toxicology of animal poisoning

TOXICOLOGY of TOXICOLOGY of ANIMAL POISONINGANIMAL POISONING

Significance:Significance: .Public health problem.Public health problem .Medical research.Medical research .Biological warfare.Biological warfare

NoteNote: : VenomVenom is an animal poison contains is an animal poison contains different types of antigens as:different types of antigens as:(proteins enzymatic as protease, (proteins enzymatic as protease, phosphodiesterases, hyaluronidases, phosphodiesterases, hyaluronidases, phospholipase) .phospholipase) .Proteins toxics: acids amines,polypeptides.Proteins toxics: acids amines,polypeptides. has to be injected into circulation has to be injected into circulation

SnakesSnakes

• Snakes are nocturnal reptiles & undergo hybridization, classified into:

•

Classification of Poisonous Classification of Poisonous snakessnakes

• According to the dominant venom:

• -Hemotoxic: Family: viperidae

• e.g. vipers (Cerastus)

• -Neurotoxic: Family: Elapidae

• e.g. cobra (Naja haj haj; Naja nigrocollis)

• -Myotoxic: Sea snakes

Types of Snake BitesTypes of Snake Bites

• -According to shape:• *Non-poisonous: U-shaped as any

animal• *Poisonous: either:• .Complete: 2 punctures due to fangs

(more dangerous)• .Incomplete: 2 parallel tailed scratches• (less dangerous)

Types of snake BitesTypes of snake Bites (cont.) (cont.)

• -According to time of Poisonous Biting:

• Generally bite is more dangerous at night & during summer

• .Defense bite: at day time

• .Business bite: at night, usually envenominated & dangerous

Snake VenomSnake Venom

• Mixture of specific toxins (peptides& small proteins as hemotoxin, neurotoxin, cardio toxin, …) and spreading factors (enzymes as hyalourindase, phospholipase A, …)

• -Neurotoxic venom:• .Dominant in cobra venom• .50-75% have low MW so, dialyzable• .Act mainly on neuromuscular junctions ->

weakness, dangerous when affect respiratory muscles -> respiratory failure

Snake VenomSnake Venom (cont.) (cont.)

• -Hemotoxic venom:• .Dominant in viper snake venom• .Have high MW so, not dialyzable• .Mainly composed of hemolysin,

thromboplastine, cardiotoxin• .Can cause: hemolysis, destruction of

vascular endothelium, cerebral hge., intestinal hge., hypotension & shock, tissue necrosis, & DIC is considered


• Snake venom consists of proteins, enzymes, substances with a cytotoxic effect, neurotoxins and coagulants.

• Phosphodiesterases are used to interfere with the prey's cardiac system, mainly to lower the blood pressure.

• Phospholipase A2 causes hemolysis through esterolysis of red cell membranes and promotes muscle necrosis.[1]

• Snake venom inhibits cholinesterase to make the prey lose muscle control.

• Hyaluronidase increases tissue permeability to increase the rate that other enzymes are absorbed into the prey's tissues.

• Amino acid oxidases and proteases are used for digestion. Amino acid oxidase also triggers some other enzymes and is responsible for the yellow color of the venom of some species.

• Snake venom often contains ATPases which are used for breaking down ATP to disrupt the prey's energy fuel use.


• Spitting of the venom is a defensive reaction . The snake tends to aim for the eyes of a perceived threat; a direct hit can cause temporary shock and blindness through severe inflammation of the cornea and conjunctiva. While there are no serious results if the venom is washed away at once with plenty of water, the blindness caused by a successful spit can become permanent if left untreated. Contact with the skin is not in itself dangerous, but open wounds may become envenomated.

Clinical ManifestationsClinical Manifestations

• The manifestations & severity of the case are depended on:

• -Amount of venom injected • -Species of snake & nature of venom• -Site of bite• -Time of bite• -Condition of fangs• -Pathogens in mouth of snake• -Death may occur immediately due to

neurogenic shock

Clinical ManifestationsClinical Manifestations (cont.) (cont.)

• *Neurotoxic Venom:• Start 15-45 minutes after biting• -Local: fang mark (2 punctures), pain,

redness, hotness, swelling,& may wet gangrene (generally less prominent than with hemotoxic venom)

• -Systemic: 1st sign is ptosis & numbness in lips & tongue – giddiness – heaviness in bitted limb – salivation & vomiting – blurred vision – dysarthria – dysphagia – bradypnea – convulsions – coma & death due to resp. failure


• *Hemotoxic Venom:• -Local: prominent and include: fang marks,

severe pain, redness, ecchymosis, hotness, edema and swelling of affected limb & dry gangrene

• -Systemic: nausea, vomiting – hypotension with rapid weak pulse – bleeding from mucous membranes – acute renal failure due to hemoglobinuria – coma and death due to circulatory collapse

ManagementManagement

• -First aid:• .Reassurance of patient is important• .First step is to examine the site of bite and decide if

the bite is poisonous or not to avoid unnecessary use of polyantivenom as it is risky and expensive

• .Immobilize the affected limb • .Stop venom absorption as possible using

tourniquet proximal to bite (just enough to obstruct lymph drainage not venous drainage) and make 2 small incisions over fang marks, and suction

• .Don’t use ice fomentations to avoid gangrene or give aspirin to avoid bleeding

Management Management (cont.)(cont.)

