After reading this essay you will learn about:- 1. Introduction to Veterinary Toxicology 2. Scope of Veterinary Toxicology 3. Kinds of Poisons 4. Intoxication 5. No Effect Level 6. LD50 7. Toxicokinetics 8. Selective Poisons Selectivity 9. Mechanism of Action 10. Factors Modifying Toxicity 11. Metabolism of Foreign Chemicals 12. Diagnosis of Poisoning Cases 13. Line of Treatment of Poisoning Cases.
Contents:
- Essay on the Introduction to Veterinary Toxicology
- Essay on Scope of Veterinary Toxicology
- Essay on the Kinds of Poisons
- Essay on Intoxication
- Essay on No Effect Level
- LD50
- Essay on Toxicokinetics
- Essay on the Selective Poisons Selectivity
- Essay on the Mechanism of Action
- Essay on the Factors Modifying Toxicity
- Essay on the Metabolism of Foreign Chemicals
- Essay on Diagnosis of Poisoning Cases
- Essay on Line of Treatment of Poisoning Cases
Essay # 1. Introduction to Veterinary Toxicology:
Toxicology is the branch of pharmacology which deals with the studies of harmful effects of drugs and other chemicals administered in over recommended (toxic) doses on the biological system. It is also defined as a branch of science that deals with the poisons.
Any substances that produce harmful effects in an organism to which it is administered, either deliberately or by accident-is a poison. Toxicity of a substance is dose related since a substance at low dose is without effect, may produce deleterious effects at some higher dose. Trace elements (such as selenium) which are essential in the diet in low concentrations, are frequently toxic at higher levels.
In the recent years, toxicology has been emerging very fast as one of the most important discipline of medical sciences for both human as well as animals life. Most of the things including food and environment are being increasingly polluted due to uncontrolled, indiscriminate and injudicious use of agrochemicals, rodenticides, insecticides and weedicides, including industrial effluents and byproducts, gases from motor vehicles, warfarins and sewage from the cities etc.
Even the milk, meat and eggs are sometimes reported to be polluted due to residues of a number of harmful drugs, preservatives, food additives and other many unaccounted pollutants. This has resulted in great imbalance in the eco-system and thus threating the survival of lives on the earth.
Veterinary toxicology is concerned more specifically with the knowledge of the poisons that affect animals and birds and the substances which are present in animals products e.g. milk, meat, eggs etc. can injure the health of human beings, consuming them. The conditions under which toxicity occurs, and its treatment and control are especially important in veterinary toxicology. It is also concerned with the determination of the safety of drugs and chemicals intended for direct use by humans.
Essay # 2. Scope of Veterinary Toxicology:
The scope of veterinary toxicology is increasing day-by-day due to increased use of chemicals in animal husbandry and agriculture. In the present time, toxicologists have? developed very sophisticated methods for detection of toxic levels of chemical compound in animals, plants and animal produce.
Still there is scope of veterinary toxicologists to establish doses of chemotherapeutic agents, toxic weeds and plants, agrochemical agents, industrial waste products etc. causing acute and chronic toxic effects in various species of animals.
We yet do not know how the presence of above toxic agents in body of various species of animals have an adverse effect on their reproduction, growth, efficacy of food utilization and behaviour.
The scope of veterinary toxicology is being discussed under following sub-headings:
(i) Pastures containing toxic weeds and plants:
Animals in rural area are generally maintained on pastures. Animals may be poisoned due to the consumption of toxic weeds and plants.
(ii) Agrochemicals:
Excessive use of fertilizers, insecticides and pesticides have increased the agricultural production. Simultaneously it has also increased the toxicity in both human and animals. In the near future veterinary toxicologists will be needed to determine the toxic levels of these agrochemicals in fodder and animal system in order to prevent the toxicity in animals.
(iii) Industrial contaminants:
Due to day-by-day growth in industries many pollutants are being accumulated in water and crops and thereby damage to animals. Veterinary toxicologists are awakening to the industrial hazards and a time will come when they will be actively engaged and think how to reduce these toxic effluents in animals food chain.
(iv) Therapeutic in-toxicities:
Indiscriminate prescription of some antibiotics or chemotherapeutic agents produce toxicity in animals. Bioavailability differences of many drugs from different sources can produce hazard to the patient.
