In this series of Knowing your Jargon (KYJ) we will look at Phamacokinetics (what our body does to drugs).
Over the next few days we look at :
Absorption - (covered KYJ79)
Transportation
Hepatic First Pass
Protein binding
Bioavailability
Half life
Distribution
Metabolism and metabolites
Excretion
In the last episode we looked at absorption. Once absorbed into the blood stream a drug is considered to be bioavailable.
Today we look at transport. Drugs travel in blood in 2 ways.
First of all they can be carried in their active state, or an inactive state needing to be converted in the liver to have an action.
Blood as a cocktail of cells and plasma (salts, water and protein).
Drugs are dissolved in the plasma water, or they bind to protein. While the most abundant drug carrier is Albumin, there are other proteins called globulins, glycoproteins, or lipoproteins that act as secondary transporters.
Think of a blood as being like a drug smuggler and their luggage, travelling to Bali. The dope is either bound to the boogie board (all taped up for later use) or in the smuggler's pocket, for quick access.
When bound to plasma proteins, the drug is not immediately usable, but when dissolved in the plasma water (in solution), it is available for immediate use. Given any absorbed drug, it is important to know that a drug's action is largely related to the fraction or percentage of a drug that is bound to protein vs the unbound fraction.
Some drugs have high protein binding eg Warfarin is about 98% protein bound, meaning only 2% is usable. In contrast morphine is about 25-30% protein bound, meaning that up to 75% of this drug is available to exert its effects.
If a drug is highly bound then we generally say it has a low volume of distribution and a long half life.
Suppose you gave me an antibiotic: "Robicillin" that was 60% protein bound.
You gave 1000mg
400mg is working at killing "Timmingsosis"
As the drug is used up or metabolised, it is being released from the plasma in proportion. At all times that drug is 60% protein bound and 40% is doing the work. The unbound vs bound fraction stays in balance. Thus the protein acts like a reservoir steadily releasing the drug. Eventually the concentration of unbound drug will dwindle requiring that another dose of the drug is administered to maintain effectiveness.
But if I had a medical condition where I had low albumin in my body (nephrotic syndrome, liver failure, malnutrition), then once all that albumin is saturated or bound to Robicillin, then it stays in the water of the plasma in a higher concentration. Effectively becoming toxic like being overdosed. Say I only had half my albumin. The drug normally 60% plasma protein bound (PPB) can now only bind half to protein (eg 30% PPB) meaning instead of 40% being available, now 70% or 700mg is exerting its action.
It is probable therefore that once a drug is given in a high enough dose, it has fully saturated the healthy person's plasma proteins, and is now toxic.
Toxicity can also occur when two drugs compete for plasma binding. If drug A is administered at the same time as drug B, then proteins could become saturated earlier giving rise to inadvertent potency or toxicity.
A common example is Warfarin and antibiotics (like Ciprofloxacin and clarithromycin). If these are given then the AB bind to plasma proteins reducing the PPB of Warfarin, hence more warfarin in solution increasing bleeding potential. Even Panadol, aspirin and other anti inflammatories, make this happen.
In this episode we touched on the issue of transporting drugs bound to plasma proteins. In summary the bound fraction of the drug is not used or active. Any situations that make more drug available in unbound form can potentate the drug, and some drugs will potentiate others as they compete to bind to plasma proteins.
Albumin is the principle plasma protein, and manufactured in the liver.
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Time now to diarise a few notes and reflect on this revision - all our KYJs are claimable for 0.25 CPD for RNs , ENs and Scheduled Medicines endorsed RNs; but you have to make reflective notes and keep as evidence.
These KYJs meet NMBA standards
3.2 Uses best available evidence, nursing expertise and respect for the values and beliefs of individuals/groups in the provision of nursing care:
• uses relevant literature and research findings to improve current practice
4.2 Participates in professional development to enhance nursing practice
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Smashing that CPD, a few minutes at a time.
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