Pharmacogenetics: Slide 3

smarTTeaching - pharmacology:
Slide 4:

Pharmacogenetics 1. Define the term, pharmacogenetics.

is defined as the study of variability in drug response due to heredity.
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2. In what context is the term pharmacogenetics used?
Pharmacogenomics
It is used in relation to genes determining drug metabolism.

Name: Nthabiseng Rammolla 3. What does the term pharmacogenetics refer to?
Refers to how genes determine or influence drug metabolism.

Pharmacogenomics.
Slide 5:
Slide 6:
2. Describe the meaning of pharmacogenomics.
A broad term that refers to all the genes in the genome that may determine drug response.

2. Distinct between pharmacogenetics and pharmacogenomics.

There is no real difference (arbitrary) the words are used interchangeable.

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History of Pharmacogenetics. Slide 7. 2. a.) Date:

Slide 8. b.) What was described by Galton?

1. When did pharmacogenetics started? c.) Describe the difference between identical and fraternal twins.

It is traced back to 510 B.C. via Pythagoras observation of the ingestion of fava beans that resulted in a.) Date:

a a potentially fatal reaction in some individuals. b.) What was discovered by Bateson?

2. Who observed the first pharmacogenetic case?

3. What was observed by Pythagoras?
4. a.) Where were the earliest evidence of fava beans found?
b.) Where is the origin of Fava beans?
c.) As what were Fava beans considered in Egypt?
d.) Why did Pythagoras forbade people to eat Fave beans?

Slide 9:
5. a.) Date:
b.) Who established the rule of heredity?
Notes:
c.) Explain heredity

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3. a.) Date: 3. a.) Date:
b.) Who “coins” the term, pharmacogenetics? b.) What was discovered by Smith and Eichelbaum?
c.) What was established by Vogul and Motulsky?
d.) a.) Date: c.) What causes the oxidation of debrisoquine and sparteine?
b.) What was established by Evans? d.) What is debrisoquine used for?
c.) Who was the first to synthesize isoniazid? e.) Explain the meaning of “genetic polymorphisms of drug-metabolizing enzymes”.
Slide 11:
1. a.) Date:
2. b.) What was published by Kalow?
c.) When was the term pharmacogenetics first used?
d.) Who was the first to use the term, pharmacogenetics?
2.a.) Date:
b.) What was established by Sjogvist et. al.?
c.) Name one of the follow regarding tricyclic anti-depresant:
i.) representative drug:
ii.) contraindication: Notes:
iii.) side effect:

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 d.) Describe the meaning of “inherited diseases”.
c.) Describe the meaning of heredity.

5. a.)Date:
d.) What is genetic material composed of? b.) What was established by Snyder?
e.) What is the basic unit of heredity called? c.) Write the abbreviation for phenylthiocarbamide.
d.) What type of chemical substance is PTC?
f.) Write another general term for paired genes.
g.) Describe the meaning of “allele”.
4. a.) Date:
b.) What was developed by Garrod?
c.) Write Garrod’s suggestion regarding enzymes.

Notes:

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 ____________________________________________________________________________________
e.) Describe the uniqueness of PTC.
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Slide 10:
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a.) Date:
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b.) What was described by Bonicke et. al.?
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c.) What is isoniazid used for?
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d.) How is isoniazid removed from the body?
2. a.) Date:
b.) What was conceptualize by Motulsky?
e.) Name the three types of acetylators inherited by individuals.

c.) What was concluded by Motulsky?

f.) Explain the meaning of the term, phenotype.
g.) Describe the propagation of slow acetylates amongst different ethnic groups.

Notes:

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 Slide 12:
f.) What can be caused by polymorphism of drug-metabolizing enzymes?
1. a.) Date:
g.) What type of drug is sparteine?
b.) Which journal’s first edition was published during this year?
4. a.) Date:
c.) When was the term, pharmacogenetics introduced?
b.) What was discovered by Weinshikboum and Sladek?
2. a.) Date:
b.) What was described by Goldstein et. al.?
c.) Explain the role of TPMT.
c.) Describe the role of CYP2C19.
d.) What will result from a defect in TPMT?
5. a.) Date:
b.) What was described by Kupfer and Wedlund?
c.) What is mephenytoin used for?

Notes:

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3. a.) Date:
b.) Which term appeared during this year in the literature?
4. a.) Date:
b.) What was completed during this period?
c.) What was the aim of the Human Genome Project?
b.) Describe the aim of the Pharmacogenomics Research Network.
4. Describe the potential of pharmacogenetics.
Development of a Discipline: Slide 15.
Slide 16.
1. What was studied by Garrod?
2. What was first realized by Garrod?

Pharmacogenomics – Genes and Drugs: Slide 13.

Slide 14.
1. Write the abbreviation for the term, pharmacogenetics.
2. Describe the meaning of pharmacogenetics.

3. Which section of drug therapy has a genetic component?

Notes:

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3. Explain the following conditions: 3. Explain the meaning of the term, recessive inheritance.
a.) Alcaptonuria:
b.) Porhyria: Taste Blindness. Slide 18.
4. Explain the meaning of the substance, sulphonal. Slide 19.
1. a.) What was the first experimental PGx-related study that was done.
Slide 17.
4. What was interpreted by Bateson regarding Garrod’s report?
2. Explain the term, Chemical Individuality in Man.

