Exam

Question 1

Which “steps” are involved in a risk assessment procedure?

Answer 1

Hazard characterization, Exposure assessment, Dose-response assessment, Risk characterization, (Risk management).

Question 2

How would you test a new chemical entity to gain knowledge about its toxicological properties?

Answer 2

– Acute toxicity LD50 , Dose-response, single dose
– Irritation, sensibilization
– NOAELs, 28 days repeated exposure
– Gene mutation tests in vitro
– Limited toxicokinetics

Question 3

volume of distribution

Answer 3

a primary determinant of the concentration of a toxicant in blood that is used to quantify distribution throughout the body. It is defined as the volume in which the amount of drug would need to be uniformly dissolved to produce the observed blood concentration. Is the apparent space into which an amount of chemical is distributed in the body to result in a given plasma concentration

Question 4

Steady state

Answer 4

occurs when the amount of a drug being absorbed is the same amount that’s being cleared from the body when the drug is given continuously or repeatedly. Steady-state concentration is the time during which the concentration of the drug in the body stays consistent.

Question 5

How could we change the drug molecule in order to increase the Vd? What would the consequence regarding the drug’s behavior in the body be?

Answer 5

increase Vd : make it more lipophilic… will increase distribution into fatty tissues, Vd increases, plasma concentration will decrease, drug will be stored for a longer period of time.

Question 6

Which medical signs and conditions are expressed and are considered being part of reduced male fertility? Also describe the effects on different cells of the testicle.

Answer 6

Hypospadia, cryptorchidism and reduced semen quality. Increased occurrence of testicular cancer may also be mentioned. Effects on Leydig cells and Sertoli cells of the testicles, in addition to sperm production and development.

Question 7

What is the main organ responsible for the metabolism of xenobiotics?

Answer 7

Liver

Question 8

Which CYP enzyme is the most abundant in humans?

Answer 8

CYP3A4

Question 9

Which enzyme metabolizes ethanol?

Answer 9

Alcohol dehydrogenase

Question 10

Ethanol metabolism: 0-order, 1st-order or 2nd- order kinetics?

Answer 10

0

Question 11

Where in the body is lead (Pb) stored?

Answer 11

Skeleton/bones

Question 12

What is the main organic form of mercury that accumulates in the food chain?

Answer 12

Methyl-mercury

Question 13

What is the name of the cells that produce myelin?

Answer 13

Oligodendrocytes

Question 14

Why do we have a blood-brain barrier?

Answer 14

To protect the brain/CNS from xenobiotics

Question 15

All drug’s causing dependence is activating what system in the brain?

Answer 15

Mesolimbic dopamine system

Question 16

What is the main reason for nanoparticles’ increased reactivity in bulk solutions?

Answer 16

Increased surface/area ratio

Question 17

The antifungal drug ketoconazole specifically inhibits a cytochrome P450 isozyme responsible for the biotransformation of many drugs, among them midazolam. In a patient taking ketoconazole (200 mg/day PO), what would be the difference, if any, in this patient’s exposure (AUC0-24h) to midazolam if midazolam was administered intravenously (IV) vs. orally and why?

Answer 17

increased exposure by the oral route because ketoconazole inhibits both the intestinal and hepatic P450 isozymes.

Question 18

What form of mercury was the cause of Minamata Bay disease?

Answer 18

Organic mercury

Question 19

What condition will increase transport of a substance across the blood-brain barrier?

Answer 19

Lipid solubility

Question 20

L-dopa is the name of a pro-drug. Explain shortly the concept of pro-drugs and give an example of such a drug

Answer 20

A prodrug is a drug which is not active in its original form, but which works by being chemically converted (metabolized), either spontaneously or by an enzymatic reaction, into its active form. Clopidogrel (Plavix) is a medication that can prevent heart attacks and strokes. It’s a prodrug that’s absorbed in the intestine and activated in the liver. Acid-reducing medications like omeprazole (Prilosec) can make clopidogrel less effective by preventing it from becoming active. Other example is Kodein.

