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Cantharidin Poisoning: A Review
Norman Nyazema

Dr Norman

PhD Nyazem?e BSc,

Dept of Clinical Pharmacology Medical School: University of Zimbabwe PO Box A 178 AVondale Harare Zimbabwe

Curriculum

vitae

Dr Norman Nyazema is a Senior Lecturer and Chairman in the Department of Clinicai Pharmacology,Medical School, University of Zimbabwe. He has a specialinterest in pharmaco-epidemiology, promotion of rational drug use in the Dr Nyazema studied community and ethnopharmacology. pharmacologyat the New Medical School, Liverpool University. He has done extensiveresearchand published widely in ethnopharmacology.

KEYWORDS: Poisoning;Cantharidin
medicinal uses of cantharides as the powdered beetle have been well documented in medical literature t'2'3'4,5. Universallyr cantharides were used for their aphrodisiac properties or as a cure for impotence. In southern Africa, the insect is used by traditional medical practitioners for constipation and unspecified abdominal pains (this is the major use in view of the importance attached to bowel function), as an abortificient and to treat sexually transmitted diseases such asgonorrhoea r,5. These and other therapeutic uses of the blister beetles have been overshadowed by the reported cases of acute toxicity due to ingestion of the powdered insect 6'7'8. Patients often present with vomiting, epigastric pain, bloody diarrhoea and frank haematuria.

n almost all parts of the world where the blister beetles are found, they are or have been employed for medicinal purposes because of the effects of the active principle, cantharidin (Fig 1). There are several species of the blister beetle found in southern Africa that contain a significant amount of cantharidin. There are about forty speciesof the beetle which belong to the three geneta, Decapoloma, Mylabris and Cynollyrat. The most widely distributed genus is Mylabris and the most commonly used species in this genus is Mylabris alternata (Fig 2). The

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SA HUISARTSPRAKTYK FEBRUARIE 1989

The Zimbabwean strain of Mylabris alternata studied showed a 0. the compound was once legally formulated and marketed in various pharmaceutical dosage forms for a variety of purposes. Cynollyta sapp hirin a yielded l. Mylabris pustulata contain 2% of dried cantharidin'3.cerate of blister beetle which was used externally in the form of wax or ointment. iii) Tincture of cantharides. the compound was used long ago for treatment of pleurisy.were its vesicant. seemsto support its use as a wart remover2. Various methods of extraction employed have shown that different species of the beetle contain different amounts of cantharidin. 2: Myalbris alternata. Many of the reported caseswere of ingested cantharidinor cantharides. Recommended Treatment The recommended treatment for these poisonings is emptying of the stomach by inducing emesis or by aspiration and lavageand the use ofactivated charcoal and sodium sulphate.3Yot2 . are:i) Pulvis cantharides . A once common product was cantharone. arthritis and various It has been used as dermatological conditionsr5.55T0 content of cantharidin in the dried cantharidese. 1 GH. All studies agree that the toxicity of the beetle is due to canrharidin. The patient must also be given demulcent drinks freely (but not oils or fats) analgesics.t)orldBlister beetles purposes widefor medicinal The main actionsfor which cantharidinwasused besidesas an aphrodisiac. Toxicity Experience around the world has shown that the toxic effectsof the blisterbeetleareclinicallymore important than the supposed therapeuticeffects. iv) Collodion picis cantharidum . the active ingredient in hair tonics for its rubefacienteffect. pneumonia. v) Cantharidin ointment in benzoated lard once used as a dressing to produce vesication.1r.}Vot0 and C anthar i s aesi ca t or i a gave 0. The anti-cancer action of cantharidin that has been demonstrated in mice.r2.the powdered blister beetle.used externally as cantharidin pitch plates. Percutaneous absorp- Fig. Uses Before the toxic effects of cantharidin had been brought to light. The lowest yield was obtained from Epic auta p estif era 0. CANTHARIDIN treatment of warts. a l0To mixture of cantharides in alcohol and castor oil.6%13. counter-irritant and rubefacient actions3. a 0r7% collodion of cantharidin which was used for the are still used'z. 7l SA FAMILY PRACTICE FEBRUARY 1989 SA HUISARTSPRAKTYK FEBRUARIE 1989 . Research in the field has been focused on the quantification and qualification of the toxic principle in the beetle e'r0. an acid anhydride of cantharidic acid. With respect to its counter-irritant action.r2'r4.Cantharidin Poisoning Fig. which have since been phased out because of toxicity. and anti-inflammatory agent such as hydrocortisone. ACID CANTHARIDIC These reported casesof poisoning by cantharides have stimulated interest in the field of pharmacology. ii) Cestan cantharidis . Other pharmaceutical products of cantharidin.