• -Specific treatment:• Antivenoms can be classified into

monovalent (when they are effective against a given species' venom) or polyvalent (when they are effective against a range of species, or several different species at the same time).

• We use polyantivenom

Management Management (cont.)(cont.)

• .Indication: envenominated bite with systemic manifestations

• .Why poly- & not mono-antivenom: because we have many species & the exact type of bitted snake may be not known

• .Dose: depends on severity of bite not age or body size so, a pediatric dose equal an adult dose: mild give 3-5 vials – moderate give 5-10 vials – severe cases give 10 vials & maintain with more vials according to situation

Specific Treatment (cont.)Specific Treatment (cont.)

• -Precautions in giving polyantivenom:

• .Examine expired date, can be used when badly needed if it is clear

• .Shake the vial, if there is any turbidity, rings or color changes, stop administration

• .Make skin sensitivity test (produced in horses), if patient is sensitive, give antivenom diluted by slow IV drip& prepare

• Anti allergic kit.

Antivenoms are purified by several processes but Antivenoms are purified by several processes but will still contain other serum will still contain other serum proteinsproteins that can act that can act

as as antigensantigens..

• Some individuals may react to the antivenom with an immediate hypersensitivity reaction (anaphylaxis) or a delayed hypersensitivity (serum sickness) reaction and antivenom should, therefore, be used with caution. Despite this caution, antivenom is typically the sole effective treatment for a life-threatening condition, and once the precautions for managing these reactions are in place, an anaphylactoid reaction is not grounds to refuse to give antivenom if otherwise indicated. Although it is a popular myth that a person allergic to horses "cannot" be given antivenom, the side effects are manageable, and antivenom should be given as rapidly as the side effects can be managed.

Supportive TreatmentSupportive Treatment

• -Open IV line and correct fluid, electrolytes and acid-base balances

• -In all cases of snake bite either poisonous or nonpoisonous, we have to give broad spectrum antibiotics and anti-tetanic serum owing to pathogens found in snake mouth

Natural and acquired immunity Natural and acquired immunity • Although individuals can vary in their physiopathological

response and sensitivity to animal venoms, there is no natural immunity to them in humans. Some ophiophagic animals are immune to the venoms produced by some species of venomous snakes, by the presence of antihemorrhagic and antineurotoxic factors in their blood. These animals include King snakes, opossums, It is quite possible to immunize a person directly with small and graded doses of venom rather than an animal. According to Greek history, King Mithridates did this in order to protect himself against attempts of poisoning, therefore this procedure is often called mithridatization.

• . However, unlike a vaccination against disease which must only produce a latent immunity that can be roused in case of infection, to neutralize a sudden and large dose of venom requires maintaining a high level of circulating antibody (a hyperimmunized state), through repeated venom injections (typically every 21 days). The long-term health effects of this process have not been studied. For some large snakes, the total amount of antibody it is possible to maintain in one human being is not enough to neutralize one envenomation[citation needed]. Further,.

SCORPIONSCORPION

• -Scorpion belong to Arthropods, and all of them are poisonous & their venoms are more potent than that of snakes & numerically more than snakes, so they represent more public health problem especially in southern areas

• -9 species are known in Libya, 2 of them are more abundant & more dangerous

• -Generally, more dangerous & causing more morbidity & mortality in children.

Leiurus quinquestriatusLeiurus quinquestriatus

• Androctonus amoreuxi

Scorpion VenomScorpion Venom

• -Generally more toxic, more variability of specific toxins & more multiplicity of antigens than snake venom

• -Consists of amino acids, peptides & small proteins (mainly neurotoxin, nephrotoxin, cardiotoxin, hemolytic toxin,histamine, serotonin, anti-ACh-esterase) & enzymes as

phospholipases, hyaluronidases, phosphodiesterase.• -Inject able LD: few up to 50 μg• -Human have unique variable susceptibility to

scorpion venom

Toxic Mechanism of Scorpion Toxic Mechanism of Scorpion VenomVenom

• -Neurotoxin: block voltage-gated Na+ & Ca++ channels → prolonged action potential & excessive release of catecholamine → adrenergic manifestations

• -Anti-cholinesterase → accumulation of Ach → cholinergic manifestations

• Thus, this will lead to marked CV effects

• Scorpion venom may contain multiple toxins and other compounds. The venom is composed of varying concentrations of neurotoxin, cardiotoxin, nephrotoxin, hemolytic toxin, phosphodiesterases, phospholipases, hyaluronidases, glycosaminoglycans, histamine, serotonin, tryptophan, and cytokine releasers. The most important clinical effects of envenomation are neuromuscular, neuroautonomic, or local tissue effects.

• Autonomic excitation leads to cardiopulmonary effects observed after some scorpion envenomations. Somatic and cranial nerve hyperactivity results from neuromuscular overstimulation. Additionally, serotonin may be found in scorpion venom and is thought to contribute to the pain associated with scorpion envenomation.

