Pharmacokinetics 1 Flashcards
What determines a drug response?
Concentration at its site of action, which is in equilibrium with the concentration obtained in blood
What is pharmacodyamics?
What the drug does to the body
What is pharmacokinetics?
What the body does to the drug
What two factors determine the route of drug administration?
- Speed of onset
2. Convenience
What does ADME stand for?
Absorption, distribution, metabolism, excretion
What is drug absorption?
Movement of drug from site of administration to site of measurement
What is drug distribution?
Reversible transfer of absorbed drug into and out of various tissues in the body from the bloodstream
What is drug metabolism?
Conversion of a drug to a usually more water soluble compound
What is drug excretion?
Loss of unchanged drug from the body in the urine or faeces including biliary excretion
What is drug elimination?
Metabolism and excretion of a drug (everything after the distribution equilibrium)
What is drug disposition?
Distribution and elimination of a drug (all process which occur after a drug has been absorbed)
What is first pass metabolism?
The metabolism of a drug before it reaches the systemic circulation after oral administration
What is bioavailability?
The amount of drug which reaches systemic circulation
What happens to orally administered drugs once swallowed?
Transport proteins absorb the drugs through the gut wall to the liver, where the drugs are metabolised
What occurs during the metabolism of a drug in the liver?
The liver usually adds a water soluble molecule to the drug as water soluble molecules are easier for the kidney to remove
What happens to lipid soluble or small drugs which are hard for the kidney to excrete?
Usually travel to tissue reservoirs e.g. muscle
What is the main reason a drug may not be orally administered?
Low oral bioavailability
What are 4 reasons a drug may have low oral bioavailability?
- Poorly absorbed due to low lipid solubility
- Destroyed by acid or enzymes
- Causes major gut adverse conditions
- Has a large first pass effect
What is a method of administration to avoid first pass effect?
Sublingual administration
What 6 chemical properties determine the amount of drug in systemic circulation after oral administration?
- Stability to acid
- Stability to digestive enzymes
- Solubility in aqueous solution
- Lipid solubility
- Molecular weight
- pKₐ
What 4 physiological variables determine the amount of drug in systemic circulation after oral administration?
- Presence and type of food
- Blood flow to GIT and liver
- Gastric motility
- pH of stomach and intestinal contents
What is the greatest risk of pH on a drug?
Can cause the drug to become ionized, forming a charge on the drug making it harder to move through the phospholipid bilayer
What is the volume of distribution of a drug?
A measure of how easily the drug leaves the bloodstream
How does a drug stay in the blood stream if it is particularly acidic or alkaline?
Attach to proteins as proteins are large molecules so find it hard to pass out of the bloodstream
What determines the extent and ease of a drug’s distribution?
The drugs physicochemical properties
What plasma proteins do acidic drugs tend to bind to?
Albumin
What plasma proteins do basic drugs tend to bind to?
a1-acid glycoprotein
What 3 factors can affect plasma binding proteins?
- Age
- Inflammatory conditions
- Pathologic stress
What is a free drug?
An active version of a drug, not bound to a plasma protein, which is able to distribute to tissues and exert pharmacological action
What equation allows the calculation of the volume of distribution of a drug?
Amount in Body = Vd x [Plasma]
Vd = Amount in Body / [Plasma]
What is the first step to make a lipid-soluble molecule water-soluble?
Phase I reactions uncover or add chemical reactive group by oxidation, reduction or hydrolysis
What is the second step to make a lipid-soluble molecule water-soluble?
Phase II reactions involve attachment of an additional chemical group (conjugation) by glucuronidation, acetylation or sulphation
What enzymes carry out Phase I Metabolism reactions?
Superfamily of enzymes Cytochrome P450 (CYP)
What is the general equation for Phase I Metabolism reactions?
Drug-H + 0₂ (in presence of CYP) = Drug-OH
What happens when pro-drugs are metabolised?
Metabolised to more active metabolites
Give an example of the metabolism of a pro-drug?
Enalapril is metabolised to enalaprilat
Where do Phase II Metabolism reactions mainly occur?
Liver
How would Drug-glucuronide be excreted and why?
Bile or urine as it is inactive and polar
What 5 things can cause interindividual differences in drug metabolism?
- Age
- Disease conditions
- Genetic variation
- Enzyme induction
- Enzyme inhibition
What is the most common cause of drug interaction?
One drug can increase or decrease the metabolism of another drug
What is enterohepatic recycling of a drug?
Drug conjugates excreted in bile are hydrolysed in lower intestine, releasing original drug for reabsorption into the bloodstream, so prolonging action
What is the apparent volume of distribution?
The volume of plasma into which the drug appears to be dissolved
What is the elimination half life?
Time taken for the amount of drug in the plasma to decrease by half
What is clearance?
The volume of plasma cleared of drug per unit time e.g. litres/hour
What is MTC?
Minimum toxic concentration
What is MEC?
Minimum effective concentration
What is the window between the MEC and MTC called?
Therapeutic window
