This section is from the book "A Text-Book Of Pharmacology, Therapeutics And Materia Medica", by T. Lauder Brunton. Also available from Amazon: A text-book of pharmacology, therapeutics and materia medica.
Purified extract of ergot, commonly called ergotin or ergotine, or Bonjean's ergotine.
Preparation. - By evaporating the fluid extract of ergot, 4 fl. oz., by a water-bath to a syrupy consistence, and when cold mixing with 4 fl. oz. of spirit. Let it stand for half an hour, then filter, and evaporate the filtered liquid to the consistence of a soft extract.
Composition. - The chemical composition of ergot is still very imperfectly known, and the active principle (or principles) to which its most important action, that of causing contraction of the uterus, is due, has not been satisfactorily isolated. The active principles were formerly said to be ergotin and ecbolin, but these do not seem to be pure substances. The term ergotin has been applied to several substances. According to Schmiede-berg, two pure principles have been isolated - ergotinic acid and an alkaloid, ergotinine. According to Dragendorff and Podwyssotzki, the active principles are sclerotinic acid and a colloid substance, scleromucin. Sclerotinic acid is impure ergotinic acid. In addition to ergotinic acid, ergotinin, and probably several other principles, ergot contains about 35 per cent. of oil, a peculiar sugar (mykose), and two colouring matters, scleroxanthin and sclero-erythrin.
The most recent researches are those of Robert, who states that ergot contains three active principles : ergotinic acid, sphacelinic acid, and an alkaloid, cornutine.
Dose. - 2 to 5 grains.
Injectio Ergotini Hypodermica (ergotin 1, camphor water 2 parts; mix by stirring together just before using).
Dose (by subcutaneous injection), 3-10 min.
General Action. - There is a great difference of opinion as to the action of ergot, due to its preparations undergoing change so rapidly, and hence not being of the same strength. They become quite inactive if kept for any length of time. In certain parts of Germany, where rye-bread is much used, epidemics of ergotism have occurred. These epidemics depend both upon the continued large doses of ergot and upon the deficiency of food, the nutritive part of the rye being replaced by the fungus. The deficiency of food is probably an important factor, since continued therapeutic doses of ergot rarely produce ergotism, though occasionally they do so.
There are two varieties of symptoms seen in ergotism : (1) the gangrenous; (2) the anaesthetic or convulsive. Both begin with gastro-intestinal disturbance, causing loss of appetite, nausea, vomiting, and diarrhoea.
The gangrenous symptoms are redness of the skin followed by well-marked gangrene in the part. The cause of this gangrene is probably stasis due to the great contraction of the small blood-vessels.
The nervous symptoms are giddiness, with symptoms of irritation and paralysis of sensory nerves, or more probably of sensory centres, e.g. the posterior columns of the spinal cord. The irritation is indicated by a sensation as of insects crawling over the skin, flying pains, etc, the paralysis by loss of sensation in the hands and feet. Sclerosis has been found in the postero-lateral columns of the cord in such cases. Spasms may occur, and even convulsions of an epileptic nature.
Special Action. - Ergotinic acid causes ascending paralysis of the spinal cord and brain, both in frogs and mammals, with loss of voluntary motion, paralysis of the vaso-motor centre, and fall of blood-pressure, while respiration and reflex irritability continue. It does not appear to have the power of increasing the uterine contractions, and so cannot be regarded as the most important constituent of ergot. Ergotinine is also not the active principle, as it is present in very small quantity in ergot, and is to some extent removed by ether without the ergot losing its power.
Sphacelinic acid causes at first great spasmodic contraction of the blood-vessels, with rise of blood-pressure and subsequently symptoms of gangrene. The heart is unaffected. The gangrene in fowls appears to be due to permanent occlusion of the smaller arteries by a hyaline substance, which is formed during the time they are spasmodically contracted. In rabbits, guinea-pigs, and cats the substance is not formed, and no gangrene appears, but their walls degenerate, and blood is effused into various organs. When brought into contact with the intestine, sphacelinic acid, or its sodium salt, causes an inflammatory condition resembling that of typhoid fever, and ergot should therefore be avoided in this disease. Sphacelinic acid causes tetanus of the uterus (Robert). Cornutine causes spastic rigidity in frogs, lasting many days, even when given in very minute doses (1/32 of a milligramme) . In warm-blooded animals half a milligramme causes salivation, vomiting, diarrhoea, and active movements of the uterus, which are clonic and not tonic. The vessels are contracted and the blood-pressure raised. Sphacelinic acid and cornutine are therefore the principles which cause uterine contraction (Robert). As these active principles have not yet found their way into common use, it will be better for practical purposes at present to take the results of experiments, not with pure principles isolated from ergot, but only of an extract such as Bonjean's ergotin, although it is evident that the effects of different preparations may vary according to the proportions of ergotinic acid, sphacelinic acid, and cornutine which they contain. Thus if there be much ergotinic acid, the blood-pressure may be reduced, while if much sphacelinic acid and cornutine be present the blood-pressure will be raised.
