Ergot alkaloids are obtained from a fungus that infects grains like rye and act on receptors like alpha-adrenergic, dopamine, and serotonin receptors. They have various uses including treating migraines, postpartum hemorrhage, and hyperprolactinemia but can cause side effects like vasospasm, gangrene, and hypotension, so they are contraindicated in conditions like hypertension, pregnancy, and peripheral vascular disease. Bromocriptine, a semi-synthetic ergot alkaloid derivative, is useful for treating Parkinson's disease, suppressing lactation, and reducing prolactin levels in hyperpro

1. ERGOT ALKALOID
Dr. Maria Qammar
MBBS, M-Phil

2. ERGOT ALKALOIDS
 Ergot alkaloids are obtained from claviceps purpurea,a
fungus that infects grasses and grains- especially rye-
under damp growing or storage conditions.
 This fungus synthesizes many biologically active agents
including:
 Acetylcholine, histamine, tyramine and many unique
ergot alkaloids which effect:
 alpha-adrenergic receptors
 dopamine receptors
 Serotonin receptors

3. Ergot Poisoning (St. Anthony’s fire)
Most dramatic effect of poisoning are:
• Dementia
• Florid hallucinations
• Prolonged vasospasm which results in gangrene
• Stimulation of uterine smooth muscle

4. Classification:
Chemistry: Tetracyclic ergoline
A) Natural Alkaloids: Two major families.
 Amine alkaloid: e.g. ergometrine, lysergic acid
 Peptide alkaloid: e.g ergotamine, ergocryptine,
ergotoxine.
B) Semi-Synthetic Derivatives of Ergot Alkaloids:
dihydroergotamine, dihydroergotoxine,
bromocriptine.
C) Synthetic Derivatives of Ergot Alkaloids:
Cabergoline, Pergolide

5. MECHANISM OF ACTION
They have complex mechanism of action. They act on no of receptors.
This action is due to ergoline a tetracyline nucleus. Their effects
include
1- agonist, partial agonist antagonist action at alpha adenoreceptor.
2- They also have agonist action on serotonin receptors ( 5 hydroxy
tryptamine ) and CNS dopamine receptors.
3- Some members of the ergot family have a high affinity for presynaptic
receptors while others are more selective for post- junctional receptors.

6. 3-They also have powerful stimulant action on
uterus, that may be due to agonist or partial
agonist effect on 5 HT receptors. Structural
variation increase the selectivity of certain
members of the family for specific receptor types.

8. Pharmacological action
1- On central nervous system
 Naturally occurring alkaloids are powerful hallucinogens.
 Synthetic ergot compound, Lysergic acid diethylamide
(LSD), produces hallucinations, so abuse of this drug is
still widespread.
 Bromocriptine acts on dopamine receptors  is useful in
parkinsonism.
 Chemoreceptor trigger zone is stimulated to produce
vomiting.
 Bromocriptine, cabergoline & pergolide have the highest
selectivity for the pituitary dopamine receptors---
suppress prolactin secretion

9. Depressant action:
They depress vasomotor center to cause
hypotension

10. 2. Vascular Smooth Muscle:
 Ergotamine & related compounds cause
vasoconstriction of most BV.
 Ergotamine dissociates very slowly from α
receptors, so it produces very long lasting agonist
and antagonist effects at these receptors. This
dual effect reflects the drug’s partial agonist
action.
 There is little or no effect at β adrenoceptors.
 Specific anti-migraine action of ergot derivatives
 partial agonist action on prejunctional
neuronal 5-HT receptors.

11. Peripheral Vasocontriction:
It is the most prominent effect so cause
rise in B.P due to stimulation of alpha,
serotonin and tryptamine receptors
they also cause direct stimulation of
smooth muscles of blood vessels.

12. 3- Action on heart
Usually cause bradycardia even when blood pressure is not
ed this is predominantly due to vagal activity.

