Renal Pharm: Renal Stone Flashcards
What sex is more likely to get renal stones ?
Men
List 5 dietary risk factors for nephrolithiasis
- Low Dietary Calcium (yes, counterintuitive but low calcium lead s to Ca+ binding oxalates in the GU system).
- Calcium supplements
- High animal protein intake
- High sodium
- Low fluid intake.
List 7 Systemic risk factors for nephrolithiasis
Primary Hyperaldosteronism Renal Tubular Acidosis Obesity Gout Diabetes mellitus Crohn's Gastric Bypass.
You have a family history of kidney stone. By what factor are you at increased risk for stone ?
2x
What are the 4 main constituents of most calcium containing stones ?
- Calcium (Hypercalciuria >300/250 mg/day urine calcium in men/women)
- Oxalate (Hyperoxaluria >45 mg/day urine oxalate)
- Urate (Hyperuricosuria >800/750 mg/day urine uric acid in men/women)
- Citrate (Hypocitraturia <320 mg/day urine citrate)
What are the three kinds of non-calcium containing stones ?
Uric Acid Stones
Struvite Stones
Cystine Stones.
What percent of stones are seen unilaterally ?
80% (thus 20% bilateral)
Where do you usually see the largest stones in the GU ?
Renal Pelvis and Calyx (Staghorn)
Calculi larger than 10 mm…
will not pass
Calculi between 5-10 mm..
Have variable passage
Calculi 5 mm and less …
should pass w/o problems.
Extracorporeal shock-wave lithotripsy is indicated for stone of what size and location ?
<2 cm; upper ureteral stone
Ureteroscopy is an indicated treatment for stones of what size and location ?
<2 cm; lower ureteral stone
Percutaneous removal or lithotripsy is indicated for stones of what size and location ?
> 2 cm; complex calculi (staghorn); cystine stone
Narcotic analgesics work at what receptors
Mu and or Kappa receptors
What is the main narcotic analgesic given to treat of renal colic ?
Morphine sulfate (Standard of care for morphine sulfate)
Besides the obvious efficacy of dealing with renal colic, what is another advantage of giving narcotic analgesics ?
inexpensive treatment option
List the adverse effects seen with narcotic analgesics
POTENTIAL FOR ABUSE Sedation Nausea Respiratory Depression Smooth Muscle Spasm
How do NSAID’s work to reduce pain an inflammation ?
Inhibit cyclooxygenase and thus the production of inflammatory mediators such as prostaglandins
What are the advantages of using NSAID’s as opposed to narcotics for the control of renal colic ?
NO POTENTIAL FOR ABUSE Found to be just as effective Less sedation Less Nausea Less Respiratory depression
What are the inherent disadvantages of using NSAIDS ?
Expensive
Only one is indicated for IV use
What is the only NSAID approved by the FDA for IV usage ?
Ketorolac !
Why are Calcium Channel Blockers (CCB) useful in facilitation of the passage of stones ?
CCB’s Suppress smooth muscle contraction and reduce ureteral spasm
What is the main CCB indicated for facilitating passage of URETERAL stone ?
Nifedifpine (Short duration of therapy, up to 10 days)
How do selective Alpha 1 Adrenergic Receptor Blockers work to facilitate renal stone passage in the ureter ?
Decrease ureteral smooth muscle tone and frequency and force of peristalsis
What are the two Alpha 1 Adrenergic Receptor Blockers indicated for facilitation of renal stone passage in the ureters ?
Tamsulozin, Terazosin (Indicated for short term use, 10 days)
Do the use of CCB’s and Alpha 1 Adrenergic Receptor Blockers prevent the formation of future stones ?
Nope. Not preventative.
What percentage of stone formers will form another stone after passing their first ?
50% ( in 10 years )
What is the most common form of stone ?
