Lecture 6 - Factors affecting ADME

Question 1

What is different about older animals in regards to their GI tract that makes them more susceptible to some drugs?

Answer 1

Slower gastric emptying

Decreased gastric secretion

Question 2

What is different about older animals in regards to their body composition that makes them more susceptible to some drugs?

Answer 2

Increase in total body fat

Decrease in muscle mass

Question 3

What is different about older animals in regards to their renal function that makes them more susceptible to some drugs? How does this differ from other types of renal disease?

Answer 3

Decrease in renal excretion - do not see an increase serum creatinine

Question 4

What is different about older animals in regards to their hepatic function that makes them more susceptible to some drugs?

Answer 4

Decrease in metabolism - but no decrease in conjugations

Question 5

What comes first in older animals, hepatic or renal issues?

Answer 5

Renal

Question 6

What three components of disease effect drug metabolism greatly?

Answer 6

Fever + Infections + Inflammation

Question 7

What mechanisms occur with disease that cause a change in drug metabolism?

Answer 7

Pro-inflammatory cytokines increase capillary leakage

Increased extravascular distribution of drugs

Question 8

What happens to Vd with an increased extravascular distribution of drugs?

Answer 8

Increases

Question 9

What causes a decrease in Vd in regards to illness?

Answer 9

Binding to inflammatory exudates

Question 10

What changes to drug metabolism do you see with meningitis or encephalitis?

Answer 10

Increased penetration into the CNS

Question 11

What is a major characteristic of renal impairment?

Answer 11

Decrease in creatinine clearance

Question 12

Why do you see such a difference in absorption per os between species?

Answer 12

Due to the differences in pH’s of the GI tract

Question 13

What happens to drugs that are weak acids within a herbivores stomach?

Answer 13

they have a higher gastric pH (more basic) therefore weak acid drugs are going to be ionized and trapped within the lumen of the GI tract = decreased absorption

Question 14

What changes in the movement of fat soluble drugs in animals with lower body fat?

Answer 14

Exist at higher concentrations at target tissues (Vd will be lower)

Question 15

What is a big factor that effects distribution of a drug?

Answer 15

Fat content of an animal

Question 16

What is a big factor when it comes to variability in metabolism between species?

Answer 16

Liver enzyme function

Question 17

What is different about greyhounds in regards to liver function?

Answer 17

Lacking enzymes needed for thiobarbituates, leading to prolonged recovery times

Question 18

What are cats missing in their phase II pathways that effect drug metabolism?

Answer 18

Deficits in glucuronidation enzymes

Question 19

What happens when a cat is deficient in glycyronidation enzymes?

Answer 19

Glutathione depletion 
Increased cellular oxidative stress 
Hepatotoxicity 
Increase Fe3+ to Fe2+
Decrease O2 supply

Question 20

What part of kidney do excretion rates depend on the most?

Answer 20

Proximal + Distal convoluted tubules

Question 21

What is the biggest culprit for difference between species when it comes to excretion?

Answer 21

Molecular differences

Question 22

What occurs with ruminants and xylazine?

Answer 22

Sheep have a variant alpha2-adrenergic receptor in their brain stem, therefore the use of this drug can lead to
Hypoxemia + Pulmonary edema + Death

Question 23

What animals, given in lecture, experience morphine mania?

Answer 23

Dogs + Cats + Horse

Question 24

Which of the three animals discussed in lecture are most sensitive to morphine?

Answer 24

Horses

Question 25

What side effects are seen in dogs when given morphine?

Answer 25

EEG patterns of excitation

Question 26

What symptoms do cats experience when given morphine?

Answer 26

Clinical signs of excitation

Question 27

What symptoms do horses experience when given morphine?

Answer 27

Clinical signs of excitation + dysphoria

Question 28

What are the possible reasons for morphine mania?

Answer 28

Release of acetylcholine
Release of histamine
Levels of opioid receptors in the brain

Question 29

What is allometry?

Answer 29

Correlation of physiological functions across body sizes

Question 30

What is allometry used for clincally?

Answer 30

To determine drug conversions (especially for chemotherapy)

Question 31

What is a very important application of dose converstion?

Answer 31

Gives you a starting point for clinical trails

Question 32

Why are young animals more sensitive to certain drugs?

Answer 32

BBB not fully developed
Liver not fully functional
Renal excretion not as great