Snake antivenoms: adverse reactions and production technology

Morais, Víctor; Massaldi, Hugo

doi:10.1590/s1678-91992009000100002

Cited by 61 publications

(57 citation statements)

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“…Segura et al (6) observed that the reduction of phenol to a concentration of 0.15 g% maintains the physical stability of antivenoms and decreases their liability of forming aggregates (6). Other researchers corroborate such finding, especially if the protein content is elevated, which may lead to loss of antivenom activity and to adverse reactions due to activation of the immune response (4,21,(26)(27)(28)(29)(30). At the same time, the decrease of m-cresol concentrations may diminish antivenom toxicity to humans, particularly in certain circumstances in which high doses are required, such as in the two cases mentioned by Buntain (31) and Ganthavorn (32) (750 to 1150 mL of antivenom).…”

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confidence: 78%

“…Turbidity in equine antivenoms depends, at least, in one way, on the interaction between initial protein concentration in the serum, and addition of phenol during fractionation of serum (10). Protein aggregation -besides loss of activity and safety of antivenom -is another important indicator of product instability caused by phenols, which are hydrophobic substances that may induce an increase in protein denaturation (3,12,21). García et al (12) found differences in the augmentation of aggregate levels and dimmers among antivenoms stored for three years that were devoid of phenol and contained different preservatives, meaning that these substances could accelerate the normal denaturation process.…”

Section: Introductionmentioning

confidence: 99%

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What is the optimum concentration of m-cresol in antivenoms?

Abd-Elsalam¹,

Abdoon²,

Al-Ahaidib³

2011

J. Venom. Anim. Toxins incl. Trop. Dis

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Antivenoms against snake and scorpion envenomations are usually equine in nature and composed mostly of F(ab`)2; additionally, phenol and m-cresol are mainly employed for their preservation. Although there is no study on this subject, m-cresol is utilized by most manufacturers in a concentration that ranges from 0.15 to 0.35 g%. Decreasing the concentration of m-cresol to its minimal effective level may protect victims from its toxic effects and keep the antivenom stable during its shelf life without forming any aggregates. In the present work, different concentrations of m-cresol, ranging from 0.1 to 0.35 g%, were used with some selected batches of snake and scorpion antivenoms. A low concentration of 0.15 g% showed an acceptable preserving result that complies perfectly with antimicrobial specifications stated by the British Pharmacopoeia. Tested antivenoms (in 12 batches), when kept in a cold room for 39 months (more than their shelf life), retained their physical, chemical and microbiological activities according to the specifications of pharmacopeias. The present data demonstrated that reduction of m-cresol concentration to 0.15 g% in case of equine F(ab`)2 antivenoms will improve safety of such preparations and preserve their stability during their shelf life.Key words: antivenoms, preservative, m-cresol, stability. Original PaPer The Journal of Venomous Animals and Toxins including Tropical Diseases ISSN 1678-9199 | 2011 | volume 17 | issue 1 | pages 12-22 INTRODUCTIONAntivenoms are refined and concentrated preparations of equine serum globulins -mostly F(ab`)2 -obtained by fractionating blood from healthy horses that were previously immunized with different type of venoms (1, 2). For more than a century, antivenoms have been used effectively as the only treatment for snakebites and envenomations caused by other poisonous animals including spiders and scorpions (3). Most antivenoms are produced in liquid form to lower their cost and ease their use. Currently, there are eight antimicrobial preservatives commonly used in licensed parenteral products of which m-cresol and phenol are habitually employed by manufacturers as preservatives in antivenom formulations (4-6). Usually, phenol concentrations in antivenoms range from 0.15 to 0.5 g% (7-10). Combinations of phenol and thimerosal in different ratios have also been effectively used in some antivenom preparations (11,12). M-cresol, a phenol derivative, is frequently utilized as preservative in numerous antivenom preparations in concentrations that range between 0.15 and 0.35 g% (4,7,13).Despite their efficacy as additive, the use of these agents involves the possibility of some adverse effects. It is well known that phenol and cresol are toxic to humans in certain amounts (5,(14)(15)(16)(17)(18)(19). Repeated exposure may cause harmful effects on the liver and kidney. Additionally, potential development of multiple organ failure with persistence of organ dysfunction associated with the overdose of injectable phenol was already reported (20). Turbi...

