Pharmacology- Drug Movement in the Body Flashcards
pharmacodynamics
what the drug does to the body
pharmacokinetics
what the body does to the drug
Absorption
from site of administration and enters plasma
Distribution
drug reversibly leaves the bloodstream and is distributed into interstitial and intracellular fluids
Metabolism
drug transformation by metabolism by liver and other tissues
Excretion
drugs and/ or their metabolites leave the body via urine, faeces or bile
where are lipid soluble drugs most likely to diffuse across?
lipid bilayer membranes
Ways in which small molecules cross the cell membrane
- passive diffusion
- facilitated diffusion
- active transport
- endocytosis
Passive diffusion
Molecule goes directly through the lipid or aqueous pores formed by aquaporins which transverse the lipid bilayer
Many lipid soluble drugs cross cell membranes in this way
Facilitated diffusion
Specialised carrier proteins which bind the drug on one side of the molecule, causing a conformational change. it then releases it on the other side.
doesn’t require energy; does require a conc gradient
Active transport
drug moved via specialised carrier proteins.
requires energy and can move drug molecules against the concentration gradient
Endocytosis/ pinocytosis
invagination of part of the membrane
drug is encased in a small vesicle then released inside the cell
Transport of large drugs across the cell membrane eg B12
Which type of transport can show saturation kinetics?
facilitated diffusion and active transport
Principle sites of carrier mediated drug transport
- blood brain barrier
- GIT
- placenta
- renal tubule
- biliary tract
proportion of ionisation of a drug depends on which 2 factors
pKa of the drug and local pH
pKa
pH at which 50% of the drug is ionised and 50% is unionised
For most drugs, which form are they in to be able to permeate the membrane?
non-ionised
Henderson-Hasselbalch equation and its purpose
determine proportions of ionised and unionised drugs in a given pH environment
pKa=pH+log(AH/A-)
pH-pKa=log(A-/AH)
Where do weak bases accumulate?
compartments with low pH
Where to weak acids accumulate?
compartments with high pH
Where are weak acids absorbed?
in the stomach due to its low pH
Where are weak bases absorbed?
in the intestine, due to its higher pH
Where does most oral route drug absorption occur?
small intestine due to its large surface area
what do people in the pharmaceutical field look into?
developing devices for drug delivery and release into the optimal physiological environment to facilitate drug absorption
Which compartment are small water soluble molecules delivered to?
total body water
Which compartment are large water soluble molecules delivered to?
extracellular water
Which compartment are highly plasma protein-bound molecules, large molecules, highly charged molecules
delivered to?
blood plasma
Which compartment are highly lipid soluble molecules delivered to?
adipose tissue
Apparent volume of distribution (Vd)
the extent to which a drug partitions between plasma and tissue compartments
Vd= dose/[drug]plasma
how to determine Vd from drug blood plasma conc
administer drug dose, obtain sample, separate RBC and plasma, assay fro [drug]plasma, calculate Vd
where are drugs with a decreased Vd generally retained?
vascular compartments
where are drugs with an increased Vd generally retained?
adipose, muscle and other non-vascular compartments
For drugs with equal potency, will a drug with a high Vd require a higher or lower dose than that of a low Vd?
Higher dose
The most abundant plasma protein
Albumin
How do most drugs bind to albumin?
with low affinity via electrostatic and hydrophobic forces
What does plasma protein binding reduce?
Reduces the availability of the drug for diffusion to target organ
may also reduce transport of drug to non vascular compartments
What happens to [drug]plasma as Vd increases
it decreases
