ergot alkaloids

see also:

• ergometrine
• serotonin receptors and pharmacology
• migraine

• non-selective 5HT agonists/antagonists - varies with agent - see also serotonin receptors and pharmacology
• dopamine D2 agonists - see also dopamine
• alpha adrenergic agonists - see also sympathomimetics
• esp. on sm.muscle;
• ergometrine is used as a uterotonic

• see migraine
• antimigraine effect is probably via same mechanisms as for the triptans, but clinical use is complicated by stimulation of dopamine D2 receptors in brainstem & gut, causing V&D, and of vascular adrenergic & 5HT2 receptors, causing potent & sustained vasoconstriction of systemic and coronary arteries
• for decades, ergots were the only drugs specifically for migraine, but there are no good trials to support their efficacy and they are difficult to use because of poor oral & rectal bioavailability (<3%) and erratic PK & clinical response profiles
• dose & route should be individualised
• to prevent “ergot headaches”, use should be restricted to 1-2 days per week
• response rate & therapuetic gain for oral ergotamine is in the same range as for NSAIDs & ~10% less than that for oral sumatriptan
• individual pts however, may respond better
• rectal ergotamine seems to produce slightly better & less variable responses
• recurrence rate may be marginally less frequent & time to recurrence is some hours longer than with sumatriptan & thus may have a role in pts with long lasting attacks

• are frequent, often severe & may last for hours:
  • N/V/D/muscle cramps/malaise
  • peripheral vasoconstriction causing cold & tingling fingers & toes
  • sustained contraction of coronary & other arteries (more so than with triptans)
  • “ergot headaches”

• rare, but life-threatening severe generalised vasospasm
  • ⇒ acral cyanosis, digital necrosis, intermittent claudication
  • ⇒ infarcts of heart, brain & other organs
• Rx with direct acting vasodilators (IV nitroglycerine)

• agonist on central & antag. on peripheral: 5-HT1-like & 5-HT2

• 5-HT1-like partial agonist-antagonist & 5-HT2 antagonism;
• only feeble vasoconstrictor & oxytocic activity;
• decr. 5-HT effects of: vasoconst., pressor, sm.muscle
• protective for migraine takes 1-2D to develop & as long to wane on stopping Rx
  • ⇒rebound headache
• no use in acute migraine though;
• combat diarrhoea & malabsorption in carcinoid syndrome;
• use in post-gastrectomy dumping synd;