Indian J Physiol Pharmacol 2008; 52 (3) : 311–314 OPINION PATHOPHYSIOLOGICAL APPROACH TO THE MANAGEMENT OF SCORPION ENVENOMATION S. B. DESHPANDE*, R. PANDEY AND A. K. TIWARI Department of Physiology, Institute of Medical Sciences, Banaras Hindu University, Varanasi – 221 005 ( Received on July 3, 2008 ) Abstract : Indian red scorpion (Mesobuthus tamulus; MBT) produces lethal stings and is a matter of concern in certain parts of India. MBT envenomation produces multi-systemic involvement, thus presents difficulty in the management. Symptomatic treatment has been practiced earlier that failed to relieve the toxic effects of the venom. Therefore, present manuscript deals with pathophysiologically based approach in the management of toxicity considering the merits and the demerits of treatment protocols so as to evolve a consensus in the treatment strategies of scorpion envenomation. Key words : Indian red scorpion stings anti-scorpion venom insulin α-blockers parasympatholytics kinin synthesis inhibitors kinin antagonists INTRODUCTION presently available management protocols on scorpion envenomation. This will enable Scorpion stings are important causes of to evolve a consensus on the effective morbidity and mortality in India and treatment strategy of scorpion stung throughout the world (1). Indian red scorpion victims. (Mesobuthus tamulus; MBT) envenomation presents with multi-systemic abnormalities In recent years, a number of toxins have posing a great health problem (2–8). Even been isolated from MBT venom such as though the scorpion stings are responsible Iberiotoxin, a high conductance Ca2+ for the high morbidity and mortality in activated K+ channel blocker (14); certain parts of India, the broad outline of Tamulustoxin, a novel K+ channel blocker scorpion envenomation and consensus in the (15); Insect toxins like lepidopteran-selective treatment strategies with their merits and toxin (16) and BtITx3 (17); Tamapin, a small demerits are yet not available (9–13). This conductance Ca2+ activated K+ channel concerns not only the physicians, the blocker (18); BTK-2, an inhibitor of voltage- patients and the attendants but the scientific gated K+ channels (19); PoTx, a high workers also. Therefore, present manuscript molecular weight polypeptide pulmonary discusses the merits and demerits of oedema producing toxin (20), etc. Of these *Corresponding Author : Phone : 91-542-2369069; Fax : 91-542-2367568; E-mail: [email protected] 312 Despande et al Indian J Physiol Pharmacol 2008; 52(3) Iberiotoxin and PoTx are lethal (14, 20). useful in patients presenting with hypertension Mechanism of action of each of these toxins (sympathetic dominance). In case of is different. Therefore, variability in hypotensive patients with parasympathetic symptoms and signs is likely to persist. dominance, parasympatholytics may be Hence, the treatment of scorpion used under close observation as the envenomation syndrome can only be effective parasympathetic effect is often transient. when the underlying pathophysiology of Either of these drugs pharmacologically individual case is considered. antagonize the autonomic activity without reversing the underlying pathophysiology. Recently, utility of anti-scorpion venom (ASV) in the management of scorpion A study elsewhere has presented the envenomation syndrome has been reported comparison of ASV along with other (9, 10, 21, 22). In situations where the treatments including prazosin (10). However, identification of the species of scorpion is it is very difficult to compare the effectiveness possible, a species specific ASV is the of ASV v/s prazosin in the above study treatment of choice (22). But in most of the design. ASV and prazosin have different scorpion stung cases, identification of mechanisms of action, they should not be scorpion species is difficult. In such considered as replacement of one another situations, an ASV raised against a particular rather patients should be treated with ASV species will not be able to protect. Since or prazosin or both as per the need. scorpion venom contains many toxins as mentioned before, an ASV raised against all Metabolic abnormalities, myocarditis, the toxic principles present in various electrocardiographic alterations, hemodynamic scorpion venoms (polyclonal ASV) is a better changes and pulmonary oedema are reported alternative (14–20). However, studies after scorpion envenomation (3–5). These elsewhere have contradictory opinion abnormalities were successfully reversed by regarding the effectiveness of ASV (10). This insulin administration (3–5). However, the may be due to the fact that the scorpion detailed study on the mechanism of action venom is poorly antigenic (23), thus, the of insulin is required in scorpion stung cases. antisera raised may not be able to neutralize the toxins effectively. Therefore, the Pulmonary edema is an important cause availability of proper and effective ASV is a of death after scorpion stings (5, 10). Kinins necessity. Further, ASV should be used at are being implicated in the pathophysiology earliest possible time after the sting to get of pulmonary edema (6). PoTx is emerging effective response as bio-distribution of crude as an important cause for production of venom occurs in vital organs/systems within lethal pulmonary edema after scorpion 5 minutes (24). Therefore, time of injection envenomation which mediates its action involving B receptors (20). Therefore, the of ASV also affects the efficacy. 