pharm, established efficacy
- higher cost and restrictions in presence of CV disease
- inhibit activation of trigeminal afferent nociceptors, cranial vasoconstriction
-triptans
- mimic angina
- contraindications - ischemic heart disease, HTN, cerebrovascular disease
- tingling, sensation of warmth, dizzy, flushing, neck pain, stiffness
triptans
