Pharmacology of Renal Failure

Question 1

Impact of CKD on pharmacologic tx

Answer 1

• decreasing fxn (decreased ability to eliminate drugs/regulate solutes) & increasing complications ==> complicated/coordinated pharmacologic tx
• altered bodily response to meds via pharmacokinetic and pharmacodynamic

Question 2

Impact of CKD on absorption/bioavailability of drugs

Answer 2

• limited impact except for GI alterations may affect bioavailability
• drug-drug interactions:
  
  • posphate binders & bile acid sequestrants ==> reduce availability of drugs given concomitantly

Question 3

Impact of CKD on drug distribution

Answer 3

• both decreases & increases ==> increased unbound drug & C_p
• e.g. any given dose of digoxin will result in a higher C_p due to the smaller V_d
• e.g. CKD pts taking phenytoin have increased V_d ==> greater levels of free phenytoin and greater ability to distribute outside of the plasma and greater potential for toxicity

Question 4

CKD impact on drug metabolism

Answer 4

• insulin = metabolism decreased in CKD ==> dosage reduction necessary
• active hepatic metabolities accumulate in CKD ==> drug toxicity
  
  • e.g. meperidine (aka “Demerol” = opoid/sedation) metabolites
  • e.g. acetominophen metabolites

Question 5

Dosing adjustments neccesary in CKD (general)

Answer 5

• stage 1 & 2 = no dosage adjustment neccessary
• stage 3 & 4 = renally eliminated drugs require dosage reduction

Question 6

Arteriolar resistance (@ glomerulus) impact on GFR and drugs that affect resistance

Answer 6

• Dilate Afferent
  
  • increased GFR
  • <== Dopamine; Caffeine (=Adenosine antagonist)
• Constrict Afferent
  
  • decrease GFR
  • <== NSAIDs via decreased PGs
• Constrict Efferent
  
  • increase GFR
  • <== AgII
• Dilate efferent
  
  • decrease GFR
  • <== ACE-Is, ARBs via decreased AgII

Question 7

Diuretics adjustment in CKD

Answer 7

• thiazide = first-line HTN
  
  • decreased efficacy as GFR falls b/c less drug reaches site of action
  • ==> addition of more potent loop diuretic
• Diuretic resistance develops @ later stages ==> use synergistic combos of diuretics

Question 8

Dosage considerations in CKD for diabetes medications

Answer 8

• oral hypoglycemics
  
  • glyburide: half-life prolonged
  • metformin: NOT recommended if Cr > 1.5
• insulin = half-life prolonged

Question 9

Dosage considerations in CKD for HTN medications

Answer 9

• Diuretics
  
  • Thiazides lose effectiveness as renal fxn declines ==> add loop diuretics
  • avoid potassium-sparing diuretics
• ACE-Is
  
  • used through all stages ==> moniter for hyperkalemia/Cr elevations
  • may cause ARF in hypovolemic pts
• Beta-blockers
  
  • atenolol: half-life prolonged
• No adjustments neccesary in other meds

Question 10

Dosage considerations in CKD for hyperlipidemia medications

Answer 10

• Fibrates
  
  • Gemfibrozil recommended fibrate @ CKD stage 5
• No other adjustments needed

Question 11

Pharm tx of Anemia in CKD

Answer 11

• Epoetin Afla & Darpepoetin Alfa
  
  • MOA: glycoproteins w/bio activity=EPO
  • Pharm: parenterally (SC) weekly
  • AE: HTN
• Iron supplements/tx
  
  • MOA: aid in hemoglobin/RBC production
  • Pharm: oral w/poor absorption; IV often required
  • AE: oral=GI complaints; IV=allergy, hypotension, headaches

Question 12

Pathophys/Pharm tx of Renal Osteodystrophy in CKD

Answer 12

• decreased renal fxn => elevated serum phosphate => decreased Ca²⁺ => increased PTH
• PTH initially normalizes Ca²⁺/PO₄ ==> long term = osteodystrophy
• Compounded by kidney inability to activate Vit D => further reduction of Ca²⁺
• Tx:
• Phosphate binding agents
• Vit D agents
• Calcimimetics

Question 13

Pharmacologic properties of phosphate binding agents

Answer 13

• e.g. Calcium acetate (PhosLo); Sevelamer (Renagel)
• MOA: Bind dietary phosphate in GI tract to form insoluble compounds excreted in the feces ==> decreasing phosphate
• Pharmacokinetics: Given orally, best taken with meals.
• Side effects: Primarily GI side effects – Hypercalcemia possible with Ca⁺⁺ salts; CNS toxicity with Al⁺⁺⁺ salts limits use.

Question 14

Pharmacologic properties of Vit D compounds

Answer 14

• e.g. Calcitriol/1,25-dihydroxy vit D₃
• MOA: Suppresses PTH secretion indirectly by stimulating intestinal calcium absorption + decreasing PTH synthesis in parathyroid gland.
• Pharmacokinetics: Available in oral (Stage 1-4) and intravenous (Stage 5) dosage forms
• Side effects: Hypercalcemia and hyperphosphatemia possible.

Question 15

Pharmacotherapy for acute hyperkalemia

Answer 15

• hemodialysis
• temporary tx:
  
  • IV calcium gluconate
  • insulin + glucose
  • sodium bicarbonate
  • nebulized albuterol
• MOA:
  
  • insulin/glucose, albuterol, sodium bicarb: shift K into cells
  • calcium: antagonizes cardiac conduction abnormalities

Question 16

Pharmacotherapy in chronic hyperkalemia

Answer 16

MOA: Cation exchange resin that binds (exchanges) potassium for sodium in intestine.

Pharmacokinetics: Oral (more effective) and rectal.

Side effects: Constipation, fecal compaction, nausea, vomiting.