The ectopics.One hour after swallowing. Fatal arrythmias in cantharidinpoisoningcould not be explainedby any electrolyte change in the blood and are suggestedto be due to the direct cardio-toxic action of the drug. on the gut mucosa It is the direct effect of cantharidin on the gut gastricmotility leadingto mucosa that stimulates increased influx of water into the gut lumen which causes the diarrhoea. On the ECG. is manifestedas haematuriaand proteinuriaT Cantharidin also irritates the urinary bladder leadingto increased contractilefrequencyof the detrusormuscle. Cantharidin 175 mg. and transient T inversion. Post-mortem examination of the kidneys of one victim of grosshaemorrhage revealed cantharidinpoisoning into the tubules with damage to the tubular epithelium6. magnesium trisilicateand paracetamol. h e h a d d e v e l o p e d a s e v e r e h e a d a c h e . The damage to the nephrone leads to glomerulonephritis which andglomerularnecrosis 8. O Patient A 36 year old man went to a ngangafor treatment of dysuriaand umbilical abdominalpain.corrodes the oesophageal lining.the man started vomiting.Severeinflammation and vascularisation of the genito-urinary tract of rats were priapism can lead to impotence due to the permanent penile damage that resultsr6. Reproductioe system Toxicity of cantharides on the rat foetushasbeen demonstratede. throat and pharynx.in addition to local effects in the mouth.elevations waxingand waningof T waves of the ST segment.who swallowed of a preparation containingcantharidin. Prolonged severe SA FAMILY PRACTICE FEBRUARY 1989 tz SA HUISARTSPRAKTYK FEBRUARIE1989 .After oral administration.a severe burning pain is felt involving the lips and throat. blistering and ulcerating effects of cantharidin havebeenreported. He responded to treatmentincluding IV fluid plus tetracycline. tachycardiawas thought to be a compensatory mechanism of the body to the cantharidininduced 67.peri-pelvic and periuteric haemorrhage hasalsobeenreported. followed by bloody diarrhoea. O Patient A 25 year old man admitted to Parirenyatwa Hospital. making swallowingvery painful. developed e l e c t r o c a r d i o g r a p h i c h a n g e si n d i c a t i v e o f myocardial damage. sodium succinate and with ampicillin'3. Crampy abdominalpains causedby the excoriating. when swallowed. Cantharidin-induced for P wave toxic atrial fibrillation wasresponsible were deformationwhile the other ECG changes due to toxic myocarditis.tachycardia. In females. stomachwashand pethidine.Cantharidin Poisoning tion of cantharidin leading to systemictoxicity must not be under-rated since its high lipoid/ waterpartition coefficientpermits rapid diffusion acrossthe stratum corneum. When he was brought to Parirenyatwa Hospital. O Patient about2 ml An 18yearold woman. A caseof systemic poisoning after contamination of the skin hasbeen reportedin a 22 month old childT. which responded to treatment with hydrocortisone. Suddendeath was attributed to ventriculardysrrythmiasT.H e responded to treatmentwith IV fluid. cantharidincardiohypotension toxicity showedas deformedP waves. the compoundirritates the urethra and together with its rubefacient action causesincreased blood flow to the penis leading to severe priapism.In men. Urinog enital tract effects The most common systemic toxic effect of cantharidin is renal damage 6'8. Today the toxic effectsare regarded a. Cantharidin has been shown to Before the toxic effect was discoaered it was aery widely used for a z)ariety of purposes observedfollowing chronic exposureto cantharidin. He was given an unknown amountof cantharides powder to drink and developed haematuriashortly after. G astrointes tinal tract Cantharidinhasa blisteringeffecton the mucous membranes. doses of the compoundwere frequentventricular fibrilation or asystole.s moreimportant than the therapeutic effects Car dioo ascular eff ec t s Cantharidin has been reported to have arrhythmogenic and cardiotoxic effects after systemic The arrhythmiasassociated with high absorption. slowly recoveredafter ingestinghalf a powder to treat urethal teaspoonof cantharides discharge.