Calcium oxalate
List 5 risk factors for the formation Calcium oxalate
Increased Urine Calcium Increased Urine Oxalate Increased Uric Acid Decreased Urine Volume (Decreased ?) Citrate
Radioopaque
What are two risk factors for the formation of
Increase urine calcium
Increased Urine pH
Radiopaque
Are uric acid stones radiopaque ?
NO . Radiolucent
List the risk factors for Uric Acid Stone
Increased urine uric acid
Decreased urine pH and volume.
What are the risk factors for formation of Struvite stones.
Increased urine pH and presence of urease + bacteria (proteus )
List the risk factors for cystine stones
GENETIC INHERITANCE
What is the only pharm treatment aimed at reducing the Ca+ load in the urine ? (Preventative treatment for hypercalciuria caused stones)
Thiazide diuretic
How do thiazides decrease urinary Ca+ ?
Thiazides block the Na/Cl symporter on the lumenal side of the distal convoluted tubule
This will stop the influx of Na into the cell, however the Na/K+ pump on the basolateral side will continue to work, depleting Na+ within the cell.
To compensate for this Na+ loss, the Na/Ca++ anti-port on the basolateral surface will switch polarity. This means that Na+ will be pushed into the cell while Ca++ is shuttled out into the blood.This will cause a gradient for Ca++ reabsorption causing more Ca++ influx into the cell from the lumenal Ca++ channels. This will effectively lessen the amount of Ca++ in the urine.
Thiazide diuretics cause what electrolyte disturbance ?
Hypokalemia in metabolic acidosis
Thiazides may precipitate which condition characterized by increased uric acid in the blood ?
Gout . Thiazides may lead to hyperuricemia
What can be given with a thiazide diuretic to reduce the occurrence of hypokalemia ?
Amiloride (K+ sparring diuretic)
Why can you give amiloride and not triametrene to help lessen the occurrence of hypokalemia when preventing renal calculi?
Triamterene is highly insoluble in urine and may increase incidence of stone formation
As a preventative measure , how much fluid should a person who is predisposed to hypercalciuria and stones take in to effectively lessen the chance of recurring stones ?
2-2.5 L of fluid daily
Should a person with high cholesterol be on a thiazide diuretic ?
Sure, but there is a chance that a thiazide will cause Hyperlipidemia ! So be careful.
Where does most oxalate production occur in the body ?
The liver : Technically, the liver produces glyoxylate which will be converted to oxalate
Primary hyperoxalurias Type I-III occur due to…
Rare autosomal recessive disorders of glyoxylate metabolism.
Type I hyperoxaluria is an AGT deficiency(enzyme) and is treated with what ?
pyridoxine: converted to an essential cofactor of AGT enhancing its function.
What are the three kinds of Secondary Oxalurias
Enteric
Dietary
Idiopathic
What occurs in Enteric Oxaluria that leads to the formation of Calcium containing stones ?
In enteric oxaluria, small bowel disease causes a fat malabsorption. Fat in the lumen binds calcium (normally calcium binds oxalate). Oxalate is then free for absorption instead of being lost in feces.
How is Enteric Oxaluria treates ?
Low Fat and low oxalate diet. With calcium supplementation to bind oxalate in the lumen.
Dietary hyperoxaluria is caused by excessive intakes of which foods ?
Those high in oxalate like Spinach, Nuts, Chocolate.
What drug can be given to treat dietary hyperoxaluria ?
Cholestyramine. (Oxalate binding resin)
Citrate complexes with Calcium in the urine, this decreases calcium hyper saturation. Under what condition is citrate excretion enhanced ?
Alkalosis of the urine
One of the treatment modalities for Hypocitrauria induced stones is to alkalize the urine. What is the target pH ? Why ?
Between pH 6-7
If pH is over 7 it may precipitate calcium phosphate stones.
What pharmacologic agent is the preferred drug used to alkalize the urine in treatment of hypocitrauria (calcium oxalate stone) ? What non-pharm agent can be used ?
