Pharmacokinetics Flashcards
The 4 processes of ADME determine what?
the plasma concentration of drug over time
What is parenteral administration? eg?
route of admin which does not involve the intestinal tract
eg. IV, IM, SC
3 factors affecting drug absorption…
- route of admin
- drug formulation
- chemistry of drug
Where are drugs transported?
aqueous phase of blood plasma
Apart from IV admin., ADME must involve what process?
transfer across cell membranes
What aspect of the lipid bilayer creates the hydrophobic interior?
fatty acyl side chains
What are the factors influencing rate of absorption?
- biological membranes (rate depends on lipid solubility)
- molecular size and shape + solubility at site of absorption
- degree of ionisation (most drugs are weak acids or bases and present as both ionised + unionised forms)
Can ionised/unionised molecules freely cross lipid cell membranes? why?
ionised - no as they are hydrophilic
unionised - yes as they are lipid soluble (lipophilic)
Weak acid is most unionisedin a fluid with … pH?
acidic eg. weak acid absorbed in stomach
Weak base is most unionisedin a fluid with … pH?
basic eg. weak base absorbed in small intestines
What does pH partition mean?
only uncharged forms of weak acids or bases can diffuse across lipid membranes
- protonated form for weak acid
- unprotonated form for weak base
Weak acids/bases accumulate where?
weak acids - compartments of high pH
weak bases - compartments of low pH
Drugs are mainly absorbed by …?
passive diffusion (down concentration gradients)
Active transport occurs where (in the body) typically?
kidneys, liver, nervous system
Does facilitated diffusion require energy?
no - does not go against electrochemical gradient
Absorption from GI is favoured when drug is in its … form?
unionised - more lipophilic
What are the drug properties influencing transfer across cell membranes?
small or big molecules acidic or basic water or lipid solubility extent of protein binding existence of active transport system
Re. drug distribution, drug is first delivered where?
heart, liver, kidney, brain and other well-perfused organs
Factors that affect drug distribution…
blood flow barriers (eg. BBB, intestine, placenta) protein binding (carrier protein)
What is biotransformation?
metabolism of drug
T or F - All drugs undergo one or more metabolic conversions
false - most do but some drugs get excreted unchanged
Major site of drug metabolism?
liver
Where are other drug metabolism enzymes found (apart from liver)?
kidney
lung
plasma
GI epithelium
In order to facilitate elimination, what needs to happen to a lipophilic compound? where?
It needs to be converted to a more HYDROPHILIC one - liver
