What is a toxin?
name two different toxins
It is an agent capable of producing a deleterious response in a biological system.
- Poison and Venom
What is poison?
- A substance capable of producing deleterious biological responses if present in sufficient amounts.
- Potential enrichment of hydrophobic toxins in the body.
- Potential conversion of substances into toxic derivatives.
How is poison taken?
It is swallowed, inhaled or absorbed through the skin
How is venom taken?
It is actively injected into the bloodstream via a bite or sting
What are the classification of harmful effects?
- Two mechanistic categories of harmful effects:
(a) effects related to the principal pharmacological action of the drug
(b) effects unrelated to the pharmacological action - Two different patterns of incidence:
(a) excessive effect of the drug, which occurs in any subject given a large dose
(b) aberrant effects unrelated to normal drug action
What is therapeutic index (TI)?
The ratio of the dose that produces toxicity/lethality to the dose that produces a clinically desired or effective response in a test population.
Formula for therapeutic index
LD50/ED50
LD50 = the lethal dose for 50% of the test population or 50% mortality in test system, i.e. cells in culture
ED50 = effective dose for 50% of the test population
TD50 = the dose of drug that cause a toxic response in 50% of the population
What are examples of narrow TI drugs?
- Digoxin
- Lithium
- Gentamicin
- Warfarin
- 5-FU (5-fluorouracil)
What does a narrow TI exhibit?
Narrow TI drugs exhibit a samll margin of safety between the therapeutic effect of a drug and its toxic effects.
What is digoxin?
Used for acute treatment of heart conditions such as atrial fibrillation. It decreases the function of sarcalemmal Na+/K+ ATPase pump of cardiac myocytes.
What is lithium?
Used for acute treatment of manic phase in manic depression. Interference with the neuro-transmission process via reduced sensitivity to transmitters in nerves.
What is gentamicin?
Used for broad-spectrum antibiotics for the treatment of bacterial infections. It acts by inhibition of bacterial protein synthesis.
What is warfarin?
It is an anti-coagulant drug employed in the prevention of thrombosis. It inhibits the synthesis of biologically active forms of Ca2+-dependent clotting factors.
What is 5-FU?
It is an anti-metabolite cancer drug. It inhibits thymidylate synthase causing interruption of thymidine synthesis and thus lack of essential nucleosides for DNA replication.
What is toxicology?
What are xenobiotics?
- It is the study of the adverse effects of xenobiotics on living organisms.
- Xenobiotics are chemicals that are foreign to living organisms.
What are toxicokinetics and toxicodynamics?
- Toxicokinetics is the absorption, distribution, metabolism, storage and excretion of an agent.
- Toxicodynamics are the effects of the chemical and its metabolism on an organism.
What is mechanistic toxicology?
It is the identification and analysis of the molecular mechanisms by which xenobiotics exert toxic effects in a biological system.
What is target organ toxicity?
In sufficient amounts, many xenobiotics trigger an organ-selective pattern of toxicity.
What are the major targets of organ-selective toxicity?
- Liver
- Kidney
- Respiratory system
- Nervous system
- Heart and vascular system
- Reproductive system
- Immune system
- Blood
- Skin
- Eye
What are target organ toxicity due to?
- Major route/ pathway of exposure
- Ingestion (GI-tract)
- Inhalation (lungs)
- Topical (skin)
- Intravenous (bloodstream)
- Pattern of distribution in a biological system
- Metabolism / Biotransformation
- Bioactivation process may produce toxic derivative
- Concentration factor
- Dependent on uptake, accumulation and excretion of toxin
- Tissue-specific susceptibility to toxic insult
- Based on anatomical and physiological differences between individual classes of cells
- In sufficient amounts, many xenobiotics trigger an organ-selective pattern of toxicity
What are the modifying factors in response to toxins?
- Frequency of exposure to a toxin
- Accumulation of toxins in the body
- Duration of exposure to a toxin
- Inter-individual differences in toxic responses
- Genetic polymorphism in physiologically important genes
