Drug Absorption and Distribution Flashcards
Pharmacodynamics:
what drug does to body, characterised by affinity, potency, efficacy by calculating K, EC50, EMAX
Pharmacokinetics
what the body does to drug
- Absorption:
drug is absorbed from site of administration into circulation
- entry into plasma
Distribution:
drug reversibly leaves bloodstream, distributed into intracellular fluids
Metabolism:
drug transformation by metabolism - liver and other tissues
Excretion (elimmination):
drug and/or drug metabolites excreted in urine, faeces or bile
Passive diffusion
- Small, lipid soluble, non-polar Drugs
- High concentration gradient
- Directly through lipid/aquaporins
Facilitated diffusion
Larger, water-soluble drugs, polar drugs
- Can show saturation kinetics: limited amount of carriers
- Drug may accumulate in compartments
- may show adverse effects if drug is susceptible to saturation kinetics
Active transport
- Transported against concentration gradient
- Requires carrier proteins w ATP
- Water-soluble drugs
- Can show saturation kinetics
Blood brain barrier:
brain and blood vessels supplying brain have tight junctions which regulate molecules entering brain
Endocytosis
- Bulk low (large molecules) through circulatory system
- Invagination of cell membrane where drug is encased in vesicle and released inside cell
what does the degree of ionisation depend on
pKa of drug and local pH
pKa:
pH at which 50% of drug is ionised and 50% is unionised
what is the Henderson-Hasselbalch equation used to determine
proportions of ionised and unionised drugs in a given pH environment
pH trapping
- Drugs are trapped in compartments that have particular pH
- Occurs as diff compartments have diff pH which tolerate drugs differently
Weak bases:
better abosrbed in acidic environment
Weak acids:
better abosrbed in alkaline environement
Non-polar drugs:
can easily cross membrane to be metabolised (as they are lipophillic)
Drug distribution
- Mouth
- Walls of small intestine
- Trasnported to liver by portal vein
Vd:
extent to which drug spreads between plasma and tissue compartments
Low Vd:
drugs retained in vascular compartments - mostly in plasma
High Vd:
drugs retained in non-vascular compartments – adipose, muscle etc.
Determining Vd
- Administer dose
- Obtain blood sample
- Seperate plasma from RBC
- Assay for concentration of drug plasma [drug]plasma
- Calculate Vd using Vd = Dose/[drug]plasma
Albumin:
most abundant plasma protein, high affinity for hydrophobic drugs
