Drugs - Postabsorption Flashcards
What 3 things effect the extent of distribution?
Lipid-solubility of drug
Blood flow to tissue/organ
Binding of drugs to proteins
Once the drug is in the bloodstream, what does distribution involve?
Transfer of the drug in and out of various tissues in the body from the bloodstream.
This is a 2 way process - forward and reverse
What organ receives the greatest blood flow (and therefore receives the drug most quickly)?
Kidneys
What is protein binding? Why can this be a good thing?
Where free drug binds to proteins in the plasma, such as albumin.
This reduces the amount of free drug. Only free drug can diffuse across membranes to have an effect as the proteins are too big.
This is good for drugs like warfarin (an anti-coagulant) as it prevents too much free drug causing internal bleeding.
When thinking about protein binding, why is it important that you know every single drug a patient is taking before administering a new one?
As drugs like warfarin rely on protein binding to ensure that the levels in the blood are not too high, we need to know if there are potentially any other drugs competing for the proteins.
What are the 2 most common routes of absorption for drugs?
Passive Diffusion
Facilitated Transport
What route of administration has the most rapid effect? Is it reversible?
I.V.
No
What 2 processes are involved in drug removal?
Metabolism
Excretion
What does lipophilic mean?
This is where drugs recirculate around and around the body, constantly having an effect.
What is drug metabolism?
The enzyme-mediated conversion of a lipid-soluble compound into a more water-soluble one.
This prevents the drug constantly re-circulating and allows us to excrete it
Which is the main organ where drug metabolism takes place?
Which part of this organ?
The liver.
The smooth endoplasmic reticulum.
Other than the liver, can you name up to 5 other sites that metabolise drugs?
Kidney Lung GI Tract Brain Plasma
If a patient has liver damage, what should we do when administering a drug?
Reduce the dosage as according to the BNF.
This is because they cannot metabolise as well as a healthy patient and the normal level would be toxic
Other than the liver, what other organ can have an effect on metabolism if damaged?
The kidneys
What are the two phases of metabolism called?
Phase 1
Phase 2
In metabolism, does Phase 2 always follow Phase 1?
No. Usually, but not always
What happens in Phase 1 of metabolism?
The chemical structure of the drug is modified (to be less lipid and more water soluble)
Usually prepares the drugs for Phase 2
Sometimes Phase 1 can result in pharmacological activation.
What is this?
Where the product becomes more chemically reactive than the original ‘parent’ drug = more potent
e.g. pro drugs - prednisone becomes Prednisolone
codeine becomes morphine, GTN becomes nitric oxide
Do all drugs rely on pharmacological activation to have an effect?
No, but some do - such as prednisone, codeine and GTN
What happens in Phase 2 of metabolism?
The drug is ‘conjugated’ to large molecules such as amino acids and sulphate groups. It then becomes:
water-soluble so can be easily excreted
increases in molecular weight so can’t fit in target site
Undergoes pharmacological inactivation
What is pharmacological inactivation?
Where the drug:
decreases in receptor affinity
and excretion is enhanced
What effect can alcohol or carbamazepine have on drug metabolising enzymes?
They can induce liver enzymes which may be used to metabolise a particular drug - this will reduce its effectiveness
What effect can fluoxetine or grapefruit juice have on drug metabolising enzymes?
They can inhibit liver enzymes. This means it can prolong the effect of a drug as it will not be metabolised as quickly, thereby resulting in toxic levels
How are water-soluble drugs and drug metabolites excreted?
List the 4 ways in order of excretion amount
Urine
Bile
Faeces
Lungs/skin/sweat