Question 21

Active CNS drugs often have poor lipid solubility

Answer 21

WRONG

Question 22

Endothelial enzymes in the blood brain barrier can contribute to decreased CNS effect of some drugs

Answer 22

CORRECT

Question 23

Concominant administration of an PgP-inhibitor can contribute to increased CNS effect of some drugs

Answer 23

CORRECT

Question 24

Receptor mediated transport is the main mechanism for CNS drugs to pass the blood brain
barrier

Answer 24

WRONG

Question 25

Process requiring energy

Answer 25

Facilitated diffusion

Question 26

ADME characteristics

Answer 26

Toxicokinetic

Question 27

Transport by a carrier

Answer 27

Active transport

Question 28

Process preventing systemic effects

Answer 28

First pass effect

Question 29

Reaction with the toxicological receptor

Answer 29

Toxicodynamic

Question 30

What is true about the biotransformation of xenobiotics?

Answer 30

* Phase I modification makes a compound more watersoluble * Phase I modification can results in bioactivation of a xenobiotic. * Hydrophilic metabolites do not require phase I or phase II metabolism to be excreted in the urine. * Biotransformation can be part of the mechanism of toxicity of a chemical.

Question 31

What general type of substances may produce a type I hypersensitivity reaction? Give examples of substances and situations where humans may be exposed to them both in private life and at work.

Answer 31

Proteins. Flour and bakers. Latex in gloves and health workers. Icocyanates and industry workers. Pollen and inhalation indoors and outdoors.

Question 32

What is atopy?

Answer 32

* Atopy is a hypersensitivity reaction, a immediate hypersensitivity (Type 1) reaction. the genetic tendency to develop allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis (eczema). Atopy is typically associated with heightened immune responses to common allergens, especially inhaled allergens, and food allergens * Atopy is a predisposition to an immune response against diverse antigens and allergens leading to CD4+ Th2 differentiation and overproduction of immunoglobulin E (IgE). The clinical consequence is an increased propensity to hypersensitivity reactions.

Question 33

In which parts of the body may type I hypersensitivity reactions manifest and what are the main symptoms?

Answer 33

* Sensitization occurs as the result of exposure to antigens by dermal contact or through the respiratory or gastrointestinal tract. * Mucosa of the airways, the nose and on the eyelids, the skin and the intestine. Partly blocked airways with impaired breathing, irritation of the nose, swollen and itching eyelids, redness and itching of the skin, distressed digestion.

Question 34

Describe the mechanisms of the type I hypersensitivity reaction. You may illustrate with a sketch to help the explanation. If you'd like to use a sketch/figure, please upload it om the next page.

Answer 34

* Sensitization occurs as the result of exposure to antigens by dermal contact or through the respiratory or gastrointestinal tract. Most people would mount an IgM, IgG, or IgA immune response to these antigens and clear them without any allergic symptoms. Unclear why they become allergens in certain individuals who respond by mounting an IgE immune response instead, but the mechanism appears to involve genetic or/and environmental determinates and likely some type of triggering event, for example acute pathogen exposure and emotional stress.

Question 35

A part of the type I reaction may be defined as a type IV hypersensitivity, which one?

Answer 35

The cellular reactions with granulocytes and T-cells may be considered a type IV reaction, whereas the IgE antibody and histamine reactions are considered purely type I reactions.

Question 36

Describe shortly what reproduction toxicology is.

Answer 36

Toxic effects from xenobiotica on male and female reproductive organs. * Reproductive toxicology is the study on the male or female reproductive system that may result from exposure to chemical or physical agents * Toxic effects from xenobiotica on male and female reproductive organs.

Question 37

In which phases of life are men and women ́s reproduction most vulnerable to toxic chemicals? Explain shortly the reason for this.

Answer 37

In men from puberty with development of sperm cells. In women from before birth and the whole period they produce egg.