Antitoxins and antivenins

Introduction

• Antitoxins and antivenins (also called antivenoms) are immunologic agents used for the prevention or treatment of poisoning caused by biological toxins or animal venoms.

• They are prepared from the serum or plasma of animals (often horses or sheep) or humans immunized against a specific toxin or venom.

• These products provide passive immunity, supplying antibodies that neutralize the toxic components before they can bind to tissue receptors and cause irreversible damage.

• Widely used in the management of diseases caused by bacterial exotoxins (e.g., diphtheria, tetanus, botulism) and envenomation from snakes, spiders, scorpions, and marine creatures.

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Mechanism of Action

• Contain polyclonal antibodies (whole IgG or fragments such as F(ab’)₂ or Fab) specific to the toxin or venom.

• Bind to free circulating toxin or venom components in the bloodstream.

• Prevent toxin or venom from attaching to target cells and initiating damage.

• Do not reverse damage that has already occurred; early administration is critical for maximal effectiveness.

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Types

1. Antitoxins

• Used against toxins produced by bacteria.

• Examples:

  • Diphtheria antitoxin – neutralizes Corynebacterium diphtheriae exotoxin.

  • Tetanus immune globulin (TIG) – neutralizes Clostridium tetani toxin.

  • Botulism antitoxin – neutralizes Clostridium botulinum neurotoxin.

  • Gas gangrene antitoxin – against Clostridium perfringens alpha-toxin (less common today).

2. Antivenins (Antivenoms)

• Used against toxins in venoms from animals.

• Examples:

  • Snake antivenoms – for envenomation from cobras, vipers, rattlesnakes, etc.

  • Scorpion antivenoms – e.g., for Centruroides sculpturatus.

  • Spider antivenoms – e.g., for Latrodectus (black widow) and Loxosceles (brown recluse).

  • Marine antivenoms – e.g., for box jellyfish (Chironex fleckeri), stonefish, blue-ringed octopus.

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Formulation Types

• Whole IgG – complete antibody molecule; longer half-life but higher risk of serum sickness.

• F(ab’)₂ fragments – enzyme-digested to remove Fc portion; reduced risk of hypersensitivity, retains bivalency.

• Fab fragments – smallest active unit; rapid distribution and clearance; lower risk of delayed reactions but may require repeat dosing due to shorter half-life.

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Production Process

• Immunization of animals with inactivated or attenuated toxin or venom.

• Collection of plasma containing high-titer antibodies.

• Purification and concentration of antibodies.

• Formulation into sterile, injectable preparations.

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Administration

• Route: Intravenous (most antivenoms, botulism antitoxin), intramuscular (tetanus immune globulin, some antitoxins), intradermal (rare).

• Dose: Depends on severity, type of toxin/venom, and product potency.

• Timing: Early administration is essential, ideally within hours of exposure.

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Indications

Antitoxins

• Diphtheria: adjunct to antibiotics in confirmed cases.

• Tetanus: post-exposure prophylaxis in non-immune individuals; treatment of clinical tetanus.

• Botulism: treatment of foodborne, wound, or inhalational botulism.

Antivenins

• Systemic envenomation with evidence of neurotoxicity, coagulopathy, or cardiovascular compromise.

• Rapidly progressive local tissue damage from venomous bites/stings.

• Prophylactic use rarely indicated except in high-risk occupational exposure in some regions.

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Advantages

• Immediate passive immunity.

• Potentially life-saving in severe toxin or venom exposure.

• Specific to the causative toxin or venom.

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Limitations

• No reversal of established tissue damage.

• Requires proper storage (cold chain for most).

• Limited shelf-life.

• Availability often restricted to specialized centers.

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Adverse Effects

Immediate Reactions

• Anaphylaxis (rare but potentially life-threatening).

• Urticaria, bronchospasm, hypotension.

Delayed Reactions

• Serum sickness (immune complex-mediated; occurs 5–14 days after administration).

• Fever, rash, arthralgia, lymphadenopathy.

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Contraindications

• No absolute contraindications when life-threatening envenomation or toxemia is present.

• Relative caution in patients with known hypersensitivity to equine or ovine proteins; premedication with antihistamines or corticosteroids may be used.

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Precautions

• Skin sensitivity testing for equine-derived products (not always reliable or recommended in emergencies).

• Facilities for management of anaphylaxis must be available.

• Monitor patient closely during infusion and for several hours after.

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Drug Interactions

• No significant pharmacokinetic drug–drug interactions.

• Avoid concurrent live vaccines soon after administration, as passive antibodies may interfere with vaccine efficacy.

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Special Populations

• Pregnancy: Generally used when indicated; benefits outweigh potential risks.

• Pediatrics: Doses often same as adults; severity-based rather than weight-based.

• Elderly: No special dosing but may have higher risk of adverse reactions.

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Future Directions

• Development of recombinant monoclonal antibodies as antitoxin/antivenin alternatives.

• Synthetic antivenoms targeting conserved venom epitopes.

• Improved purification to minimize immunogenicity.

• Broader-spectrum antivenoms effective against multiple species.