Ergot alkaloids

- Ergot alkaloids produced by “ Claviceps purpurea " ( rye ergot fungus ).

- This fungus synthesizes histamine, Ach, tyramine and other biologically active products in addition to score or more of unique of ergot alkaloids.

- These alkaloids have effects on α-adrenoceptor, dopamine and 5-HT receptors.

- Ergotism; is the name for severe pathological syndromes affecting humans or other animals that have ingested plant material containing ergot alkaloid.

- Ergotism symptoms (depend on the alkaloids mixture): dementia , hallucinations , persistent vasospasm (gangrene may develop), uterine muscle stimulation ( may cause abortion in pregnancy)

Ergot Alkaloids Classification
Peptide Alkaloids
Ergotamine (Amigraine®)	Bromocriptine (Parlodel®)
Amine Alkaloids
Ergometrine or Ergonovine (Methergin®)	Methysergide (Sansert®)
Lysergic Acid Diethylamide (LSD)( Delysid®)

 

Pharmaco -dynamics	Brain	- LSD is a powerful hallucinogens (drug abuse). -Bromocriptine is a D2 agonist in CNS , Cause ;   # Suppress pituitary prolactin hormone release .    #Control extrapyramidal system ( see CNS chapter ).
	Blood vessels	- Action of ergot alkaloids on vascular smooth muscle mainly vasoconstriction, due to partial agonist effect at α1-adrenorecptor and may be the result of effect at 5-HT2 receptor. - Ergometrine have strong vasoconstriction action.
	Uterine	- Action of ergot alkaloids on uterine smooth muscle ;   # At very small dose à Contraction and relaxation.   # At high dose à Powerful & prolonged contraction. - Ergometrine is drug of choice in obstetric application.
	GIT	- Action of ergot alkaloids on GI smooth muscle ; variable sensitivity   (nausea , diarrhea and vomiting ), may induced even by low dose in some patients , due to action on GI serotonin receptors or CNS emetic centers. - The ergot alkaloids have little or no significant effect on bronchial and   urinary smooth muscles.
Therapeutic Uses	1 ) Migraine : - Ergotamine can also effective when given during the acute attack of migraine , It is often combined with Caffeine to facilitate absorption of ergot alkaloids . - Dose : Initial dose : 2 mg under the tongue , another 2 mg tablet may be taken at               30 minute intervals if necessary ( must not exceed three tablets in any 24-               hour period) , Total weekly dosage should not exceed five tablets ( 10 mg ). - Methysergide which was used for migraine prophylaxis in the past , was withdrawn because of toxicity (e.g. retroperitoneal fibrosis) 2 ) Hyperprolactinemia:      - Bromocriptine is extremely effective in reducing the high levels of prolactin         hormone , due to agonist effect on D2-receptors.      - Dose : 2.5 mg two or three times daily .      - Cabergoline ( Dostinex®)  is a semisynthetic derivatives of the ergot alkaloids , is a        potent D2 - receptors agonist with less side effects than Bromocriptine.          - Dose : 0.25 mg twice a week , dosage may be increased by 0.25 mg twice                           weekly(1 mg twice a week). 3) Postpartum Hemorrhage ( PPH ):      - Ergot derivatives prevent bleeding after childbirth by causing spasm in smooth        muscle.      - Ergometrine or Ergonovine is drug of choice due to ; effective with 1-5 minutes        and less toxic than other ergot derivatives.             - Dose : 0.2 mg injection after delivery of the anterior shoulder ( IM ), Dose may                           be repeated as required ( after 2-4 hours ).      - Oxytocin ( see endocrine chapter ) is more preferred. 4 ) Diagnosis of Variant Angina :      - Ergometrine or Ergonovine given IV produces prompt VC during coronary        angiography to diagnose variant angina.
Toxicity	- GI disturbance : Diarrhea , nausea and vomiting .       à Due to action on GI serotonin receptors or CNS emetic centers . - CNS ; Hallucination and drowsiness . - Prolonged vasospasm ; may cause gangrene and require amputation .           - Especially ; Ergotamine and Ergonovine .           - Treated by Prazosin ; selective α1 receptors blocker. - Chronic therapy with Methysergide may cause ; retroperitoneal fibrosis,   subendocardial fibrosis, fibroblastic changes in the pleural cavity à cardiac murmur     (abnormal heart sound).
Contra Indication	- Vascular Diseases ( peripheral vessels or coronary artery ). - Pregnancy ( because they cause uterine contractions , fetal distress , gastrointestinal   atresia and miscarriage ) .
FDA warning	- Co-administration of Ergotamine with LMEIS inhibitors (e.g. Erythromycin). LMEIs elevates the serum levels of ergotamine, increase the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities (gangrene).

 

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