Exam3lLec8Pharmacogenetics

Question 1

Pharmacogenetics is what?

Answer 1

is a field concerned with unusual (idiosyncratic) drug responses that have a hereditary basis.

Question 2

A pharmacogenetically related response is different from an _ or _ phenomenon (an adverse reaction to a drug resulting from previous sensitization to the same drug or a closely related one)

Answer 2

Overdose or allergic

Question 3

Many drugs are metabolized by what?

Answer 3

Cytochrome P50 Enzyme:
* CYP3A (60%)
* CYP2D6 (25%)

Question 4

What is another name for Debrisoquine Hydroxylase?

Answer 4

• P4502D6
• CYP2D6

Question 5

What are the tests for determining metabolizer phenotype of Debrisoquine Hydroxylase?

Answer 5

• Debrisoquine
• Sparteine
• Dextromethorphan ⭐️

Question 6

What are the four phenotype cateogories?

Answer 6

• poor metabolizers (PM)
• Intermediatre metabolizes (IM)
• Extensive metabolizers (EM)
• Ultra rapid metabolizers (UM)

extrensive and ultra metabaloers are grouped to be called fast metabolizers

Question 7

What are genotyping tests for mutant alleles ?

Answer 7

Polymerase chain reaction (PCR)
* Advenaces in the molecular genetics of this polymorphism has lead to the promotion of PCR

amplify cyp2d6

Question 8

The CYP2D gene clusters on a given allelic DNA fragment may contain between _ copies of functional genes

Answer 8

zero to thirteen copies

Question 9

Which CYP enzymes are pseudogenes and function gene?

Answer 9

• CYP2D7 and CYPD8 are pseudogenes
• CYP2D6 is function gene

Question 10

What is the location of CYP2D6 and it’s inheditance?

Answer 10

located on the long arm of chromsomes 22 and is autosomal (passed down from mom and dad)

Question 11

What are the major classes of currently used drugs which their metabolism are significantly affected by the CYP2D6 polymorphism? ⭐️

Answer 11

1. Antiarrhythmic agents
2. B-adrenergic receptor antagonists
3. anti-psychotics
4. tricyclic antidepressent

Question 12

What happens with patients that take B blockers?

Answer 12

is estimated that 15 to 20 percent of patients who undertake therapy with the b-blockers are forced to discontinue their use due to adverse reactions

Question 13

Flecanide and propafenone:
1. What type of class?
2. Big or narrow therapeutic window
3. What group of metabolizersdoes this drug affect and what are their symptoms?
4. What P450 enzyme is defective?

⭐️ ⭐️ ⭐️ ⭐️

Answer 13

1. antiarrhythmic agents
2. narrow therapeutic window
3. High concentration (PM) can lead to ventricular tachycardia or fibrillation
4. CYP450 2D6

Question 14

What happens in PM individuals that take tricyclic antidepressants? SX? ⭐️

Answer 14

• They have a narrow therapeutic window
• Symptoms of the overdose are sedation and tremors for pm

Example is Nortriptyline

doctors think the drug is not working in pm pts and they incr dose causing overdose

Question 15

The more CYP2D6=

Answer 15

the less time in system or lower T 1/2

the less functional cyp2dr the more time or higher T 1/2

Question 16

What is the impact of therapy in fast, intermediate, poor metabolizers with ACTIVE DRUG and INACTIVE metabolite? ⭐️

Answer 16

Fas: dont reach the TW
Intermediate: are within the therapeutic window
Poor metabolism: reach toxic concentration

reverese occurs in prodrug

Question 17

codeine is example of drug which require metabolic activation by what?

Answer 17

cyp2D6-> prodrug

Question 18

Codeine is nearly ineffective as an _ in 5 to 10 percent of population (_).

Answer 18

Codeine is nearly ineffective as an analgesic in 5 to 10 percent of population (PM).

Question 19

• What is a prodrug, that is used for breast cancer?
• How does it work?
• How does this drug affect group PM?

⭐️⭐️⭐️⭐️

Answer 19

Tamoxifen, a prodrug, is used for breast cancer. Tamoxifen is a competitive antagonist of estrogen receptor. There is high risk of relapse in PM since drug was never converted to active

Question 20

POOR metabolizer=

Answer 20

• codeine ineffective
• Tamoxifen relapse

Question 21

What is the impact of therapy in fast, intermediate, poor metabolizers with INACTIVE PRODRUG and TOXIC metabolite 🌟

Answer 21

Fast: you reach toxic concentration
Intermediate: within the therapuetic range
Poosr: does not reach the therapeutic window bc its not converted to acrtive drugs

Question 22

What is caused by glucose-6-phosphate dehydrogenase deficiency ⭐️

Answer 22

Increased Susceptibility to Drug-Induced Hemolysis

Question 23

What drug causes acute hemolysis in approximately 10% of African Americans? ⭐️

Answer 23

anti-malarial drug primaquine

Question 24

Why does anti malarial drug primaquine cause acute hemolysis ⭐️

Answer 24

due to reduction in concentration of reduced glutathione (GSH) because there is a Glucose-6-Phosphate Dehydrogenase Deficiency (no NADPH)

Question 25

There are approximately 300 G6PD variants. What are the two main variants?

Answer 25

A-type that mainly occurs in African Americans and a more severe type in Mediterranean population (Mediterranean type).

Question 26

What drugs are affected by N-acetyltransferases in PM? ⭐️

Answer 26

The metabolism of the
* isoniazid
* procainamide (ant-arrhy)
* hydralazine (for HTN)
* caffeine are affected

In pm: can cause drug induced lupus erythematosus

CHIP

Question 27

What side is fast acetylaters and slow? ⭐️

Answer 27

Left: fast
Right: slow

Question 28

What does procainamide and hydralazine in PM individuals cause? ⭐️

Answer 28

Drug-induced Lupus Erythematosus can develop with prolong use of drugs with aromatic amines

Hydralazine was seen in the polymorphism of N-acetyltransferases