Eckerling, B.

Gans, B.

Sax, B.

English

AJOL - African Journals Online

22 Augustus 1959 S.A. TYDSKRIF VIR GENEESKUNDE 707THE USE OF PH 203 (pANTHESINE HYDERGINE) IN THROMBO-EMBOLICDISEASES IN OBSTETRICS AND GYNAECOLOGY*B. GANS, M.D., B. ECKERLING, M.D. and B. SAX, M.D.From the Obstetrical and Gynaecological Department, Beilinson Hospital, Petah Tiqva, IsraelThrombopWebitis, pWebothrombosis and pulmonary in-farction are amongst the most serious complications follow-ing operations and deliveries. Progress in medicine hasnot succeeded in limiting them. ' ·3 Out of the great numberof prophylactic and therapeutic methods tried, viz. exercises,early ambulation, elastic bandaging, zinc-lime casts, veinligation and others, anticoagulants-dicoumarol and heparin-are the most successful. However, the possibility ofserious bleeding should always be considered when anti-coagulants are used.4The action -of dicoumarol has a latent period of 24-96hours. The fact that it is given orally prevents its use in theimmediate post-operative period. The drug is dangerousin patients who have a low albumin blood level or liverdamage, as well as in patients suffering from ulcers in theintestinal tract. It presents hazards during and immediatelyafter delivery as well as during and after an operation. Itcrosses the placental barrier and it is excreted in the milk,thus endangering the foetus and the newborn.5 ,6 The actionof heparin. is of short duration and necessitates· frequentdetermination of clotting time.These disadvantages do not deter us from using anti-coagulant drugs, although they compel constant readinessand necessitate laboratory facilities and rather frequentexamination, and the search continues for new and moreadvantageous drugs in this field. 7•12In 1940 Ochsner and De Bakey,'3 from New Orleans,following Leriche and Kunlin,14 published a report whichlaid stress on the occurrence of reflex constriction of ar-terioles and' veins in a whole region as a result of a lesionof part of it. This leads to extensive damage to the circula-tion of the region, resulting in hypoxia and damage to thecapillary endothelium. Increased.-exudation occurs. as wellas a rise in tissue pressure, resulting in oedema and pain.Leriche15 believes that novocaine used as a local anaestheticblocks the painful reflex induced by trauma or vasculardiseases and restores the neurovegetative equilibrium.Others'6.'9 used novocaine or alcohol with good results,injecting them directly into the sympathetic ganglia or theconnective tissue surrounding them to relieve pain in adetermined region.In 1951 Rappert,9 of Vienna, in acute cases of thrombo-pWebitis, tried the action of procaine by intravenous drip,combined with hydergine in tablet form or by injection.In the course of experiments procaine was replaced by itsderivative, panthesine, which was found as efficient yetless prone to produce unpleasant side-effects such as dizzi-ness, nausea and a fall in blood pressure.In contrast to anticoagulants, clinical trials with a com-bination of panthesine and hydergine have shown thatthey do not affect the coagulation of the blood. Panthesineis a local anaesthetic (p-aminobenzoyl-N-diethyl-Ieucinolmethane sulphonate). It also produces anticholinergic,* We are indebted to the Pharmaceutical Laboratories San-doz, Basle, Switzerland, for placing at our disposal the necessaryquantity of PH 203.antihistaminic, spasmolytic and sedative effects. It is lesstoxic than procaine. Hydergine is a mixture of the methanesulphonates of dihydro-ergocornine, dehydro-ergocristineand dihydro-ergokryptine in equal proportions. Contraryto their natural forms, which constrict blood vessels, thehydrogenated alkoloids relax the arteriolar tonus.20Recently, Hausarnmann2l reported good results afterprophylactic treatment with PH 203 (panthesine 200 mg. +hydergine 0·3 mg.) of 309 surgical patients, as comparedto an untreated control group of 253 cases. Konigs22 pub-lished a postpartum