• Children and elderly persons are at the greatest risk for morbidity and mortality. A smaller child, a lower body weight, and a larger ratio of venom to body weight lead to a more severe reaction. Furthermore, elderly persons are more susceptible to stings because of their decreased physiologic reserves and increased debilitation.

• The long-chain polypeptide neurotoxin causes stabilization of voltage-dependent sodium channels in the open position, leading to continuous, prolonged, repetitive firing of the somatic, sympathetic, and parasympathetic neurons. This repetitive firing results in autonomic and neuromuscular overexcitation symptoms, and it prevents normal nerve impulse transmissions. Furthermore, it results in release of excessive neurotransmitters such as epinephrine, norepinephrine, acetylcholine, glutamate, and aspartate. Meanwhile, the short polypeptide neurotoxin blocks the potassium channels.

Factors Affecting Severity of Factors Affecting Severity of Scorpion StingScorpion Sting

• -Age & body size of the victim

• -Species & size of scorpion

• -The amount of venom injected

• -Site & number of stings

• -Individual susceptibility to venom


• -Local: .severe intense pain• .edema & ecchymosis• .numbness & tenderness• -CVS: .sinus arrhythmias• .hypertension• .Atrial extrasystol & PVC• .pulmonary edema• .ischemic changes in ECG• CV complications are more in children with

increased LDH & CPK


• -CNS: .agitation, paresthesia ,irritability & (restlessness, severe involuntary shaking &jerking extremity due to somatic skeletal neuromuscular dysfunction).

• .cerebral edema → convulsions & coma• -Others: .nausea & vomiting• .hypothermia• .blurring of vision, ptosis, tongue

fasciculation slurred speech .( cranial nerve dysfunction)

• .marbling of skin (VC of bl. Ves.)• .priapism• .diaphoresis, tearing


• Respiratory arrest and loss of protective airway reflexes are common causes of mortality.

• Pulmonary edema has been described and may be secondary to cardiogenic causes and to increased capillary permeability.


• Autonomic effects include the following: • Sympathetic overdrive symptoms

predominate, causing tachycardia, hypertension, hyperthermia, and pulmonary edema.

• Parasympathetic symptoms include hypotension, bradycardia, salivation, lacrimation, urination, defecation, and gastric emptying


• Cerebral infarction, cerebral thrombosis, and acute hypertensive encephalopathy have been described with a variety of Buthidae scorpion envenomations.

• The signs of the envenomation are determined by the scorpion species, venom composition, and the victim's physiological reaction to the venom.

Management of Scorpion StingManagement of Scorpion Sting

• -First aid: like snake but, it is mandatory to control local pain (use local anaesthesia) to make the patient calm which is very important procedure in management

• -Specific treatment: use polyantivenom as in snake• -Supportive treatment: support CV functions to

avoid complications• -Symptomatic treatment:• .use Haloperidol to control agitation• .use diazepam in convulsions• .use diuretics in pulmonary edema


• Do not apply tourniquets, as the toxins are small and move extremely rapidly away from the site of the sting.A tourniquet will not help the wound, and could cause more harm if applied incorrectly.

• Do not attempt to cut the wound and suck out the poison.This can cause infection or transfer the venom into the bloodstream of the person attempting to remove the poison.


• • Scorpions cannot usually deliver enough venom to kill a healthy adult. While venom toxicity varies among species, some scorpions contain very powerful neurotoxins, which, ounce for ounce, are more toxic to humans than the venom of cobras. However, scorpions inject relatively small amounts of venom (compared to snakes), so the overall dose of toxins per sting is survivable.

Black Widow SpiderBlack Widow Spider

• Black widow spider belong to Arthropods & only female bite is clinically significant

• -The spider can be identified by a red to orange hour-glass on the thorax

• -The spider venom contains a potent neurotoxin which destroy cholinergic nerve terminals with massive release of A Ch especially at motor end plates causing severe muscle spasm & also, affect adrenergic nerve terminals that may cause increase in sympathetic outflow

Only a small amount of venom can cause serious illness, as the poison attacks the nervous system. Systemic envenomisation usually results in headache, nausea, vomiting, abdominal pain, pyrexia and hypertension.


• -Local: bite usually painless & local reaction is very rare in the form of pain, redness, edema & itching

• -Systemic: develop 1-3 hours ranging from mild affection to serious troubles & mostly in the form of severe muscle spasm leading to chest & abdominal pain, tremors & muscle fasciculation followed by muscle weakness – hypertension – nausea, vomiting & salivation

Management of Spider BiteManagement of Spider Bite

• -First line of treatment is to give IV calcium gluconate which control pain and abdominal cramps & considered as antidote

• -Other lines of therapeutic intervention include Latrodectus antivenin, diazepam, methocarbamol & opioid analgesics

• -The antivenin is reserved for patient with severe cramps refractory to other therapy because it is an equine antivenin & may cause severe hypersensitivity and should be given very carefully with close patient observation

toxicology of animal poisoning

Health & Medicine

viper snake venom

dominant venom

neurotoxic venom

cobra venom

venom absorption

hemotoxic venom systemic

given species venom

snake venomcont