W2 L1 - Introduction to ADME

Question 1

what does ADME stand for

Answer 1

Absorption
Distribution
Metabolism
Excretion

Question 2

define absorption

Answer 2

the process by which a drug enters the bloodstream from its site of administration
(Movement into body)

Question 3

define distribution

Answer 3

Reversible transfer of drug between the blood {or other site of measurement} and other tissues within the body
(Movement around body)

Question 4

define metabolism

Answer 4

Biotransformation of the drug into another chemical species

Question 5

define excretion

Answer 5

Irreversible loss of drug from the systemic blood
(Movement out of body)

Question 6

what’s elimination

Answer 6

• metabolism + excretion
• Irreversible loss of drug from site of measurement (e.g., plasma). Occurs by metabolism and/ or excretion

Question 7

L and T in (L)ADME(T)

Answer 7

• Liberation - release of the drug from it’s dosage form
• Pharmacological effect (or toxicity, T)

Question 8

is (L)ADME(T) pharmacokinetics or dynamics

Answer 8

pharmacokinetics - what body does to drug

Question 9

Drug and formulation properties determining absorption (oral)

Answer 9

• Lipophilicity
• Ionisation
• Molecular weight
• Solubility
• Permeability
• Formulation
  
  • Excipients
  • Enteric coating
  • Controlled release
  • Particle size

Question 10

Drug and formulation properties determining absorption (subcutaneous)

Answer 10

• Molecular weight < 16 kDa: Diffusion/ permeation through capillary wall is dominant route of absorption
• Molecular weight > 16 kDa: Lymphatic system is dominant route of absorption
• lymphatic system, which:
  Has larger, more permeable vessels than blood capillaries.
  Allows uptake of large molecules, particles, and even cells.

The lymphatic system then drains into the bloodstream, but more slowly than direct capillary absorption.

Question 11

what does distribution determine

Answer 11

• drug concentration in blood plasma and different tissues
  
  • unbound drug conc drives effect

Question 12

define tissue perfusion

Answer 12

• a certain blood volume flowing through a given tissue volume over a period of time
• highly perfused: Lungs, kidneys, liver, brain
  Equilibrium - Fast
• poorly perfused: Muscle, skin, adipose
  Equilibrium - slow
• “fast/slow equilibrium” refers to how quickly a drug (or substance) reaches the same concentration in the tissue as in the blood

Question 13

How are unionised and lipophilic drugs distributed

Answer 13

• Cross cell membranes easily
• Partition into lipid spaces of tissues (e.g., membranes) and bind neutral lipid/ phospholipid (NL/NP)

Question 14

How are ionised drugs distributed

Answer 14

• Basic drugs (BH+):
  
  • Electrostatic interactions with tissue acidic phospholipids (AP-)
  • Prone to lysosomal trapping (pH partitioning) - Lysosomes, which are acidic compartments inside cells — the drug gets trapped there because of pH differences.
  • So: Basic drugs tend to stay inside cells where it’s acidic, especially in organs like the liver and lungs.
• Acidic drugs bind to extracellular proteins (PR)
• Acidic drugs (A⁻):
  These become negatively charged in the body.

They prefer to stay in the fluid around cells (extracellular space).

They often bind to proteins in the blood, like albumin.

🡒 So: Acidic drugs mostly stay in the blood and outside cells.

Question 15

Distribution: Plasma protein binding

Answer 15

• unbound drug conc drives effect
• large plasma proteins not permeable
• allows measurement of drug binding using analysis
• key drug-binding plasma protein = albumin

Question 16

Issues reguarding hypoalbuminemia and toxicity

Answer 16

• Some patients have hypoalbuminemia (low concentration of albumin in plasma
• some drugs have saturable (non-linear) protein binding - when a drug binds to plasma proteins until binding sites are full, after which small dose increases cause disproportionately high free (active) drug levels, increasing the risk of toxicity

Question 17

Key sites for first-pass drug metabolism

Answer 17

• liver and intestines

Question 18

digestion vs metabolism

Answer 18

Digestion is the process of breaking down food into smaller molecules (nutrients) so the body can absorb them, occurring mainly in the digestive tract.

Metabolism is the set of chemical reactions in the body that use these nutrients to produce energy, build tissues, and regulate functions, occurring within the cells.

In short, digestion prepares nutrients, and metabolism uses them

Question 19

key sites for metabolic elimination

Answer 19

• Metabolic elimination - process where the body transforms substances (like drugs or toxins) into more easily excreted forms, primarily through metabolism in the liver, followed by excretion via urine, bile, or other routes
• liver - KEY SITE
• can also happen to a lower extent in brain, lungs, kidney, blood

Question 20

are lipophilic drugs more or less likely to be excreted

Answer 20

more likely

Question 21

how do metabolites differ to their parent drug in terms of chemistry

Answer 21

• more polar
• less lipophilic

Question 22

Factors affecting drug metabolism

Answer 22

• pregnancy
• age
• gender
• polymorphisms
• diabetes
• liver + kidney diseases

Question 23

routes used in drug excretion

Answer 23

• urine - glomerular filtration, active secretion, active/passive reabsorption - hydrophilic, uncharged drugs
• bile - active secretion - hydrophilic, uncharged drugs
• lung - passive diffusion - gaseous and volatile drugs, insoluble in blood + tissue
• saliva - pd - active transport - unionised, lipophilic drugs
• breast milk - pd - ‘’
• sweat - pd - ‘’