case of multiple thrombosis and em-bolism, in which anticoagulant therapy was unsuccessfulbut treatment with PH 203 led to rapid improvement andcure. Morger23 also employed PH 203 as a prophylacticbefore operation, and reported good results as comparedwith untreated cases in previous years.In view of these good reports we have used PH 203 inpatients with thrombopWebitis in obstetric and gynaeco-logical practice.MATERIAL AND METHODThe number of patients with thrombo-embolic complica-tions treated with PH 203 during the period from 1 November1956 to 1 March 1958 can be seen from Table 1. BesidesPH 203, and hydergine in tablet form at the conclusionTABLE ITherapeutic Prophylactic TotalObstetrics 58 4 62Gynaecology 18 8 2676 12 88of the treatment, these patients were not given any Qthertherapy than antibiotics where this was considered neces-sary. In most cases the patients received the usual physicaltreatment, viz. elevation of the affected limb, wet dressingor elastic bandage. In our department the usual routine isambulatIOn 24 hours after delivery or operation.TherapyWe have divided our therapeutic cases into 3 groups, viz.:1. Light: Superficial thrombophlebitis of the leg, 26 cases.2. Medium: Deep thrombopWebitis of the leg, 36 cases.3. Severe: Pulmonary infarction, pWegrnasia alba dolens,or deep pelvic thrombopWebitis, 14 cases.We did not take into consideration temperature and pulse,since these signs may be produced by the primary condition(after delivery or operation). Moreover, most patientsreceived antibiotic therapy, which influenced these signs.Group 1. Patients belonging to this group received 2intramuscular injections daily of PH 203 for a period of3-8 days, followed by one injection of PH 203 plus oneinjection of O· 3 hydergine for 1-3 days. At the conclusionof the treatment by injections, the patient received 2-3hydergine sublingual tablets daily at home for 7-10 days.Group 2. Patients showing symptoms of moderate severityreceived one intravenous infusion of PH 203 plus one intra-708 S.A. MEDIC'AL JOURNAL 22 August 1959~Q 9Q 9~ Q~ QQ QQ Q~ QQ Q~ 11 00 00CROUP ~muscular injection daily, for 3-5 days. After this, 2 intra-muscular injections were given per day till disappearanceof signs. Finally, hydergine injections and tablets wereadministered, as with group l.Group 3. Patients with severe thrombosis and embolismTt>-eeived one ampoule of PH 203 as an intravenous infusiontwice daily for 3-5 days; then intramuscular injectionstwice daily till disappearance of all signs. Hydergine injec-tions and tablets were given as with groups 1 and 2.The following diagram indicates the methods of treatment.CROUP 1QQ QQ QQ QQ QQ QQ 9f 00GROUP 2Copatients who were recelvmg intravenous infusion the rateof administration was slowed down when side-effects ap-peared.Two patients received intramuscular injections of PH 203because of thrombosis in one leg; both developed thrombosisin the other leg on the 8th day of treatment. This conditioncleared up on continuation of treatment.Prophylaxis.The drug was administered prophylactically .to 12women, 8 before gynaecological surgery, and 4 beforedelivery. All had a history of severe and repeated thrombo-phlebitis; some of them had had pulmonary infarction aswell. These patients received intramuscular injection ofPH 203 only-one ampoule twice daily for 3-4 days beforethe operation or delivery, on the day of operation or deliveryand after it for 6-10 days. In none of this small series of12 cases was the post-operative or postpartum course com-plicated by thrombo-embolic disease. Side-effects werelight and disappeared on continuation of the treatment.I.M. INJECTION OP PH 203D:PUSION OF 200 cc GLUCOSE PWS ONE AMPULEOP PH 203~ I.M. INJECTION OP 0.3 HYDERGINESUMMARYDISCUSSIONAn improvement in the local status, as well as in the generalcondition of the patient, was noted soon after therapywith PH 203 was started. An outstanding feature was dis-appearance of pain from the affected area. Oedema, tender-ness and Homans' sign,* if present, disappeared rapidly.It seems that the drug acts on those arterioles and veinsthat are not affected by the thrombosis but react by reflexaction from affected blood vessels. 