Renal Pharmacology Flashcards
What are four medical treatments associated with acute kidney injury?
Antibiotics, chemotherapy and radiocontrast dyes, thoracic surgery
Chronic kidney diseases develops in __ - __% of acute kidney injury survivers?
20-30%
What are some drugs on the market for treating acute kidney injury (AKI)?
there are none
What can cause renal ischemia-reperfusion in AKI?
Arterial occlusion
Hypotension
Shock
In AKI, renal iscemia-reperfusion can lead to…?
- Microvascular dysfunction
- Excess vasoconstriction
- Inflammation, oxidative stress
- Endothelial injury
- Endothelial-leukocyte interactions
Acute Kidney Injury - emerging pharmacological agents
Anti apoptotic:
Anti-inflammatory:
Anti-Sepsis:
Growth factor:
Vasodilator:
Anti apoptotic: capsase inhibitors, minocycline
Anti-inflammatory: adenosine A2A agonist
Anti-Sepsis: Insulin
Growth factor: Recombinant erythropoietin
Vasodilator: Fenoldopam, ANP
What are the two most common causes of CKD?
Diabetic Nephropathy and Hypertension
What GFR is associated with each stage of CKD?
Stage 1:
Stage 2:
Stage 3:
Stage 4:
Stage 5:
Stage 1: ≥ 90
Stage 2: 60 - 89
Stage 3: 30-59
Stage 4: 15-29
Stage 5: <15
What is the goal of treatment for CKD?
Inhibit the renin angiotensin system
What function to ACEi and ARBs serve in CKD?
- Decrease progression of albuminuria
- Decrease progression of GFR decline
- Decrease risk of ESRD
Why don’t you take NSAIDs with CKD?
Damage kidneys further
May interact with ACEi or ARB
In CKD are ACEi and ARBs more effective together or separately?
Combination therapy tends to work better, but is still controversial
What are the three management goals in diabetic nephropathy?
Good glycemic control (HbA1c < 7%)
Blood pressure control (< 140/90 mmHg)
Medications to minimize proteinuria (ACEi and ARB)
What are two upcoming treatments to combat CKD?
Bardoxolone - halted due to safety concerns
EET analogs - pending approval
Anema is most prevalent in which stages of CKD?
4-5
What are the symptoms and causes of anemia in CKD?
Symptoms: fatigue and decreased cognition
Causes: decrease in release of erythropoietin
- What is Epoetin?
- How is it administered?
- What is it’s half life?
- A human recombinant synthesized form of erythropoietin
- IV (more rapid response) and SubQ (greater response)
- 4-6 hour half life
What are the unwanted side effects of Epoetin?
- Nausea, vomiting, diarrhea
- Headache
- Flu-like symptoms
- HTN
- Thrombosis of arteriovenous shunts (Increased RBCs)
What are the physiological roles of calcium?
- Nerve conduction and regulation of cell membrane permeability
- Excitation and coupling of all types of muscles
- Secretion of endocrine and exocrine glands and release of neurotransmitters
- Intracellular messenger
- Impulse generation in the heart
- Coagulation of blood
- Bones and teeth
What 3 hormones regulate plasma calcium?
Parathyroid hormone
Calcitonin
Calcitriol
Of the calcium in the plasma, what percentage is bound to albumin?
Does hypoalbuminemia cause a decrease in calcium concentration?
40% (50% is free ionized and important form)
no decrease
What form of plasma calcium is favored in acidosis?
Free ionized form
How does Kidney failure affect calcium levels?
In kidney failure there is decreased renal excretion of phosphate and diminished production of calcitrol leading to decrease in plasma calcium
How does Kidney failure lead to metabolic bone disease and soft tissue calcifications?
Increased phorphate and reduced calcium feeeback can lead to Secondary Hyperparathyroidism which leads to metabolic bone disease and soft tissue calcifications
What are the major factors leading to an increase in PTH and secondary hyperparathyroidism?
Decreased production of Vitamin D3 (calcitriol)
Decreased serum calcium
Increased serum phosphorous
What modifications are made in each generation of Vitamin D analogs?
1st gen: Synthetic form of endogenous Vitamin D
2nd gen: Side chain modifications
3rd gen: A-ring modifications (paricalcitol)
What is the MOA of Vitamin D analogs?
- Enhancement of absorption of calcium and phosphate from intestine
- Enhances recruitment and differentiation of osteoclast precursor for remodeling-resorption of calcium and phosphate from bone
- Enhances renal tubular reabsorption of calcium
Which Vitamin D analog requires kidney 1-α hydroxylation?
Ergocalciferol
What Vitamin D analogs are used in kidney disease?
What is their half life?
Hydroxylated active forms of alfacalcidol or calcitrol (short half lives - 3 hours)
Which vitamin D analog requires IV injections?
Paricalcitol
What are the signs of vitamin D deficiency?
At what stages of CKD are vitamin D analogs indicated?
- Fractures
- Hyperparathyroidism
Indicated at stage 3 if Ca < 9.5 and P <4.6
Always indicated at stage 4
What are the phosphate binders and how do they work?
Calcium carbonate, calcium acetate, lanthanum carbonate
Decrease phosphate absorption by reacting with phosphate to form an insoluble compound
What are side effects of phosphate binders?
GI side effects
hypercalcemia
How can renal transplant cause hypercalcemia?
Patients already have high levels of PTH due to previous renal failure so addition of functioning kidney leads to extremely high plasma calcium levels
What is the function of bisphosphonates in hypercalcemia?
Which is the most long lasting?
Pyrophosphate analogs that bind to hydroxyapatite crystals in bone matrix to inhibit bone resorption
Zoledondrate can suppress bone resorption for up to a year after a single dose
What are the three generations of Bisphosphonates?
- First gen:
- Etidronate
- Tiludronate
- 2nd gen:
- Pamidronate
- Aledronate
- Ibadronate
- 3rd gen:
- Risedronate
- Zoledronate
What is the function of calcitonin?
Produced by parafollicular cells of thyroid gland
Secreted when plasma calcium rises
Lowers plasma calcium by limiting bone resorption and increasing phosphate excretion in the urine
What are some unwanted side effects of calcitonin?
Facial flushing
Headache
GI
Taste disturbance
How do you treat hyperuricemia and gout in kidney disease?
Colchicine
Allopurinol
Febuxostat
Rasburicase
Colchicine:
onset of action?
Side effects?
Onset: pain relief begins at about 18 hours and is maximal by 48 hours
SE: GI, Rash
What are the SE of the Xanthine Oxidase Inhibitors (Allopurinol and Febuxostat)?
- GI Upset
- Risk of acute gout
- Hypersensitivity (Allopurinol)
- Drug interactions
How does rasburicase work?
What are its SE?
- Recombinant version of enzyme urate oxidase
- Promotes uric acid conversion to allantoin
- Metabolized by peptide hydrolysis in plasma
- Used primarily as prophylaxis during chemotherapy
SE: Fever, nausea, vomiting, hypersensitivity, hemolysis
