4. Pharmacokinetics: Transport mechanism of drugs, absorption, distribution

Question 1

Pharmacokinetics

Answer 1

What the body does to the drug

Question 2

Give the types of transcellular transport

Answer 2

• Diffusion
• Filtration
• Facilitated diffusion
• Active transport

Question 3

Filtration

Answer 3

Bulk flow of solvent & solute through pores in the membrane

• Concentration gradient affects the rate

Question 4

Intracellular transport

Answer 4

Across gaps between endothelial & epithelial cells

• Filtration

Question 5

Degree of ionisation of a weak acid/base is determined by…

Answer 5

• The pK of the drug
• pH of its environment

Question 6

When pK of a drug = pH of surroundings

Answer 6

50% ionisation occurs

Question 7

Lower pK = stronger acid; Higher pK =

Answer 7

Stronger base

Question 8

Rate of passage accross a semipermeable membrane is dependent on…

Answer 8

• Pressure
• Concentrations
• Temperature

Question 9

Permeability accross a semipermeable membrane is dependent on…

Answer 9

• Solute size
• Solubility properties
• Chemistry

Question 10

Drug absorption

Answer 10

Movement of drug into the bloodstream

• Usually done via mucous surface

Question 11

Reasons for ↓ absorption of drugs

Answer 11

• Poor compound solubility
• Chemical instability in stomach
• Inability to permeate intestinal wall

Question 12

Relation of small molecule absorption and blood flow

Answer 12

• Absorption of small, very lipid-soluble molecules is “blood flow limited”
• Higher polar molecules are “blood flow independent”

Question 13

Bioavailability (F)

Answer 13

Fraction of drug that reaches the bloodstream unaltered

Question 14

Absolute bioavailability

Answer 14

Measures the availability of the active drug in systemic circulation after non-IV administration

Question 15

How is absolute bioavailability determined?

Answer 15

Pharmacokinetic study

• Plasma drug conc. vs Time plot
• Area under curve (AUC) for IV divided by that of non-IV administration

Question 16

Bioavailability ≠

Answer 16

Bioequivalence

Question 17

Relative bioavailability

Answer 17

Measure of the bioavailability of a drug when compared with another formulation of the same drug or delivered via a different route

Question 18

Formula to calculate relative bioavailability

Answer 18

Question 19

List the factors affecting bioavailability

Answer 19

• Poor absorption
• Degradation
• Intestinal motility
• Disease
• First pass effect

Question 20

First pass effect

Answer 20

Concentration of a drug is greatly reduced before it reaches the systemic circulation

Question 21

Topical/external administration sites

Answer 21

• Skin
• Mucous membrane
• Nose
• Mouth
• Rectum

Question 22

Enteral administration sites

Answer 22

• Oral
• Rectal
• Oro-/nasogastric
• Intra-ruminal

Question 23

Parenteral administration sites

Answer 23

• IV
• SC
• IM

Question 24

What is key for controlling the duration of drugs effect?

Answer 24

Rate of dissolution of tablets

• If not readily dissolved, may be released more gradually over time with longer duration of action

Question 25

Distribution

Answer 25

Reversible transfer of drug from one location to another * Blood leaves bloodstream → EC fluids + Tissues

Question 26

Distribution is dependent on...

Answer 26

* Permeability bewtween tissues * Blood flow * Perfusion rate * Ability of drug to bind plasma proteins & tissue

Question 27

For intracellular action drug must be...

Answer 27

Lipid soluble

Question 28

Volume of distribution (VD)

Answer 28

The volume of total body fluid into which drug "appears" to distribute * Quantifies the extent of distribution

Question 29

Volume of distribution is determined by...

Answer 29

Administrating a known dose of drug IV & measuring initial plasma conc. * Expressed in units of mass/volume

Question 30

Binding of plasma proteins

Answer 30

* Only free drug diffuses through capillary walls * Extensive binding retards rate at which drug reaches its site of action * May prolong the duration of action * Generally reversible

Question 31

Drug redistribution

Answer 31

* Relative distribution of drug changes with time * Usually highly lipophilic drugs that initially enter tissues with high blood-flow * Quickly redistribute to tissues with lower blood flow

Question 32

Blood brain barrier

Answer 32

* Ionised/polar drugs distribute poorly to CNS + chemotherapeutic agents & toxic compounds * → Must pass through endothelial cells

Question 33

Placental barrier

Answer 33

Lipid-soluble drugs cross more easily than polar drugs

Question 34

Most drugs are absorbed by...

Answer 34

Small intestine

Question 35

Rate of dissolution is described by the...

Answer 35

Noyes-Whitney equation

Question 36

List the factors that may alter absorption from the GI tract

Answer 36

* Gastric emptying time → Intestinal motility * GI blood flow * Stomach acid → Inactivating enzymes * Interactions with food & other drugs

Question 37

Absorption of small, very lipid-soluble molecules is...

Answer 37

* "Blood flow limited" * Higher polar molecules are "blood flow independent"

Question 38

Distribution

Answer 38

Reversible transfer of drug from one location to another * Where drug leaves bloodstream & enters EC fluids & tissue

Question 39

Distribution is dependent on...

Answer 39

* Permeability between tissues * Blood flow * Perfusion rate * The ability of a drug to bind plasma proteins & tissue

Question 40

For intracellular action, a drug must be...

Answer 40

Lipid soluble

Question 41

Volume of distribution (VD)

Answer 41

The volume of total body fluid into which drug "appears" to distribute * Quantifies the extent of distribution

Question 42

How is the volume of distribution determined?

Answer 42

1. By administrating a known dose of drug IV *(mass)* 2. Measuring initial plasma conc *(mass/volume)*

Question 43

Binding of plasma proteins

Answer 43

Generally reversible * The only free drug diffuses through capillary walls * _Extensive binding_ retards rate at which drug reaches its site of action & may prolong duration of action.