(v) Toxicity due to metabolites:
Toxicities may occur due to reaction with a component involved in a sequence of biochemical processes, the disturbance of which precipitates the toxic crisis. In many cases evidence has been obtained for the formation of covalent bonds between toxicants and cellular constituents, this is by no means a prerequisite for a toxic response. The nature of the bond formed is important in determining the duration of the compounds within the body. In certain cases the bond may be easily destroyed.
While majority of the compounds which are able to produce toxic effects require metabolism in order to produce a more reactive molecule. This is not always the case and many molecules which are used in therapy possess an inherent reactivity which allows reaction with cellular components.
Analgesic agents i.e. phenacetin and paracetamol both can produce toxicity when given in large doses to animals. Major pathways of phenacetin metabolism leads to paracetamol. Both compounds generate active relating species which can react with cellular macromolecules and thereby produce the toxic response.
For example, formulation of digoxin may be quite critical in a biological sense. Small alterations in dosage may result in unacceptable loss of effect or equally unacceptable intoxication. Phenytoin sodium used in the treatment of convulsive disorders has a narrow therapeutic ratio. Patients arc required careful observation during the course of treatment, because toxic effects on CNS are the most alarming.
Interaction between drugs and vehicles have been very extensively documented when considering solutions for i. v. administration. Simple addition of solution to a 20 or 25% solution of mannitol may result in the precipitation or salting out of the mannitol.
Solutions containing calcium ions can not be added to bicarbonate or phosphate solution. A common observation is the immediate precipitation of hydrocortisone sodium succinate and tetracycline hydrochloride when mixed together in dilute solution.
The reactions of gentamicin sulphate with cloxacillin, cephalothin, aminophylline or heparin are other examples of this type of response where the active in-gradient is rendered useless and potentially hazardous to the patient.
In future, there is a need of veterinary toxicology as an independent department separate to pharmacology for better exploration of toxic materials and residues in animal and horticultural produce. The time is not far away when we and our pets will get food after approval of a toxicologist.
Essay # 3. Kinds of Poisons:
Poisons Produced by Living Organisms:
Phyto-toxins:
They are toxins produced by certain plants
Bacterial toxins:
Are toxins produced by bacteria
Endotoxins:
Toxins found within bacterial cells
Exotoxins:
Toxins elaborated from bacterial cells
Mycotoxins:
Toxins produced by fungi
Zootoxins:
Toxins produced by lower animals (e.g.) bufotoxin from the toad bufo).
Venom:
Toxin of lower animals transmitted by bite or sting
The toxins are renamed after determination of their chemical characters and chemical structures. They may be toxic alkaloids, glycosides, polypetides, amines etc.
Poisons Based on their Relative Toxicity:
(i) Extremely toxic:
Such substances produce toxicity in very- small dose (i.e. microgram) and can kill the animals e.g. botulinum toxin.
(ii) Highly toxic:
When the poisonous substance produces toxicity at the dose of 1 mg to 50 mg/kg.
(iii) Moderately toxic:
The substance is toxic at the close of 50 to 500 mg/kg
(iv) Slightly toxic:
If a substance produce toxicity at the dose ranging between 0. 5 to 5 mg/kg.
(v) Practically non toxic:
Toxicity is produced at the dose of 5 to 15 gm./kg.
(vi) Relatively harmless:
If the substance produces toxicity at high dose level i. e. more than 15 gm./kg. The above classification of poisons clearly shows that every substance is not equally toxic. Duse is an important factor in deciding their degree or toxicity. For example, water is relatively harmless, however, it can produce harmful effect if given in large quantity.
Essay # 4. Intoxication:
(i) Acute-Acute toxicity is produced from a relatively large intake of toxicant over a period of time. It may be over a period of minutes, hours, or a few days. It is always hours, or a few days. It always produces the severe symptoms of toxicity. In veterinary practice, most poisoning cases are acute and treatment must be started immediately.
(ii) Chronic-When small quantities of toxicant are ingested or absorbed by the body over a period of several days, weeks, months or years. In this case the onset of toxicity is gradual. In such situations there is a plenty of time for treatment and death may not occur.
