Renal Clearance Flashcards
What factors contribute to the concentration of a drug in the body?
Absorption, Distribution, metabolism (by liver) and excretion.
Does the body view drugs as homogeneous or xenobiotic?
Drug molecules are seen by the body as xenobiotic i.e. foreign to the body.
What is Clearance?
The rate of the removal of a xenobiotic is related to the kidney and liver and is known as clearance. Clearance is proportional to the free concentration in plasma of the drug.
How can half life be calculated?
Half-life of a drug can be calculated by multiplying the constant 0.7 by the volume of distribution and then dividing this number by the clearance.
What are primary fluid compartments?
Primary fluid compartments are intra and extra cellular fluid and plasma.
Which compartment is the only compartment available to the kidneys?
Plasma is the only compartment directly available to the kidneys.
Name 4 Molecular factors affecting movement between fluid compartments
Lipophilicity – the more lipophilic a drug molecule is the more easily it can diffuse back out of the lumen back into the plasma.
Hydrophilicity – (residual electrical charge) the more charged a drug molecule is the less easily it moves back out of the lumen.
Degree of binding to plasma protein – if binding is considerable this will reduce the amount available for glomerular excretion and or removal by OATs and OCTs (organic anion/cation transporters).
Degree to which it binds to tissue proteins such as muscle effect moving drug from plasma thus decreasing availability for renal clearance. Highly lipophilic drugs partition into fat and reduces the concentration in the plasma.
How do the liver phases I and II assists excretion of xenobiotics?
Phase I and Phase II enzyme systems that both aim to increase the ionic charge on xenobiotics. This reduces lipophilicity making it more difficult for the metabolised drug molecule to diffuse back out of the tubular lumen back into plasma.
What is the difference between how easily Lipophilic vs ionised drugs can be reabsorbed passively?
Lipophilic drugs can simply move back into the plasma relatively easily across the length of the tubule dependant on the gradient. Ionised drugs can only diffuse back dependant on pH. If a weak base is sat in an alkali environment most of the molecules will be neutral as they lose protons and so can diffuse easily and vice versa for weak acids.
What are OATs and OCTs?
General purpose transporters that preferentially transport organic anion and cations. These are located on both Basolateral and apical membrane of the PCT cells. They actively secrete a wide range of endogenous xenobiotic molecules.
What’s the clinical importance of OATs and OCTs?
OATs and OCTs are both subject to competitive binding and can affect renal clearance of the drug this can be used therapeutically to extend the half-life of certain drugs.
How does hepatic function affect renal clearance?
Hepatic disease results in Phase I and II metabolism not working properly. As a result renal clearance will be reduced as the drug will not have as a high a net charge. Also if you have reduced production of plasma proteins such as hypoalbunimea this will increase the amount of free drug and so increase renal clearance.
What is the Renal Clearance model and what does this mean in reality?
The virtual rate that filtration needs to occur at for a volume to be completely cleared off a solute (ml/min)
Reality – the volume of plasma partially cleared of a given solute per unit time (ml/min)
What equation is renal clearance equal to?
Renal clearance = filtration + secretion – reabsorption
What 3 things do you need to know to calculate renal clearance?
Urinary concentration x Rate of urinary flow)/ plasma concentration
