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IC > 5-HT/Migraine > Flashcards

5-HT/Migraine Flashcards

1
Q

Serotonin

A

5-HT
-rapidly metabolized by monoamine oxidase (MAO)
Product of L-tryptophan
-90% of serotonin is found in ECL cells of GI tract, also stored in platelets and serotonergic nerve endings

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2
Q

5-HT3

A

in brainstem

Target of odansetron for anti-emesis

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3
Q

5-HT effects- CNS

A

CNS-affects sleep, sensory perception, motor, temp regulation, sexual behavior, hormone secretion
5-HT3 receptors in GI tract and medulla- vomiting

Local effects in periphery- pain and itch by sensory nerve endings (insect bites)

Coronary vascular beds have 5-HT3 receptors on vagal nerve endings- chemoreceptor reflex leading to bradycardia and hypotension

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4
Q

5-HT on pulmonary

A

stimualtion of bronchial smooth muscle

stimulates ACh release from bronchial vagal nerve endings

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5
Q

5-HT on CV

A

5-HT2- vasoconstriction (except in heart and skeletal muscle)
triphasic change in bp

platelet aggregation

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6
Q

GI tract 5-HT

A

stimulation of smooth muscle- facilitation of peristalsis

inc ach release from nervous system upon 5-ht4

Carcinoid tumors that overproduce serotonin–> diarrhea

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7
Q

Buspirone

A

5-HT1a partial agonist

non-benzodiazepine anxiolytic

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8
Q

Dexfenfluramine

A

5-HT2c agonist
appetite suppression
withdrawn due to toxicity

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9
Q

Sumatriptan

A

5-HT1b/1d agonist
Inhibition of release of vasodilating peptide calcitonin gene related peptide

constrict cerebral and meningeal vessels in tx of acute migraine headaches

AE: tingling, warmth sensations, dizziness, muscle weakness, neck pain, chest discomfort

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10
Q

5-HT4 agonists

A

Cisaperide- GERD and motility disorders

Tegaserod- partial agonist for IBS w/ constipation

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11
Q

5-HT receptor antagonists

A

Useful in treating carcinoid tumor
-inhibitors of synthesis and storage (reserpine) are too toxic

-dirty drugs- often have other targets

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12
Q

Phenoxybenzamine

A

-long acting 5-ht2 antagonist and alpha-adrenergic receptor antagonist

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13
Q

CYprohepatidine

A

5-HT2 antagonist and H1 receptor antagonist

-useful for smooth muscle effects of carcinoid tumors (serotonin syndrome tx)

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14
Q

Ketanserin

A

not approved in US
5-ht2 antagonist and alpha1 adrenergic antagonist
tx of htn and vasospastic conditions

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15
Q

Ondanestron, granisetron, dolasetron

A

5-HT3 receptor antagonist

tx of nausea and vomiting in cancer chemo

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16
Q

Serotonin Syndrome

A
  • Overrelease of too much serotonin
  • Htn, hyperreflexia, tremor, clonus, hyperthermia, hyperactive bowel sounds, diarrhea, mydriasis, agitation, coma

-preciptating drugs- SSRIs, second gen antidepressants, MAOIs, linezolid, tramadol, ondansetron, sumatriptan, st. john’s wort, ginseng

17
Q

Ergot Alkaloids

A
  • share properties of serotonin and catecholamines
  • Produced by claviceps purpurea (fungus that infects stored grains under damp storage)
  • hallucinations, convulsions, prolonged vasospasm (gangrene and fiery pain), uterine contractions resulting in abortion

some agonists and antagonists work at adrenergic receptors, 5-HT receptors, dopamine and uterine smooth muscle recepors

18
Q

Ergotamine

A

-typically used for smooth muscle stimuatlion in uterus
-potent vasoconstrictor
ergot alkaloid

19
Q

Dihydroergotamine (DHT)

A

ergot alkaloid

  • tx of migraine
  • vasoconstrictors of bv in dura
20
Q

Bromocriptine, cabergoline

A

Ergot alkaloid

works on copamine receptor -suppress prolactin secretioon and useful in treating pituitary tumor

21
Q

LSD

A

ergot alkaloid, power hallucinogen

22
Q

Ergonavine

A

ergot alkaloid used for uterine smooth muscle contraction

utilized to limit post partum hemorrhage

23
Q

Ergot Alkaloid toxicity

A

GI disturbance due to inc GI motility from activation of 5-HT receptors in CNS and GI
-prolonged vasospasm of arms and legs–> gangrene and amputation
Drowziness and hallicinations

24
Q

Migraine

A

Two of following symptoms:

  • unilateral pain
  • pain ranging from moderate-severe
  • throbbing (not rhythmic with heart beat)
  • aggravating upon movement

one or more of following:

  • nausea or vomiting
  • photophobia or phonophobia

-triggered from stress, spikes in bp, skipping meals, exercise, rain, etc

25
Q

Pathophys of migraines

A

-dural vasculature dilated- noxious stimulus from trigeminal system

26
Q

Tx of migraine

A

Preventative therapy or tx of acute migraine attack (nonspecific- nsaids, aspirin) or specific migraine (ergotamine, DHT, triptans)

27
Q

Preventative migraine therapy

A

Limited for those having >5 migraines per month
-beta blocker (propranolol, metoprolol), amitriptyline (antidepressant), anticonvulsants (valproate, topiramate), CCB (flunarizine), serotonin antagonist (methysergide- withdrawn)
Have adverse effects

all have drowziness, tiredness, some have weight gain,

other not as beneficial- verapamil (CCB) and fluoxetine (SSRI)

28
Q

Tx of acute migraine attacks

A

non specific pain therapy
tx immediately
-co administer with anti emetic drug
-avoid overuse- limit drug tx to 2-3 days
risk of transforming migraine into severe, chronic condition

29
Q

Opiate analgesics

A

for acute migraine attacks

  • meperidine, butorphanol, oxycodone, hydromorphone
  • relief for severe migraine
  • risk of dependence nad tolerance
  • AE: rebound headaches, dizziness, nausea, vomiting
30
Q

Antiemetics

A

tx acute migraines

  • metoclopramide, chlorpramazine, prochlorperazine
  • combat nausea and vomiting due to migraine or ergot alkaloid tx
  • metoclopramine is also weak 5-ht3 receptor antagonist which may also have direct effect
31
Q

ergot derivatives

A

for migraine specific acute therapy

  • vasoconstriction of cerebral and dural vessels
  • but can have variable absorption and sustained vasoconstrictor effects (contra in CAD)
32
Q

Triptans

A

sumatriptan
Selective 5-HT1D and 5-HT1B receptor agonist
-distinct advantage over ergot derivatives
-established efficacy and established safety record
-high cost
-MOA poorly defined
-inhibit activation of trigeminal afferent nociceptors
-cranial/dural vasoconstriction via 5-HT

-generally safe, but can mimic angina by constricting coronary arteries
-contra in ischemic heart disease, htn, cerebrovascular disease
-
can cause tingling, sensation of warmth, dizziness, flushing, neck pain, stiffness

IC (31 decks)

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