module 3 Flashcards
where do drugs distribute in the body?
interstitial space
bone
muscle
plasma
adipose tissue
total body water
what form will a drug be in in the plasma?
protein-bound or free (ONLY FREE DRUG CAN DISTRIBUTE TO TISSUES)
what factors affect drug distrubtion
- blood flow to tissues
- ability of the drug to move out of the capillaries
- ability of drug to move into the cell
how does blood flow affect drug distribution?
low blood flow = limited drug distrubution
what conditions reduce blood flow?
neonates
abcesses
tumors
heart failure
shock
what are barriers to entering the target tissue
hydrophilic drugs
efflux transporters
what is the most widely studied efflux transporter?
P glycoprotein (pgp)
protects us from drugs and other toxins
active transporter
kicks drug out of the cell and will be back into the plasma or excreted
why cant plasma bound proteins pass into target tissue?
proteins are large and when theyre bound to plasma proteins theyre even larger! therefore theyre unable to pass through capillary fenestrations
what are the 2 major plasma proteins?
albumin
alpha 1 acidic glycoprotein
what type of drugs bind to albumin?
- weakly acidic drugs
- lipophillic
-responsible for most binding
what types of drugs bind to alpha 1 acid glycoprotein
-weakly basic
-hydrophillic drugs
what affects albumin concentration?
malnutrition, trauma, aging, liver and kidney disease
why is it bad if we have less albumin?
increases drug toxicity as more drugs will be FREE in the plasma
what increases alpha 1 acidic glycoprotein in the blood?
aging, trauma and hepatic function increase concentration
why does it matter if theres a higher concentration of alpha 1 acid glycoprotein in the blood?
more drugs will be protein bound and therefore therapeutic drug effects will be reduced
what is the volume of distribution?
calculated volume that helps us determine the approx volume that the drug distributes into
what is the formula for VD
Vd = D/C
how many litres of total body water in 70kg person
-42 litres
how many litres of fluid in intracellular space
28l
how many litres of interstitial fluid?
10 litres
how many litres of plasma?
4 litres
what kind of drugs have a small vd?
highly protein bound
large molecular weight (cannot pass through capillary)
estimated 0.057 vd
what kind of drugs have an intermediate vd?
low weight - can pass through fenestrations
hydrophillic - cannot cross the membrane
0.2 L/kg vd
what drugs have a large vd?
low weight
lipophillic
minimal protein binding
VD can have larger than total body water
why does body fat composition matter for vd?
elderly and obese have higher amounts of body fat, therefore there is a larger area for vd
why does muscle composition mtter for vd?
elderly has decreased muscle - threfore drugs that disrtubute in the muscle will have a lower vd
