Drug Absorption and Distribution

Question 1

Factors Affecting Drug Absorption:

Answer 1

• Area of absorbing surface
  
  • Number of cell layers between site of administration and blood
  • Amount of drug destroyed by first pass liver metabolism
  • Extent of binding to food or depot binding
  • Drug dose has different effects depending on individual differences in age, sex, and body size impact

Question 2

Drug Dose and Body Size:

Answer 2

• Drug dose expressed in mg of drug/ kg of body weight
• Increased weight -> increased volume of fluid -> needs higher dosage
In females, there is a higher ratio of adipose tissue to water, same amount of drug in females results in higher blood concentration

Question 3

Drug Transport Across Membranes:

Answer 3

• Drugs that haven’t dissociated are unionized, and are lipid soluble (neutral charge)
• Rate of passive diffusion modulate by concentration gradient and blood flow to the absorbing area
Most drugs are not readily lipid soluble because they are weak acids or weak bases that become partially ionized when dissolved in water

Question 4

Ionization Factor:

Answer 4

How likely a drug is to dissociate and ionize in water

Question 5

Partition Coefficient:

Answer 5

• Concentration of a drug in oil/ concentration of a drug in water
• Drugs that are unionized have very little electrostatic charge, lipid soluble, have a high partition coefficient
Drugs that are ionized are bound to water molecules by electrostatic attraction, lipophilic, have low partition coefficient

Question 6

Drug Ionization and pKa:

Answer 6

• pKa of a drugs refers to the extent of ionization of a drug (pH of solution in which that the drug would be 50% ionized and 50% unionized)
Drugs that are weak acids become more ionized in alkaline (basic) environment, and becomes less ionized in acidic environments, vice versa

Question 7

Ionization of Aspirin:

Answer 7

• Acetylsalicylic acid is a weak acid with pKa= 3.5
• More likely to become unionized in an acidic environment than a basic environment
Once unionized aspirin cross membrane, it is carried away by blood stream, maintains concentration gradient, blood that is there becomes ionized

Diagram + Explanation

Question 8

Drug Access to the Brain:

Answer 8

• 3 fluid compartments in the brain separated by barriers
○ Blood plasma
○ Cerebrospinal fluid (part of BBB)
○ Extracellular fluid (part of BBB)
Brain is selectively permeable to drugs that are unionized at plasma pH (lipid soluble drugs) and water soluble materials moved by specific transport molecules