PED1003/L04 Drug Absorption and Distribution Flashcards
Give 2 ways that drugs move around the body.
Bulk flow
Diffusion across barriers
Give 3 ways in which a drug can cross a membrane.
Diffuse through layers
Through water channels
Through carrier proteins
Give 2 types of carrier protein that can transfer drugs across a membrane.
Solute carrier transporters
ATP-binding cassettes
When is intravenous injection used? (3)
A rapid onset of action is needed
High dose control needed
Drug poorly absorbed
Drug is unstable or metabolised in GI tract
What does the rate of absorption of an IV drug depend on? (2)
Diffusion through tissue
Removal by local blood flow
Why is the stomach a poor site for absorption?
High proportion of drugs are ionised - pH partitioning
Why is the small intestine the main site of absorption for orally administrated drugs?
Large, highly permeable SA
Highly vascularised
pH 6-7.4
Enterocytes (epithelium) contain metabolic enzymes and transproters
Give 2 examples of uptake transporters from gut lumen to enterocytes.
OATP1A2
OCT3
ASBT
PEPT1.2
Give 1 example of uptake transporters from blood into enterocytes.
OCT1.2
OATP3A1
Give 2 examples of efflux transporters from enterocytes into gut lumen.
O-gp
MRP2
BCRP
Give 3 examples of efflux transporters from enterocytes into blood.
MRP1
MRP3
MRP4
MCT1
ENT1.2
Where is a high proportion of drug lost? What is the process called?
Liver - metabolic inactivation
What is enterohepatic recirculation (EHR)? (3)
Drug enters hepatic portal vein
Transported to liver then gall bladder
Secreted in bile to small intestine
Descrie sublingual administration. Give an example (3+1)
Films and sprays
Network of capillaries under tongue
Bypasses first pass metabolism
E.g., Glyceryl trinitate for angina
Describe rectal administration. Give an example. (3+1)
Suppositories and enemas
Useful for local effects
Avoids 2/3 first pass metabolism
E.g., managing opioid withdrawal
Describe inhalation administration. Give an example. (3+1)
Powders, gases ans suspensions
Bypasses first pass metabolism
Local lung effects
E.g., anaesthetics
Describe cornea administration. Give an example (1+1)
Local eye effects
E.g., Dorzolamide
Describe nasal mucosa administration. Give an example. (1+1)
Nasal spray
E.g., gonadotrophin
Describe vaginal administration. (4)
Gels, pessaries and rings
Avoids first pass metabolism
Useful for local drug effects
pH variance may affect absorption
Describe transdermal administration. Give an example. (4+1)
Stick on patches or gels
Steady rate of delivery
Bypasses first pass metabolism
Highly lipid soluble drugs can slowly enter through skin
E.g., hormone replacement
Give 4 factors that affect crossing membranes.
pH (ionisation)
Solubility
Permeability
Gastric motility
Food
Particle size
Capsules/coatings
Give an example of where ion trapping is utilised.
Sodium bicarbonate in aspirin overdose
Give 2 ways in which gastric motility may be affected.
Disorder
Drug treatment
What is Tmax?
The time taken to get to maximum plasma concentration
What is Cmax?
Maximum concentration of compound after dosing
What is the area under a curve (AUC) equal to?
Total systemic exposure
What is bioavailability (f)?
The fraction of the drug administered that is absorbed and available to have an effect in the body
What is the equation for bioavailability (f)?
F = (AUCoral)/(AUCiv) x (doseiv)/(doseoral)
What is Ka?
Rate of absorption
