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Questions and Answers
What type of reaction occurs as a result of previous sensitization to a chemical?
What type of reaction occurs as a result of previous sensitization to a chemical?
What can result from an idiosyncratic reaction to a drug?
What can result from an idiosyncratic reaction to a drug?
Which term is used to describe substances that do not enter normal biological processes?
Which term is used to describe substances that do not enter normal biological processes?
What is the primary cause of allergic reactions?
What is the primary cause of allergic reactions?
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What is meant by dispositional tolerance?
What is meant by dispositional tolerance?
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How does NADH methemoglobin reductase deficiency affect individuals?
How does NADH methemoglobin reductase deficiency affect individuals?
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What characterizes a toxic effect?
What characterizes a toxic effect?
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Which mechanism of tolerance results from changes in tissue responsiveness to a chemical?
Which mechanism of tolerance results from changes in tissue responsiveness to a chemical?
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What is the toxicity rating of a substance with an oral LD50 of 20 mg/kg in rats?
What is the toxicity rating of a substance with an oral LD50 of 20 mg/kg in rats?
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Which factor does NOT affect the toxicity of a substance?
Which factor does NOT affect the toxicity of a substance?
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What role do proteases play in detoxication?
What role do proteases play in detoxication?
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What route of administration might lead to a quicker absorption of a toxic substance?
What route of administration might lead to a quicker absorption of a toxic substance?
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Which mechanism of toxicity involves the competition for binding to plasma proteins?
Which mechanism of toxicity involves the competition for binding to plasma proteins?
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Which of the following substances is classified as 'practically non-toxic' based on its oral LD50?
Which of the following substances is classified as 'practically non-toxic' based on its oral LD50?
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Which aspect is NOT mentioned as influencing the effect of a toxic substance on different species?
Which aspect is NOT mentioned as influencing the effect of a toxic substance on different species?
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Which of the following describes a consequence of enzyme inhibition by toxicants?
Which of the following describes a consequence of enzyme inhibition by toxicants?
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What is the potential consequence of chronic exposure to a toxic substance?
What is the potential consequence of chronic exposure to a toxic substance?
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What is LD50 commonly used to assess?
What is LD50 commonly used to assess?
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Which compound is known for inducing oxidative stress in tissues?
Which compound is known for inducing oxidative stress in tissues?
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Which substance has a toxicity rating of 3 according to its LD50 in rats?
Which substance has a toxicity rating of 3 according to its LD50 in rats?
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Which toxic effect is associated with inhibition of Cytochrome oxidase?
Which toxic effect is associated with inhibition of Cytochrome oxidase?
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Why are young and old animals more susceptible to toxicity?
Why are young and old animals more susceptible to toxicity?
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What type of response does a quantal dose-response curve represent?
What type of response does a quantal dose-response curve represent?
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What can lead to encephalopathy in children?
What can lead to encephalopathy in children?
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What type of mechanism do cholinesterase inhibitors like atropine represent?
What type of mechanism do cholinesterase inhibitors like atropine represent?
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Which of the following is an example of a chelating agent used for heavy metal poisoning?
Which of the following is an example of a chelating agent used for heavy metal poisoning?
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Which of the following describes a reversible effect in toxicology?
Which of the following describes a reversible effect in toxicology?
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What distinguishes local effects from systemic effects of toxins?
What distinguishes local effects from systemic effects of toxins?
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Which of the following is an example of an agent with both local and systemic effects?
Which of the following is an example of an agent with both local and systemic effects?
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What defines a delayed effect in toxicology?
What defines a delayed effect in toxicology?
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What is the primary goal of supportive and symptomatic treatment in cases of poisoning?
What is the primary goal of supportive and symptomatic treatment in cases of poisoning?
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Which mechanism describes an antidote that converts a poison to a non-toxic product?
Which mechanism describes an antidote that converts a poison to a non-toxic product?
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Which of the following statements is true regarding immediate versus delayed toxic effects?
Which of the following statements is true regarding immediate versus delayed toxic effects?
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Which agent is known for producing methemoglobinemia and is used as an antidote?
Which agent is known for producing methemoglobinemia and is used as an antidote?
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How do agents like mercaptopurine function in treating toxins?
How do agents like mercaptopurine function in treating toxins?
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How does the antidote Naloxone function in cases of narcotic overdose?
How does the antidote Naloxone function in cases of narcotic overdose?
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Which of the following is an example of an antidote that accelerates the excretion of a poison?
