4 - Pharmacokinetics Flashcards
What is meant by pharmacokinetics?
what the body does to the drug
how the drug is absorbed, metabolised and excreted by the body
the journey of a drug through the body
State the five stages of the journey of a drug through the body.
Administration Absorption Distribution Metabolism Excretion (Voiding)
(ADME)
What is the usual route of an ingested drug?
enters GI tract, gets absorbed in the SI, goes through the liver via hepatic portal system before entering the systemic circulation (some may go into the bile and back to the liver again)
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 (onset) 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
Carrier molecules
Pinocytosis
Finish the sentence: most drugs are either …… or …….
Weak acids or weak bases
exist in ionised (polar) or non-ionised (non-polar) form
Which factors affect the ratio of ionised to non-ionised drug (the dynamic equilibrium)?
pH of the environment
pKa of the molecules
Is aspirin acidic or basic?
What is its pKa?
acidic
pKa of 3.4
Describe and explain the difference in absorption of aspirin in the stomach and the small intestine.
Stomach pH of around 1
The pH of the stomach is lower than the pKa of aspirin, the equilibrium of the aspirin is shifted towards the unionised state
So in the stomach, aspirin mainly exists in the unionised state and is rapidly absorbed
In the small intestines which has a much more basic pH (which is greater than the pKa of aspirin)
So aspirin in the small intestine is mainly ionised and hence absorption is SLOWER in the small intestine
What is ion trapping?
When ionised aspirin enters the systemic circulation, it is in an aqueous environment. However, 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)
Capillary permeability
Localisation in tissue
What percentage of acidic drugs tend to bind to plasma proteins?
50-80%
In which state can albumin bind to drugs? Ionised or non-ionised?
Both ionised and unionised
State three types of capillary architecture.
Continuous
Fenestrated
Discontinuous
Give a broad example of localisation 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?
Kidneys (mainly)
Liver
(other methods include exhalation and through sweating)
What happens to drugs in the kidneys that means that many drugs are excreted through them?
converting the drug into something water soluble
How are drugs processed and excreted through the liver (generally)?
concentrated in the bile, which is secreted into the small intestines
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
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
