renal drug elimination

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renal drug elimination what are the three processes involved in renal elimination- renal clearance is the net of these three processes	filtration, active secretion reabsorption
If fraction of drug excreted unchanged is 0.3 and total CL of drug is 9L/h and drug is only eliminated by renal excretion and hepatic metabolism, what is the renal clearance of the drug?	fe x CL= 0.3 x 9=2.7L/h
Which of the following beta blockers is cleared solely by renal elimination? atenolol propranolol metoprolo	atenolol is really excreted, the rest undergo extensive hepatic metabolism
True or False: the pharmacokinetics of a drug that is mainly eliminated by renal excretion will not be affected by renal failure	False
True or False: morphine is metabolised to glucuronide metabolites (M6G and M3G) which are really excreted. In renal failure, these accumulate in the body and can lead to signs of opioid toxicity	TRUE
Blood passes through kidney and is filtered at the glomerulus. What are factors that will govern the ability of drug to be filtered off (diffuse through glomerulus)?	MW cardiac output glomerular integrity renal plasma flow degree of protein binding drug volume of distribution
True or False It is only unbound drug that can be filtered off st the glomerulus	True
What is active secretion, what is involved and where does it generally occur in kidney?	drug is actively secreted from blood into renal tubule via transporters. There are anionic transporters (acids) and cationic transporters for bases. These are mainly in the proximal tubule
What are two important consequences of active secretion being present?	drug-drug interactions saturable kinetics (can saturate the active secretion mechanism)
Which type of active secretion transporter does probenecid interact with	anionic (acid) transporter
which type of transporter does cimetidine interact with	cation transporter (basic drug transporter)
what will happen to the blood levels of penicillin ( weak acid) if it is co-administered with probenecid?	blood levels of penicillin will increase as the probenecid competes for the active secretion transporters and reduces the amount of penicillin that can be secreted into the tubules
Drug in the urine in the tubules can undergo passive reabsorption. What are two factors that can influence the extent of reabsorption that occurs	urine pH is drug is ionisable; only unionised drug can cross tubule membrane and get back into systemic blood urine flow rate- if urine flow is large, there will be more dilute solution (and as it is a passive process, crossing membrane is driven by concentration gradient- driving force will therefore be low)- also rate - urine will be excreted faster so less chance for reabsorption to occur
A drug has a total CL of 10L/h. The fraction excreted unchanged is 0.4. GFR=7L/h and the fraction unbound of the drug is 0.2. Does this drug undergo significant active secretion or significant reabsorption?	CLR=fe.CL=0.4 x10=4L/h If drug was only filtered off with no secretion or reabsorption then CLR=fu.GFR=0.2 x 7L/h=1.4L/h Since CLR=4L/h and only filtration would be 1.4L/h then drug does undergo active secretion
A drug has a Vd of 20L and k=0.4 per h. fe=0.6 and fu=0.5. GFR is 7L/h. Does this drug undergo significant active secretion or reabsorption?	CL=kVd so total CL= 8L/h CLR=fe.CL so CLR=0.6 x 8=4.8L/h If only filtration CLR would be fu.GFR=0.5 x7=3.5L/h since CLR is greater than fu.GFR then significant active secretion is occurring
A drug has a total CL of 5L/h. It has a fu=0.2 and fe=0.1. If GFR=7L/h, does this drug undergo significant active secretion or reabsorption?	CLR=fe.CL=0.1 x 5=0.5L/h if only filtration =fu.GFR=0.2 x7=1.4L/h Since CLR <fu.GFR there must be significant reabsorption occurring
If we administer a 600mg IV dose to a patient and we collect all urine to ensure we collect all drug that is going to be excreted and amount excreted = 300mg, what is fe?	fe= (amt excreted)/drug reaching systemic circulation fe=300/600=0.5
If we administer 600mg of drug orally and F=0.5 and we collect urine and find that 150mg is excreted in urine, what is fe for this drug?	fe=amt in urine/amt in systemic circulation= 150/(0.5 x 600)=0.5
Creatinine clearance can be estimated using cockcroft gault equation. what are some limitations of this method?	cannot accurately predict CrCL in: patients with unstable renal function cachectic (wasted) patients amputees
Which of the following drugs is most likely to be affected to the greatest extent by renal disease? drug A fe=0.5 drug B fe=0.8 drug C fe=0.1	drug B as fe=0.8 (the renal route is major route of elimination). Drug C will be affected the least as only 10% is excreted unchanged
In the Tozer equation which can be used to determine dose in renal dysfunction: dose fail=dose normal (1-fe(1-KF)) what does KF stand for?	KF is the kideny function of the patient compared to normal kidney function eg if CrCl normal is 120mL/min and patient has CrCl of 60mL/min then KF=0.5

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	Erstellt von jenny schneider vor mehr als 9 Jahre