Renal Failure/Chronic Kidney Disease Flashcards
name 4 drugs for renal failure
Antihypertensives (ACE inhibitors & Angiotensin II receptor antagonists) – Vitamin D analogs – Diuretics – Epoetin
what are 2 electrolyte disorders that can be important in renal failure and require pharm treatment
hyperphoshatemia
hyperkalemia
for review:
see slides on ACEI and ARBs
ok
Antihypertensive for Renal Failure
what do ACEI and ARBs do?
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
role of Vit D analogues?
Use in renal failure
– To manage secondary hyperparathyroidism due to low blood calcium
role of diuretics in renal failure?
• 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
Hematopoietic Growth Factors: Erythropoietins
prototype?
MOA?
- 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
Hematopoietic Growth Factors: Erythropoietins
indications (3)
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
what is hyperphosphatemia?
what does it signify?
• 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
what is hyperkalemia?
what are the levels of severity?
• 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)
meds that can induce hyperkalemia (3)
– K+ sparing diuretics (spironolactone)
– NSAIDs
– ACE inhibitors
Agents that Bind Phosphate
name 3
form insoluble phosphate complexes in the GI tract
Aluminum hydroxide
Calcium carbonate
Sevelamer hydrochloride
Aluminum hydroxide
MOA
- Binds phosphate in the GI tract
* May increase plasma aluminum levels in dialysis patients - toxicity
Calcium carbonate
MOA
• 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
Sevelamer hydrochloride
MOA
AE
contra (2)
• 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
Drugs for Treating Hyperkalemia
Sodium or calcium polystyrene sulfonate
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)
Other Agents for Hyperkalemia
glucose + insulin
- Insulin causes potassium to shift into cells by increasing Na+/K+ ATPase activity
- Glucose is provided to mitigate risk for hypoglycemia
Other Agents for Hyperkalemia
Salbutamol
• 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)
Urinary Incontinence
and/or Overactive Bladder
• 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
Desmopressin
MOA?
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
Desmopressin
AE (2)
• 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)
Mirabegron
MOA? receptors?
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
Mirabegron
AE?
generally safe – Increased blood pressure – Bladder pain – Dry mouth – Headache – Dizziness
Anticholinergics
name 2 M3 selective
name 2 nonselective
Muscarinic receptor antagonists are used to treat
overactive bladder, a form of incontinence
• M3 selective – Darifenacin – Solifenacin • Nonselective – Oxybutinin – Tolterodine
Anticholinergics
MOA?
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)
