Lecture 11

Question 1

What is Toxin?

Answer 1

It is an agent that is capable of producing a deleterious response in a biological system.

Question 2

Types of toxins:

Answer 2

-Poison is swallowed, inhaled or absorb through the skin
-Venom is actively injected into the bloodstream via a bite or sting

Question 3

Classification of harmful effects:

Answer 3

1. Mechanistic categories of harmful effects
   - Includes related and unrelated effects of pharmacological action of the drug
2. Different patterns of incidence
   -Excessive effect of drug
   -Aberrabt effect unrelated to normal
   Drug action

Question 4

What is benefit versus risk?

Answer 4

-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.

Question 5

What is therapeutic index?

Answer 5

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

Question 6

What does LD50 mean in relation to therapeutic index?

Answer 6

-LD50: lethal dose for 50% of the test population or 50% morality in test systems

Question 7

What does ED50 mean for therapeutic index?

Answer 7

-ED50: Effective dose for 50% of the test population

Question 8

What TD50 mean in relation to therapeutic index?

Answer 8

-TD50: is the dose of drug that causes a toxic response in 50% of the population

Question 9

What does a large therapeutic index (TI) indicate?

Answer 9

Indicates that the toxic concentration is significantly higher than that required for the pharmacological activity of a drug.

Question 10

In biochemical experiments, the ED50 is often expressed as:

Answer 10

-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

Question 11

What is narrow therapeutic index?

Answer 11

It is when there is a small margin of safety between the therapeutic effect (ED50) of a drug and its toxic effect (TD50)

Question 12

Examples of drugs with narrow therapeutic index:

Answer 12

-Digoxin
-Lithium
-Gentamicin
-Warfarin
-5 Fluorouracil

Question 13

Digoxin

Answer 13

-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

Question 14

Lithium

Answer 14

-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

Question 15

Gentamicin

Answer 15

-Broad spectrum antibiotic used to treat bacterial infections
-Works by inhibiting bacterial protein synthesis

Question 16

Warfarin:

Answer 16

• Anti-coagulant drug employed in the prevention of thrombosis
  -Works by Inhibiting the synthesis of biologically active forms of Ca2+ dependent clotting factors

Question 17

5-fluorouracil:

Answer 17

-Anti-metabolite cancer drug
-Works inhibits thymidylate synthase causing interruption of thymidine synthesis and thus lack of essential nucleosides for DNA replication

Question 18

Definition of Toxicology?

Answer 18

It is the study of the effect of xenobiotics on living organisms

Question 19

What are xenobiotics?

Answer 19

Chemicals that are foreign to living organism

Question 20

Two types of toxicology:

Answer 20

1. Descriptive toxicology which includes toxicity testing and safety evaluation
2. Mechanistic toxicity which includes study of molecular mechanisms and toxic potential

Question 21

Toxicokinetics:

Answer 21

It is the absorption, distribution, metabolism, storage and excretion of agent.

Question 22

Toxicodynamics:

Answer 22

It is the effects of the chemical and its metabolites on an organism

Question 23

Organ-selective toxicity includes:

Answer 23

-Mechanistic Toxicology
-Poison
-Target Organ Toxicity

Question 24

Mechanistic Toxicology (in relation to organ-selective toxicity):

Answer 24

-Identification and analysis of the molecular mechanisms by which xenobiotics exert toxic effects in a biological system

Question 25

Poison (in relation to organ-selective toxicity):

Answer 25

-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

Question 26

Target organ toxicity:

Answer 26

-In sufficient amounts, many xenobiotics trigger an organ-selective pattern of toxicity

Question 27

Targets of organ selective toxicity:

Answer 27

-Liver
-Kidney
-Respiratory system
-Nervous system
-Cardiovascular system
-Reproductive system
-Immune system
-Blood
-Skin
-Eye

Question 28

Target organ toxicity is caused by?

Answer 28

-Major route/pathway of exposure
-Pattern of distribution in biological system
-Metabolism/Biotransformation
-Concentration factor
-Tissue-specific susceptibility to toxic insult

Question 29

Modifying factors in response to toxins:

Answer 29

-Frequency of exposure to toxin
-Accumulation of toxin in body
-Duration of exposure to toxin
-Inter-individual differences in toxic response