PHARM - Pharmacokinetics - Drug Metabolism and Excretion - Week 1 Flashcards
Describe distribution equilibrium.
Most drugs administered via IV distribute rapidly, and reach a distribution equilibrium, behaving as if in a single compartment.
How does drug elimination rate relate to the amount of drug in the body?
Most drugs are eliminated at a rate proportional to the concentration in plasma.
Name two ways drugs are eliminated by the body, and where it typically occurs.
Excretion - by the kidney
Metabolism - by the liver
Describe renal excretion briefly in three simple steps.
Glomerular filtration - fluid/drug enters the collecting tubule through Bowmans capsule
Tubular secretion - fluid/drug enters the collecting tubule through the peritubular capillary (after the efferent arteriole)
Tubular reabsorption - fluid/drug re-enters the peritubular capillary
Breifly describe glomerular filtration.
The drug is taken out of the blood through the leaky fenestrated glomerulus.
What is glomerular filtration limited by? Does glomerular filtration affect drugs bound to plasma proteins?
It is limited by the glomerular filtration rate. Glomerular filtration doesnt affect plasma protein-bound drugs (i.e. theyre not filtered at this stage).
Briefly define tubular secretion. Does it affect plasma protein-bound drugs?
Takes drugs out of the blood, and uses active carriers for drugs. It can remove plasma protein-bound drugs as well.
Describe competitive inhibition for tubular secretion, and briefly give an example.
Certain drugs can mask the appearance of other drugs. It does so by competitively inhibiting tubular secretion of that masked drug.
For example, probenecid reduces excretion of acidic drugs.
Breifly describe tubular reabsorption, and how this occurs. What is this dependent on?
It puts drugs back into the blood. It is the passive movement across cell membranes of the tubule and peritubular capillary.
It is pH dependent.
What is lipid solubility affected by that affects drug diffusion?
pH
Consider the following ionisation of the acidic drug A below:
A-H A- + H+
On the left it is uncharged, and on the right, it is charged.
Describe the lipid solubility state for each, and how this will affect passage through a lipid membrane.
In its uncharged state, the drug is more lipid soluble, and thus would have better passage through a plasma membrane.
In its charged state, it is less lipid soluble, and thus has poorer passage through a plasma membrane.
Consider the following ionisation of the basic drug A below:
BH+ B + H+
On the left it is charged, and on the right, it is uncharged.
Describe the lipid solubility state for each, and how this will affect passage through a lipid membrane.
In its uncharged state, the drug is more lipid soluble, and thus would have better passage through a plasma membrane.
In its charged state, it is less lipid soluble, and thus has poorer passage through a plasma membrane.
Consider an overdose of aspirin, an acidic drug. How can urine pH be manipulated to alter its lipid solublity and thus, reabsorption/excretion?
Administer NaHCO3. This will makes the urine basic, and therefore increases the amount of ionised aspirin.
This will reduce reabsorption and increases excretion.
Describe biotransformation.
What does it involve, where does it occur, and what typically happens as a result?
It involves a chemical change to a drug, typically via enzyme-catalysed reactions.
It occurs in most tissue, most mainly in the liver.
It increases water solubility to facilitate excretion.
Describe phase I metabolism.
The creation of a functional group on a drug, such as:
-OH, -NH2, -SH, -COOH