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confidence: 78%

Section: Introductionmentioning

confidence: 99%

What is the optimum concentration of m-cresol in antivenoms?

Abd-Elsalam¹,

Abdoon²,

Al-Ahaidib³

2011

J. Venom. Anim. Toxins incl. Trop. Dis

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“…Currently, antiserum composed of specific immunoglobulins is the only treatment for snake envenomation, but there are ongoing issues with availability, effectiveness and dosing [19,20]. These antivenoms neutralize the toxicity and lethality of specific venoms, but their administration is often related with significant clinical side effects [21,22]. Additionally, the production of antivenoms is associated with high costs related to animal maintenance and also comes across animal welfare concerns, which instigates the search for innovative products for snakebite therapy [23,24].…”

Section: Introductionmentioning

confidence: 99%

Study of the Activity of Phospholipase A2 in Venom of the Transcaucasian Macrovipera Lebetina Obtusa

Topchiyeva¹,

Babayev²,

Abiyev³

2017

IJEAB

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“…The aforementioned drawbacks point to a central problem faced by antivenoms: access. Low production, inadequate distribution chains, and the need for species and regionspecific products thwart global antivenom availability (14)(15)(16). The result of low output and high production costs are antivenoms that are unaffordable to those who need them most.…”

Section: Introductionmentioning

confidence: 99%

Needs and availability of snake antivenoms: relevance and application of international guidelines

Scheske

Ruitenberg

Bissumbhar

2015

Int J Health Policy Manag

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Background: Snakebite has recently been declared a global public health emergency. Empirical data showing the true burden of snakebite is lacking. Treatment with specific antivenoms is considered the only cure. However, several factors have led to an ongoing antivenom crisis. This study offers recommendations concerning the improvement of antivenom access and control, by providing an overview of the factors limiting the successful implementation of international guidelines within the international industry and state institutions. It further investigates the reasons for the epidemiological knowledge gap regarding snakebites. Methods: Data for this study was collected using surveys with closed-and open-ended questions, which allowed for descriptive and thematic analysis, respectively. Participants for this study were selected as follows: 46 manufacturers were contacted from the open-access World Health Organization (WHO) Database for antivenom producers; 23 National Health Authorities (NHAs) of high-burden countries were contacted; and 11 poison centers or experts were randomly contacted. Results: In total, responses from 6/46 (13%) manufacturers, 10/23 (43%) NHAs, and 3/11 (27%) poison centers were received. The low response rates had a limiting effect on the coverage of this study, allowing only exploratory conclusions to be drawn. Based on the gathered information, a probable reason for the epidemiological knowledge gap is the low priority given to snakebites on public health agendas, driving interest and funding away from research in this field. As a consequence, the ensuing lack in funding is preventing state institutions and manufacturers from implementing international guidelines to the highest standards. Furthermore, manufacturers indicated that international guidelines were often not applicable in the field, lacking technical information and protocols. Conclusion: Snakebite ranks low on international public health agendas, and partially due to this low priority, NHAs have shown limited efforts in conducting epidemiological studies, training health workers on snakebite management and creating national snakebite management strategies. The lack of NHA involvement is reflected in poor access to appropriate antivenoms as well as a lack of antivenom regulation. Manufacturers are taking positive steps toward full implementation of international guidelines and are improving quality control procedures. However, in order for international guidelines to become truly useful in the field, more technical guidance is required. This study reflects that there is a general lack of knowledge transfer amongst various actors: most producers, health authorities, and experts expect increased and improved communication and guidance from leading international bodies. Due to the low response rates observed in this study, conclusions drawn herein are not representative of the global situation; yet provide an exploratory insight on the difficulties facing antivenom management. Keywords: Snakebite, Antivenom, Envenomation, Gu...

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Snake antivenoms: adverse reactions and production technology

Cited by 61 publications

References 80 publications

What is the optimum concentration of m-cresol in antivenoms?

What is the optimum concentration of m-cresol in antivenoms?

Study of the Activity of Phospholipase A2 in Venom of the Transcaucasian Macrovipera Lebetina Obtusa

Needs and availability of snake antivenoms: relevance and application of international guidelines

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