Flashcards in Pharmacokinetics I Deck (49)
What 3 things does the effect of a drug depend upon?
1) Mechanism of action and effects on cellular proteins
2) Physiochemical properties
What are the physiochemical properties of a drug?
What are the 4 considerations of concentration of a drug?
What are 'pharmacokinetics'?
The factors which come together to regulate the CONCENTRATION of the drug in the body
and therefore the concentration at the SITE of action
Why must we be aware of the pharmacokinetics of a drug?
In order to look at the possible effects of the concentration of the drug in different parts of the body
In order to know what the concentration will be at the site of action
Helps to understand possible side effects and also know if the drug will be effective
How are drugs mainly transported around the body?
In the cardiovascular system
What can happen to the distribution of the drug if the CV system is damaged?
- Impact on distribution and absorption into the different compartments of the body
How do drugs get across the various plasma membranes in 4 ways?
1) Diffuse through the lipid bilayer
2) Through aquaporins
3) HIjack carriers
What is pinocytosis and what is it important for?
- Cell engulfs extracellular fluid and internalises it
- Large peptides and antibodies
Why is the movement of drugs through aquaporins limited?
Drugs are normally too large to do this
What chemical properties determine how well a drug can diffuse through the membrane?
- Lipid solubility
What is the lipid solubility of a drug defined by?
The partition coefficient
What does a high partition coefficient mean and what molecules normally have this?
Very efficient at entering into the lipid compartment
When is a high partition coefficient beneficial?
Drugs used in the CNS - can cross the blood brain barrier
What is the disadvantage of a high partition coefficient?
More rapidly filtered by the kidney - quicker elimination
What is diffusivity defined by?
The diffusion coefficient
What is the diffusion coefficient proportional to?
- The molecular weight of the drug
Which molecules are slower to equilibrate in lipids and why?
- Large molecular weight as diffusion coefficient = 1/√molecular weight
- Smaller diffusivity
What 4 things influence drug absorption into the body?
1) Site and method of administration
2) Molecular weight
3) Lipid solubility
4) pH and ionisation
Why does the site and method of administration of a drug influence drug absorption in the body?
- Determines what barriers the drug will encounter
- Depends how the drug will make access to the CV system for transport
What are 6 ways that drugs can get into the body?
- Straight into the blood
- Into the muscle
- Into the CSF
- Through the skin
- Through the lungs
Why is intravenous delivery advantageous?
- Bypass the gut and limit breakdown
- Fast and reliable way to control the drug concentration in the plasma
What is the disadvantage of intravenous delivery?
Requires specialist knowledge - restricted to emergency situations
What are the advantages of intramuscular delivery?
Avoid digestive system
What are the disadvantages of intramuscular delivery?
- Drugs need to cross barriers to get access to the plasma, where is it distributed = slower delivery
- Must consider local blood supply to the muscle
What are the advantages of oral/rectal delivery?
What are the disadvantages of oral/rectal delivery?
- Encounters many barriers
- Need to consider BIOAVAILABILITY
- Gut has an additional perfusion system (portal system)
- Takes drug directly to the liver, where most drugs get metabolised
What are the barriers of the GI tract?
What is the bioavailability of a drug and what does it determine?
What proportion of the drug makes it to the plasma, compared with the amount ingested
Determines if the drug is suitable for oral administration