24 ,25 Apparently eventhe affected section benefits from the circulation in thesurrounding tissue and tends towards better and more rapidorganization, and even recanalization.26 Probably the.drughas an identical effect on the pulmonary blood vessels.It is interesting to note that few of pur patients neededsedation. As is well known, panthesine has a general anal-gesic effect like that of procaine. We were rather impressedby the rapidity of pain relief; the pain disappeared in theaffected region very soon after the treatment was started.As regardS administration and dosage, we believe that insevere cases one should start with. 2 intravenous infusionsdaily, at least for the first few days. Our experience in pro-phylactic treatment is limited, but we were much impressedby the 12 patients with a past history of thrombo-embolicdisease whose course after prophylactic acl.mirristration ofPH 203 was not complicated by the disease after operationor delivery.Side-effects were light and disappeared in spite of con-tinuation of the treatment. The therapy, both in thrombo-pWebitis and pulmonary infarction, and also prophylaxis,appear to be efficacious.The treatment is easy and convenient. There is no needfor laboratory examinations during therapy, and the drugmay therefore be used in certain cases on an ambulatorybasis.00AverageLength ofTreatment(days)5811·7Length ofBedConfinement(days)1- 51- 93-13TABLE ITMarkedImprovementafter(days)1-31-32-400 HYDERGINE TBL. SUBLINGUAL 0.3 Jig.For intravenous infusion PH 203 was diluted in 200 ml.of 5% glucose. The duration of the intravenous drip was90-120 minutes.Only 6 patients, all from the first group, did not requirecomplete bed rest; all the other patients were confined tobed for various periods. All were permitted to ambulatebefore conclusion of the treatment and disappearance ofthe symptoms.Table II shows in summary for each group how longit was before the marked improvement took place in thepatients' condition, the length of confinement to bed, andthe average length of treatment.GroupLightMedium ..SevereIn 9 patients (7 of these receiving intravenous drips and2 receiving intramuscular injections) secondary side-effectsappeared. These were: dizziness, feeling of fainting, tinnitus,and feeling of 'pressure' in the head. Drop in blood pressurewas not noted. The side-effects lasted for a short periodand disappeared on continuation of the treatment. In1. A survey of therapy with PH 203 in thrombo-embolic diseases following operation or delivery is presented.2. 76 women, whose primary condition was complicated* Discomfort behind knee on forced dorsiflexion of foot-asign of thrombosis in the leg.22 Augustus 1959 S.A. TYDSKRIF VIR GENEESKUNDE 709by thrombo-embolic disease, were treated, and 12 caseswere treated prophylactically.3. The results obtained were satisfactory.4. In the {;ourse of the therapy no laboratory facilitiesare required, no danger of bleeding exists, as far as thedrug is concerned, and side-effects are rare and mild.REFERENCES1. Felden, O. A. (949): Surg. Gynec. Ohster., 78, 431.2. Fowler, E. F. and Bollinger, J. A. (1954): Surgery, 36, 650.3. Lasagni, F. (1948): Gynaecologia (Basel), 145, 295.4. Barker, N. W., in KroIler. T. and Merz, \V. R. ed. (1955): AnticoagulantTherapy in Thrombosis and Embolism. p. 683. Base!: Schwabe.5. Goodman. L. S. and GiIlman. A. (1955): The Pharmacolos:ical Basi.s ofTherapeutics, pp. 355-361, 364-366, 577-583, 883-893. New York: Macmillari.6. Merz, W. R. and Breitner, J. (1956): Geburts. u. Frauenheilk., 16. 1392.