2 role of kinin synthesis inhibitor like aprotinin The α-1 adrenergic receptor antagonists was suggested (8, 20). Studies elsewhere like prazosin (25) and tolazoline (3) have been have also reported reversal of pulmonary used to treat the autonomic storm following edema by aprotinin after envenomation with scorpion envenomation. This regime may be other species of scorpions (12, 13, 26). Indian J Physiol Pharmacol 2008; 52(3) Pathophysiological Approach to the Management 313 Therefore, the treatment protocol should also pulmonary oedema. include aprotinin/B2 receptor antagonists to treat the scorpion envenomation besides Thus, with the present knowledge, it other therapies. appears irrational to advocate a fixed treatment protocol for all cases of scorpion Captopril has been used to treat the sting. Rather the treatment should be based pulmonary edema (11). Captopril being ACE- on the underlying pathophysiology of the inhibitor is known to increase endogenous particular case. ASV, insulin, α-blockers, kinins (27). Results from our laboratory parasympatholytics, kinin synthesis have shown that captopril induced inhibitors/kinin antagonists may be used cardiopulmonary changes are similar to depending on the pathophysiology of individual venom (6). Therefore, the use of captopril case. However, the rationale for therapeutic requires reconsideration in the treatment of use must be clear before any intervention. REFERENCES 1. Murthy KRK. On scorpion envenoming 7. Bagchi S, Deshpande SB. Scorpion (Buthus syndrome, problems of medical ethics and tamulus) venom toxicity on cardiopulmonary accountability in medical research in India. J reflexes involves kinins via 5-HT3 receptor Venom Anim Toxins 2002; 8: 3–17. subtypes. J Venom Anim Toxins 2001; 7: 25–44 2. Tiwari AK, Deshpande SB. Toxicity of scorpion 8. Pandey R, Deshpande SB. Protective effects of (Buthus tamulus) venom in mammals is aprotinin on respiratory and cardiac influenced by the age and species. Toxicon 1993; abnormalities induced by Mesobuthus tamulus 31(12): 1619–1620. venom in adult rats. Toxicon 2004; 44: 201–205. 3. Murthy KRK, Vakil AE, Yeolekar ME, Vakil YE. 9. Joshi SR, Sapatnekar SM. Stings and Hopes: Reversal of metabolic and electrocardiographic Toxinomics and autonomic storm in the Indian changes induced by Indian red scorpion (Buthus red scorpion (Mesobuthus Tamulus Concanesis, tamulus) venom by administration of insulin, Pocock). J Assoc Physicians Ind 2007; 55: alpha blocker and sodium bicarbonate. Indian J 11–13. Med Res 1988; 88: 450–457. 10. Bawaskar HS, Bawaskar PH. Utility of scorpion 4. Murthy KRK, Vakil AE, Yeolekar KE. Insulin antivenin in the management of severe administration reverses the metabolic and Mesobuthus tamulus (Indian red scorpion) electrocardiographic changes in acute myocarditis envenoming at rural setting. J Assoc Physicians induced by Indian red scorpion venom in Ind 2007; 55: 14–21. experimental dogs. Indian Heart J 1990; 42: 35– 11. Krishnan A, Sonawane RV, Karnad DR. 42. Captopril in the treatment of cardiovascular manifestations of Indian red scorpion 5. Murthy KRK, Shenoy R, Vaidyanathan P, (Mesobuthus tamulus Concanesis Pocock) Kelkar K, Sharma N, Birevar N, Rao S, Mehta envenomation. J Assoc Physicians Ind 2007; 55: MN. Insulin reverses haemodynamic changes 22–26. and pulmonary edema in children stung by the Indian red scorpion Mesobuthus tamulus 12. Ismail M, Fatani AJY, Dabees TT. Experimental concanesis, Pocock. Annals Trop Med Parasitol treatment protocols for scorpion envenomation: 1991; 85: 651–657. a review of common therapies and an effect of kallikrein-kinin inhibitor. Toxicon 1992; 30: 6. Bagchi S, Deshpande SB. Indian red scorpion 1257–1279. (Buthus tamulus) venom- induced augmentation of cardiac reflexes is mediated through the 13. Freire-Maia L, Matos IMD. Heparin or a PAF mechanisms involving kinins in urethane antagonist (BN-52021) prevents the acute anesthetized rats. Toxicon 1998; 36: 309–320. pulmonary edema induced by Tityus serrulatus 314 Despande et al Indian J Physiol Pharmacol 2008; 52(3) scorpion