Drug Handling and the Kidney

Question 1

pharmacokinetics descirbes the behaviour of a drug and its metabolits in terms of ___, __, __,___

Answer 1

abosprtion ,distribution, metabolsim ,elimintation

Question 2

elimination aspect of pharmacokinetics heavily relies on the kidney. Elimination is based on renal blood flow and renal clearance depends on: (three things)

Answer 2

filtration, secretion, reabsorption

Question 3

how does absorption pharmacokinetics changes with CKD?

Answer 3

• reduced absorption.
• gut edema in nephrotic syndrome
• diabetic gastroparesis
• calcium based phsophate binders

Question 4

metabolite distribution pharmacokinetic aspect change in CKD

Answer 4

• 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

Question 5

Metabolism
• May be __ with lower renal
function

Answer 5

Metabolism
• May be reduced with lower renal
function

Question 6

changes in metabolite elimination in CKD
• ___ elimination of the drug
and its metabolites
• Due to reduced __ and reduced
__

• Results in prolonged __ __ of the drug

Answer 6

• Elimination
• DECREASED elimination of the drug
and its metabolites
• Due to reduced GFR and reduced
secretion

• Results in prolonged half life of the drug

Question 7

if a person has an eGFR

Answer 7

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

Question 8

Common groups of medications to dose adjust

Answer 8

1. gout mediactions (allopurinol and colchicine. they have increased metabolites that can lead to severe drug reactions)
2. diabetic medications: metformin or sulfonylureas
3. antibiotics
4. anticaogulants
5. anti-depressants
6. opioids

Question 9

three broad ways to safely presecribe meds in reduced renal failure

Answer 9

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.

Question 10

4 aspects of a medication that might make it nephrotoxic?

Answer 10

1. reduced renal blood flow
2. tubular innjury like ischemia or crystal induced
3. interstitial inflammation
4. concentrating defect

Question 11

how are NSAIDS nephrotoxic?

Answer 11

they reduce renal blood flow via afferent arertiole constriction

Question 12

how are ACE/ARBS nephrotoxic?

Answer 12

involved in volume depletion

Question 13

outline how NSAIDS and ARBS reduce renal blood flow

Answer 13

Question 14

how do diuretics and SGLT2 inhibitos cause nephrotoxicity?

Answer 14

they both reduce renal blood flow by acting as VOLUME DEPLETORS

Question 15

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.

Answer 15

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.

Question 16

antibiotics (___ most common) can cause nephrotoxicity by ___ inflammation.

Answer 16

penicillins and cephalosporins are most common but any antibiotic can cause nephrotoxicity by INTERSTIAIL INFLAMMATION
- so can PPIs and NDAIS

Question 17

lithium, cisplatin, and amphotericin can cause ___ defects which can lead to nephrotoxicity

Answer 17

CONCENTRATING DEFECTS

Question 18

TMP SEPTRA is an antibiotic used as prophylazis and treatmnet fo PJP pneumonia. How does it affect the kidney?

Answer 18

1. it psedo deacrases the GFR and reduces creatinine secretion at the PCT
2. blocks ENAC, like a potassium sparing diuretics, so hyperkalemia can happen. It works at the CCD.
3. the sulfamethoxazole can cause interstiail nephritis
4. the SMX can also cause crystal induced nephropahty.

Question 19

what portion of the kidney does TMP-SEPTRA act on to create hyperkalemia

Answer 19

Blocks epithelial sodium channel
(ENaC), similar to potassium sparing diuretic at the COLLECTING DUCT

Question 20

calcineurin inhibitors like cyclosporin or tacrolimus (used to prevent organ rejection) can cause nephrotoxicty by what mechanism?

Answer 20

can reduce afferent arteriole dilation and can thus cause ischemic/reduced renal blood flow.

Question 21

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

Answer 21

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.

Question 22

Summary