Flashcards in Renal Pharmacology Deck (54):
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What kinds of drugs have high incidence of acute kidney injury?
patients receiving antibiotics, chemotherapy, or radiocontrast dyes
How do you usually treat AKI?
Current treatment involves fluid and blood pressure maintenance and hemodialysis. No drugs on market for treating acute kidney injury.
What categories of drugs are emerging to treat AKI since it is caused by ischemia and reperfusion injury?
4. growth factor
What are some anti-apoptotic drugs for AKI?
What are some anti-inflammatory drugs for AKI?
Adenosine A2A agonist
Phosphatidylserine binding protein
What are some anti-sepsis drugs for AKI?
What are some growth factors drugs for AKI?
What are some vasodilator drugs for AKI?
Atrial natriuretic peptide
Causes of CKD are what?
• Diabetic Nephropathy
• HIV nephropathy
• Reflux nephropathy in children
• Polycystic kidney disease
• Kidney infections & obstructions
How do Renin-Angiotensin Inhibitors help in CKD?
↓ Progression of albuminuria
↓ Progression of GFR decline
↓ Risk of ESRD
What are some beneficial effects of RAAS inhibitors?
• Only in part due to blood pressure reduction
• Extend to CKD regardless of etiology
• Occur with both ACE inhibitors and ARBs
• At recommended doses, ACEI + ARB better than either alone
What about NSAIDs in CKD?
– Damage kidneys further
– May interact with ACE inhibitors and angiotensin receptor antagonists
How does treatment of Diabetic Nephropathy in a pt with CKD help?
Management of primary disorder paramount: Good glycemic control (HbA1c < 7%), Blood pressure control Goal < 140/90 mmHg, Medications to minimize proteinuria – ACEI & ARB
Anemia occurs in CKD how can we help this?
What is Erythropoietin?
glycosylated protein hormone produced primarily in the kidney that regulates red blood cell production by reducing apoptosis and stimulating differentiation and proliferation of erythroid progenitor cells and is deficient in ESRD
Human recombinant synthesized erythropoietin?
How is Epoetin administered?
IV or SubQ: Response more rapid with i.v. but greater response with subcutaneous
• Epoetin half-life 4-6 hours
• Administered 2-3 times / week
Side effects of Epoetin?
• Nausea, vomiting, diarrhea
• Influenza-like symptoms early in treatment
• Hypertension – dose-dependent
• Thrombosis of arteriovenous shunts
**** Pure red cell aplasia subcutaneous administration in renal failure associated with antibodies of epoetin – must discontinue treatment
Plasma calcium is regulated by what 3 hormones?
Parathyroid hormone, calcitonin, and Calcitriol (active vit. D)
What forms does calcium take in the plasma?
40% is bound to plasma protein –albumin, 10% complexed with citrate, carbonate and phosphate and 50% is free ionized an important form
Kidney failure disrupts systemic calcium and phosphate homeostasis and affects what organs?
the bone, GI tract, and parathyroid glands
What does calcitriol do?
Calcitriol increases serum calcium levels
The increased phosphate and reduced calcium, feedback and can lead to what?
Secondary hyperparathyroidism which has increased PTH
What major factors can lead to Secondary
– Decreased production of Vitamin D3 (calcitriol)
– Decreased serum calcium
– Increased serum phosphorous
What are some Vitamin D analogs?
How do vitamin D analogs help with CKD?
• Enhancement of absorption of Calcium and PO4 from intestine
• Calcitriol also enhances recruitment and differentiation of osteoclast precursor for remodelling - resorption of Calcium and PO4 from bone
• Also enhances renal tubular reabsorption of Calcium
In CKD why do hydroxylated forms of vitamin D need to be used?
hydroxylation of vitamin D occurs in the kidney and the hydroxylated forms are active (alfacalcidol or calcitriol)
Ergocalciferol is inactive
Which vitamin D analogs have short half lives and which needs to be injected?
• Alafacalcidol and calcitriol have short half-lives (3 hours)
• Paricalcitol requires i.v. injections
What are side effects of vitamin D analogs?
excessive dosing leads to hypercalcemia
What are some phosphate binder drugs?
How do phosphate binding drugs work?
GI – Phosphate absorption by reacting with phosphate and form insoluble compound
How is Sevelamer different than the other phosphate bindners?
it has a calcium and aluminum free polymeric structure
What are side effects of phosphate binders?
GI side effects / hypercalcemia
How do you get Hypercalcemia and Kidney Disease?
• Prolonged kidney disease can be associated with hypercalcemia
• Renal transplant patients can have parathyroid hyperplasia and restoration of renal function and calcitriol production can lead to hypercalcemia
How could you treat the hypercalcemia?
Bisphosphonates & Calcitonin
What are the two bisphosphonates we have to know?
Etidronate (1st gen) & Zoledondrate (3rd gen)
How do Bisphosphonates work?
pyrophosphate analogues that bind to hydroxyapatite crystals in bone matrix to inhibit bone resorption
How should bisphophonates be administered?
• Actions are relatively short-lived and need to be administered weekly
• Zoledondrate can suppress bone resorption for up to a year after a single dose
What are some side effects of bisphophonates?
GI disturbances, abdominal pain, nausea, Osteonecrosis of jaw (i.v.)
What is calcitonin?
• Produced by parafollicular or C cells of the thyroid gland
• Secreted when plasma calcium level rises
How does calcitonin work?
• Main action is the lowering of plasma calcium by limiting bone resorption and it increases phosphate excretion in the urine
How do you administer calcitonin?
Intramuscular or subcutaneous injection – half-life ~20 minutes
What are some side effects of calcitonin?
• Facial flushing in most patients
• Headache - Dizziness
• GI – nausea, vomiting, abdominal Pain, diarrhea
• Taste disturbance
Hyperuricemia can occur with CKD since the kidneys eliminate uric acid what drugs can be used to help with this?
Which hyperuricemia drugs can you not use in pt with CKD?
Sulfinpyrazone & Probenecid because they increase uric acid clearance via the kidney
What does colchicine do?
• Reduces inflammation
• Given every 6-12 hours to relieve symptoms
• Pain relief begins at about 18 hours and is maximal by 48 hours
What are some side effects of colchicine?
What are the oral Xanthine Oxidase Inhibitors?
Febuxostat: non- purine
How do Xanthine Oxidase Inhibitors work?
Competitive enzyme inhibitors with Variable half-life 1-15 hours (d/t renal excretion)
What are some side effects of Xanthine Oxidase Inhibitors?
Risk of acute gout – release of uric acid from tissue deposits
Hypersensitivity to allopurinol –rashes especially in renal disease patients
Drug interactions – inhibit metabolism of azathioprine
How does rasburicase work?
Recombinant version of enzyme urate oxidase breaks down uric acid
How is rasburicase metabolized and administered?
• Metabolized by peptide hydrolysis in plasma
• Used primarily as prophylaxis during chemotherapy (can be used in CKD)