13. 4- Action on uterine smooth muscles
( oxytoxic action)
 Ergot alkaloid have stimulant action on the uterus.
 It is due to stimulation of alpha and serotonin receptors
and direct action on smooth muscles. All ergot drugs
increase motor activity of uterus, but ergonovine is more
selective and is the agent of choice in obstetric.
 In small doses ergot drugs can evoke rhythmic contraction
and relaxation of the uterus, but at higher concentration
these drugs induce powerful ,irregular and prolong
contractions.

14. 5- Action on other smooth muscles:
 No significant effect on bronchial smooth muscles
6- GIT
 Act on intestinal serotonin receptors and causes
 Diarrhoea & abdominal cramps.
 Can cause nausea & vomiting due to action on
dopamine receptors.

15. Pharmacokinetics
ABSORPTION:
Ergot alkaloids are variably absorbed from GIT.
1. Oral, doses of ergotamine is 10 time larger than i/m dose
2. Speed of absorption and peak blood level after oral administration
can be improved or ed, by addition of caffeine.
 Amine alkaloids are also absorbed from rectum and buccal
cavity and after administration by aerosol inhaler.
 Absorption after i/m injection is slow but reliable
 Semisynthetic analogs i.e;bromocriptine and cabergoline
are well absorbed from GIT.

16. Metabolism:
They are extensively metabolized in the body
Uses / indication
1- Migraine
The specific anti migraine action of ergot alkaloids is due to
their action on neuronal or vascular serotonin receptors.
Ergotamine, ergonovine and methysergide are the ergot
drugs most commonly used for the Rx of migraine

17. Doses and rout:
1- Ergotamine Oral 1 mg ergotamine plus 100 mg
caffiene, rectal, 2 mg ergotamine plus 100 mg caffiene
1- Methysergide 0.2 mg tab oral
2- Dihydroerergotamine 0.5-1 mg i.v

18. 2) Control of post partum hemorrhage
 Ergot drugs are useful only for control of late uterine
bleeding and should never be given before delivery.
 Can be given at the time of delivery of placenta. Or
immediately afterwards if bleeding is significant
ergonovine maleate 0.2 mg Usually given I/M
3) Use to hasten involution of uterus Ergonovine is given
for 4-8 wks.

19. 4) Diagnosis of variant angina
Ergonovine produces prompt vasoconstriction during
coronary angiography to diagnose variant angina if
reactive segments of coronary arteries are present.

20. 5- Senile cerebral insufficiency
 Dihydro ergotoxine, a mixture of dihydro  ergocriptine and
three similar dihydrogenated peptide, ergot alkaloids (ergoloid
mesylates) has been used for relief of senility for many years.
 Dihydro-ergotoxine causes vasodilatation instead of
vasoconstriction. Senile cerebral insufficiency is a disease of old
age, it is due to lack of blood supply because of narrowing of
blood vessels, recently this drug is used for the treatment of
Alzheimers dementia.
 There is no useful evidence that this drug has significant benefit.

21. 6- Hyperprolactinemia
 ed serum levels of the anterior pituitary harmone
prolactin are associated with secreting tumours of the
gland or hypothalamus and also with the use of
centrally acting dopamin antagonists especially
antipsychotic drugs .
 Hyperprolactinemia is associated with amenorrhea
and infertility in women as well as galactorrhea in
both sexes. So Bromocriptine and cabergoline is
effective in reducing the high level of Prolactin.

22. Contraindications
1) Coronary insufficiency as it precipitate angina
2) Hypertension
3) Pregnancy
4) Impaired renal and hepatic functions
5) Peripheral vascular disease
6) (Burgers Raynauds disease)
7) Collagen vascular diseases

23. Side effect / adverse effects
1) GIT disturbances i.e diarrhea nausea and vomiting,
because of activation of medullary vomiting center and
GIT serotonin receptors.
2) Prolong vasospasm
 It is with ergotamine and ergonovine. They cause
stimulation of vascular smooth muscles and may
cause gangrene and may require amputation.
 Can be cured with nitroprusside or nitroglycerin .

