Pharmacokinetics: Basic Principles and Drug Absorption

Question 1

Pharmacodynamics vs. pharmacokinetics:

Answer 1

• PD: actions of drug on body, specific to drug or drug class
• PK: effects of body on drug, drug movement, non-specific, general processes

Question 2

4 basic principles of pharmacokinetics:

Answer 2

• Absorption: bioavailability
• Distribution: apparent Vd
• Metabolism or excretion: clearance (Cl), Plasma half-life (T1/2)

Question 3

Routes of administration:

Answer 3

• Topical: local effect, applied directly to desired site of action
• Enteral: systemic effect, via digestive tract
• Parenteral: systemic effect: routes other than digestive tract

Question 4

Topical administration

Answer 4

application to epithelial surfaces (e.g., skin, cornea, vaginal, nasal mucosa)

Question 5

Enteral administration

Answer 5

• oral
• sublingual
• rectal

Question 6

Parenteral

Answer 6

• inhalation

- injection

Question 7

Intrathecal injection

Answer 7

into subarachnoid space via a lumbar puncture needle to access the CSF

Question 8

IM injections

Answer 8

• given in a large muscle mass

- best for larger volumes and when fast absorption is desired

Question 9

Subcutaneous (SC/SQ)

Answer 9

• below dermis and epidermis

- when a slow, more prolonged effect is desired (e.g., insulin, many immunizations, heparin)

Question 10

Intradermal

Answer 10

• into dermis, just below epidermis

- longest absorption time, used for allergy tests and local anesthesia

Question 11

Factors influencing drug absorption from gut:

Answer 11

• drug structure
• formulation
• gastric emptying can affect rate but not quantity
• first-pass metabolism

Question 12

How drug structure affects drug absorption from the gut

Answer 12

• highly polarized/ionized compounds absorbed poorly
• weak acids and bases undergo pH partitioning
• peptides broken down by digestive enzymes (e.g., insulin)

Question 13

Effect of gastric emptying on absorption of drug

Answer 13

• food generally slows absorption rate due to delayed gastric emptying and stimulation of gastric acid secretion
• fasting, malnutrition

Question 14

Describe first pass metabolism

Answer 14

• drug absorbed from GI to portal vein to liver where they are metabolized
• results in only a proportion of drug reaching systemic circulation
• first pass metabolism can also occur in the lungs (MAO, peptidases) and gut (digestive enzymes, bacterial enzymes)

Question 15

Route of administration determined by:

Answer 15

• physical characteristics of drug
• speed which drug is absorbed/released
• need to bypass hepatic metabolism and achieve high conc. at particular sites

Question 16

Characteristics of typical plasma level curve after administration of an IV bolus:

Answer 16

max plasma conc. at T=0, immediately after dosing

Question 17

Typical plasma level curve after a single oral dose of a drug

Answer 17

• max plasma conc (Cmax) reached at a time Tmax after administration
• onset of action when plasma level reaches minimum effective concentration

Question 18

Area under the curve

Answer 18

• measure of the total amount of drug that enters the body after administration
• actual area calculated from a plasma-conc-time curve
• units of AUC are concentration*time (e.g., mg hr L^-1)

Question 19

Bioavailability (F): what is it?, what does it determine?, how is it determined?

Answer 19

• the fraction of the administered dose that reaches the systemic circulation as intact drug
• bioavailability determines dose required by different routes of administration
• compare plasma level of drug obtained after admin (oral/IM) w/ plasma level following IV admin

Question 20

Drug Distribution

Answer 20

process by which a drug reversibly leaves blood stream and enters the extracellular fluid and/or cells of the tissue (intracellular fluid)