ADME

Question 1

Drug ionisation effects on absorption?

Answer 1

Weak bases - ionised in acidic pH, absorbed in SI

Weak acids - unionised in acidic pH but also absorbed in SI due to large SA

Question 2

Complications of IV admin

Answer 2

Fear/pain, infection, theombophlebitis (vein inflamm), extravasation/infiltration, emboli, anaphylaxis/hypersensitivity, overdose

Insufficient mixing
Stability of meds in solution - light (TPN), temp (insulin/TPN), conc (amiodarone), pH (midazolam)
Interaction of meds with syringe/bag

Question 3

Factors affecting distribution

Answer 3

CO and blood flow
Plasma protein binding
Lipid solubility
Degree of drug ionisation
pH of compartments
Capillary permeability

Question 4

Albumin binding

Answer 4

Lipid soluble drugs bind non-specifically
Weak acids bind to a specific saturable site

High albumin causes dehydration and low free drug levels
Low albumin causes burns, renal and hepatic disease and malnutrition, free drug levels increase

Question 5

Phase 1 metabolism

Answer 5

Introduces or unmasks a functional group

• Oxidations - cytochrome p450, alcohol dehydrogenase
• Reductions - ketone reduction, anaerobic cytochrome p450 metabolism
• Hydrolysis - ester hydrolysis (e.g. cholinesterases), amide hydrolysis

Question 6

Phase 2 metabolism

Answer 6

Detoxified, water soluble, easily secreted products
Suitable for secretion in bile or urine

e.g. methylation/acetylation (methyltransferase/acetyltransferase), sulfation (sulfotransferation)

Question 7

Biliary excretion

Answer 7

Transfer of drugs from plasma to bile - organic cation transporters, organic anion transporters, p-glycoproteins

Concentrated in bile, delivered to intestine
Hydrophilic drug conjugates
Hydrolysis of conjugate can occur - reabsorption of liberated drug, enterohepatic circulation

Question 8

Renal excretion

Answer 8

GF
Tubular secretion
Diffusion across renal tubule