Pharmacokinetics 1

Question 1

Pharmacokinetics

Answer 1

What does the animal do to the Drug

Absorption

Distribution

Metabolism

Elimination

Question 2

Absorption

Answer 2

From the site of administration into the vasculatrure

Exculdes IV injections

Oral, Subcutaneous, Intramuscular, Transdermal, Inhalation, Rectal

Question 3

Distribution

Answer 3

Throughout the body

Plasma protein binding, tissue barriers, intracellular, blood flow, lipophilicity, transporters

Question 4

Metabolism

Answer 4

SOme, but not all drugs are chemically changed

Hepatic (phase 1/2), non-hepatic

Question 5

Elimination

Answer 5

Drug and Metabolites

Renal elimination, biliary secreations, exhalation

Question 6

Pharmacodynamics

Answer 6

What the drug does to the animal

Effects the drug elicits

Question 7

Factos that affect drug delivery to specific tissue:

Plasma Protein Binding

Answer 7

If a drug is stuck ona plasma protein, it may not enter into the tissue

Question 8

Factors affecting drug delivery:

Anatomic Barriers

Answer 8

Extra barriers decreasing/restricting drug movement

Blood-Brain Barrier

Blood-Prostate Barrier

Blood-Occular Barrier

Blood-Bronchus Barrier

Question 9

Factors affecting drug delivery:

Drug Lipophilicity

Answer 9

Can the drug diffuse across a lipid membrane?

Does it need to?

Question 10

Factors affecting drug delivery:

Blood Flow

Answer 10

Actual blood flow:

• Tissue mass is more important thatn total blood flow
• Low:
  
  • Adipose tissue, bone
  • Poorly Perfuse
• Intermediate:
  
  • Muscle, Skin, GI tract
• High:
  
  • Lungs, Brain, Heart, Kidneys, Liver, Endocrine glands
  • Well perfuce

Question 11

Factors affecting drug delivery:

Drug Transporter

Answer 11

p-glycoprotein

Question 12

Factors affecting drug delivery:

Drug Ionization

Answer 12

A charged drug does not diffuse through lipid membranes well.

Question 13

Fenestrated Capillary

Answer 13

Aqueous pores are similar in regards to drug movement

Question 14

Drug Movement:

Diffusion:

Lipid

Answer 14

Across biologic membranes

Question 15

Drug Movement:

Diffusion:

Aqueous

Answer 15

Through pores, within body cavity

Question 16

Drug Movement:

Diffusion

Answer 16

Not saturable, no competition, not specific

Always moves from a higher concentration to lower

Physiochemical properties of the drug affect movement

Protein binding

Lipophilicity

Molecular Weight

Ionization: pKa

Properties of the cell membranes / capillaries

Question 17

Drug Lipophilicity and Transporters

Answer 17

• Transporter (active or facilitated) can potentially move soem drugs across cell membranes IF the drug is a Substrate for the transporter
• Transporter / Substrate affinity is specific
• Transporter can be in either direction depending on orientation of the transporter
  
  • Amino acid transporters move hydrophilic gabapentin into the CNS
  • P-glycoprotein transporter effluxes loperamide, an opioid, out of the CNS
  • Morphine, an opioid, is not affected sustantially by transporters so lipophilic morphine does penetrate into the CNS can eleicit central effects
• Transporters may have limited anatomic locations - may be organ specific and may not be located throughout body

Question 18

Carrier Mediated Drug Transporters:

Fcilitated Diffusion

Answer 18

No energy expended

Protein carrier provides pathway for substrate across membrane

Ion channels, Glucose Transporters

Moves from High concentration to Low Concentration

Saturable and Specific

Question 19

Carrier Mediatied Drug Transporters:

Active Transport

Answer 19

Energy expended

Saturable and Specific

Can go with or against concentration gradient depending on orientation

Genetic Mutations can inactivate or up-regulate transporters

Question 20

Impact of Blood Flow on Tissue Drug Exposure

Answer 20