Which of the following is an example of an antidote that accelerates the excretion of a poison?
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In the treatment of methanol poisoning, which substance is used to block the formation of toxic metabolites?
In the treatment of methanol poisoning, which substance is used to block the formation of toxic metabolites?
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What is the mechanism of action for antidotes that create inert complexes with poisons?
What is the mechanism of action for antidotes that create inert complexes with poisons?
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Which combination of substances is used to treat organophosphate poisoning?
Which combination of substances is used to treat organophosphate poisoning?
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Study Notes
Allergic Reaction
- An adverse reaction to a chemical caused by previous sensitization to that chemical or a similar one
- It is caused by antigen-antibody reactions
- Often occurs at low doses of the chemical
- Can be severe and even fatal
Idiosyncratic Reaction
- Genetically determined abnormal reactivity to a chemical
- May involve extreme sensitivity to low doses or extreme insensitivity to high doses
- Example: standard dose of succinylcholine in certain patients can produce prolonged muscle relaxation and apnea due to atypical pseudocholinesterase in plasma.
- Sensitivity to Nitrites and other methemoglobinemia causing chemicals can occur due to a deficiency of NADH methemoglobin reductase (autosomal recessive trait)
Toxic Effect
- Damage to a biological system or process caused by a poison or drug at high doses
Xenobiotics
- Substances that do not enter biological processes or are not used as a source of energy or nutrition
- Considered foreign compounds
- Examples: drugs, heavy metals, insecticides
Tolerance
- Decreased responsiveness to a toxic effect of a chemical due to prior exposure to that chemical or a structurally related chemical
- There are two major mechanisms:
-
Decreased amount of toxicant reaching the site (dispositional tolerance)
- Examples: CCL4 (decreased formation of reactive metabolite trichloromethyl radical) and Cadmium (induce metallothioneine)
- Reduced responsiveness of a tissue to the chemical
-
Decreased amount of toxicant reaching the site (dispositional tolerance)
Detoxification of Protein Toxins
- Proteases are involved in the inactivation of toxic polypeptides and venoms
- Example: Thioredoxin reduces the disulfide bond of erabutoxin and phospholipase
Log Dose-Toxic Response Effect
- Binding of the ultimate toxicant with a target molecule at the target site leads to the development of a toxic response
- According to log doses of toxicant, there is either a graded or quantal (all or none) toxic response.
- Quantal LDR is mainly used for determining ED50, TD50, LD50 and for estimating the safety of drugs
Mechanism of Toxicity of Toxicant
- Direct damage effect by an irritant toxin: Riot gasses, strong acid or alkalis.
-
Displacement of some important element by competition for binding: disturbance or damage to biological systems.
- Examples:
- Lead and Calcium in children's CNS leading to encephalopathy
- Sulphonamide and Hypoglycemic drugs (plasma protein [albumin]) leading to hypoglycemic coma.
- Examples:
-
Inhibition of some important enzyme: inhibition of biological processes
- Examples:
- Cyanide: inhibits cytochrome oxidase leading to histotoxic anoxia
- Lead: inhibits ALAD (aminolevulinic acid dehydratase) leading to Anemia
- Examples:
-
Induction and Oxidative change or lipid peroxidation in certain tissues: damage to cell membrane and necrosis or DNA damage (mutation)
- Examples:
- CCL4: affects the liver
- Ozone (O3): Oxidative stress in tissues
- Examples:
Toxicity Rating
- Super Toxic: Oral LD50 in rat < 5mg/kg (Example: Strychnine)
- Extremely Toxic: Oral LD50 in rat 5-50mg/kg (Example: Opium)
- Very Toxic: Oral LD50 in rat 50-500mg/kg (Example: Phenobarbitone)
- Moderately Toxic: Oral LD50 in rat 500-5000mg/kg (Example: Kerosene)
- Slightly Toxic: Oral LD50 in rat 5000-15000mg/kg (Example: Ethanol)
- Practically Non Toxic: Oral LD50 in rat > 15000mg/kg (Example: Linseed oil)
Factors Affecting Toxicity
-
Physical and Chemical Nature:
- Physical form (gas, liquid, solid, radiation) affects absorption by different routes
- Chemical form (due to metabolism or isomerization) also affects toxicity (Examples: Carcinogens)
-
Single or Repeated Exposure:
- According to dose and exposure (acute, subacute, subchronic, chronic)
- Chronic exposure can lead to the development of resistance (tolerance), allergy, and accumulation
- Species: Different species have different effects due to differences in anatomy (monogastric and ruminant) and metabolism (lacking of some enzymes)
-
Size, Age, and Sex:
- LD50 varies according to animal weight
- Young and old animals are more susceptible to toxicity due to low metabolism, excretion, and resistance
- Sex has a low effect, but in rats, it may be more significant due to physiological performance and resistance.
