Flashcards in Pharmacokinetics II Deck (51)
What are the 4 major water compartments in the body?
What percentages of the body weight do these conribute to?
1) Extracellular fluid
2) Intracellular fluid (20-40%)
3) Transcellular fluid (2.5%)
4) Fat (20%)
How does the volume of a compartment affect a drug?
Concentration of a drug in that compartment at equilibrium
What percentage do the water compartments contribute to the body weight?
What are the 3 components of extracellular fluid and how much body weight percentage?
1) Plasma (4.5%)
2) Interstitial fluid (30-40%)
3) Lymph (1-2%)
What is interstitial fluid?
Extracellular fluid which bathes cells and tissues
How are drugs distributed to different parts of the body?
In the plasma
Where is the bioavailability of a drug measured?
In the plasma
How does fat impact the pharmacokinetics of a drug? (4)
- Made of lipids
- Non- polar drugs can easily enter and accumulate here
- Poorly perfused
- Varies between different people
Examples of the compartments of the body which are tightly regulated and why(2)
- Protected by the placenta
- Protected by the BBB
What is the distribution of the drug based upon?
- Lipid solubility
What is the BBB impermeable to and why?
Water soluble molecules, they have poor lipid solubility
Examples of drugs which can't cross the BBB?
- Chemotherapy drugs
(poor lipid solubility)
Examples of which molecules easily cross the BBB?
What happens to tight junctions during inflammation?
Where is the chemoreceptor zone in the body and what does this do?
- Outside of the BBB
- Induces vomiting - can happen during drug treatments
How does the protein albumin affect the free concentration of drugs in the plasma?
- Binds to acidic drugs
- Reduces the concentration of drug in the plasma
What are the 3 considerations of drug dose, regarding albumin?
When low doses of free drug are needed- need to increase dose to overcome binding to albumin
When high doses of free drug are needed - already taking a high dose
- Binding to and from albumin can decrease/increase the concentration of drug in the plasma - dangerous
Taking another drug can displace the original drug from albumin - increasing free concentration of the original drug
How does the partition into body fat effect the free concentration of drug in compartments why is this a disadvantage?
- Drug accumulates in the body fat
- Changes the amount and duration of drug in the body
- Difficult to predict the concentration of drug where you want it to act
What drugs are more likely to partition into the body fat?
Lipid soluble drugs
What affects drug concentration in the body?
Absorption (permeability, lipid solubility, into fats)
Where does drug metabolism mostly occur?
In the liver
What are the 2 biochemical reactions in the liver?
Phase 1 - catabolic reaction
Phase 2 - synthetic (anabolic) reactions
What happens in phase 1 in the liver?
- Produce more reactive compound
- By oxidation, reduction or hydrolysis
- Adds a reactive group (-OH) which serves as a point of attack for phase 2 reaction
What happens in phase 2 in the liver?
- Conjugation to produce an inactive product
What is conjugation?
Attachment of a substituent group
What are the microsomal enzymes present in the liver?(3)
- Cytochrome P450
- Alcohol dehydrogenase
Where is cytochrome P450 found?
Embedded in the membrane of the smooth muscle endoplasmic reticulum of the liver
Which enzyme can cause drug concentration to increase and why?
Alcohol dehydrogenase as it is easily saturated
What does enzyme induction cause?
- Increase metabolic enzyme in the body
- Cause drug to have a less effect as concentration decrease