Drug Handling and the Kidney Flashcards
pharmacokinetics descirbes the behaviour of a drug and its metabolits in terms of ___, __, __,___
abosprtion ,distribution, metabolsim ,elimintation
elimination aspect of pharmacokinetics heavily relies on the kidney. Elimination is based on renal blood flow and renal clearance depends on: (three things)
filtration, secretion, reabsorption
how does absorption pharmacokinetics changes with CKD?
- reduced absorption.
- gut edema in nephrotic syndrome
- diabetic gastroparesis
- calcium based phsophate binders
metabolite distribution pharmacokinetic aspect change in CKD
- there will be a decreased distribution in some cases
- volume depletion
- muscle wasint
- reduced albumin
- can also have increased distribution in some cases
- edema, ascites,
- reduced albumni
Metabolism
• May be __ with lower renal
function
Metabolism
• May be reduced with lower renal
function
changes in metabolite elimination in CKD
• ___ elimination of the drug
and its metabolites
• Due to reduced __ and reduced
__
• Results in prolonged __ __ of the drug
• Elimination
• DECREASED elimination of the drug
and its metabolites
• Due to reduced GFR and reduced
secretion
• Results in prolonged half life of the drug
if a person has an eGFR
if a person has an eGFR <30, or if the mediations have a narrow therapeutic window , a dose adjustment may be necessary to safely prescribe meds in reduced renal function
Common groups of medications to dose adjust
- gout mediactions (allopurinol and colchicine. they have increased metabolites that can lead to severe drug reactions)
- diabetic medications: metformin or sulfonylureas
- antibiotics
- anticaogulants
- anti-depressants
- opioids
three broad ways to safely presecribe meds in reduced renal failure
1. dose adjustment
2. measure theraputic levels
- aminoglycosides, vancomyicn, CNIs, anti-arrhthmics, antipsychotics, antiepileptics
3. check for interactions
- prescription
- over the counter like St Johns Wort
grape fruit juice can pose cytochrome interference.
4 aspects of a medication that might make it nephrotoxic?
- reduced renal blood flow
- tubular innjury like ischemia or crystal induced
- interstitial inflammation
- concentrating defect
how are NSAIDS nephrotoxic?
they reduce renal blood flow via afferent arertiole constriction
how are ACE/ARBS nephrotoxic?
involved in volume depletion
outline how NSAIDS and ARBS reduce renal blood flow
how do diuretics and SGLT2 inhibitos cause nephrotoxicity?
they both reduce renal blood flow by acting as VOLUME DEPLETORS
Amino glycosides and Cisplatin (Chemo) can lead to ___ ____ injury, a mechanism of nephrotoxicity
Acyclovir, septra and methotrexate can lead to ____-induced ___ injury, a mechanism of nephrotoxicty.
Amino glycosides and Cisplatin (Chemo) can lead to ISCHEMIC TUBULAR injury, a mechanism of nephrotoxicity
Acyclovir, septra and methotrexate can lead to CRYSTAL-induced TUBULAR injury, a mechanism of nephrotoxicty.
antibiotics (___ most common) can cause nephrotoxicity by ___ inflammation.
penicillins and cephalosporins are most common but any antibiotic can cause nephrotoxicity by INTERSTIAIL INFLAMMATION
- so can PPIs and NDAIS
lithium, cisplatin, and amphotericin can cause ___ defects which can lead to nephrotoxicity
CONCENTRATING DEFECTS
TMP SEPTRA is an antibiotic used as prophylazis and treatmnet fo PJP pneumonia. How does it affect the kidney?
- it psedo deacrases the GFR and reduces creatinine secretion at the PCT
- blocks ENAC, like a potassium sparing diuretics, so hyperkalemia can happen. It works at the CCD.
- the sulfamethoxazole can cause interstiail nephritis
- the SMX can also cause crystal induced nephropahty.
what portion of the kidney does TMP-SEPTRA act on to create hyperkalemia
Blocks epithelial sodium channel
(ENaC), similar to potassium sparing diuretic at the COLLECTING DUCT
calcineurin inhibitors like cyclosporin or tacrolimus (used to prevent organ rejection) can cause nephrotoxicty by what mechanism?
can reduce afferent arteriole dilation and can thus cause ischemic/reduced renal blood flow.
furosemide is a loop diuretics that is used in volume overload managemnet, as well as in hypercalcemia and hyperkalemia and hypertension. It acts on the ___ channel in the ____ area of the kidney.
Based on how Furosemide is
filtered and secreted, need __ doses at lower levels of kidney function or neprhotic syndrome because of lower __, and less of furosiemide is delivered to the kidney for same effectiveness
It acts on the NKCC2 channel in the TAL area of the kidney.
Based on how Furosemide is
filtered and secreted, need HIGHER doses at lower levels of kidney function or neprhotic syndrome because of lower ALBUMIN, and less of furosiemide is delivered to the kidney for same effectiveness.
usually, you need to reduce the maount of druf given, but furosemide often needs higher doses when the person has CKD or kidney injury.
Summary
