Excretion

Question 1

Excretion of drug

Answer 1

-Renal is most important pathway in terrestrial vertebrate animals
-also use excretion in bile, pulmonary excretion, lactation, and the saliva, sweat, hair/nails

Question 2

3 processes affecting blood level of drug through renal excretion

Answer 2

1. Glomerular filtration- filtration of drug from blood into kidney tubules
2. Tubular reabsorption- if lipophilic, drug reabsorbed
3. Tubular secretion- pumped from blood into urine

Question 3

How does pH affect the reabsorption of a drug in kidney?

Answer 3

• Urine is acidic

-Weak acid in urine will be more likely reabsorbed because more non-ionized

-Weak base in urine will be more likely to be ionized and therefore excreted

Question 4

Tubular secretion in kidney

Answer 4

1. Organic anion transporters and organic cation transporters facilitate movement of drugs into the convoluted tubule
2. Active transport pumps in convoluted tubules will pump against the concentration gradient, removing drugs from the body

Question 5

Extrarenal excretion

Answer 5

1. biliary excretion
   2.pulmonary excretion (exhalation)
   3.Lactation
2. Minor routes of excretion (saliva, sweat, hair, nails)

Question 6

Biliary excretion

Answer 6

-important for removing larger molecules (MW>300 g/mol)

-Everything is taken to the liver and deposited in sinusoids which is surrounded by hepatocytes containing transporters.

Transporters: facilitated transport (OAT and OCT) and active transport proteins to remove drugs from body in bile

Question 7

Enterohepatic cycling

Answer 7

-drugs or drug metabolites excreted in the bile into the intestine can be reabsorbed and distributed back to the liver
**can increase the half-life of a drug, which if toxic then can increase toxicity of liver

Question 8

Pulmonary excretion

Answer 8

• important for volatile and gaseous drugs (NO, N2O)

Ex. breathalyzer test: ethanol is 90% metabolized in liver, 2% in expired air

Question 9

Lactation

Answer 9

-Route of elimination for lipophilic drugs because lipophilic drugs easily reside in the fat stores

-0.1-2% maternal dose

-important for neonatal exposure and food products

Question 10

Minor routes of excretion

Answer 10

-saliva (eg nicotine)
-sweat
-hair, nails- drugs sometimes accumulate in keratinous tissues (eg heavy metals)

Question 11

Drug interactions upon coadministration

Answer 11

-co-administration of two or more drugs= altered clearance of one or more drugs

Question 12

Types of drug interactions

Answer 12

1. summation
2. Synergism
3. Potentiation
4. Antagonism

Question 13

Summation (additivity)

Answer 13

Two drugs administered together combine their effects

2+2= 4

Question 14

Synergism

Answer 14

The effects of 2 drugs in combination exceeds the sum of their individual effects

2+2 = 10

Question 15

Potentiation

Answer 15

A drug with no effect intensifies the effect of a second drug

2+0 = 10

Question 16

Antagonism

Answer 16

The effect of 2 drugs in combination is less than additive

2+2=1

Question 17

Drug interactions during biotransformation

Answer 17

induction and inhibition of phase 1 and phase 2 enzymes

Question 18

Drug interactions during distribution

Answer 18

Competition between binding sites can result in displacement of a drug causing increased free drug and greater response

Question 19

Drug interactions during excretion

Answer 19

Decreased clearance due to inhibition of renal excretion
- usually competition for renal facilitated transport or active transport proteins

Question 20

Drug interactions during absorption

Answer 20

Substances affecting pH of GI tract can alter absorption
like is nonionized in like