Chen Ruiting. 3. Toxicity studiesof the Zimbabwean strain of Mylabris alternata in rats. Polak A. Gelfand M. Arch Dermatol 1977.2nd ed. Harisberg J. 1965:450. Thomson uf M. 5. Two patientswho developed a Guillain-Barre type of flaccid paralysistwo weeksafter acutetoxic effectsof cantharidin and subsided. with a persistanterection. et al. Cohen L. Cantharidin poisoning with neurological complications. 73 SA HUISARTSPRAKTYK FEBRUARIE 1989 . 17. Donald T. Isolation of cantharidin from Cyanollyta sapphirina. A textbook of pharmacology (2nd Ed).214 (3):591-2. Chin Med J 1980. Manual of medical therapeutics (22ndEd). Forensic Sci Int 1979 l3(3):182-92. 1963: Cantharide-powder is aery popular amongblack malesas an aphrodisiac . Ndemera B. 8. Goodman L and Gilman A. Iyer B H and Guha P C. 1982: 1730. Hua Ze. This has been confirmed by results from pregnanr mice which weregiven oral doses of cantharidin. et al. Pitman Medical Publishing House Co Ltd.were reported in JohannesburgrT.28th ed. Fung H Y M. 13. Fiesen J M. London: The PharmaceuticalPress. 4. Presto A J and Muecke E L. Hepatotoxicity The hepatotoxicity of cantharidin has been reported. SalamaR B. Martindale W. Mambo Press:Gweru. 93(3): 183-7. is questionable. 7. In this respect. The patient was also put on high fluid intake. Unpublished B Pharm project.haematuria. Rabkin S S. 65:614-5.Cantharidin Poisoning causecontractionof the isolateduterine muscle. Rosenberg E W.Cantharidin did not induce abortion in these animals but in utero death of the foetus. 9. A dose of Spanish Fly. Drummond R. S Afr Med J 1984. Department of Pharmacology. Bangalore: Indian Institute of Science.The priapism respondedto aspirationand diazepam. University of Zimbabwe. Poisoning by cantharidin. Seaeralspecies of the blister beetle Africa contain found in southern large amountsof cantharidin References l. Neroous systetn Rare cases of fatal clonic convulsionsand loss of consciousness due to the drugshavebeenreported 6'7.1970:994. However. 10. Costrini W. This usually happens well before the patient comes to consult the western type of health system. London: Blackwell Scientific Publication. 1985:308. Unfortunately.Poisoningmay occur during this time as an untoward effect in the normal use of the traditional remedy or of incorrect use. London: The MacMillan Co. 4th ed. Sexual hygiene and pathology. Oliven J F. 15. for his valuable comments. The pharmacological basis of therapeutics. Acknowledgement Many thanks to Prof Pieter Joub_ert. Deseta J C H. Brit Med I 1954. 56: 174-6. Ferris J A J.2: 1384-6. The traditional medical practitioner in Zimbabwe. Yang Jinlong. London: Little Brown Co 1979: 25.26:268-9. the employment of cantharidin by traditional healers in Zimbabwe as an abortificient. Bowman $0 C. Mavi S. Nickolls L C. MEDUNSA. Cantharidin poisoning.ll38: 1154. J Phafm Sci 1967. has been shown8. Isolation of cantharidin from Epicauta pestifera. J Pharm Pharmacol 1974. Varying degreesof hepatic parenchymatousdegeneration and lossof cell individuality because of distortion of cytoplasmicborders. Mabaya D. diffuse pain in the abdomen and headache. Carver J D. Studies on antitumor actions of cantharidin. 1980.Scatteringof bile pigment containing hepatocytes and alsoan intestitial oedemawith slight fatty changes in the liver have been observed6. Walter u7 G. patients come to hospital when it is too late to do anything when much damage hasalready beendone. 1986.Brit Med I l95a. 12. 6.the cantharides powder is very popular among males who use it as an aphrodisiac with dire consequences. 14. Pathological features of cantharidin induced cardiomyopathy: lack of correlation between electron microscopic and histopathological myocardial damage. J Am Med Assoc 1970. ll. SA FAMILY PRACTICE FEBRUARY 1989 3t-9. However. Treatment of warts at home.with dire consequences Comment practising medicine among Blacks in Physicians southernAfrica should continueto be awarethat many of their patients use traditional remedies. this does not mean that this is what happens in an intact animal. Cantharidin Mylabris pustulata. O Patienr A 3l year old man presentedat Parirenyatwa Hospital. The extra pharmacopoeia. 16. 2.2:1386-7. Rand M J.