Essay # 5. No Effect Level:
For most toxicants, the largest dose is without deleterious effects over a given period of time. The presence of chemical in feed or in the body does not mean that the feed is poisonous or the animal is poisoned. A guideline of permissible residues in food intended for human consumption have been established. However, such guidelines for most of the toxicants is not available for animal species.
6. LD50:
The dose of a substance which is lethal to 50% of the animal is known as LD50. It is the calculated value that represents the estimation of the dose required to produce death in 50% of the animals and is therefore, always accompanied by means of estimation of the error of the value, such as the probability range of the value. The LD50 of a compound is estimated by graphic method of Litchfield and Wilcoxon (1949).
Essay # 7. Toxicokinetics:
It deals with the movements of toxic chemicals in biological systems. Its goal is to quantitate the dynamic time course of absorption, distribution, metabolism and excretion processes in living animals. The concepts of pharmacokinetics are valuable and similar for the concept of toxicokinetics.
Toxicokinetics are of utility for elucidating how, why and to what extent kinetic events can affect the disposition of toxicants in the body. Many of the pharmacokinetic methodologies and principles are directly applicable to the work of toxicologists. Both pharmacokinetics and toxicokinetics are concerned with the time course and tissue or organ specificity of chemical agents.
The basic difference between pharmacokineticist and toxicologist is that pharmacokineticist is mainly interested in establishing and maintaining the therapeutically effective levels of medicinal agents in the body, the toxicologist is concerned with avoiding toxicity and assess whether and what safe levels exist.
Pharmacodynamics deals with the biochemical and physiological effects of chemicals and their mechanisms of action. The term toxicokinetics and toxicodynamics are used to emphasize the special concerns of the toxiciologist.
Essay # 8. Selective Poisons Selectivity:
If a substance influences one kind of living cell without affecting others, it is known as selective poison. Man has found many substances that are selectively not toxic to the cells of his body but toxic to the invading organisms. These substances employed by man are called drug when used for the treatment of humans or animals. On the other hand there are many agricultural agents that suppress the growth of weeds, insects or fungi in crops.
These agents are selectively toxic to weeds, insects and fungus and thus, beneficial to crops. Selective poisons are harmful to uneconomic species like bacteria, protozoa, helminths, weeds, insects and fungus and in such dosage they seem to be harmless to the economic species like man, animal and crops.
General anaesthetics, illustrate the selective use of toxicity in the sense that it is selectively toxic for the central nervous system and completely reversible with time. General anaesthetics combine a high toxicity for the central nervous system with negligible toxicity to other tissues. All toxicity rapidly and completely disappears when administration is stopped.
Essay # 9. Mechanism of Action:
The mechanism by which poisons of various kind produce their toxicity is mentioned as below:
(i) Local injury to tissue:
(a) Acids
(b) Alkalis, Phenols
(c) Heavy metals
(d) Venom-snake, bee stings
(ii) Necrosis of epithelial cells:
(a) Certain plant toxins
(b) Thallium
(c) Cresols, phenols etc.
(iii) Functional effect of central nervous system without lesions:
(a) Strychnine
(b) Chlorinated hydrocarbons
(c) Hydrocyanic acid
(iv) Injury to blood and vascular system:
(a) Hemolysis-Lead, copper, castor bean, nightshades, phenothiazine, saponins
(b) Bone marrow-Benzene, trichlorethylene, brackenfern, crotalaria, radioactive compounds, high intake of vit. A.
(c) Injury to endothelium-e.g. ergot, thallium
(d) Methaemoglobin-Nitrous oxide (NO2), chlorates
(e) Clotting malfunction-warfarin, dicoumarol.
(v) Blocking enzyme systems:
(a) Arsenic-Sulfhydryl, Phosphate tie-up
(b) Organophosphates-Cholinesterase
(c) Hydrocyanic acid-cytochrome oxidase
(d) Sodium fluoroacetate-TCA cycle
(e) Heavy metals in general
Essay # 10. Factors Modifying Toxicity:
(a) Coarse or fine
(b) Formulation-plant or animal
(c) Oily or aqueous
(d) Solubility
(e) Valency-trivalent arsenic is more toxic than pentavalent
Essay # 11. Metabolism of Foreign Chemicals:
(i) Oxidation:
Very common. Alcohols become aldehydes, sulfur compounds become sulfoxides and sulfones.
