Toxicology

Significant increase in water solubility.

What is the result of reactants going through Phase II?

Xenobiotic

A substance that does not occur naturally in the human body.

Biotransformation

Alteration of the parent drug molecule and formation of a drug-endoobiotic conjugates are the major purpose of _____________.

Poison

Any agent capable of producing deleterious response in a biological system, seriously injuring function, or producing death.

Acute. less than 24 hours Subacute. Up to 1 month or less Subchronic.Up to 3 months Chronic. More than 3 months.

Define the length of the following: Acute Exposure Subacute Exposure Subchronic Exposure Chronic Exposure

The Central Dogma in toxicology. Toxicokinetics -> Initiation -> Toxicodynamics. Toxicokinetics = ADME Toxicodynamics = Molecular response -> cellular response -> organ response -> organism response

Describe the toxicological process.

1. Structural manifestations (Teratogenesis) 2. Growth retardations 3. functional impairments 4. Death of the organism

Developmental Toxicology study which manifestations of adverse effects?

Lipophilic Non polar Non excretable Toxicant Drug --> Biotransformation --> Water Soluble Polar Endobiotic Toxciant Drug

Major Diagram for Biotransformation:

Facilitation of excretion Detoxification Bioactivation/toxification Drug inactivation Drug activation

There are 5 things outcomes of drug biotransformation. Can you name them?

1) Identify the adverse effect and 2) use that information to predict responses in exposure situations.

What are the 2 major goals of toxicology?

Drug molecules undergo conjugation reactions with endogenous substances (endobiotics) and go through glucuronidation, acetylation, and sulfation.

What goes on during Phase II reactions?

"What is there that is not poison? All things are poison and nothing is without poison. Solely the dose that a thing is not a poison." - Paracelsus, The father of toxicology The right DOSE differentiates a poison from a remedy.

What is the Famous statement in toxicology?

Dose-Response concept. The magnitude of the toxic effect will be related to how many altered molecular targets are available and the concentration of the toxin.

What is the first principle of Toxicology?

Create or Unmask a chemical group (OH, NH2, SH, or COOH) through hydrolysis, reduction, or oxidation.

What is the goal of Phase 1 Reactions?

Organogenesis occurs within 3-8 weeks so this is when teratogens have the most profound effects. Before the 3rd week, most teratogens usually result in death. After organogenesis, teratogens may affect growth and functional maturation of organs but do not significantly affect the basic developmental plan.

What is the importance of developmental timing of of drug exposure? (When is it worse to give a pregnant mother a drug?)

Small increase in hydrophilicity.

What is the result of reactants going through phase I?

Molecular Target Concept: Toxic action of a chemical is a consequence of the interaction between the chemical and the molecular target.

What is the second principle of toxicology?

Exposure -> Internal Dose -> Biological Effective Dose -> Early biological effects -> Altered structure/function -> disease The first 3 are toxicokinetics, while the last 3 are toxicodynamics.

What is the toxicological Paradigm?

The study of poisons (toxic agents). Study of the adverse effects that result from the interactions between toxic agents.

What is toxicology?

THE LIVERRRRRRRRRr

Which organ is the most important for biotransformation of toxicants/drugs?

1 process 1 statement 2 fundamental principles 1 paradigm

With are the fundamentals of toxicology?

clinical

____________ toxicology is concerned with disease caused by or uniquely associated with toxic substances.