Drug Availiability Flashcards
What is a partition coefficient?
A way of calculating how well a drug is dissolved in oil or water
Which compound crosses the phospholipid bilayer most easily - a polar or a nonpolar compound?
A nonpolar compound
- small polar compounds can also cross the phospholipid bilayer, having a molecular weight of 1000 or less
How do we determine the partition coefficient?
- add drug to a flask containing half oil and half water and shake it
- siphon water, measure the drug content in the the water, then do the same for the oil
- the partition coefficient measures how hydrophobic or lipophobic a compound is
What extra steps do pharmacologists have to take into account when considering enteral drugs?
They have to take into account the pH of the stomach (1 pH or 2 pH) as well as the pH of the intestines (pH 5- 6.5)
What is physiological pH?
The human pH level (around 7.4)
What is a pKa?
a calculation that represents the pH at which the drug is 50% water soluble and 50% fat soluble
- it is the pH of the solution from which we calculate the partition coefficient
What does how well a drug will be polarized determine?
How well it will react in different pH environments
What is the first rule to remember about the polarity of a weak acid (exam question)?
A weak acid will become LESS ionized in an ACIDIC environment (it will become more fat soluble in an acidic environment)
What is the second rule to remember about the polarity of a weak base (exam question)?
A weak base will be less ionized in an alkaline environment (it will become more water soluble in an acidic environment)
What determines how well a drug will be absorbed in a specific environment?
The drug’s pKa (the pKa is the standard for the relativity of the pH of the environment)
What does amphoteric mean?
A compound that has 2 pKa’s (one at an extreme acid and one at an extreme base)
What other factors determine the absorption of a drug?
- body size (the bigger the body, the higher the fat percentage, and the fat to water ratio is different)
- gender (females have a higher percentage of fat and a lower percentage of water)
- Age (children are smaller but have a faster metabolism)
What is corticosteroid binding globulin?
A transporter protein for cortisol (which is unionized)
What is adipose tissue?
Body fat
What happens when a particle is more ionized?
It stays in the blood longer (because it is hydrophilic)
What is one way that a drug gets distributed in the body?
Via transporter proteins
What is one example of a transporter protein?
Albumin (mostly for unionized compounds)
What is depot binding?
When the drug gets stuck in carrier proteins and adipose tissue
What are fenestra?
Gaps in a capillary that allow for crossing of particles
What do the capillaries of the blood-brain barrier lack?
Fenestra
What are the only three ways a particle can cross the blood-brain barrier?
- having a transporter (like L-Dopa, the precursor to dopamine)
- being a nonpolar compound
- being a small compound
What is biotransformation?
Biologically changing the compound (aka metabolic clearance)
Where does most metabolism take place?
In the liver
What is the goal of metabolism (exam question)?
The goal of metabolism is to make the compound more ionized (therefore making it more abundant in the blood, and not leaking to other membranes…this makes it easier to eliminate)
- metabolism also deactivates (or sometimes activate) the compound, but this is really incidental
What is the area postrema?
One of the few regions of the brain not protected by the blood-brain barrier (is the vomiting centre of the brain)
- detects toxic substances in the bloodstream
What are some ways that we eliminate a drug?
- defication
- urination
- perspiration
- respiration
- through breastmilk
What is one example of the body metabolizing a drug to activate it?
Aspirin is inactive until the body breaks it down into salicylic acid
Describe a phase I reaction in metabolism?
- is non-synthetic
- has three processes
- oxidation (removes electrons)
- reduction (adds electrons)
- hydrolysis (adds H2O, an ion)
- goal is to make it more ionized*
Describe a phase II reaction in metabolism?
- is a synthetic process
- has four processes:
- methylation (adds a methyl group)
- acetylation (adds an acetyl group)
- glutathione
- glucurinidation
What is the difference between a synthetic and a non-synthetic process?
A synthetic process adds a compound to make it more polarized, while a non-synthetic process manipulates the ions already present in the compound
What is a p450 enzyme?
A group of enzymes that are mostly responsible for biotransformation
What is a metabolite?
A product of metabolism
