Name the 4 states of drug disposition
The process by which a drug enters the blood stream from its site of administration.
Occurs in several sites in the body
The process by which a drug leaves the circulation and enters the tisseus perfused by the blood.
Once in tissues, further blood-independent distrubtion may occur by diffusion.
The process by which tissue enzymes catalyse the chemical conversion of a drug to a more polar for that it can readily excreted from the body.
The proces that remove the drug from the body.
Metabolism + excretion
Overview of drug disposition?
Name the 4 physiochemical factors controlling drug absorption?
- Chemical stability
- Lipid to water coefficient
- Degree of ionisation
The drug must dissolve in order to be absorbed.
Must have a degree of water solubility
Some drugs are destroyed by acid in the stomach or enzymes in the GI tract.
eg. insulin- not given orally as it is polypeptide (therefore destroyed by acid)
Lipid to water coefficient
Absorption of a drug must commonly relies upon diffusion across the biological membranes.
Drugs must have a degree of hydrophobic and hydrophilic characteristics.
What happens to the rate of diffusion when the lipid solubility of a drug is increased?
Rate of diffusion is increased.
Partition coefficient ?
The measure of the difference in solubility of the compound between two compartments
Difference in parition coefficient for hydrophobic and hydrophilic drugs?
Hydrophobic drugs will have a high partition coefficient- ie prefer to be distributed to hydrophobic compartments such as the lipid bilayers.
Hydrophilic drugs will have a low parition coefficient- ie. prefer to be distributed in aqueous compartments such as blood serum.
Degree of ionisation?
Many drugs exist as weak acids or basses existing in both ionised (A-, BH+) and unionised (AH, B) forms
Acidic degree of ionisation?
Basic degree of ionisation?
The meaning of pH?
What form of ionisation will readily diffuse across the lipid bilayer?
Degree of ionisation
50% of drugs is ionised
ionised forms of acid and basic?
Unionised forms of acid and basic?
Absorption of weak acids are faciliated by?
The pH of the stomach lumen.
Where are bases readily absorbed?
Until they reach the small intestine
Are weak or strong acid/bases readily absorbed?
Weaker acids/basics are more readily absorbed
Where is the majority of absorption takes place?
In the small intestine
Because of the large surface area
Acidic drugs are less ionised in what kind of environment?
Basic drugs are less ionised in what kind of environment?
The rate of the stomach emptying and movement throughout the intestines.
Modified by some drugs and the presence of food (ie. absorption will increase with food present)
Name the 5 factors that affect GI absoption
- Gastrointestinal motility
- pH at the absorption site
- Blood flow in the stomach and intestine
- For way the drug is maufactured
- Physiological interactions
How does the pH affect the GI absorption
pH varies along the length of the GI tract
How does the blood flow affect the GI absorption
Increased by the presence of food.
More blood: the faster the rate of absorption
How does the way the drug is manufactured effect the GI absorption?
The drug can be customised to be take effect in the intestine and not the stomach or any other site
How does the physiological interactions affects the GI absorption?
The rate of absorption is sometimes comprimised when other compounds are present such as other drugs or calcium-rich foods
The fraction of drug that reaches the systemic circulation after oral ingestion.
Amount in systemic circulation/ Amount administered
The fraction that reaches the systemic circulation after absorption
Amount in systemic circulation/ Amount reached.
Drugs (orally) are absorbed can be inactivated by enzymes in the gut wall and liver before reaching the systemic circulation and body tissues
Enteral route of drug administration
Via the GI tract
Name the 4 enteral route of drug administration?
- Sublingual (below tongue)
- Buccal (drug on cheek)
What is the partenal route of drug administration?
Avoids the GI tract
Name the 6 parental route of drug administration?
- Subcutaneous (needle to fatty tissue)
- Transdermal (patches)
- Topical (directly onto the skin)
What must the drug be located before it can be distributed to body fluid compartments?
Must be in the systemic circulation
Graphical representation of the different body fluid compartments and the volumes each hold?
What is the interstitial water?
The fluid in the space between cells
eg. fluid that lines the spinal cord, brain and joints
What is the intracellular water
The fluid contained inside the cell membranes
What 2 kinds of drugs are able to move between compartments?
- Free drug molecules that are not bound to proteins.
- Unionised drugs
- Unionised drugs
Volume of distribution
Vd= dose/ plasma concentration
Why is volume of distribution equation needed?
As drugs are not evenly distributed in the body.
Drug retained in the vascular compartment
Restricted to extracelular water
Distribution throughout the body