(ii) Reduction:
Less common. Aldehydes are reduced to alcohols, ketones are reduced to secondary alcohols, pentavalent arsenic is reduced to trivalent arsenic.
(iii) Hydrolysis-Frequent:
Increase elimination of a compound by converting it to a more readily excretable substance.
(iv) Conjugations:
Glucuronic acid and sulfate conjugations are utilized in most animals.
Essay # 12. Diagnosis of Poisoning Cases:
(i) Types of evidence:
(a) History or circumstantial
(b) Symptomatic
(c) Pathologic
(d) Chemical
(e) Experimental
(ii) Obtaining the history-most important:
(a) General-
(i) Number of animals in the unit, number affected.
(ii) Time affected and course of disease.
(iii) Ask pertinent questions. Rarely is information volunteered.
(iv) Understand the facts and circumstances that may have caused poisoning. Do not accept client’s diagnosis.
(v) Determine possibility of other conditions.
(b) Essential information for a poisoning case-
(i) Water-wells, tanks, stagnant ponds, algae, rarely running water.
(ii) Accumulation of minerals and substances in soil resulting in high levels in plants.
(iii) Industrial contamination.
(iv) Pesticides, rodenticides, herbicides, insecticides.
(v) Fertilizers-ammonia.
(vi) Junk piles and dumps, old buildings used for chemical storage.
(vii) Drugs-especially tonics and medicinal minerals.
(viii) Feed stuffs-may be contaminated during manufacturing may be mouldy, may be chemically treated.
(ix) Toxic plants.
(x) Malicious poisoning.
(c) Did animals have access to the toxicity?
(d) Was there sufficient amount of material to cause clinical signs or death?
(e) In the case of plants, is there evidence that the toxic plants were eaten?
Essay # 13. Line of Treatment of Poisoning Cases:
(i) General-must be given promptly:
(a) Symptomatic treatment accompanied by good care.
(b) May be no specific antidote.
(c) May be residual effects such as liver damage and kidney damage.
(ii) Eliminate the source of poison:
(a) Feed and water.
(b) Rubbish piles, old sheds etc.
(c) Change the environment.
(iii) Remove unabsorbed poison from the body:
(a) Wash with soap and cold water, clip hair and wool.
(b) Remove poisons from gastrointestinal tract.
(c) Emetic, lavage, surgery, cathartics.
(d) Give gastric lavage to anaesthetized animal.
(e) Tannic acid-Alkaloid and glycosides.
(f) General de-toxicants:
(i) Calcium gluconate
(ii) Dextrose
(iii) Thiosulphate
(iv) Symptomatic treatment:
Atropine sulfate: is the pharmacological antidote for poisoning due to the organic phosphorus and carbamate compounds.
Oximes: Protopam chloride, 2-PAM and DAM act to reverse cholinesterase inhibition and are, therefore, specific antidotes.
(a) Control central nervous signs.
(b) Keep respiratory tract open, oxygen, stimulants.
(c) Shock-fluids, blood, oxygen, warmth.
(d) Control vomition-sedation and soothe stomach.
(e) Control diarrhoea-intestinal protectants, astringents.
(f) Maintain fluid and electrolyte balance.
(g) Antibiotic to control secondary infections.
(v) Inactivation of unabsorbed poison:
(a) Potassium per-magnate (1:5,000): oxidizing agent for strychnine
(b) Tannic acid (strong tea)
(c) Milk
(d) Tincture of iodine
(e) Raw egg white
(f) Bentonite
(vi) Inactivation and removal of absorbed poisons:
(a) (i) Diuresis-if the kidney is functioning well
Oral fluids
Dextrose
(b) Specific antidotes
(i) Chloral hydrate or Barbiturates-convulsions
(ii) Atropine sulfate and protopam chlorides- organophosphorus pesticides
(iii) BAL-Arsenic and other heavy metals
(iv) Ca Ethyl diamine tetracetate (EDTA)-Lead
(v) Dithizone-Thallium (With caution)
(vi) Amyl-nitrate-cyanide (especially small animals)
(vii) Methylene blue-Nitrate, sodium chlorate
(viii) Sodium thiosulphate and sodium nitrate-cyanide
(ix) Vit K or K1-Prothrombin deficiency, warfarin, pindome.