Pharmacogenomics

Question 1

What are the 2 synonyms of pharmacogenomics?

Answer 1

Pharmacogenetics

Pharmacoproteomics

Question 2

What are the 3 main mechanisms of pharmacogenomic differences?

Answer 2

1. Alterations in drug metabolism
2. Alterations in drug target
3. Alteration in drug transport issues

Question 3

1. Which of the following is pharmacokinetics?
2. Which of the following is pharmacodynamics?

Alteration in drug metabolism

Alteration in drug target

Alteration in drug transport

Answer 3

1. Alteration in drug metabolism & alteration in drug transport
2. Alteration in drug target

Question 4

What are the 2 mechanisms of altered drug metabolism?

Answer 4

1. Undesirable effects
2. Drug inactivity

Question 5

What are the 5 overall outcomes of pharmacogenomic differences?

Answer 5

1. Toxicity
2. Unwanted side effects
3. Prolonged effects
4. Drug failure
5. Exploitable

Question 6

What is isoniazid cleaved into that makes it toxic?

Answer 6

Inactive metabolite + acetylhydrazine

Question 7

Acetylhydrazine is a strong _____.

Answer 7

Electrophile

Question 8

How does a strong electrophile cause hepatocellular death?

Answer 8

Strong electrophiles (acetylhydrazine) will bind to any charged molecule, especially intracellular proteins. Within hepatocytes, the electrophile will bind to proteins, cause swelling, and hence, hepatocellular death.

Question 9

What does the acetaminophen undergo in a cat that causes hepatocellular injury?

Answer 9

Sulfonation

Question 10

What is the treatment for acetaminophen in a cat?

Answer 10

Acetylcysteine

Question 11

How does acetylcysteine treat acetaminophen toxicity in a cat?

Answer 11

Acetylcysteine - acetaminophen - SO4 is excreted as a polar, non-toxic entity into the urine

Question 12

Opioid metabolites inhibit the removal of ___ from the ___ in ___ and ___.

Answer 12

Opioid metabolites inhibit the removal of dopamine from the synapses in horses and cats.

Question 13

Opioid metabolites act as CNS ____.

Answer 13

Opioid metabolites act as CNS stimulants.

Question 14

Opioid analgesic reactions in horses and cats is an example of which of the following?

Intraspecies difference

Interspecies difference

Individual difference

Answer 14

Interspecies difference

Question 15

Atropine in a bovine is an example of which pharmacogenomic difference?

Answer 15

Drug inactivity

The extrahepatic enzyme plasma esterase + hepatic metabolism rapidly inactivate the drug.

Question 16

Primidone in cats is an example of which pharmacogenomic difference?

Answer 16

Drug inactivity: Lack of an enzyme for activation of a prodrug

Cats are unable to convert primidone to phenobarbital

Question 17

What are the 3 examples of the following?

Altered target of a drug: No activity of the drug

Answer 17

1. Fluroquinolone antibiotics
2. Genetic mutations
3. Receptor mutations

Question 18

1. Genetic mutations that yield inactive receptors cause receptors to be insensitive to ____.
2. Receptor mutations that cause an auto-active R cause receptors to be insensitive to ____.

Answer 18

1. Agonist
2. Antagonist

Question 19

Which of the following changes causes receptors to be hyperactive?

Genetic mutations OR receptor mutations

Answer 19

Receptor mutations

Question 20

Give an example of an altered taget of a drug causing an undesirable side effect:

Answer 20

Erythromycin

Causes gastrointestinal distress

Question 21

1. Erythromycin is a motilinR ____ for motilinR subtypeA.
2. Becuase of this, patients with ____ will develop the gastrointestinal distress associated with this drug.

Answer 21

1. Erythromycin is a motilinR agonist for motilinR subtypeA.
2. Becuase of this, patients with subtypeA will develop the gastrointestinal distress associated with this drug.

Question 22

What is the alternative drug to ivermectin in collies?

Answer 22

Selamectin

Question 23

Ivermectin sensitivity in collies is associated with a deletion mutation of the ____ gene.

Answer 23

MDR-1

Question 24

Ivermectin : collies

Is this an interspecies, intraspecies, or individual difference?

Answer 24

Intraspecies

Question 25

The multi-drug-resistance gene (MDR-1) in collies encodes for what large transmembrane protein?

Answer 25

P-glycoprotein

Question 26

Where is the p-glycoprotein for which mdr-1 encodes located with the collie's body?

Answer 26

Blood-brain-barrier

Question 27

Ivermectin : collies This is an example of which of the 3 mechanisms of pharmacogenomic differences?

Answer 27

Altered drug transport issues

Question 28

What are the 2 forms of altered drug transport issues?

Answer 28

1. Toxic accumulation of a drug 2. Selective tissue distribution of a drug

Question 29

You have a patient with a porto-systemic shunt that causes prolonged drug effects in that patient. Is this an example of intraspecies, interspecies, or individual pharmacogenomic differences?

Answer 29

Individual

Question 30

Sulfonamides produce a rare metabolite that can cause photosensitivity. What type of undesirable effect would this be an example of?

Answer 30

Toxic effect

Question 31

1. Auto-active TSH-R will cause what condition in your patients? 2. Can you give these patients drugs?

Answer 31

1. Hyperthyroidism 2. No, their receptors (auto-activeR) are insensitive to any antagonistic stimulus

Question 32

What is the enzyme of gene in greyhound's linked to propofol hydroxylation?

Answer 32

CYP2B11

Question 33

What is the enzyme or gene in Beagle's linked to celecoxib metabolism?

Answer 33

CYP2D15

Question 34

What is the enzyme or gene in all dog breeds linked to sulfonamid hypersensitivity?

Answer 34

N-acetyltransferase

Question 35

What is the enzyme or gene in labrador retriever's that puts them at risk for toxicity when using thiopurines?

Answer 35

TPMT

Question 36

What is the enzyme or gene in Bedlington Terrier's that is associated with copper storage hepatopahty?

Answer 36

Murr-1

Question 37

What are Boxer's sensitive to?

Answer 37

Acepromazine