ergots Flashcards
what is ergot?
a spur
dark brown horn shaped peg that projects from ripening ears of rye in place of rye grains
ergot contains ___
ergotoxine
2 types of ergotism
gangrenous (caused by ergotoxine)
convulsive or spasmotic (not caused by ergotoxine)
epidemic outbreaks of gangrenous ergotism resulted from ____
consumption of ergotised rye
describe what gangrenous ergotism is
primarily due to effects of ergotoxine, produces vigorous and prolonged occlusion of the arterioles, food/leg becomes inflamed/hot alternating with sensations of cold (this is called St. Anthony’s Fire), numbness, dry gangrene, painless loss of limb
structure of ergot alkaloid
ergoline ring structure; 4 rings
_______ is used to prepare ergonovine and ergotamine
lysergic acid
3 classes of ergot alkyloids
clavines
ergopeptines
ergoamides
which sites do ergot alkaloids act on
5HT1A, 5HT1B, 5HT1D, dopamine D2, and norepinephrine receptors
examples of 5HT1B and 5HT1D agonist drugs
triptans and ergots
examples of 5HT3 antagonist drugs
setron antiemetics
effects of ergots on blood vessels
a significant and prolonged vasoconstriction that may result in ischemia and gangrene
effects of ergots on the uterus
direct uterine smooth muscle stimulation (alpha adrenergic and 5HT receptors) that will potentially result in abortion or miscarriage in a pregnant uterus
when might ergots be used for their uterine effects?
AFTER THE DELIVERY OF THE PLACENTA to prevent hemorrhage/blood loss
CNS effects of ergots
hallucinations
inhibit prolactin secretion (useful to treat hyperprolactinemia)
which ergots may be used as oxytocics after delivery of the placenta?
ergonovine, methylergonovine
indications for ergnovine and methylergonovine
following delivery of the placenta for management of uterine atony, hemorrhage, subinvolution
administered only after placental expulsion because prior administration may result in ENTRAPMENT of the placenta
ergot contraindications
CYP3A4 inhibitors/inducers
pregnancy- category x- risk of spontaneous abortion
induction of labor- risk of stillbirth
acronym for migraine
POUND
Pulsatile
One day duration (4-72h)
Unilateral location
Nausea, vomiting, photophobia, phonophobia
Disabling intensity
which ergots are used for migraines
ergotamine
dihydroergotamine
structure of ergotamine and dihydroergotamine
peptide alkaloids- Alanine-Proline-Phenylalanine
depolarization theory for migraine pathogenesis
wave or neuronal and glial cell activity- trigeminovascular system activated- release of CGRP by trigeminal afferents- inflammatory mediators released- meningeal inflammation- cortical sensitization
indications for ergotamine and dihydroergotamine
ACUTE therapy of vascular headaches: migraine and migraine variants, cluster headaches
NOT RECOMMENDED FOR CHRONIC PROPHYLAXIS
MOA for ergots in migraines
agonist at 5HT1B and 5HT1D receptors (like triptans) but also partial agonist at 5HT2, alpha adrenergic, and dopamine D2 receptors
onset/duration of dihydroergotamine
onset in 15-30 minutes
duration 3-4 hours
what are other effects of ergotamine/dihydroergotamine to look out for when treating migraine?
potent emetic effect (via stimulation of CTZ)
uterine stimulant
what is cafergot
oral ergotamine tartrate + caffeine
works together to reduce dilation of cranial blood vessels
less effective than triptans
triptan MOA
selective for 5HT1B, 5HT1D
triptans are ____ selective than ergots, resulting in _____
more selective, resulting in fewer side effects
adverse effects of ergotamine and dihydroergotamine at a therapeutic dose vs overdose
therapeutic dose: nausea, vomiting, weakness, paresthesias, myalgias
overdose: severe vasoconstriction, peripheral ischemia, fingers/toes, numbness/tingling/cold, endarteritis, acute arterial occlusion, gangrene of the extremities
how much ergotamine leads to overdose
> 15 mg/24h or 40 mg in 2-3 days
treatment of ergotamine overdose
ACEi such as captopril 50 mg TID
can also use anticoagulants, nitroprusside etc
what are the warnings that come along with ergot use
pregnancy category x
FDA boxed warning: concomitant use with strong CYP3A4 inhibitors can result in life threatening ergot toxicity
avoid prolonged administration or excessive dosage
rebound headache: patients taking the drug for extended periods of time may experience withdrawal symptoms
which ergots may be used for inhibition of prolactin secretion or glycemic control in T2DM
bromocriptine
cabergoline
bromocriptine and cabergoline MOA
potent D2 receptor agonist
indications for bromocriptine
hyperprolactinemia associated dysfunctions (amenorrhea, prolactin-secreting adenomas), acromegaly, treatment of T2DM as adjunct to diet & exercise
indications for cabergoline
hyperprolactinemia, prolactin-secreting tumors, reduce breast milk production
ergots for parkinson’s disease
NO!!! not effective
agents that are effective in treatment of parkinson’s disease
ropinirole
pramipexole
rasagiline
rapid withdrawal is serious for which drugs
D2 agonists
which drugs are D2 agonists
ropinirole and pramipexole
which drug is MAO-B inhibitor
rasagiline
