Pharm-Kidney toxity NSAIDs and Acute renal failure

Question 1

What are the causes of reduced drug elimination through the kidneys in the elderly?

Answer 1

1. Reduced renal Blood Flow

2. Perturbations in GFR

Question 2

Where are most drugs and their active metabolites eliminated?

Answer 2

Through the kidney

Question 3

What must be adjusted in those with reduced renal function?

Answer 3

Drug Dosage in order to

• Avoid accumulation of their metabolites
• Adverse reactions
• Aggravation of renal involvement

Question 4

What are the three processes that contribute to the renal clearance of a drug?

Answer 4

1. GFR
2. Tubular secretion
   - Primarily in renal proximal tubule
3. Tubular reabsorption

Question 5

What does it mean when a drug is perfusion rate limited?

Answer 5

The extraction rate (secretion) is not limited to the unbound fraction of drug.

Question 6

What does it mean when a drug secretion is capacity rate limited?

Answer 6

The extraction ratio is limited by the reversible binding of the drug to plasma proteins or its location in red blood cells.

Question 7

What sort of process is tubular reabsorption?

Answer 7

Passive process for the majority of drugs and drug metabolites

Question 8

What drives the reabsorption process?

Answer 8

The extensive reabsorption of filtered water along the renal tubule

Question 9

What are the features of a drug which may govern its reabsorption?

Answer 9

1. Lipophilicity
2. pKa
3. Molecular weight

Question 10

What are the peptide transporters responsible for the tubular reabsorption of peptide like drugs such as B-lactam antibiotics and ACE inhibitors.

Answer 10

1. PEPT1

2. PEPT2

Question 11

Where are the PEPT1, and PEPT2 transporters located?

Answer 11

Apical membrane of the renal epithelial cells

Question 12

Are prostaglandins a primary regulator of renal function in healthy individuals?

Answer 12

NO.

Question 13

What compounds modulate the effects of both systemic and locally produced vaso-constrictor hormones?

Answer 13

Eicosanoids

Question 14

Which prostaglandins are the predominant mediators of physiologic activity.

Answer 14

1. PGI2

2. PGE2

Question 15

What are the actions of the prostaglandins in the kidney?

Answer 15

1.Induce vasodilation in interlobar arteries afferent and efferent arterioles and glomeruli

Question 16

In what situations do prostaglandins become essential to the kidneys?

Answer 16

1. Development of true intravascular volume depletion (vomitting diarrhea) PG synthesized to optimize renal blood flow.
2. Effective decrease in renal blood flow as seen with CHF, cirrhosis
3. PGI2 and PGE2 counteract Angiotensin II, endothelin, vasopressin and catecholamines that would normally maintain systemic BP at the expense of renal circulation

Question 17

How do the eicosanoids conduct their function?

Answer 17

Prserve GFR by antagonizing arteriolar vasoconstriction and blunting mesangial and podocyte induced by these endogenous vasoressors

Question 18

What induces PG synthesis in CKD?

Answer 18

Intrarenal mechanisms activated to increase perfusion of remnent nephrons

Question 19

NSAID administration in a CKD patient would lead to?

Answer 19

acute reductions in renal blood flow and GFR

Question 20

What are the roles of PGs in the loop of Henle?

Answer 20

1. PGE2 decreases cellular transport of sodium chloride in TALH cells and collecting duct
2. Increase renin secretion
3. inhibit c-AMP synthesis and oppose the action of antidiuretic hormone

Question 21

What is the Net effect of chronic NSAID consumption.

Answer 21

A mild dose dependent increase in BP

Question 22

What other drugs mimic NSAID nephrotoxic effects?

Answer 22

COX-2