Flashcards in Pharmacokinetics: Absorption and Distribution Deck (28):
What is Pharmacokinetics?
The science and study of the factors which determine the amount of chemical agents at their sites of biological action after the application of an agent or drug.
What are the 4 main topics that are studied in pharmacokinetics?
Describe the "perfect drug"
1. Stable form to introduce to the body
2. Pass into the body
3. Reach it's biological target
4. Remain long enough in the body to achieve a therapeutic effect (blood stream)
5. Not produce harm in the body
6. Exit the body when the job is done
Describe the absorption phase?
When the drug must cross the lipid bilayer membrane and pass the polar and fatty acid regions (lipophillic) to get to it's desired target
What properties of the drug determine the absorption phase?
The chemical properties of how lipophilic and hydrophilic they are
What may happen if a drug is too lipophilic?
1. Be insoluble in aqueous media
2. Bind too strongly in plasma proteins
3. Distribute into lipid bilayers
What may happen if a drug is too hydrophilic?
Cannot cross the plasma membrane
What does amphiphilic mean?
Can be hydrophilic or lipophillic
How does molecule size affect absorption in relation to the way it goes from extracellular to intracellular?
1. Smaller= diffusion= going down concentration gradient
2. Medium = Aqueous channels = aqua porin allows water to pass through
3. Larger= carrier proteins (ATP needed)
What environment is the extracellular, the membrane and intracellular in?
1. Extracellular- hydrophillic
2. Membrane- Hydrophobic
3. Intracellular- hydrophillic
What is ionisation?
Protonation or deprotonation resulting in a charged molecule
How can you tell if a drug is in an unionised form and why is it important to have this form?
1. When the pKa and pH value are equal values and there are equal amounts of ionised and unionised form
2. Unionised form means it can pass through if it's in an acidic environment
Describe the concept of pH trapping?
1. A weakly acidic drug crosses the membrane to the side with higher pH (urine pH 6 to plasma pH 7.2)
2. A basic drug crosses the membrane to the side with the lower pH (plasma pH 7.2 to urine pH 6)
3. The drug becomes trapped in the plasma or urine
What are the four groups of enteral treatment?
2. Sublingual- beneath tongue
What is topical treatment?
Application to the epithelial surfaces- example: skin, cornea, vagina, nasal mucosa
What are the four groups of injection parenteral treatment?
4. Intrathecal- spinal fluid
Why do we need to consider the different ways of drug administration?
1. Different administration methods have different speeds of delivery
2. Metabolism of compound- sublingual administration of isosorbide dinitrate passes through the liver to metabolise first
3. Targeting- intrathecal injection targets spinal cord directly
What is bioavailability?
The fraction of administered dose that reaches the systemic circulation.
What are the 4 factors that affect the absorption of a drug?
1. GI motility
2. Splanchnic blood flow
3. Formulation of medicine
4. Physiochemical properties of drugs.
How can incomplete metabolism occur?
1. Incomplete absorption and loss in faeces
2. 1st pass metabolism- starts metabolising the drug before it reaches the blood stream
Where abouts is the drug distributed to in the body and to what proportions?
1. Intracellular 2/3 and extracellular 1/3
2. Extracellular contains interstitial fluid that has plasma
What is the volume of distribution?
The volume of fluid thats required to contain the total amount of drug in the body at the same concentration as present in the plasma
How do you work out volume of distribution and what is it measured in?
1. Total amount of drug in the body/blood concentration
2. Measured in litres, cannot be smaller than the volume of intravascular plasma which is 3 Litres
What are the physiochemical properties of a drug?
1. Size of drug (larger molecules don't cross membranes well)
2. pKa of a drug (pH different between plasma and tissue can lead to accumulation)
Example: hydrophobic substances tend to become enriched in fat tissue
What are the pharmacological properties of the drug?
1. Binding of molecule to particular plasma or tissue proteins that might allow specific uptake into tissue
What are the four factors that affect distribution of drugs into tissue?
1. Physiochemical factors
2. Pharmacological properties
3. Blood flow in the organ and tissue
4. Barriers of organ and tissue
How does blood flow effect distribution of drug to various organs?
1. The rate at which a drug is distributed to various organs depends on the proportion of cardiac output the organ receives
2. Brain, heart, liver and kidney receive more compared to skin bone and fat