56. Movement of drugs through the body: Drug absorption and distribution Flashcards
what is Pharmacodynamics
what the drug does to the body.
drug acting at a particular drug target resulting in the activation or inhibition of a cellular signalling pathway and eventually resulting in a change in a physiological process.
what is Pharmacokinetics
what the body does to the drug!
how easily the drug is absorbed in the body, is the drug distributed in certain tissue more than others, how the body metabolises the drug or eventually excretes it.
affinity
Ki
Potency
EC50
efficacy
Emax
absorption rate constant
Ka
If you have a very high Plasma Concentration of a drug what does this do
toxic effects
if you have a very low Plasma Concentration of a drug what does this do
Sub-Therapeutic effect
if you have a middle of the road Plasma Concentration of a drug what does this do
therapeutic effects - THIS IS WHAT WE WANT
so why is pharmacokinetic analysis important
helps us determine a dose of drug that will result in the appropriate blood plasma conc. to be safe and effective
what is ADME
absorption
distribution
metabolism
excretion
how do drugs move around in the body
Bulk Flow- this would be via the circulatory system (blood stream)
Diffusion of drug molecules over short distances
Solubility is important- lipid soluble drugs are more likely to diffuse across lipid bilayer membranes
how fast do large drug molecules move in comparison to small ones
Large drug molecules move more slowly than small one
Name the 4 ways in which drugs can cross cell membranes
Passive diffusion
facilitated diffusion
Active transport
Endocytosis(Pinocytosis)
More info down here
1. Passive Diffusion directly through the lipid or through aqueous pores formed by aquaporins that transverse the lipid bilayer. Many lipid soluble drugs cross cell membranes in this way.
2. Facilitated Diffusion via specialised carrier proteins that bind the drug on one side of the bind molecule on one side of the membrane then change conformation and release on the other side. Does not require energy, but does require a concentration gradient
3. Active Transport via specialised carrier proteins Requires Energy and can move drug molecules against the concentration gradient.
4. Endocytosis (pinocytosis)- invagination of a part of the membrane. The drug is encased in a small vesicle then ‘released’ inside the cell.
the ……. the log p the greater the lipid solubility
greater
what are the principal sites of carrier mediated drug transport (both facilitated diffusion and active transport)
- Blood brain barrier
- Gastrointestinal Tract
- Placenta
- Renal Tubule
- Biliary Tract
Many drugs are ‘…….’ acids or ‘……’ bases
weak
endocytosis transports what kind of drugs and give an example
large drugs eg vitamin B12
the proportion of ionisation of a drug depends upon both the ‘’’’’’ of the drug and the local ‘’’’’’’
pKa
pH
what are the base and acid ionisation equations
BH+ <—> B + H+
AH <—> A- + H+
The ………… equation can be used to determine proportions of ionised and un-ionised drugs in a given pH environment
Henderson-Hasselbalch
what are the Henderson Hasselbalch equations for acids and bases
pKa= pH+log(AH/A-)
pKa= pH+log(BH+/B)
what is aspirins pKa
3.5
negatively charged aspirin diffuses across the membrane of th egastric mucosa and gets……….
trapped in the plasma
good absorption
absorption of weak acids is facilitated where
pH of the stomach lumen
absorption of weak bases and majority of absorption (even weak acids) happens where
small intestine
if they have a pKa above 10 or below 3 (aka strong acids/bases) they are
poorly absorbed
Ionised (Charged): These forms are usually ……. (hydrophilic) and find its easy/hard cross lipid cell membranes.
water-soluble (hydrophilic)
hard to cross lipid cell membranes.
Unionised (Uncharged): These forms are typically ……(lipophilic) and can/can’t cross cell membranes
lipid-soluble
can
where does most oral route drug absorption occur and why
in the small intestine due to the large surface area
The Apparent Volume of Distribution (Vd) equation
Vd = dose/drug(plasma)
Lipophilic drugs cross membranes easily and Vd is generally ………..than total body volume.
greater
It is more difficult for hydrophilic or ionized drugs to cross membranes so Vd is closer to total body volume of water. what is the total body volume of water
42 L
If you have a low Vd what does this mean
drugs are retained in vacular compartments
If you have a high Vd this means?
it has spread to tissues and non vascular compartments, muscle and adipose
give an example of a drug which is hydrophilic or ionised with a Vd=10
aspirin
give an example of a drug which is lipophilic or unionised with a Vd of 1221
Amitriptyline
if two drugs have equal potency which drug will need a larger dose. the drug with a high Vd or a low Vd
high
what is the most abundant plasma protein that binds to mostly acidic drugs.
Albumin
what other plasma proteins bind drugs
Beta globulin and acid glycoprotein
High protein binding can slow drug elimination by….
preventing metabolism in the liver and glomerular filtration
Plasma protein binding reduces what
the availability of the drug for diffusion to the drug target organ
what is pKa
the measure of acidity or basicity of a drug molecule
It is also the pH of the solution at which 50% of the drug will be ionised and 50% will be unionised.
