Pharmokinetics Flashcards
What is absorption of a drug ?
2
Movement of drug from site of administration in the body to the site of measurement
What’s distribution?
2
Reversible transfer of absorbed drug into and out various of variable tissues in the body from the bloodstream
What is drug metabolism ?
2
Conversion of drug to a usually more water soluble compound
What’s excretion ?
2
Loss of unchanged drug from the body in urine or faeces !!
What’s the first pass effect ?
2
Metabolism with takes place before the drug reaches systemic circulation after oral administration.
When is oral route not preferred ?
4
- low lipid solubility
- destroyed by acid / enzymes
- major gut adverse effects
- large 1st past effect ( low oral bioavailability)
what’s elimination half life?(1)
time taken for the amount of drug in the PLASMA or BODY to decrease by a half .
what’s bioavailability ? (1)
fraction of the drug which reaches the systemic circulation.
what’s volume of distribution ?
how much is acc in the target tissue
- amount of drug In the body (g) / concentration of drug in the blood PLASMA .
It is useful for predicting if drug will be concentrated in the blood or tissue .
how can a drug be absorbed ?
4
1) passive diffusion
2) facilitated diffusion
3) Active transport
4) Endocytosis (larger drugs)
what affects distribution of the drug ?
name 3 and explain their reasons …
6
1) chemical stability (PH of stomach )
2) stability after digestive enzymes = peptides are broken down by protease
3) solubility in aqueous solution ( they need dissolution before they can be absorbed )
4) lipid solubility will determine if they can go through the lipid bilayer
5) molecular weight - smaller molecules can diffuse through the bilayer more easily
what chemical properties affect distribution of the drug ?
name 3 and explain their reasons …
6
1) chemical stability (PH of stomach )
2) stability after digestive enzymes = peptides are broken down by protease
3) solubility in aqueous solution ( they need dissolution before they can be absorbed )
4) lipid solubility will determine if they can go through the lipid bilayer
5) molecular weight - smaller molecules can diffuse through the bilayer more easily
6) Free drugs - drugs which don’t bind to the plasma proteins. (acidic drugs bind to plasma protein called Albumin = slows the distribution process).
what physiological properties affect the distribution of a drug in stomach? (4)
1) Presence of a type of food
2) blood flow to GI tract and liver
3) Gastric motility - determines how long drug is exposed to absorption surface ( movement of digestive system)
4) pH of the stomach
what’s first order kinetics ?
2
- half life remains constant because the rate of elimination is proportional to the concentration of drug in the body .
ie : 16% Is always eliminated = curved graph
What Zero order kinetics ? (2)
-half life increases as the rate of elimination is constant ie : always 200 mg decrease =straight line graph
What is steady state concentration ? (2)
(When doses of a drug are repeatedly administered, the drug will accumulate in the body until the rate of administration is equal to the rate of elimination.)
-time at which the concentration of the drug stays constant , normally after 4-5 half lives.
when would you use a high loading dose ? (1)
When rapid achievement of steady state concentration is needed, a large ( ie: IV ) loading dose could be applied .
what’s a maintenance dose? (1)
calculated to achieve steady state concentration , replacing the drug that was eliminated .
how does the liver metabolise lipid soluble drugs ?
6
1) PHASE 1 = redox and hydrolysis ( unmasking or addition of a polar functional group ). Catalysed by Cytochrome P450
2)PHASE 2=add another water soluble and less reactive group to the molecule.
ie:acylation , sulfanation, glutathione conjugation.
Poor conjugates which can not diffuse across membrane hence their easily eliminated from the body !
where are most polar molecules excreted ? (1)
Kidney in urine
what general factors affect drug metabolism? (5)
1) age
2) disease
3) genetic variation causing absence of enzymes
4) enzyme induction (making enzymes )
5) enzyme inhibition ( prohibiting the making of enzymes)
How do you calculate the amount of drug in the body ?
2
Amount in body ( tissues etc) =VD x plasma concentration
>45L is good distribution !