- General State of Health: Diseased and debilitated animals are more susceptible to toxicity
- Diet: Any change in diet (vitamins, minerals, protein, fat) will affect toxicity
- Route of Administration: Different routes have different absorption rates; some poisons are only toxic by certain routes (snake venom)
Treatment of Poisoning
-
General Treatment:
- Decontamination: Remove the poison from the body by using methods like inducing vomiting, gastric lavage, or administration of activated charcoal.
- Enhancing elimination: Increase nonspecific elimination from the body by using diuretics, ion trapping, or dialysis (hemodialysis, peritoneal dialysis, or hemoperfusion).
-
Supportive and symptomatic treatment:
- Aim to keep the vital functions of the body working until the poison is neutralized by the antidote or eliminated
- Treat symptomatically, for example:
- Coma: Stimulant (amphetamine)
- Convulsion: Anticonvulsant (Phenobarbitone)
- Dehydration due to diarrhea or vomiting: IV physiologic solution
-
Specific treatment by antidote:
-
Mechanism 1: Antidote complex with poison making it inert
- Aims to reduce the concentration of free poison and dissociate it from tissues
- Examples:
- Chelating agents (BAL, pencillamine, EDTA-Ca) are used to treat heavy metal poisoning (As, Hg, Cd, Pb)
- Pralidoxime (2PAM) + atropine for organophosphate insecticide poisoning (irreversible choline esterase inhibitor)
- Specific antitoxin and antibodies for botulinum toxin, tetanus toxin, diphtheria toxin, and snake venom poisoning
-
Mechanism 2: Antidote accelerates metabolic conversion of poison (detoxification)
- Leads to a non-toxic product
- Example: Thiosulfate treatment for cyanide poisoning
-
Mechanism 3: Antidote blocks metabolic formation of poison (intoxication) from less toxic precursor
- Examples:
- Ethanol for Methanol poisoning
- Acetate – monocetin for Fluoroacetate (rodenticides) poisoning
- Examples:
-
Mechanism 4: Antidote specifically accelerates excretion of poison
- Examples:
- Chloride for Bromide poisoning
- Calcium salts for Strontium poisoning
- Examples:
-
Mechanism 5: Antidote competes with toxicant agent for essential receptor (Displacement competition)
- Examples:
- Oxygen (O2) for Carbon Monoxide (CO) poisoning
- Nalaxone for Morphine and related narcotics poisoning
- Examples:
-
Mechanism 6: Antidote blocks receptor responsible for toxic effect (causing blocker)
- Example: Atropine for cholinesterase inhibitors poisoning (neostigmine, edrophonium)
-
Mechanism 7: Antidote restores normal function by repairing of damaged processes or by bypassing the effect of poison by compensation with the inhibited end product
- Examples:
- Methylene blue for agents that produce methemoglobinemia (NO2, Cl, Sulphonamide, Acetnilide)
- Purine for Mercaptopurine (anticancer-DNA antagonist) to inhibit purine synthesis by bypassing the effect
- Examples:
-
Mechanism 1: Antidote complex with poison making it inert
Scope of Toxic Effect
-
Local versus Systemic Effect:
- Local effect occurs at the site of application (example: caustic chemicals, inhalation of irritant chemicals like Riot gasses)
- Systemic effect requires absorption and distribution to the organ or site of toxic effect (target organ) (example: Hg, Cd)
- Some toxic agents show both local and systemic effects (snake venom)
-
Reversible versus Irreversible Effect:
- The ability to regenerate determines whether the effect is reversible or irreversible (example: Liver, CNS)
-
Immediate versus Delayed Effect:
- Some toxic agents need a latent period (years) to exert their effect (example: Carcinogens like diethylstilbestrol, this is called a delayed effect)
- Most toxic agents show an immediate toxic effect depending on the dose (example: CN)
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Description
Test your understanding of adverse drug reactions including allergic, idiosyncratic, and toxic effects. This quiz covers the mechanisms behind these reactions and the role of xenobiotics in pharmacology. Perfect for students studying pharmacology or related fields.
