Renal Failure/Chronic Kidney Disease

Question 1

name 4 drugs for renal failure

Answer 1

Antihypertensives (ACE inhibitors & Angiotensin II
receptor antagonists)
– Vitamin D analogs
– Diuretics
– Epoetin

Question 2

what are 2 electrolyte disorders that can be important in renal failure and require pharm treatment

Answer 2

hyperphoshatemia

hyperkalemia

Question 3

for review:

see slides on ACEI and ARBs

Answer 3

ok

Question 4

Antihypertensive for Renal Failure

what do ACEI and ARBs do?

Answer 4

ACE inhibitors and ARBs reduce the risk for major
adverse cardiovascular events (e.g. stroke, heart
attack, heart failure) in people with chronic renal
failure/chronic kidney disease versus placebo

Question 5

role of Vit D analogues?

Answer 5

Use in renal failure

– To manage secondary hyperparathyroidism due to low blood calcium

Question 6

role of diuretics in renal failure?

Answer 6

• Often used to treat edema due to nephrotic syndrome and congestive heart failure
• Facilitate extracellular fluid volume control, lower
tendency to develop hyperkalemia & decrease blood pressure
• Potassium-sparing diuretics should be used cautiously in people with chronic renal failure

Question 7

Hematopoietic Growth Factors: Erythropoietins

prototype?
MOA?

Answer 7

• stimulate RBC production
• prototype: epoetin alfa (recombinant human erythropoietin, rHuEPO, EPO)
• other: darbepoetin alfa

MOA

• endog protein that stimulates RBC production
• EPO is typically released in response to hypoxia and is largely synthed in kidneys, small amount from liver
• pt with defic. = anemic which is common in pt with renal failure
• once released, EPO binds to receptor on surface of committed erythroid progenitor cells in bone marrow
• binding to this receptor mediates a variety of intracellular effects through tyrosine kinases including inhibition of apoptosis
• prevent RBCs from dying at early stage
• EPO promotes prolif through Janus protein kinase-2 (JAK2) pathways

Question 8

Hematopoietic Growth Factors: Erythropoietins

indications (3)

Answer 8

indications:
anema, advanced renal failure, associated w/ chemotherapy and AIDS

People with chronic renal failure/chronic kidney
disease often have impaired erythropoietin levels
and subsequent anemia, thus treatment with EPO
can be beneficial

Question 9

what is hyperphosphatemia?

what does it signify?

Answer 9

• Electrolyte disorder associated with elevated phosphate levels in the blood
– Blood phosphates > 1.46 mM (4.5 mg/dL)
• Hyperphosphatemia is a hallmark of advanced chronic kidney disease (CKD), independent predictor of CV diseases
– CKD prevalence in adults is ~5 – 8% and progressively increases with age

Question 10

what is hyperkalemia?

what are the levels of severity?

Answer 10

• Electrolyte disorder associated with elevated potassium levels in the blood
– Blood potassium > 5.5 mM
– Mild (5.5 – 5.9 mM)
– Moderate (6.0 – 6.4 mM)
– Severe (> 6.5 mM)

Question 11

meds that can induce hyperkalemia (3)

Answer 11

– K+ sparing diuretics (spironolactone)
– NSAIDs
– ACE inhibitors

Question 12

Agents that Bind Phosphate

name 3

Answer 12

form insoluble phosphate complexes in the GI tract

Aluminum hydroxide
Calcium carbonate
Sevelamer hydrochloride

Question 13

Aluminum hydroxide

MOA

Answer 13

• Binds phosphate in the GI tract

* May increase plasma aluminum levels in dialysis patients - toxicity

Question 14

Calcium carbonate

MOA

Answer 14

• Most common form of prescribed phosphate binder
• Binds phosphate in the GI tract
• Also address hypocalcemia often seen with
hyperphosphatemia in patients with chronic kidney
disease
• Hypercalcemia and accelerated vascular calcification
(artery walls) are concerns

Question 15

Sevelamer hydrochloride
MOA

AE
contra (2)

Answer 15

• Most common non calcium-based phosphate binder
• Is an anion exchange resin
• Lower phosphate binding capacity than ones previously discussed
• Less likely to lead to tissue calcification than calcium carbonate
• Additional beneficial effect of lowering LDL cholesterol
• Adverse effects include GI disturbances and it may
reduce the bioavailability of fat-soluble vitamins
• Contraindicated in hypophosphatemia or bowel
obstruction

Question 16

Drugs for Treating Hyperkalemia

Sodium or calcium polystyrene sulfonate

Answer 16

Cation Exchange Resins bind potassium in the colon

• Bind potassium in the colon in exchange for sodium or calcium
• Often prescribed with sorbitol to prevent constipation
• Combination with sorbitol may be associated with
increased risk for GI adverse events (bleeding, ischemic colitis, perforation)

Question 17

Other Agents for Hyperkalemia

glucose + insulin

Answer 17

• Insulin causes potassium to shift into cells by increasing Na+/K+ ATPase activity
• Glucose is provided to mitigate risk for hypoglycemia

Question 18

Other Agents for Hyperkalemia

Salbutamol

Answer 18

• β2 adrenoceptor activation is also linked to increased
Na+/K+ ATPase activity and will cause potassium uptake into cells
• Dose (10 – 20 mg) usually via nebulizer is significantly higher than what is used for bronchospasm (4x higher than when used in asthma)

Question 19

Urinary Incontinence

and/or Overactive Bladder

Answer 19

• Enuresis is normal in very young children
• Disordered micturition is also extremely
common in adults
• It is not easy to prevent incontinence without
causing urinary retention

Question 20

Desmopressin

MOA?

Answer 20

Analogue of vasopressin (antidiuretic hormone) used
for nocturnal enuresis in children
– Acts on vasopressin 1 (V1) and V2 receptors
– V2 receptors are present in the collecting ducts of the nephron
– V2 receptor stimulation activates pores known as “aquaporins” that facilitate water reabsorption

Question 21

Desmopressin

AE (2)

Answer 21

• Desmopressin is more specific for V2 receptors and
has a longer half-life than vasopressin
• Desmopressin can be administered intravenously,
subcutaneously, or intranasally (preferred for people
not in hospital)

– Water intoxication (hyponatremia)
– Hypotension (if administered intravenously)

Question 22

Mirabegron

MOA? receptors?

Answer 22

The human bladder contains high expression levels of
β3 adrenoceptors
• β3 adrenoceptor activation induces relaxation of the detrusor smooth muscle and increases bladder capacity
• Mirabegron is the first approved β3 adrenoceptor agonist for the treatment of overactive bladder

Question 23

Mirabegron

AE?

Answer 23

generally safe
– Increased blood pressure
– Bladder pain
– Dry mouth
– Headache
– Dizziness

Question 24

Anticholinergics
name 2 M3 selective
name 2 nonselective

Answer 24

Muscarinic receptor antagonists are used to treat
overactive bladder, a form of incontinence

• M3 selective
– Darifenacin
– Solifenacin
• Nonselective
– Oxybutinin
– Tolterodine

Question 25

Anticholinergics

MOA?

Answer 25

The bladder expresses all 5 muscarinic (M) receptors, but M3 receptors mediate contraction of the detrusor muscle in the bladder, which facilitates emptying of the bladder (micturition)