Pharmacokinetics: Drug Excretion Flashcards
Where are the majority of drugs removed in the body?
- renal system and out through urine
- BUT GIT also contributes
What are the 2 principles that determine drug clearance?
1 - metabolism in the liver (how much enters the circulation)
2 - renal excretion (GFR in kidney)
What is the entero-hepatic circultion?
- entero relates to the GIT
- hepatic relates to the liver
- secretion from liver to bile and into GIT
- then reabsorbed by GIT and back to the liver
The entero-hepatic system ensures the recycling of bile acids that are created in the liver and sent to the liver, before being pumped into the GIT. Here 95% of biles are then reabsorbed. How can this process affect drugs?
- drugs can be conjugated with bile in the liver
- bile is then secreted into the GIT
- some drugs are reabsorbed and some are excreted in stool
The entero-hepatic system ensures the recycling of bile acids that are created in the liver and sent to the liver, before being pumped into the GIT. Here 95% of biles are then reabsorbed. How can this process affect drugs?
- drug is metabolised by the liver and enters circulation
- drug returns to the liver and becomes conjugated with bile
- bile is secreted inot GIT, where drug will become seperated and can be reabsorbed again and repeat this cycle
The entero-hepatic circulation ensures the recycling of bile acids that are created in the liver and sent to the liver, before being pumped into the GIT. Here 95% of biles are then reabsorbed. This same process can occur with certain drugs, such as the contraceptive pill. If this pill was not recycled in the entero-hepatic circulation what would that mean?
- women would have to take the pill more frequently
The renal system is the main site for drug excretion. What are the 2 forms that can be excreted?
- water soluble = metabolised by liver, enter systemic circulation and then excreted
- water insoluble = metabolised by liver, enter systemic circulation, small excreted, return to liver into enterohepatic circulation, some can be lost in stool, some can be reabsorbed and enter systemic circulation and then excreted by kidney
What characteristics do drugs need to have if they are filtered by the glomerulus?
- water soluble
- small enough to be filtered
- unbound (not bound to albumin)
If a drug cannot be filtered by the glomerulus, what can the kidneys do instead?
- secrete from the capillaires into the proximal tubules
Although drugs are generally excreted from the kidneys through filteration in the glomerules or secretion from capillaries in the proximal tubules, what else can happen to drugs in the tubules?
- reabsorbed in proximal and distal tubules
- pH and urine rate determine how much is reabsorbed
What 3 factors determine renal clearance of a drug from the kidneys?
1 - filtration at the glomerula
2 - secretion into the proximal tubule
3 - reabsorbtion in the proximal and distal tubule
If a drug is hydrophillic (water soluble) what generally happens to it in relation to excretion?
- metabolised by the liver and enters systemic circulation
- enters the kidney and is excreted
If a drug is lipophillic what are the 2 different things that can happens to it in relation to excretion?
1 - drug is metabolised (hydrolysed) in the liver and enters the circulation, where is excreted through the kidney
2 - drug is metabolised (hydrolysed) in the liver and enters the circulation where some is excreted through the kidney. The rest returns to the liver and enters the enterohepatic circulation and repeats until drug has been completely secreted
What are the four most important factors affecting drug clearence?
- renal function
- renal blood flow
- glomerular filtration rate (GFR)
- protein binding
If renal function is impaired what can this do to drug excretion?
- drug excretion is impaired and can cause toxicity
What is Cmax in relartions to drugs?
- maximum concentration of a drug in plasma
What is tmax in relartions to drugs?
- time it takes a drug to reach Cmax (max concentration in blood)
When looking at a graph which shows the drug plasma concentration curve, what does the area under the curve denote?
- overall exposure of the drug
What does the half-life of a drug releate to?
- time taken for the drug concentration to reduce by half in the blood
What does steady state refer to in drug administration?
- amount of drug in the plasma has built up to a concentration level that is therapeutically effective
- regular doses are administered to balance the amount of drug being cleared (drug therefore remains active)
- rate of administration = rate of elimination
- normally needs around 3-5 half lives
Steady state refers to the amount of drug in the plasma that has built up to a concentration level that is therapeutically effective. To achieve this regular doses are administered to balance the amount of drug being cleared (drug therefore remains active) which generally requires around 3-5 half lives. Why is knowing the steady state important?
- therapeutic effect occurs here
What is therapeutic index (TI)?
- TI = TD50 / ED50
- large TI = Wide Therapeutic window
- small TI = Narrow Therapeutic Window
The dose interval is how often drugs are given. What determines the dose interval?
- half life of the drug
- if it stays in the system for longer you dont need to take it as often
