ADME Flashcards
What are the TWO main important factors for ADME ?
lipophilicity and hydrophilicity
what is logP ?
it is the measure of the lipophilic / hydrophilic nature of a molecule
what are the characteristics of lipophilic and hydrophilic molecules ?
lipophilic
1. insoluble in aqueous environment
2. Binds strongly on plasma proteins
hydrophilic
1. soluble in aqueous environment
2. Inability to cross plasma membrane
what biopharmaceutical factors affect lipophilicity and hydrophilicity ?
- Permeability and solubility
- Size matters
- Use of diffusion, aqueous channels and carriers.
- Ionisation and pH trapping
- if an ion is thrown on a membrane, it will repel. Therefore we need ion channels
- unionised form of drugs will pass membrane while ionised will not
- acidic drug can exist in unionised state thereby more likely to pass plasma membrane
- basic drugs are less acidic, therefore more like to dissociate to ionised form .
What is oral bioavailability
Extent and rate at which a drug enters systemic circulation and reaches the target area
List FOUR factors affecting absorption
- 1st pass metabolism
- Gastric emptying
- modified release formula
- Food : eating can change the pH of the stomach which can then impact absorption
what is volume of distribution (Vd). State its formula and units
Is a pharmacokinetic parameter that relates the total amount of drug in the body to the concentration in the bloodstream
Vd = Amount of drug in body (D)
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Plasma concentration (Cp)
Units = Litres /kg
Discuss FOUR factors that affect distribution
- Physiochemical properties of drug
- size of drug molecules
Larger molecules do not easily cross membrane. For example heparin
- pKa of drug
pka difference between plasma and tissue can lead to accumulation - hydrophobic substances tend to become enrich in fat tissue (obesity can influence distribution of drugs
- Barriers of organ or tissue
- lipid soluble drugs can pass readily from mother to fetus
- presence of blood brain barrier
Name 5 characteristics of a perfect drug
- passes into the body
- Reaches its biological target
- Stays in the body long enough to achieve its therapeutic end
- Does not produce harm while in the body
- Exits the body when its job is done
Drug metabolism occurs at TWO sites. For each site state the organs it occurs at.
- At tissue level
- liver, kidney and lungs
- At intracellular level
- smooth endoplasmic reticulum
Outline phase 1 metabolism
In phase 1, the reaction changes the structure of the drug molecule.
So from drug to derivative.
e.g oxidation, reduction and hydrolysis
Drug ———— Derivative
What is 1st pass metabolism
When some of the drug gets metabolised before it reaches its site of action
Describe the role of conjugation in relation to phase II metabolism
- Form covalent bonds
- Increase water solubility
- Form an inactive product
Describe TWO factors that affect metabolism
- Genetic factors
- External factors
e.g consumption of grape fruits can lead to increased concentration of drug in blood due to inhibition of the enzyme CYP3A4 . Which is dangerous for drugs with low therapeutic index such as immunodepressant, statins, CCB
Explanation: Grapefruit juice can block the action of intestinal CYP3A4, so instead of being metabolised, more of the drug enters the blood and stays in the body longer