Flashcards in Renal Pharmacology Deck (17):
How would you calculate the half life of a drug?
(0.693 x volume of distrubution)/clearnace
How do lipophilicity and hydrophilility affect the behaviour of a drug?
The more lipophilic a drug molecule is the more easily it can diffuse out of the lumen, whereas the more chardge a drug has the less easily it can move out of the lumen
What is the significane of a high volume of distrubution?
The drug is lipophilic and leaves the plasma
What is the significance of a low volume of disturbution?
The drug is highly chardged and confined to the plasma
How does the apparent volume of distribution affect renal clearance?
Large volume of distrubution reduces the amount of drug available in the plasma of excretion by the kidney, and a low volume of distruction increases the amount of drug availbale in the plasma for excretion by the kidney
How does hepatic clearance affect renal clearance?
The liver has a large metabolic system to deal with xenobiotics such as drugs, this consists of phase 1 and phase 11 enzyme systems that recognise xenobiotics and by adding electrical charge the lijpophilicity is reduced which makes it more difficult for the drug molecule to diffuse out of the lumen back into the plasma
What happens in acidic urine?
Weak acidic anions such as salicyte will be more likely to be protonated, and become electro neutral and therefore more lipophilic
What happens in alkaline urine?
More alkaline urine means that the weak acid anions will be protonated and therefore more will be excreted whereas weak bases such as morphine will be more likely to lose a proton, become electrically neutral and therefore more lipophilic, which means tha tit can diffuse more easily across the urine into the plasma
How can cardiac disease affect renal clearance?
The reduced cardiac output will reduce the vascular supply and therefore reduce the GFR, which reduces the renal clearance of the drug or metabolite,
How can hepatic disease reduce renal clearance?
Hepatic disease results in reduced drug metabolism by phase I and II enzymes will result in reduced renal clearance, there may be reduced production of plasma proteins in cirrhosis and therefore there will be a decrease in free drugs found in the plasma and therefore increase the amount of available drug
What is the model definiation of renal clearance?
The virtual volume of plasma that would totally cleared of a given solute per unit time, but in relatily the large volume kf plasma partially cleared of a solute per unit time
How can we measure physiological clearnace?
Renal clearance is the filatration + secretion - absorption
What are some of challenges in getting a detailed measurement of renal clearance?
Filtrate secretion reabsorption, mixed and variable, for many cases need straight forward, minimally invasive and
What are some of the features of the physiological markers used in measuring renal clearance?
Not syntheised, degraded or stored by the kidney, if we have a substance that is only filtered and not secreted or stored we can estimate the GFR
What are the two clinical markers commonly used for measuring GFR?
Inulin and creatinine
What is inulin
An inert molecule that is only filtered, and is not secreted or absorbed, and therefore the inulin clearance is equal to the Glomeular filtration rate