~ Ochsner, A. and De Bakey, M. r. (1940): J. Amer. Med. Assoc., 114, 117.8. Ravdin, r. S. and Kirby, C. K. (951): Surgery, 29, 334.9. Rappert, E. (1952): Zbl. Chir., 77, 1729.10. Caithamel, \V. (1955): Uber die B~handlung der LUllgenl'mbolie. Kongress·referatband der inrernationalen Tagung Uber Thrombose und EmboJie.p. 651. Basel: Schwabe.11. Klausgraber, F. (1956): Wien. med. Wschr., 106,945.12. Morger, R. (1957): Praxis, 46, 331.13. Ochsner, A. and De Bakey, M. 1. (1950): J. Amer. Med. Assoc., 144, 831.14. Leriche, R. and KUnlin, J. (1934): Presse med., 42, 1481.15. Leriche, R. (1927): Ibid., 35,497.16. MandJe, F. (1925): Arch. klin. Chir., 136. 495.17. Idem. (1947): Para\'~rrebraJ Blork in Diagnosis, Prognosis and Thnapy.p. 34. New York: Grune and Strattoo.18. Swetlow, G. 1. (930): Amer. J. Surg., 9, 88.19. White, J. C. (1930): J. Amer. Med. Assoc., 9~, 13S2.20. Popkin, R. J. (1951): Angio!o"v. 2, 114.21. Hausarnmann. E. (1957):'Sch,veiz. med. Wsch·r., 87,219.22. K6nigs, J. (1957): Med. Klin., 52, 1659.23. Morger, R. (1958): Praxis. 47, 549.24. Bauer, G. (1940): Acta chir. scand., vol. 84, suppl. 61.25. Chao\). de Fuente and Diaz. Garcia (1952): Rev. din. esp., 45, 277.26. Vog!er, E. (1953): Fonschr. Romgenstr., 79, 354.THE JOURNAL OF DR. MACKRILLC. H. PRICF, Head of the Department ofPharmacy, Rhodes University, Grahamstoll'nLying in the Cory Library for HistoriCal Research in the RhodesUniversity is a manuscript book, the journal kept by one of theearly doctors of the Cape Colony, Joseph Mackrill (1762-1820) 1who made his mark in his history by the introduction of buch~into medicine in Britain' and the introduction of tobacco growinainto the Cape. <>The book, which has survived the 140 years since the writer'sdeath in a tolerably good condition, is rarely dated, and only onone or t",:o <?ccaslOllS records the happenings of the day. Hecollected m It a great deal of miscellaneous information hisinclinatio~s being very catholic. The subjects of his writing 'varyfrom medIcal notes to earthquakes, from Indian water mills tothe ~<?ra of the Cape, and bear witness to the high degree oferudl~l?n to be found amongst the Cape's early medicalpractitIOners.Dr. Mackrill appears to have been a ship's surgeon or a confirmedtravel.ler: He had a distinct leaning towards geography. HisdescnptlOns and notes touch upon South America the USASouth Africa and India; on one occasion he rec'orded withsome precision the exact location of a hitherto uncharted rock.Whether Dr. Mackrill was a regularly qualified practitionerdoes not appear from records, but he registered with the SupremeMedical Committee of the Cape and was licensed to practice as asurgeon in ] 807. It is highly probable, therefore, that he wastramed as a surgeon by apprenticeship either with a surgeon orsurgeon-apothecary. Perhaps he attended one of the privatescho~ls of anatomy in London, but he is not mentioned anywhereas belllg M.C.S., or L.S.A., the usual qualifications in those daysfor persons who had not graduated M.D. of a University.The first medical note in his diary is entitled, 'For preventingsudden Death from drinking cold water'. 'Twenty drops ofLaudanum', he writes, 'repeated every twenty minutes until painand spasm are releived (sic)'. The dose may be increased from40 to 60 drops repeated as above 'if the Symptoms are very urgentand the Patient adult'.It is natural to expect that· Dr. Mackrill would feature in hisarmamentarium remedies unknown to the modem practitioner.'Salep, the dried root of the Orchis', is referred to as being extremelynutritious and 'should always be carried by Ships on long voyages'.'Sago or Palma Japonica' is mentioned as 'the best food for Childrenas it never ferments in the Stomach'.Of the more familiar but now almost defunct broom he says:'Fulk, the first Earl of Anjou, went in Pilgrimage to Jerusalemwhere he was soundly scourged with Broom stalks which growthere. He ever after took the surname of Plantagenet or Broomstalkand which descended from Henry 2 to Richard 3d inclusive'.Still in frequent use is senega, of which he "''rites, 'Polygala,Milkwort, the Seneka or Rattlesnake