Lecture 11 Flashcards
What is Toxin?
It is an agent that is capable of producing a deleterious response in a biological system.
Types of toxins:
-Poison is swallowed, inhaled or absorb through the skin
-Venom is actively injected into the bloodstream via a bite or sting
Classification of harmful effects:
- Mechanistic categories of harmful effects
- Includes related and unrelated effects of pharmacological action of the drug - Different patterns of incidence
-Excessive effect of drug
-Aberrabt effect unrelated to normal
Drug action
What is benefit versus risk?
-It is an important part of the evaluation process of a novel drug where it is judged by its therapeutic potency against its toxic side effects.
What is therapeutic index?
It is the ratio of the dose that produces toxicity/lethality to the dose that produces a clinically desired or effective response in a test population
What does LD50 mean in relation to therapeutic index?
-LD50: lethal dose for 50% of the test population or 50% morality in test systems
What does ED50 mean for therapeutic index?
-ED50: Effective dose for 50% of the test population
What TD50 mean in relation to therapeutic index?
-TD50: is the dose of drug that causes a toxic response in 50% of the population
What does a large therapeutic index (TI) indicate?
Indicates that the toxic concentration is significantly higher than that required for the pharmacological activity of a drug.
In biochemical experiments, the ED50 is often expressed as:
-EC50: Excitatory concentration of an agonist to achieve 50% of maximum activity
-IC50: Inhibitory concentration of an antagonist to achieve 50% inhibition of a biological activity
What is narrow therapeutic index?
It is when there is a small margin of safety between the therapeutic effect (ED50) of a drug and its toxic effect (TD50)
Examples of drugs with narrow therapeutic index:
-Digoxin
-Lithium
-Gentamicin
-Warfarin
-5 Fluorouracil
Digoxin
-Used for acute treatment of heart condition such as atrial fibrillation
-Works by decreasing the function of sarcalemmal Na+/K+ -ATPase pump of cardiac myocytes
Lithium
-Element used for acute treatment of manic phase in depression
-Work by interfering with neuro-transmission process probably via reduced sensitivity to transmitters in nerves
Gentamicin
-Broad spectrum antibiotic used to treat bacterial infections
-Works by inhibiting bacterial protein synthesis
Warfarin:
- Anti-coagulant drug employed in the prevention of thrombosis
-Works by Inhibiting the synthesis of biologically active forms of Ca2+ dependent clotting factors
5-fluorouracil:
-Anti-metabolite cancer drug
-Works inhibits thymidylate synthase causing interruption of thymidine synthesis and thus lack of essential nucleosides for DNA replication
Definition of Toxicology?
It is the study of the effect of xenobiotics on living organisms
What are xenobiotics?
Chemicals that are foreign to living organism
Two types of toxicology:
- Descriptive toxicology which includes toxicity testing and safety evaluation
- Mechanistic toxicity which includes study of molecular mechanisms and toxic potential
Toxicokinetics:
It is the absorption, distribution, metabolism, storage and excretion of agent.
Toxicodynamics:
It is the effects of the chemical and its metabolites on an organism
Organ-selective toxicity includes:
-Mechanistic Toxicology
-Poison
-Target Organ Toxicity
Mechanistic Toxicology (in relation to organ-selective toxicity):
-Identification and analysis of the molecular mechanisms by which xenobiotics exert toxic effects in a biological system
Poison (in relation to organ-selective toxicity):
-Among xenobiotics, a very wide spectrum of doses produces injury to biological system
-Potential enrichment of hydrophobic toxins in body
-Potential conversion of substances into toxic derívales
Target organ toxicity:
-In sufficient amounts, many xenobiotics trigger an organ-selective pattern of toxicity
Targets of organ selective toxicity:
-Liver
-Kidney
-Respiratory system
-Nervous system
-Cardiovascular system
-Reproductive system
-Immune system
-Blood
-Skin
-Eye
Target organ toxicity is caused by?
-Major route/pathway of exposure
-Pattern of distribution in biological system
-Metabolism/Biotransformation
-Concentration factor
-Tissue-specific susceptibility to toxic insult
Modifying factors in response to toxins:
-Frequency of exposure to toxin
-Accumulation of toxin in body
-Duration of exposure to toxin
-Inter-individual differences in toxic response
