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Anascorp antidote– A big relief

I remember, faintly, that was a pleasant September morning. Everyone was in a festive mood. I was playing at my Grandpa’s house sitting under an umbrella when I suddenly felt a pierce on my big toe. I just thought that was an ant big enough to have bitten me but then confused to see that creature creeping out of the umbrella. Just curious, I called up my mom and told her that “creature” has bitten me, just to see her face alarming and jump outside with broom to kill that. Very innocent of me….That was a scorpion!

First aid was given to me while I was still puzzling about what was going on without knowing the impact of the bite. Out there in the hospital there was an injection administered, must be have been an alpha1 adreno-receptor antagonist, I presume. FDA has recently approved the first ever scorpion anti venom – a real good thing, especially for infants and children.

All about it – the Venom

Diving deep to see what is happening on a neuron´s cell membrane, normally, there are various forces at work which, at rest, are in dynamic equilibrium. At rest the cytoplasmatic side is negatively charged vis-à-vis the outside. There is an electrical gradient of 70 mV which attempts to move ions from an area with high charge density to an area of low charge density. Several ions show a concentration gradient. The concentrations of Na+ and K+ ions on the opposite sides of the membrane differ widely. There is a high potassium concentration inside the cell, while outside the cell this concentration is low. The opposite is true for the sodium concentrations. There is thus both an electrical and a chemical gradient. There is a sodium-potassium pump in the nerve membrane. For every three sodium ions that are pumped out, two potassium ions are brought into the cell. Many potassium ions leak out of the cell, which further increases the negative charge of the interior of the membrane. The nerve cells also have various ion channels, including sodium channels which are opened when there is a specific electrical voltage (voltage-gated channels).

Scorpion venom contain sets of small basic proteins that are responsible for the neurotoxic activities of the venoms. These toxins display considerable variations in amino acid composition, but they generally consist of 60-70 amino acids and are cross linked by four disulfide bridges. The partial or complete primary structures of about 25 toxins, from several different species of scorpions, have been determined[1]. The amino acid sequences display a number of common features, including the same general locations of the eight cysteine residues, similar disulfide bridging patterns, and the location of several invariant or conserved residues. Thus, the available chemical data suggest that all of the scorpion toxins probably have similar three dimensional structures.

Scorpion venom is a mixture of various active substances, but generally the neurotoxins are the most important. The venom of C. sculpturatus contains a peptide neurotoxin that opens Na+-channels (β -toxin). The venom causes depolarisation, the action potentials grow longer and the nerves fire non-stop. Other components in the venom inhibit the deactivation of Na+-channels (α -toxins) and thus have a similar clinical effect. Overall, the toxin looks like a right hand fist. However, little of the venom can penetrate the blood-brain barrier. There follows a massive release of neurotransmitters, both acetylcholine and noradrenaline from nerve endings and adrenaline from the adrenal medulla. The main part is formed by the catecholamines.

 

All about it – the Antivenom

Anascorp (Equine) Injection, it is approved as an orphan drug and it’s a first drug exclusively approved for Centruroides scorpions sting. An orphan drug is one that is specifically designed to treat rare conditions and diseases.

Anascorp [Centruroides (Scorpion) Immune F(ab’)2 (Equine) Injection] is a sterile, nonpyrogenic, lyophilized, polyvalent preparation of equine immune globulin F(ab’)2 fragments, manufactured from plasma of horses immunized with venom of C. noxius, C.l. limpidus, C.l. tecomanus, and C.s.suffusus. The product is obtained by pepsin digestion of horse plasma to remove the Fc portion of immune globulin, followed by fractionation and purification steps. The F(ab’)2 content is not less than 85%, F(ab) content is not more than 7%, and the product contains less than 5% intact immunoglobulin. The manufacturing procedures that contribute to the reduction of risk of viral transmission include pepsin digestion, ammonium sulfate precipitation/heat treatment, and nanofiltration.

Mechanism of Action

Anascorp is composed of venom-specific F(ab’)2 fragments of immunoglobulin G (IgG) that bind and neutralize venom toxins, facilitating redistribution away from target tissues and elimination from the body.[2]

First aid measures

It is highly recommended not to carry out any first aid measures such as cauterization, amputation, application of tourniquets, etc. It is up to the first helper to decide whether traditional remedies such as aspiration and application of a black “healing” stone are appropriate treatments, however, the patient should be transferred to a medical facility without delay. It is recommended that first aid be limited to the following measures:

∗ Rapid but careful cleaning of the wound (alcohol, antiseptic or soap),

∗ slight compression of the bitten/stung limb with a bandage (unless edema is present),

∗ Immobilization of the bitten /stung limb,

∗ Mild analgesic and sedative treatment (paracetamol and antihistamines),

∗ Transfer to a medical facility / specialized hospital department (A & E).

 

Prevention

Scorpions tend to avoid contact. To prevent chance meetings,

  1. Remove trash, logs, boards, stones, bricks and other objects that would make good hiding places for scorpions from around your home.
  2. Keep grass closely mowed, and prune bushes and overhanging tree branches, which can provide a path to your roof for scorpions.
  3. Store garbage containers in a frame that allows them to rest above ground level.
  4. Caulk cracks, install weather stripping around doors and windows, and repair torn screens.
  5. Avoid storing firewood inside your house.
  6. Always wear shoes outdoors, especially around water sources, such as swimming pools and fountains.
  7. Shake out your shoes and clothing before wearing them in areas where scorpions are common.
  8. When hiking or camping, wear long sleeves and pants and check your sleeping bag and clothing for scorpions every evening.
  9. When traveling in other countries — especially if you’re camping or staying in rustic accommodations — shake out your clothing and bedding often and sleep under a mosquito net. If you have a known allergy to insect stings, carry an epinephrine injector, such as EpiPen.
  10. Carefully move a scorpion. If you find a scorpion near your home or campsite, don’t panic. Use tongs to gently remove the scorpion to a safer location.

Scorpion-sting is indeed a public health hazard. Besides abiding by the above preventive measures, which should be meticulously followed, primary health centers, especially in rural areas, where the chances of the presence of scorpions are greater, should be reasonably equipped, so that cases of scorpion-sting are given proper urgent first-aid measures, while referring the patient to a large hospital, so that the life of the patient is saved.


[1] Krifi M.H, Savin S, Debray M, Bon C, Ayeb M.E, Choumet V. Pharmacokinetic studies of scorpion venom before and after antivenom immunotherapy. Toxicon, 2005;45:187–198.

 

[2] Rochat, H., Bernard, P. & Couraud, F. (1979) in Neurotoxins:Tools in Neurobiology, eds. Ceccarelli, B. & Clementi, F. (Raven,New York), Vol. 3, pp. 325-334.

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