Pharmacokinetics-> Drug Transfer, Absorption

Question 0

Enzyme kinetics

Answer 0

Rate of enzyme reaction
Small dose causes large change as enzymes can’t keep up-> easily out of therapeutic range
Reaction rate against conc of substrate, graph shows Vmax

Question 1

Zero order elimination

Answer 1

Capacity limited

Rate of drug elimination is independent of plasma conc-> usually because enzymes have become saturated

Question 2

Possible mechanisms of drug transfer across membranes

Answer 2

Filtration-> requires high hydrostatic pressure -> GFR-> elimination
Active transport-> drugs structurally related to endogenous chemicals-> tubular secretion -> elimination
Bulk flow of water-> water soluble drugs
Passive diffusion-> most drugs

Question 3

Passive diffusion factors

Answer 3

Rate:
Conc gradient across membrane, influenced by blood flow
Surface area available 
Thickness of membrane 
Molecular size and lipid solubility
Amount:
Rate of transfer 
Residence time in membrane

Question 4

Effects of lipid solubility

Answer 4

Biological membranes of lipid barriers
Most drugs are weak electrolytes-> ionise
Only unionised species can cross membranes
Extent of ionisation depends on H+ conc-> pH -> depends on drugs pKa value
Acidic drugs favoured at alkaline pH and vice versa

Question 5

Henderson-hasslebach equation

Answer 5

pH - pKa= log [base][acid]
Shows amount of drug ionised
Use pKa to predict charged to uncharged ratio

Question 6

Weak acid drug absorption

Answer 6

Absorption from stomach and intestine

Largely present in ionised form at blood pH-> unlikely to enter brain

Question 7

Weak bases

Answer 7

Negligible absorption from stomach
Good absorption in intestine
Largely unionised at blood pH-> likely to enter brain
Likely to be secreted into stomach and saliva

Question 8

Absorption in the mouth

Answer 8

Passive diffusion
For-> thin epithelium, rich vascularity, slightly acidic pH
Against-> small surface area, short residence time
Sublingual absorption usefully when rapid effect required-> avoid first pass metabolism

Question 9

Stomach drug absorption

Answer 9

Bulk flow-> ethanol
Passive diffusion
-> for-> acidic conditions, favour acid absorption
-> against-> relatively small surface area, short residence time

Question 10

Small intestine drug absorption

Answer 10

Main site of absorption
Passive diffusion
For-> large surface area, pH favours weak acid and base absorption, good blood flow, long residence time
Active transport

Question 11

Rectum and colon absorption

Answer 11

Similar to small intestine
Smaller surface area but good blood supply
Useful for people with GI distrubances

Question 12

Factors effecting GI absorption

Answer 12

Acid labile-> delays absorption onset
Acid labile -> reduces total amount absorbed
Formulation dissolving time
Presence of food-> prolongs residence time
GI secretions and enzymes-> destroy/inactivate drugs
-> iron binds quinolones
-> Ca binds tetracyclines
-> Al binds tetracyclines

Question 13

Percutaneous absorption

Answer 13

Through the skin
Drugs intended for topical use may be absorbed and can cause problems
Dermis is almost totally freely permeable to drugs
Epidermis behaves as simple lipid barrier-> more permeable inflammation
Patches-> convenient
Absorption from conjunctival sac similar

Question 14

Pulmonary absorption

Answer 14

Inhalation
Passive diffusion-> usually local effects-> usually trapped in lungs
Size of particle determines where deposited

Question 15

Intra muscular

Answer 15

Injection
Bioavailability=1
Need to balance lipid and water solubility
-> water solubility-> keep drugs in solution for long enough to be absorbed
-> lipid soluble-> to allow absorption
Faster onset and rate of absorption
Different absorption in different muscle groups
-> suspension rather than solution for depot injections