Pharmokinetics Flashcards
What does ADME stand for
absorption, distribution, metabolism, excretion
2 different types of administration?
Administration can be systemic, where the entire organism is exposed to the drug, or local, where it is restricted to one area of the organism
3 different routes of administration?
Routes of administration can also be enteral, so through the GI tract, or parenteral, via everything but the GI tract, inhalational
2 examples of sites of parenteral administration
Intraperitoneal (because the peritoneum has a rich blood supply) or intravenous
Two ways drugs move around the body?
Bulk flow transfer and diffusion transfer
What is bulk flow transfer? When is it used? Example of bulk flow transfer
in the bloodstream where it will move in bulk to the tissues. E.g. intravenous injection. This is when treatment is needed immediately
What is diffusion transfer? When is it used? Example of bulk flow transfer
molecule by molecule over short distances. This is for slower, controlled and over a longer period of time administration. This is what happens with tablets and creams etc
Methods for crossing barriers that drugs use
diffusing (if the drug is lipid), diffusing through aqueous pores in the lipid (if the drug is polar), carrier molecules and pinocytosis
What is the pH of aspirin
Acidic
How will an acidic drug fare in the stomach
when acid enters the stomach where the acidity is around pH 1 then it is more likely to stay unionised and non-polar due to the equilibrium. This means in this state it can cross the lipid bilayer and so there is a lot absorbed in the stomach (this can irritate the stomach)
How will an acidic drug fare in the small intestine
When the aspirin moves to the small intestine, the pH is much more basic meaning a lot more of the aspirin is likely to become ionised. This makes it a lot more difficult for it to get through the membrane as it is a non-polar phospholipid barrier. This leads to slower absorption in the small intestines
What is ion trapping
The unionised form of the drug is mopped up by proteins in the blood. They are basically trapped as such and this is known as ION TRAPPING. This provides another obstacle preventing the drug from being absorbed into tissues.
What to do with aspirin to prevent stomach irritation
Enteric coating
What are the benefits of enteric coating for acidic drugs
it will resist the stomach acid and only be broken down in the small intestine. Here it can give a prolonged slow release and absorption of the drug, which is useful for treating chronic conditions
what does the ratio of ionised:unionised drugs depend on
Transport proteins, and pH
4 factors affecting drug distribution
Regional blood flow, extracellular plasma protein binding, capillary permeability and localisation in tissues
Explain how localisation in tissues affects drug distibution
fat doesn’t perfuse very well usually (are poorly perfused) so it is found in very lipophilic environments; therefore, drugs that are lipophilic tend to localise and partition themselves into fatty tissues (brain, testes…). This means the drug will persist in the tissue and continue its pharmacological activity in that tissue, e.g. marijuana
Explain how Regional blood flow affects drug distibution
tissues well perfused are likely to be exposed to a higher conc. of the drug. Some tissues may increase in perfusion when their activity increases, e.g. skeletal muscle. Highly metabolically active tissues need to be well perfused with a higher blood flow and denser capillary network than less active tissues
Explain how extracellular plasma protein binding affects drug distibution
anything bound to a plasma protein is not bioactive and is unavailable for absorption. 50-80% of acidic drugs tend to bind to plasma proteins establishing a dynamic equilibrium. Albumin can bind both ionised and non-ionised drugs
Explain how capillary permeability affects drug distibution
small gaps exist between endothelial cells allowing ionised forms of drugs (e.g. aspirin) to pass through. These gaps are aqueous. Capillary architecture can have a significant impact on how well these drugs can travel through (fenestrated/continuous/discontinuous). Also the tissue composition effects absorption, e.g. the brain has a thick lipid blood brain barrier which only allows certain drugs through
what’re the 2 main routes of excretion
liver and kidney
what are the minor routes of excretion
lungs, skin, GI secretions, saliva, sweat, milk and genital secretions (every body fluid can constrain drugs as drugs partition themselves into it)
which organ holds the majority of the responsibility of excreting a drug
Kidnet
What does the kidney do to a drug
converts it into something water soluble which is then urinated
how do drugs enter the kidney and why
Through active secretion as most drugs are too big to enter through ultrafiltration
what happens to drugs regarding excretion in the glomerulus
nothing, drugs aren’t filtered as they’re too big
what happens to drugs regarding excretion in the proximal tubule
active secretion of drugs and reabsorption of lipid soluble drugs
what happens to drugs regarding excretion in the distal tubule
reabsorption of lipid soluble drugs
where are lipid soluble drugs reabsorbed and why/how
in the proximal and distal tubules of the kidneys as urine is an aqueous environment and the drug may have become more unionised and more lipid in the pH of the urine allowing it to be reabsorbed easily
what type of drugs are actively reabsorbed in the kidney
Drugs that look like amino acids or glucose
why might treatment with sodium bicarbonate cause increased excretion of aspirin
IV sodium bicarbonate will make urine pH higher, this means aspirin is more ionised in the urine, this makes it less lipid soluble and so it is less reabsorbed in the proximal and distal tubules
how does the liver contribute to drug excretion
liver picks up drugs from the GI tract, drugs are concentrated in the bile which is then excreted into the intestines
What drugs are likely to be disposed of by the liver
drugs with an Mr of 1050 or greater
what transport mechanism does the liver employ to get drugs into bile, what is this method meant for and how do drugs get involved
Active transport, meant for transporting bile acids and glucoronides into bile but drugs can hitch a ride as they have a high Mr and can be non-polar
What poses a problem for excretion via the liver? what’re the consequences of this problem? what can stop this problem?
the enterohepatic circulation; leads to drug persistence and prolongs the half-life of the drug. This does not go on forever however as every time the drug enters the liver it could be metabolised where it will then be sent off on a different route
what does bioavailability mean
proportion of the administered drug that is available within the body to exert its pharmacological effect. This is regarding post-hepatic concentration, the amount that leaves the liver to enter systemic circulation. (the amount of drug that gets into the systemic circulation).
what is the apparent volume of distribution
the volume in which a drug appears to be distributed, an indicator of the pattern of distribution. Polar drugs won’t be distributed very far as they are more likely to just remain in the blood. It is a theoretical mathematical concept
what is a biological half-life
time taken for the concentration of the drug in the blood/plasma to fall to half its original value
what is clearance
the volume of plasma cleared of a drug per unit time. This relates to both the volume of distribution and the rate at which the drug is eliminated. This is incorporating excretion through the bile and the kidneys and all other routes
what are first order kinetics of a drug
The rate of elimination of a drug where the amount of drug decreases at a rate that is proportional to the concentration of drug remaining in the body
What are zero order kinetics of a drug
A constant amount of drug is removed per unit time
What drugs follow first order kinetics
Most drugs
An example of a drug that follows zero order kinetics?
Alcohol
