L3 - Drug Absorption and Distribution

Question 1

ADME

Answer 1

Absorption
Distribution
Metabolism
Excretion

Question 2

Physiochemical Factors of Drug Absorption

Answer 2

Solubility - has to dissolve to be absorbed
Chemical Stability - has to survive acidic conditions if oral administration, or GI tract enzymes
Lipid-Water Partition Coefficient - Rate of diffusion increases with lipid solubility
Degree of Ionisation - only unionised forms readily diffuse across barrier (passive diffusion - Fick’s Law), Henderson-Hasselbalch equation indicated ionisation at pH

Question 3

Most drugs absorbed in:

Answer 3

Small Intestine, acids can be absorbed in the stomach

Question 4

GI Tract Absorption modified by:

Answer 4

GI motility
pH at absorption site
Blood Flow to stomach and intestines
Manufacturing of the tablet/capsule
Physicochemical interactions (Ca2+ rich foods)
Transporters

Question 5

Oral Availability

Answer 5

Fraction of drug that reaches systemic circulation after oral ingestion

Question 6

Systemic Availability

Answer 6

Fraction of drug that reaches the systemic circulation after absorption

Question 7

Enteral Route of Administration:

Answer 7

Means via GI Tract
Per Os (Oral)
Sublingual/Buccal (under tongue/cheek)
Per Rectum (rectal)

Question 8

Per Os

Answer 8

Oral
+ simple, convenient, non-sterile, good absorption

• inactivation, food binding, variable absoprtion, first pass metabolism, difficulty swallowing in some patients

Question 9

Sublingual/Buccal

Answer 9

Under tongue/cheek
+rapid, avoids first pass, avoids gastric acid

• few drugs suitable

Question 10

Per Rectum

Answer 10

Rectal
+ rapid, avoids first pass, avoids gastric acid, nocturnal administration, can be used when oral route compromised eg vomiting

• variable absorption, distasteful

Question 11

Parenteral

Answer 11

Non-GI tract
Intravenous
Intramuscular
Subcutaneous (eg insulin, inject into body fat)
Inhalation
Transdermal (patch)
Topical (creams)

Question 12

Intravenous

Answer 12

+ rapid, continuous infusion, 100% availability, route for drugs that can damage tissue

• Sterile requirements, sepsis, high level at heart

Question 13

Intramuscular

Answer 13

+ rapid onset if lipophilic, depot inject for slow release

• painful, tissue damage with some drugs, absorption variable, dependant on muscle blood flow

Question 14

Subcutaneous

Answer 14

+ ideal for drugs requiring parenteral administration (eg peptides)

• Few disadvantages, tissue damage over time in same spot

Question 15

Inhalation

Answer 15

+ local effect, large surface area, volatile agents (eg anaesthetic gases)

• self-administration requires certain level of skill

Question 16

Transdermal

Answer 16

Skin Patch
+slow administration over time (smooth plasma conc)

• local skin irritation, few suitable drugs

Question 17

Topical

Answer 17

Cream
+ ideal for local effect

• few disadvantages

Question 18

Body Fluid Compartments:

Answer 18

Plasma Water = 2.8L
Interstitial Water = 11.2L
Intracellular Water = 28L
Transcellular Water = 1.4L

Question 19

Volume of Distribution (Vd) =

Answer 19

Apparent volume drug would have to be dissolved in, in order to give same concentration as plasma

Vd = dose/Cp

Vd < 10L = retained in vascular system
Vd = 10-30L = largely restricted to extracellular water
Vd > 30L = suggest accumulation in tissue, or well distributed throughout all body