Flashcards in Pharmacokinetics and Drug Metabolism Deck (35)
State the five stages of the journey of a drug through the body.
What is the difference between enteral and parenteral administration?
Enteral – using the GI tract
Parenteral – everything except the GI tract
What are the advantages of intravenous administration?
It gives rapid systemic exposure and a high bioavailability
State the two ways in which drug molecules move around the body.
Bulk Flow Transfer – in the bloodstream it will move in bulk to the tissues
Diffusion Transfer – molecule by molecule over short distances
State four methods by which drugs can cross lipid membrane barriers.
Diffusion through the lipid membrane (if appropriately lipophilic)
Diffusion through aqueous pores
Finish the sentence: most drugs are either ...... or ......
Weak acids or weak bases
Which factors affect the ratio of ionized to non-ionized drug?
pKa of the drug
pH of the environment
Describe and explain the difference in absorption of aspirin in the stomach and the small intestine.
Aspirin has a pKa of 3.4
The stomach has a pH of around 1 so when the aspirin enters the stomach, as the pH of the stomach is lower than the pKa of aspirin, the equilibrium of the aspirin is shifted towards the unionized state
So in the stomach, aspirin mainly exists in the unionized state and is rapidly absorbed
Eventually, the aspirin will reach the small intestines which has a muchmore basic pH (which is greater than the pKa of aspirin)
This means that aspirin in the small intestine is mainly ionized and hence absorption is SLOWER in the small intestine
What is ion trapping?
Some ionized aspirin will enter the systemic circulation, which is an aqueous environment
As it is ionized it will not be able to move into the tissues and hence is ‘trapped
State four factors affecting drug distribution.
Regional blood flow
Extracellular binding (plasma-protein binding)
Localisation in tissue
In which state can albumin bind to drugs? Ionized or non-ionized?
Both ionised and unionised
State three types of capillary architecture.
Give a broad example of localization of a drug in tissue.
Lipophilic drugs tend to localise in fatty tissues e.g. brain and testes
What are the two main routes of drug excretion?
What types of molecule tend to get excreted via the biliary route?
Large molecule weight molecules
The liver allows concentration of large molecular weight molecules that are very lipophilic
Via what form of molecular movement do most drugs tend to get excreted into urine?
What happens to drug-protein complexes at the glomerulus?
They are not filtered into the filtrate
Where does active secretion of acids and bases occur in the nephron?
Proximal convoluted tubule
What can happen to lipid soluble drugs in the proximal and distal convoluted tubules?
They could be reabsorbed
Why might treatment with I.V. sodium bicarbonate increase aspirin excretion?
IV sodium bicarbonate will increase the pH of the blood
This will increase the amount of aspirin that is ionised
Becoming ionised will mean that the aspirin is more water-soluble and less lipid-soluble so the kidneys can more easily excrete it and less aspirin is reabsorbed in the proximal and distal tubules
This increases the rate of aspirin excretion
What is the main purpose of the active transport systems that secrete drugs into bile?
They are meant to be for the active transport of glucuronides and bileacids into the bile but drugs can hitch a ride on this mechanism
What is a potential problem with biliary excretion of xenobiotics?
Enterohepatic cycling – it can become reabsorbed and return to the liver via the enterohepatic circulation
This leads to drug persistence
The proportion of the administered drug that is available within thebody to exert its pharmacological effect
Define apparent volume of distribution.
The volume in which a drug appears to be distributed – an indicator of pattern of distribution
Define biological half-life.
The time taken for the concentration of a drug (in blood/plasma) to fall to half its original value
The volume of plasma cleared of a drug per unit time
Define First-Order kinetics.
When the rate of drug excretion is proportional to the concentration of drug remaining within the body
Log of drug concentration is proportional to time
Define Zero-Order kinetics.
A constant amount of drug is removed from the body per unit time
What does zero-order kinetics suggest about the enzymes involved?
It suggests that the enzymes are saturated
Once the enzymes are saturated, the rate of removal of a drug peaks and remains constant
NOTE: most drugs follow first-order kinetics