Absorption & Distribution Flashcards
Enteral
Refers to anything that hits the stomach/digestive system
Parenteral
Anything that doesn’t involve the stomach/digestive system
First pass metabolism
The conc. of a drug is greatly reduced before it reaches systemic circulation
Routes of admin. that reduce first pass metabolism
- suppository
- intravenous
- intramuscular
- sublingual
What effects bioavailability?
- First pass metabolism; enzymes, mucosa & liver metabolise drugs
- Drug formulation; size, salt form, excipients influence absorption
- Solubility of the drug; very hydrophilic/hydrophobic is poor
How to measure bioavailability
- Compare plasma levels of a drug after oral vs IV
- Plot plasma conc. v time
- Measure AUC - total systemic exposure to drug
- Difference reflects extent of absorption
Bioequivalent
When two drugs have;
* comparable bioavailability
* similar time to achieve peak plasma conc.
* same active ingredient
Lipophilicity
The more lipophilic a molecule the better the brian penetration
Mechanisms for drug membrane passage
- Passive diffusion
- Carried mediated mechanisms
- Paracellular Transport
- Ion Trapping
Passive diffusion
From high conc. to low conc.
Dominates transmembrane movement of most drugs
Not saturable
Low structual specificty
What does passive diffusion depend on?
- Conc. of drug
- Oil/water partition coefficient
- Surface area of absorbing membrane
Carried mediated mechanisms
- Facilitated diffusion
- Active transport
Carried mediated mechanisms
- Facilitated diffusion
- Active transport
Facilitated diffusion
- Requires transmemrane integral proteins
- No energy required
- Movement in direction of conc./elctrochemical gradient
- Carrier protein may be highly selctive
Active transport
- Requires transmembrane integral proteins
- structurly selective
- Can be against conc./electrochemical gradient
- saturable process
- in or out of cell
- binds molecule on one side - changes conformation and releases on other
Paracellular Transport
Small molecules can go between cells
What limits paracellular transport?
Capillaries of CNS and various epithelial tissues with tight junctions
pH and ionisation
Many drugs are weak acids or bases - ionized or unionized forms
Distribution
Following absorption
drug distributes into interstitial and intracellular fluids
1st phase of distribtion
well-perfused organs recieve most of drug
* Brain
* liver
* kidney
2nd phase of distribution
Slower delivery to:
* muscle
* most viscera
* skin
* fat
How is tissue distribution determined?
By the partioning of the drug between blood and the partiular tissue
How is tissue distribution determined?
By the partioning of the drug between blood and the partiular tissue
Barriers to cross
- Epethelial barriers
- Capillary barriers
