module 1: section 4

Question 1

What are the primary organs involved in absorption?

Answer 1

stomach/intestines, lungs, skin

Question 2

Describe the absorption in GI tract

Answer 2

• Main absorption through intestine due to large SA and physiological characteristics
• toxicants with low pKa absorbed through stomach since its acidic
  -rectum and buccal common for drug administration
  -esophagus epithelial layer is cornified so minimal absorption occurs

Question 3

what is the main mechanism for GI absorption

Answer 3

passive diffusion
- if resembles nutrients: protein-mediated transport
-if very large: endocytosis

Question 4

How does presence of food affect absorption in GI tract?

Answer 4

-can delay absorption due to time lag in drug getting from stomach to intestine
-can increase absorption due to increased circulation during fed state

Question 5

How are toxicants absorbed in the respiratory system?

Answer 5

through inhalation of gases and aerosols

Question 6

How is absorption limited in the respiratory system?

Answer 6

The lungs are protected by the respiratory tract from full dose exposure to a toxicant

Question 7

how is absorption not limited in respiratory system?

Answer 7

The thin epithelial membrane in alveolar region allows for efficient absorption of chemicals

Question 8

Describe the path of absorption through the skin

Answer 8

Epidermis is the hardest to penetrate due to cornification, then if passed a toxicant will easily move thru the dermis, then the hypodermis has larger nerves and blood vessels so toxicants can quickly get absorbed in this layer

Question 9

What individual factors affect absorption through the skin

Answer 9

• area of body exposed: epidermal layer is cornified different across the body
• presence of pre-existing skin condition: may increase or decrease absorption

Question 10

what environmental factors affect absorption through the skin?

Answer 10

• temperature: incr in temp increases dermal absorption due to enhanced blood flow
• humidity: increases dermal absorption due to influence on hydration levels of the skin

Question 11

Why is it important to know the detailed characteristics of absorption of a particular drug?

Answer 11

Allows for optimal and safer dosing and drug designers can create formulations of drug that is safer

Question 12

describe the path of chemical distribution

Answer 12

chemical absorbed into body, circulation takes chemical away from absorption site throughout the body, chemical passed through other biological membrane, enters tissue cells, may enter EC space

Question 13

What 4 factors affect toxicant distribution?

Answer 13

1. tissue perfusion
2. tissue barriers
3. protein binding
4. extent of metabolism

Question 14

describe tissue perfusion

Answer 14

tissues that are more highly perfused are likely to experience higher distribution of toxicant

Question 15

describe tissue barriers

Answer 15

distribution is not homogenous throughout the body because of anatomical barriers in certain areas of the body

Question 16

describe protein binding

Answer 16

toxicants more highly protein bound have harder time when crossing membranes due to restrictions than unbound free toxicants

Question 17

describe extent of metabolism

Answer 17

toxicants more metabolized have reduced/altered distribution since metabolism is mainly for elimination of toxicants

Question 18

What are the common routes of excretion?

Answer 18

liver (hepatic) and kidney (renal)

Question 19

Describe the path of excretion in renal

Answer 19

Passes from glomerulus to bowman’s capsule to proximal tubule

Question 20

glomerular filtration rate

Answer 20

the amount of blood that passes through the glomeruli each minute
- decreased rate=decreased excretion = prolonged toxicant effects

Question 21

Describe active tubular secretion

Answer 21

Active transporters in the renal tubule move toxicants from the blood into filtrate for excretion
- drugs that cause kidney-specific toxicity could be due to the blocking of transporters in the kidney during active transport

Question 22

Describe passive tubular reabsorption

Answer 22

concentration of a toxicant is higher in the renal tubules than in the blood so some lipid soluble drugs can be reabsorbed back into the blood as they move down the concentration gradient

Question 23

What 2 factors determine renal excretion?

Answer 23

Size: toxicants must be able to fit through the pores in blood capillaries of the glomerulus to pass through the tubular lumen of the nephron
water solubility: water soluble compounds can be filtered from circulation but cannot be reabsorbed unless actively transported

Question 24

Describe biliary excretion

Answer 24

toxicants in the blood are brought to the liver via the portal vein, sinusoids receive this blood and carry it to the central vein while hepatocytes filter and remove toxicants, toxicants move to the bile canaliculi and transporter proteins remove water soluble toxicants, then toxicants move to bile duct and get excreted into the intestines.

Question 25

What 3 methods are in enterohepatic circulation?

Answer 25

1. conjugation: when a water soluble toxicant conjugated with a larger water-soluble moiety is first metabolized by the liver, then excreted into bile, passed to intestine 2. hydrolysis: removal of water-soluble moiety returning to its parent form allowing for reabsorption 3. reabsorption: toxicant returns to liver via portal vein and exposed to toxicant metabolizing enzymes

Question 26

what makes a toxicant more or less likely to be excreted via one route over the other?

Answer 26

physiochemical properties of toxicant - biliary excretion: large, conjugated toxicants that contain both lipophilic and hydrophilic groups -renal: small, water-soluble toxicants