Applied Pharmacokinetics: Drug Absorption

Question 1

In simple terms, define Pharmacokinetics

Answer 1

“What the body does to the drug”

Question 2

List 4 pharmacokinetic principles

Answer 2

1. Absorption
2. Distribution
3. Metabolism
4. Excretion

Question 3

Define drug absorption

Answer 3

Describe the drug movement feom site of administration to site of measurement.

Question 4

What is the diameter of the cell membrane

Answer 4

10nm thick

Question 5

What’s the significance of the plasma membrane in drug absorption?

Answer 5

Forms a barrier in drug absorption

Question 6

Briefly describe the dynamic fluid mosaic model of the PLBL.

Answer 6

Made up of phospolipid bilayer, hydrophobic tails facing each other and hydrophilic head outside (charged)
Fluid : move freely
Mosaic : appearance not smooth has proteins and cholesterol and other substances embedded in it.

Question 7

What are the functions of the proteins in PLBL?

Answer 7

1. Receptors
2. Ion channels
3. Transporters to elicit signaling pathways
4. Provide selective targets for drugs

Question 8

Describe characteristics of passive simple diffusion.

Answer 8

1. Drugs move down concentration gradient
2. Rate of diffusion
   • Proportional to surface area and concentration gradient
   • Inversely proportional to membrane thickness
   • Other factors: fat solubility, molecular size, degree of ionization, type of membrane (i.e blood brain barrier)
3. Bound (large) vs unbound

Question 9

Describe characteristics of active transport.

Answer 9

1. Involves
   • Transport proteins *receptors
   • Energy
   • Movement against gravity
   • Selectivity
   •Cimpetative inhibition by co-transported molecule
2. Transport proteins are in region specific fashion

Question 10

List 2 factors affecting drug absorption.

Answer 10

1. Blood flow
2. Physical and chemical properties of drug.

Question 11

How does blood flow affect drug absorption?

Answer 11

IM drugs are absorbed slow in areas where blood flow is low

*Clinical application: IM drugs should not be given in patients with shock

Question 12

How do the physical and chemical properties of drugs affect drug absorption?

Answer 12

1. Non- ionized drugs ( weak bases) are lipid soluble and diffuse easy
2. Ionized drugs (acids) are lipid insoluble and penetrate with difficulty
3. Capillaries with fenestrae I.e gut are more penetrable than epithelium allows free movement of molecules weights <5000da Ionized and non- Ionized
4. Ionic receptor sites require drugs to carry positive charge I.e adrenagic and cholinegic receptors

Question 13

Name 2 Determinant of drug ionization.

Answer 13

1. pKa of drug and
2. pH of the environment

Question 14

Define pKa of a drug?

Answer 14

Is the pH value of the solution in which 50% of the drug has dissociated.
Meaning 1/2 is ionized and 1/2 in non-ionized

Question 15

What is the physiological pH value?

Answer 15

7.45

Question 16

At physiological pH how do drugs with low vs high pka behave?

Answer 16

Low pka are none-ionized
High pka ionized

Question 17

In gastric acid pH how do drugs behave? .

Answer 17

Basic drugs are ionized therefore better absorbed in small intestines where pH is alkaline.

Question 18

How can a drugs fat solubility be enhanced? Give an example

Answer 18

By adding hydrophobic group -CH2 which increases lipid:water partition coefficient.

Thiopental has a lipid: water partition coefficient of 10 therefore accumulated in fat and delays recovery.