ergots

Question 1

what is ergot?

Answer 1

a spur
dark brown horn shaped peg that projects from ripening ears of rye in place of rye grains

Question 2

ergot contains ___

Answer 2

ergotoxine

Question 3

2 types of ergotism

Answer 3

gangrenous (caused by ergotoxine)
convulsive or spasmotic (not caused by ergotoxine)

Question 4

epidemic outbreaks of gangrenous ergotism resulted from ____

Answer 4

consumption of ergotised rye

Question 5

describe what gangrenous ergotism is

Answer 5

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

Question 6

structure of ergot alkaloid

Answer 6

ergoline ring structure; 4 rings

Question 7

_______ is used to prepare ergonovine and ergotamine

Answer 7

lysergic acid

Question 8

3 classes of ergot alkyloids

Answer 8

clavines
ergopeptines
ergoamides

Question 9

which sites do ergot alkaloids act on

Answer 9

5HT1A, 5HT1B, 5HT1D, dopamine D2, and norepinephrine receptors

Question 10

examples of 5HT1B and 5HT1D agonist drugs

Answer 10

triptans and ergots

Question 11

examples of 5HT3 antagonist drugs

Answer 11

setron antiemetics

Question 12

effects of ergots on blood vessels

Answer 12

a significant and prolonged vasoconstriction that may result in ischemia and gangrene

Question 13

effects of ergots on the uterus

Answer 13

direct uterine smooth muscle stimulation (alpha adrenergic and 5HT receptors) that will potentially result in abortion or miscarriage in a pregnant uterus

Question 14

when might ergots be used for their uterine effects?

Answer 14

AFTER THE DELIVERY OF THE PLACENTA to prevent hemorrhage/blood loss

Question 15

CNS effects of ergots

Answer 15

hallucinations
inhibit prolactin secretion (useful to treat hyperprolactinemia)

Question 16

which ergots may be used as oxytocics after delivery of the placenta?

Answer 16

ergonovine, methylergonovine

Question 17

indications for ergnovine and methylergonovine

Answer 17

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

Question 18

ergot contraindications

Answer 18

CYP3A4 inhibitors/inducers
pregnancy- category x- risk of spontaneous abortion
induction of labor- risk of stillbirth

Question 19

acronym for migraine

Answer 19

POUND
Pulsatile
One day duration (4-72h)
Unilateral location
Nausea, vomiting, photophobia, phonophobia
Disabling intensity

Question 20

which ergots are used for migraines

Answer 20

ergotamine
dihydroergotamine

Question 21

structure of ergotamine and dihydroergotamine

Answer 21

peptide alkaloids- Alanine-Proline-Phenylalanine

Question 22

depolarization theory for migraine pathogenesis

Answer 22

wave or neuronal and glial cell activity- trigeminovascular system activated- release of CGRP by trigeminal afferents- inflammatory mediators released- meningeal inflammation- cortical sensitization

Question 23

indications for ergotamine and dihydroergotamine

Answer 23

ACUTE therapy of vascular headaches: migraine and migraine variants, cluster headaches

NOT RECOMMENDED FOR CHRONIC PROPHYLAXIS

Question 24

MOA for ergots in migraines

Answer 24

agonist at 5HT1B and 5HT1D receptors (like triptans) but also partial agonist at 5HT2, alpha adrenergic, and dopamine D2 receptors

Question 25

onset/duration of dihydroergotamine

Answer 25

onset in 15-30 minutes duration 3-4 hours

Question 26

what are other effects of ergotamine/dihydroergotamine to look out for when treating migraine?

Answer 26

potent emetic effect (via stimulation of CTZ) uterine stimulant

Question 27

what is cafergot

Answer 27

oral ergotamine tartrate + caffeine works together to reduce dilation of cranial blood vessels less effective than triptans

Question 28

triptan MOA

Answer 28

selective for 5HT1B, 5HT1D

Question 29

triptans are ____ selective than ergots, resulting in _____

Answer 29

more selective, resulting in fewer side effects

Question 30

adverse effects of ergotamine and dihydroergotamine at a therapeutic dose vs overdose

Answer 30

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

Question 31

how much ergotamine leads to overdose

Answer 31

>15 mg/24h or 40 mg in 2-3 days

Question 32

treatment of ergotamine overdose

Answer 32

ACEi such as captopril 50 mg TID can also use anticoagulants, nitroprusside etc

Question 33

what are the warnings that come along with ergot use

Answer 33

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

Question 34

which ergots may be used for inhibition of prolactin secretion or glycemic control in T2DM

Answer 34

bromocriptine cabergoline

Question 35

bromocriptine and cabergoline MOA

Answer 35

potent D2 receptor agonist

Question 36

indications for bromocriptine

Answer 36

hyperprolactinemia associated dysfunctions (amenorrhea, prolactin-secreting adenomas), acromegaly, treatment of T2DM as adjunct to diet & exercise

Question 37

indications for cabergoline

Answer 37

hyperprolactinemia, prolactin-secreting tumors, reduce breast milk production

Question 38

ergots for parkinson's disease

Answer 38

NO!!! not effective

Question 39

agents that are effective in treatment of parkinson's disease

Answer 39

ropinirole pramipexole rasagiline

Question 40

rapid withdrawal is serious for which drugs

Answer 40

D2 agonists

Question 41

which drugs are D2 agonists

Answer 41

ropinirole and pramipexole

Question 42

which drug is MAO-B inhibitor

Answer 42

rasagiline