Notes:

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 2. Why did PGx emerged as a discipline during this period.
2. Why was PTC synthesized?
3. How was PTC detected by people?
Slide 23:
4.) What is phenylthiocarbamide?
1.) Example 1:
a.) What was observed during World War II?
Slide 20:
b.) What causes an acute haemolytic crises?
4. What was concluded by Snyder?
2. Explain the meaning of autosomal-recessive fashion.

Landmark Discoveries: Slide 21.

Slide 22.
5. When was PGx recognized as a discipline?

Notes:

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2. Explain the following: 4. What is the risk of carrying a G6PD variant?
a.) haemolytic crises, Slide 25.
1. Example 2.
b.) primaquine, a.) What condition could result from succinylcholine treatment?

c.) G6PD, b.) Describe the time laps effect of succinylcholine exposure.

Slide 24:
1. What was suspected to account for Favism?
2. Where is G6PD located?
3. How many G6PD variants are known?

Notes:

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c.) What causes the prolonged effect of succinyl choline exposure? Slide 26:
1. Name an example of a genetic defect in drug biotransformation.
d.) How is pseudocholinesterase deficiency inherited?
2. Describe each of the following. 2. With which drug was acetylation polymerization first observed?
a.) succinylcholine:
3. Describe the meaning of acetylation.
b.) apnea: 4. Describe the pharmacological action of isoniazid.
c.) pseudocholinesterase:
d.) autosomal recessive trait:

Notes:

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 Slide 29:
1. What was assessed by Vessel and co-workers?
Drugs Reactions, Enzyme and Genetics: Slide 27
2. Which drugs’ genetic control of its steady-state plasma levels was shown?
Slide 28.
3. What was concluded from the twin studies?
1. What was described by Motulsky?
4. Which disorders was proved to precipitate by the administration of drugs?
2. Which barbiturate-precipitate attack was described by Motulsky?

3. What else was indicated by Motulsky?

4. When was the first conference on PGx held?

5. Describe each of the following:

a.) primaquine:
b.) barbiturate:
c.) porphyria:
d.) hyperbilirubinemia:

Notes:

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3. Explain the following: 2. What initiated research in pharmacogenetics?
a.) nortriptyline:
b.) inducible hepatic porphyria: 3. Explain the meaning of CYP2D6.
c.) malignant hyperthermia:
4. Which drug’s metabolism are affected by the CYP2D6-enzyme system?
Ecogenetics and Toxicogenetics: Slide 30
Slide 31.
4. Explain the meaning of ecogenetics:
2. Write three examples of ecogenetic variation.
Slide 32.
3. Explain the meaning of toxicogenetics.

Drug-Metabolizing Enzymes: Slide 33

Slide 34.
4. When was pharmacogenetic research introduced?
Notes:

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5. Explain the following: 2. Describe the genetic poly-morphism concluded from this drug.
a.) debrisoquine -
b.) spartein – 3. Explain the following:
a.) debrisoquine.
Explain the following:
a.) anti-depressants-
b.) anti-arrhythmics –
c.) opioids –

The CYP2D6 Paradigm: Slide 35

Slide 36
6. Explain the Smith case of 1975 at the St. Marys Hospital Medical School in London.

Notes:

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b.) 4-hydroxyl-debrisoquine. Transporters and Drug Targets: Slide 39.

Other Drug-Metabolizing Drugs: Slide 37. Slide 40.

Slide 38. 1. Which other forms of gene polymorphism has been discovered?

1. Which other polymorphism of cytochrome P450 was discovered? 2. Write an example of the polymorphism in (1).

2. What causes polymorphism? 3. Describe the following:

3. Which other polymorphism resulted from CYP2CP mutations? a.) gefitinib

4. Describe the following:

a.) mephenytoin –
b.) phenytoin –
c.) warfarin -

Notes:

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b.) epidermal growth receptor – 4. Describe the advantage of genomics.

Multifactorial Drug Response: Slide 41. Pharmacogenomics in Drug Discovery and Drug Development. Slide 45.
Slide 42. Slide 46.
1. What causes most of a drugs inefficacy and toxicity? 1. What will be the result of identifying all genes involved (cause, modify, contribute) in a disease?
2. Name environmental effects that could have an effect on drug treatment
outcomes.
3. Name four pharmacokinetics and pharmacodynamics determinants that could interact with genes.
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Effects of Drugs on Gene Expression: Slide 43.
Slide 44:
4. What is produced by most drug actions?
5. How is drug metabolism induced?
3. What is the consequences of induced drug metabolites?

Notes:

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Personal Medicine: Slide 47.
Slide 48.
1. Describe the future impact of PGx.

Therapeutic Lessons from Pharmacogenetics: Slide 49.

Slide 50.
2. Describe 3 conclusions regarding pharmacogenetics.

Slide 51.
3. Describe 4 conclusions regarding pharmacogenetics.

Notes:

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