24. 3) Fibroplastic changes:
• Occurs in retroperitoneal space, pleural cavity and
endocardial tissue of the heart. These changes may
present as hydronephrosis ( from obstruction of ureters)
and cardiac murmur ( from distortion of valve of the
heart). This occurs with Methysergide.
4) Drowsiness and hallucination with methysergide

25. TOXICITY WITH ERGOT DRUGS
Ergot is misused for illegal abortion so poisoning can
occur.
Sign and symptoms of acute poisoning
1) Nausea,
2) vomiting and diarrhoea
3) Hypotension
4) Drowsiness

26. Chronic poisoning sign and symptoms
1) Gangrene
2) Pulsation in legs is weak
3) Coldness of extremities
4) Muscular pain
5) Chest pain
6) Headache
7) CNS stimulation can cause convulsion
8) Chronic therapy with Methysergide is associated with
fibroplastic changes in retroperitoneal space due to
vasoconstriction and  blood supply.
9) hydronephrosis

27. Treatment of ergot poisoning
1. Withdraw the drugs.
2. Symptomatic measures i.e
a) Vasodilator like nitroprusside i/v to counter act
vasoconstricton
b) Anti – coagulant
c) Anti – emetic centrally acting i.e phenothiazine to
depress the dopamine receptors.

28. Bromocriptine ( parlodel )
1. It is a semisynthetic derivative of ergot alkaloids
2. It is potent dopamine D2 receptor agonist.
3. It act, by stimulating dopamine, receptor in the CNS,
CVS, pituitary hypothalamic axis and, GIT

29. Pharmacokinetics
Bromocriptine rapidly absorbed from GIT. Extensive 1st
pass metalbolism. Plasma ½ life is 3 hours after oral,
administration. Most of metabolites are excreted in bile
Dose: 2 – 4 mg three time a day

30. Therapeutic uses / indication of
bromocriptine
1. For Rx of Parkinsonism
 It acts directly on post synaptic dopamine receptors in
the nigrostriatal system.
 It is useful in previously untreated and disabled pts. and
those who can not tolerate levodopa.

31. 2- For prevention or suppression of lactation
It prevent the release of prolactin by stimulating
dopamine receptors in the pituitary to inhibit lactation.
3- For Rx of hyperprolactinaemia associated with
hypogonadism, galactorrhea, infertility
It reverse anovulatory infertility associated with
hyperprolactinaemea due to which there is
gonadotrophin inhibition and ed levels of estrogen
and progesterone .

32. 4. For cyclical benign breast disease i.e mastalgia (
breast pain) and cyclical menstrual disorders
5. For Rx of acromegaly bromocriptine es growth
harmone release in normal subjects but suppresses
growth hormone release in acromegaly
6. Hepatic encephalopathy

33. S/E
Nausea, vomiting due to stimulation of chemo receptor
trigger zone. serious post partum cardio vascular toxicity

34. MCQ
 A 33 years old woman attempted to induce an abortion
using ergotamine.Her legs became cold with absent arterial
pulses.Which of the following is most usefull antidote for
reversing severe ergot induce vasospasm?
 A) Bromocriptine
 B) Cimetidine
 C) Ergotamine
 D) Ketanserin
 E) LSD
 F) Nitroprusside
 G) Sumatriptan

35. MCQ
 A 26 years old woman presents with amenorrhea and
galactorrhea.Her prolactin level is grossly elevated.
Which of the following is most useful in treatment of
hyperprolactinemia?
 A) Bromocriptine
 B) Cimetidine
 C) Ergotamine
 D) LSD
 E) Ondansetron

36. SEQ’S
1) Write down clinical uses of ergot alkaloids.
2) What are the side effects and contraindication of
ergot alkaloids usage?