Nedim Lecture Review: Absorption, Disposition, Excretion of Toxicants Drug development/Drug toxicology

Question 1

What are the composite actions for the disposition of a chemical(s)?

Answer 1

absorption, distribution, biotransformation,
and elimination

Question 2

How are toxins transported?

Answer 2

Passive, active, special, facilitated transport

Question 3

What are the factors that determine which molecules can pass through the membrane?

Answer 3

Physicochemical properties such as molecular weight, hydrophilicity, and polarity

Question 4

Define Passive Transport ( in this case)

Answer 4

Fick’s law - chemicals move from regions of higher concentration to
regions of lower concentration without any energy expenditure.

Question 5

Define special transport (in this case.)

Answer 5

Particles that are too large to pass through aqueous pores/ insoluble in lipids to diffuse across the lipid domains of membranes.

Nevertheless, they are often transported very rapidly across membranes, even against concentration gradients.

Question 6

Define active transport ( in this case)

Answer 6

Movement of chemicals against electrochemical or concentration gradients

Saturability at high substrate concentrations

Selectivity for certain structural features of chemicals

Competitive inhibition by chemical congeners or compounds that are carried by the same transporter

Requirement for expenditure of energy, so that metabolic inhibitors block the transport process.

Question 7

Define facilitated transport (in this case)

Answer 7

This process facilitates transport carrier-mediated transport that exhibits the properties of active transport except that the substrate
is not moved against an electrochemical or concentration gradient, and the transport process does not require the input of energy

Question 8

Define absorption. Where does absorption occur?

Answer 8

the process by which toxicants cross body membranes to enter the bloodstream is called absorption.

location: GI tract, lungs, and skin.

Question 9

Absorption and acid/base

Answer 9

If a toxicant is an organic acid or base, it can be absorbed by simple diffusion in the part of the GI tract where it exists in its most lipid-soluble (nonionized) form.

Question 10

Other factors that influence the
absorption of xenobiotics?

Answer 10

pH,
* presence of food,
* digestive enzymes,
* bile acids,
* bacterial microflora in the GI tract,
* motility and permeability of the GI tract.
* For example, snake venoms, which are proteinaceous moieties, are much less toxic by
the oral route relative to intravenous exposure because they are degraded by digestive
enzymes of the GI tract.

Question 11

What are the several factors that can influence the absorption of toxicants through the skin?

Answer 11

(1) the integrity of the stratum corneum,
(2) the hydration state of the stratum corneum,
(3) temperature, solvents as carriers,
(4) molecular size.

Question 12

Distribution

Answer 12

primarily by blood flow and the rate
of diffusion out of the capillary bed into the cells of a particular organ or tissue, and usually
occurs rapidly.

volume of distribution (Vd),

Question 13

Which organ has high-capacity storage?

Answer 13

kidney and liver

Question 14

Which compounds are found in the bone matri x

Answer 14

fluoride, lead, and strontium

Question 15

What are the 2 barriers that protect the brain?

Answer 15

the blood–brain barrier (BBB) and blood–cerebral spinal fluid barrier (BCSFB).

Question 16

How are toxicants exit the body?

Answer 16

kidneys,

• The second important route of elimination of many xenobiotics is through feces, and
  the third, primarily for gases, is through the lungs.

All body secretions appear to have the ability to excrete chemicals; toxicants have
been found in sweat, saliva, tears, and milk.

Question 17

What is biliary excretion?

Answer 17

the excretion of xenobiotics and/or their metabolites is most often the major source of fecal excretion, but a number of other sources can be significant for some
compounds?

Question 18

Define pharmacokinetics and
pharmacodynamics.

Answer 18

• Pharmacokinetics - What the body does to drugs?
• Pharmacodynamics - What drugs do to the body?

Question 19

Define the phases in clinical testing

Answer 19

Phase I: A few doses are given to a few healthy volunteers to determine safe dosages, routes of administration, absorption, metabolism, excretion, and toxicity.

Phase II: A few doses are given to a few subjects with the disease or
symptom for which the drug is being studied, and responses are
compared with those of healthy subjects.

Phase III: The drug is given to a larger and more representative group
of subjects.

Phase IV: The FDA evaluates the data from the first three phases for drug safety and effectiveness, allows the drug to be marketed for general use, and requires manufacturers to continue monitoring the
drug’s effects.

Question 20

Define Pharmacokinetics

Answer 20

• Pharmacokinetics involves drug movement through the body (ie,
  “what the body does to the drug”) to reach sites of action,
  metabolism, and excretion.
• Specific processes are:
• Absorption,
• Distribution,
• Metabolism (biotransformation)
• Excretion

Question 21

Define Pharmacovigilance

Answer 21

the science and activities relating
to the detection, assessment, understanding and prevention of adverse effects or any other medicine-related problem.