Potassium Citrate
Lemonade ! High levels of citrate, allows better binding of Ca++ in the urine
How does citrate lower the occurrence of caclculi formation ?
Citrate inhibits stone formation by complexing with calcium in the urine, inhibiting spontaneous nucleation, and preventing growth and agglomeration of crystals.
Uric acid contributes to the formation of calcium oxalate stones. What is the predominant factor in uric stone formation ?
Acidic pH !
Like in hypocitrauria, the main preventative treatment for Hyperuricosuria is to alkalize the urine. To what level must this be done ?
pH 6-7
what drug is given to alkalize the urine in hyperurocosuria ?
Potassium Citrate (just like in hypocitrauria)
Another method of reducing the incidence of calcium containing stones is to decrease Uric acid load in the body. This can be done by ingesting/decreasing which foods ?
increase alkali-rich foods such as fruits and vegetables and decrease high protein diets such as animal meat
What pharmacological treatment can be given to decrease the Uric Acid load in the body ? (if dietary restriction fails)
Allopurinol
What enzyme is inhibited by allopurinol ?
Xanthine oxidase/
Xanthine oxidase metabolizes Allopurinol to which metabolite that has the ability to inhibit the same enzyme ?
alloxanthine
What is the half life of allopurinol ?
1-2 hours
Are cystine stones calcium containing ?
NOPE (Calcium,Oxalate, Citrate and Urate all lead to calcium containing stones)
Non-Calcium Stones:
Cystine
Struvite
Uric Acid (Uric Acid can lead to both)
Describe what occurs due to the genetic disorder that leads to Cystine stones ?
brush borders of proximal tubule is defective for the reabsorption of cystine, resulting in increased urinary cystine excretion
Cystine is insoluble in urine and excess results in formation of cystine stones
One of the three non-pharmacoligic measures for preventing Cystine stones is fluid loading. What is the target fluid load for this therapy ?
> 3L of urine per day.
Cystine Stone prevention includes a Low Salt Diet and to _______ the Urine.
Alkalize
What is the target pH for prevention of Cystine stones ?
pH >7.5
If fluid loading, salt reduction, and alkali therapy are ineffective what pharmaceuticals are used to provent cystine stone formation ?
Tiopronin or d-penicillamine
How does tiopronin or d-penicillamine work ?
Cystine is a dimer of cysteine linked by disulfide bridge. Tiopronin and penicillamine are thiols that can break the disulfide bridge and form a more soluble complex with monomeric cysteine
What are the side effects of tiopronin or D-penicilamine use ?
Gastrointestinal side effects
Dermatological complications (rash, prurites)
Hematologic abnormalities (bleeding, anemia, leukopenia, thrombocytopenia, eosinophilia)
Neurologic complications (Myasthenic syndrome)
What MUST be present for struvite stones to form ?
Infection of the upper urinary tract with Urease+ bacteria (Proteus mirabilis, Klebsiella pneumoniae, Providencia)
As the urinary pH rises (over 7.2), struvite crystals begin to form . What is often trapped in the crystalline structures ?
The Urease + bacteria
What damages the the GAG surface epithelium in the urinary system, leading to stag horn calculus formation ?
Ammonia (formed from breakdown of Urea by the bacteria)
What is the treatment for an existing Struvite stone ?
COMPLETE removal via percutaneous nephrolithotomy (possibly combined with lithotripsy)
Sterilization of area so that Bacteria are no longer present . (Ab’s should be guided by culture after removal of stone)
What may be done to the urine to help break up large struvite stones ?
ACIDIFICATION….helps dissolve stones
What drug can be used to irrigate out a portion of the kidney that produces struvite stones due to Urease + bacterial infection ?
Hemacidrin (10%)
For patients who are not candidates for surgery, what drug can be given to inhibit Urease (enzyme) activity ?
acetohydroxamic acid
What are the side effects associated with acetohydroxamic acid ?
Headache, loss of appetite, nausea, vomiting