Root, is a species muchused in Virginia and with great success in the pleurisy'. It seemshighly probable that he had come into first-hand contact with theuse of senega in the American colonies, a theory supported bymany references to this country. Indeed so wide were Mackrill'stravels that he could only have been a ship's surgeon.Mackrill did not accept every suggested remedy. Under 'in-flammation of the Eyes' he records 'It is very confidently reported,however extraordinary it may appear, that the Down under theWings of the Turkey Buzzard, being applied to the Eyes, relievesalmost immediately, every Species of Inflammation, whether fromInjury or Disease'.'Rheumatism', he says 'is relieved by a strong Tincture of PokeBerries in Brandy, a Wine Glassfull every night and morning,Ib i Berries to a Quart of Brandy.' He seems to have been up todate in making his medicines pleasant and interesting to thetaste!Antimony was in common use in those days, as old prescriptionbooks testify, and it is not difficult to guess that many peopledied as a result of overdosage. Dr. Mackrill wrote: 'The tooviolent effect of Antimony when it acts by vomit, may be restrainedand carried thru the Intestines by means of a little commonsalt in any small Drink or by a draught of water acidulated withthe Acidum Vitroli Dilutum.'It is revealing to study entries made concerning remedies which'are now in daily use. 'Digitalis, by some powerfully recommended',he notes, 'in all inflammatory Diseases particularly-by othersregarded as destructive and poisonous and every bad Qualityascribed to it. If perhaps we steer a middle Course, we shalloften find it a very -salutary Remedy. Dr. Thornton a man ofgreat Eminence on the Mountains of medical Science, has frequentlyfound it the best of all Remedies in the Scarlet Fever. I havegreat Reason to be of opinion that a long continued use of it inany Disease is attended with fatal consequences-but I will notdiscard it.'Practitioners of today will find it strange to read of tea as amedicament. 'Bohea tea', to use the old description, was recom-mended 'in very strong Infusion and the Leaves also eaten'.'When there is no visceral Disease occasioning the Dropsy it maysucceed by virtue of its diuretic and astringent properties.'Under the heading 'Nephritic Complaints', camphor dissolvedin water and spirits of wine is recommended as 'certainly anexcellent Remedy'.In a later jotting he writes: 'Two remarkable-!>ymptoms attendingpretty uniformly an Inflammation of the Liver are not noticedby any Writer upon the subject; these are an almost indiscribable(sic) tingling at the Extremities of the Fingers of the Right handand numbness of the arm and a coldness of the Pinis (sic).'Snake bite has always been a great source of worry to physiciansand before the advent of antivenin all sorts of remedies weretried empirically. 'Olive oil internally and externally applied isperhaps the safest and most effectual of all Remedies; Oil ofVitriol externally to the Bite'-certainly a most drastic remedy.Mackrill is credited with having introduced buchu into Europeanmedicine,' but he says very little about it in his notes. 'Bucku(Diosma) used in bruises internally and externally. With thestinking powder of the leaves the Hottentots perfume or stinkthemselves.'He certainly seems to have been of an enquiring turn of mind,paying great attention not only to the flora of the countries hevisited, but also speculating upon the probable medical uses ofthe plants he came across. 'Stoebe, bastard Ethiopian Elickrysum(sic}-its roots smell strongly of Valerian and are perhaps as

The use of PH 203 (Panthesine hydergine) in thrombo-embolic diseases in obstetrics and gynaecology

https://www.ajol.info/index.php/samj/article/download/173299/162703

The use of PH 203 (Panthesine hydergine) in thrombo-embolic diseases in obstetrics and gynaecology

Abstract

Similar works

Full text

Available Versions

AJOL - African Journals Online