ppt

1. Foundations of Pharmacology in
Renal Disease
Comprehensive, Detailed PPT

2. Why Pharmacology Changes in
Renal Disease
• Kidneys handle drug excretion, metabolism,
filtration, secretion
– Acute or chronic kidney disease reduces drug
clearance
– Risk of accumulation, toxicity, and prolonged half-
life
– Need for dose adjustments and drug selection

3. Key Renal Pharmacokinetics
Concepts
• Glomerular Filtration Rate (GFR): indicator of
kidney function
– Creatinine clearance (CrCl) often estimates GFR
– Reduced filtration → reduced elimination of
renally cleared drugs
– Tubular secretion and reabsorption also altered

4. Drug Absorption in Renal Disease
• Gastric pH changes → affects weak
acids/bases
– Edema and delayed gastric emptying → alter
absorption
– Interactions with phosphate binders → reduce
bioavailability

5. Drug Distribution Changes
• Fluid overload → ↑ volume of distribution
(Vd) for hydrophilic drugs
– Hypoalbuminemia → ↑ free fraction of protein-
bound drugs
– Uremia → altered tissue binding

6. Metabolism Changes
• Non-renal clearance may compensate
– Hepatic CYP enzymes affected in uremia
– Drugs with active metabolites need caution

7. Drug Elimination Changes
• Reduced renal clearance → dose adjustments
needed
– Half-life increases: risk of toxicity
– Dialysis may remove drugs variably depending on
size, protein binding, Vd

8. Principles of Dose Adjustment
• Reduce dose OR extend dosing interval
– Use drug-specific renal dosing guidelines
– Monitor drug levels when available (e.g.,
vancomycin, aminoglycosides)

9. Drugs Unsafe or Cautioned in CKD
• NSAIDs → reduce renal blood flow
– Metformin → risk of lactic acidosis
– Morphine → active metabolites accumulate
– Potassium-sparing diuretics → hyperkalemia

10. Impact of Dialysis on
Pharmacology
• High-flux vs low-flux membranes affect
removal
– Drug properties determining dialyzability: size,
protein binding, Vd
– Timing: post-dialysis dosing preferred for
dialyzable drugs

11. Antibiotic Dosing in Renal Disease
• Beta-lactams: adjust by CrCl
– Vancomycin: AUC-guided dosing, dialysis removal
– Aminoglycosides: extended dosing, careful
monitoring
– Fluoroquinolones: variable renal clearance

12. Other Special Drug Classes
• Anticoagulants: DOACs need renal adjustment
– Antidiabetics: metformin, SGLT2 inhibitors
considerations
– Opioids: prefer fentanyl, hydromorphone

13. Therapeutic Drug Monitoring
• When to monitor: narrow therapeutic index
drugs
– Use levels to guide dose changes
– Consider timing around dialysis

14. Practical Clinical Approach
• Assess renal function trend
– Review all medications for renal dosing
– Check for drug–drug interactions
– Plan dialysis timing with dose
– Educate patient on dosing and toxicity signs

15. Flowchart: Dose Adjustment in
Renal Disease
Assess Renal Function (GFR/CrCl)
Check Drug Elimination Pathway
Drug Mainly Renally Cleared?
YES → Reduce dose or extend interval
NO → Standard dose (monitor)
Dialysis Patient? → Adjust around HD/PD
Monitor clinical response & drug levels

16. Clinical Table: Renal Dosing
Adjustments
Drug Adjustment Needed? Notes
Metformin Yes Avoid if eGFR < 30
Vancomycin Yes AUC-guided dosing
Ceftriaxone No Mostly biliary clearance
Gabapentin Yes Reduce dose in CKD
Morphine Avoid Active metabolites
accumulate

17. Diagram: Nephron Handling of
Drugs
Glomerulus – Filtration
Proximal Tubule – Secretion
Loop of Henle
Distal Tubule
Collecting Duct – Reabsorption

18. Detailed Pharmacokinetic Changes
in CKD
• Absorption Changes
– Delayed gastric emptying → slower onset
– Increased gastric pH → altered absorption of weak
acids/bases
– Drug binding by phosphate binders → reduced
absorption
• Distribution Changes
– Fluid overload → ↑ Vd for hydrophilic drugs
– Hypoalbuminemia → ↑ free fraction (e.g.,
phenytoin)

19. Dialysis and Drug Removal:
Detailed Concepts
• Determinants of Dialyzability
– Molecular weight: small molecules removed easily
– Protein binding: high binding → less removal
– Volume of distribution: large Vd → minimal
removal
– Water solubility: hydrophilic drugs removed more
• Hemodialysis Characteristics
– High-flux membranes remove large molecules
– Short duration but high clearance
– Post-HD dosing preferred for dialyzable drugs

20. How to Adjust Drug Doses in CKD –
Detailed Approach
• Step 1: Estimate renal function
– Use eGFR or Cockcroft–Gault CrCl
– Use adjusted body weight in obese patients
– Consider AKI, which invalidates equations
• Step 2: Identify drug elimination pathway
– If >50% renally cleared → adjust dose
– If active metabolites accumulate → adjust
– Check renal dosing guidelines (KDIGO / Lexicomp /
Sanford)
• Step 3: Decide adjustment strategy