Action of Extract of Ergot. - A solution of Bonjean's ergotin injected into animals causes an affection of the nervous system indicated by inco-ordination, anaesthesia, and paralysis; and death is due to paralysis of respiration.
The muscles are unaffected; the motor nerves are not paralysed, but on the contrary have their power somewhat increased.
The sensory nerves are paralysed, but it is uncertain whether the action is central or peripheral. The spinal cord is paralysed.
Circulation. Heart. - Its action on the frog's heart is not well marked; sometimes the injection of ergot produces slowing of the pulse-rate with stoppage in diastole, and in these cases direct mechanical irritation immediately after the poisoning does not cause the heart to contract.
Slowing and diastolic arrest occur after section of the vagi, but not after administration of atropine; hence they are due to the action of the ergot on the inhibitory apparatus in the heart itself.
Vaso-motor System. - The blood-pressure is considerably raised. When injected into the jugular vein, the blood-pressure, according to Holmes, is first lowered and then raised considerably, which he explains by supposing that the ergot passing to the right side of the heart causes contraction of the vessels of the lungs (by acting on their muscular walls), and hence lessens the supply to the aortic system and produces a fall of blood-pressure; but when it reaches the medulla it stimulates the vasomotor centre, and causes contraction of the vessels throughout the body and consequent rise of blood-pressure. This explanation is confirmed by the fact that if ergot is injected into the femoral artery, instead of a fall occurring at first there is a rise due to contraction of vessels in the limb, then a fall as soon as the blood reaches the lungs, and lastly a final rise.
This explanation is not accepted by Wood, who considers that the primary fall is due to the sudden introduction of a large quantity of ergot into the heart causing temporary paralysis, which will pass off as the drug is removed by the circulation.
The final rise of blood-pressure no doubt is due to the action on the medulla, for, if the cord be divided, very little rise follows the injection of ergot.
One other factor, which usually receives very little attention, must be taken into account (as well in this drug as in many others), viz. the effect on the blood-pressure of contraction of the internal viscera, as the intestines or uterus, for by contraction their blood will be driven out, and a rise of blood-pressure produced without any action on the vessels.
Respiration is usually slowed from the beginning, but in some animals (dogs) it is first quickened and then slowed. Death is due to paralysis of the respiratory centre.
Secretion. - The urine is increased in quantity, and the bladder tends to contract, due to the effect of the drug on its unstriped fibres.
Alimentary Canal. - Ergot markedly increases the peristaltic movements of the intestine.
Uterus. - Ergot causes contraction of the uterus, especially of the pregnant uterus. This contraction is not usually so much rhythmical as tetanic in nature, with occasional increases in violence. There is no complete relaxation between the spasms, as in the ordinary labour-pains. This is probably due to an action on the unstriped fibres of the uterus, since ergot causes contraction of involuntary fibres throughout the body, but it may be due wholly or in part to an action on the uterine centre in the spinal cord.
Uses. - Ergot is chiefly used in medicine for two purposes: (1) to cause contraction of the uterus; (2) to check haemorrhage by causing contraction of the vessels.
It is sometimes used to hasten delivery when the power of the uterine contractions is not sufficient to expel the foetus. But the tetanic nature of the contraction produced by ergot must be borne in mind. It does not increase the power of the labour-pains, but only the tonic contraction of the uterus. It should be carefully avoided if there be any mechanical obstruction to delivery, such as a rigid and undilated os uteri, a contracted pelvis, or an abnormal presentation, for in such cases it may so far interfere with the circulation in the uterus and placenta as to asphyxiate the foetus, or cause such contraction of the uterus as to produce rupture of its walls. After the child is expelled, the tetanic nature of the contraction produced by ergot is useful, and hence it is used to prevent post-partum haemorrhage. In these cases, it is administered either in the form of powdered ergot in warm water, or of the liquid extract, or by subcutaneous injection of ergotin. The last method gives the most rapid results, but if the ergotin is injected just beneath the skin it causes irritation and may lead to an abscess, hence it should be injected deep into a muscle, such as the gluteus maximus.
Ergot is also used very largely in the practice of gynaecology, for example, in chronic metritis, in sub-involution of the uterus, after abortions, to promote the expulsion of retained membranes, and in all atonic conditions of the uterus.
It is also used in certain cases of leucorrhoea, also in atony of the bladder and enlarged prostate.
It is used to check haemorrhage in fibroid tumours of the uterus; in haemoptysis (either internally 3 ss. of liquid extract every two, three, or four hours, or subcutaneously injected). In haematemesis also it is sometimes useful.
In some cases of chronic constipation it is useful, and appears to give tone to the bowel.
Subcutaneous injections of ergotin have been used in purpura, erythema, and in the prurigo of Hebra. Temporary improvement sometimes follows the internal administration of ergotin in urticaria.