L21 Urinary Tract Infection and Kidney Stones Flashcards
Pathogenesis of Nephrolithiasis (kidney stones)?
Not enough liquid in the urine to dilute out waste chemicals, such as calcium, oxalate, and phosphorous
Waste chemicals become concentrated, and crystals begin to form
Leads to hard mass in kidneys
Nephrolithiasis Epidemiology?
1/5 males and 1/10 females during their life
Peak Age 20-40
Increasing prevalence of diabetes/obesity and changing diet increasing prevalence of kidney stones
Calcium oxalate is the most common (75%)
Magnesium ammonium phosphate (15%)
Urate/uric acid (5%)
Symptoms of Nephrolithiasis?
Asymptomatic usually when stone stays in kidney
Stone grows or moves out of kidney => Renal colic
– Severe/spasmodic pain
– loin to groin
– Penile pain
Risk factors for Nephrolithiasis?
Previous stones/FHx
Gastric bypass (oxalate nephropathy), short bowel syndrome
Frequent upper UTI
Meds: Indinavir, acyclovir
Dehydration
Acidic urine (uric acid stones)
Hypercalciuria (calcium crystals)
Low dietary calcium (bone demineralization)
Acute Medical Management of Nephrolithiasis?
When is Urology Intervention Indicated?
Step 1: Analgesia:
NSAIDs (Diclofenac , keterolac)
Stones irritate kidney =>increased prostaglandin production
NSAIDs Inhibit prostaglandins => reduce GFR => reduce renal pelvic pressure
Decrease urethral smooth muscle tone
Analgesia is at least as effective as opioids but w/ lower incidence of SE n+v
Opioids (Morphine, Pethidine)
Faster onset of action when given parenterally
Usually best when given in combination
Step 2 and 3: Fluids and Stone Passage
Rehydration: IV Fluids, PO fluids
α-adrenoreceptor antagonists (Alpha blockers)
Ureter contains α adrenergic receptors (Antagonism leads to vasodilation, reduced smooth muscle tone, increased urine output
Calcium channel blockers e g nifedipine
CCBs inhibit calcium channels in ureter => alleviate contractions & spasm
Urology
Indicated when urosepsis with obstruction
Acute renal failure
Unyielding pain
Stones > 10 mm
Procedures: Extracorporeal shock wave lithotripsy, stenting, laparoscopic stone removal
Non-Pharmacological Prevention of Nephrolithiasis?
Hydration (Fluids to allow 2 L urine/day)
Dietary Modification
Reduce animal protein intake [uric acid]
Increase fruit and veg
Limit oxalate intake (spinach, peanuts, cashews)
Low sodium diet [lowers calcium in urine]
Maintain moderate DIETARY calcium intake
Pharmacological Prevention of Nephrolithiasis?
Thiazides
Can target high urine calcium hypercalciuria
Inhibit the sodium chloride cotransporter in the distal
tubule. Lower intracellular Na favors Ca reabsorption via basolateral Ca/Na Channel => Lowers calcium excretion ~50% (Risk of Hypercalcemia)
90% reduction in new stone formation
If Thiazides not tolerated…
Alkaline agent (potassium bicarbonate)
Increases calcium reabsorption
Can reduce uric acid kidney stones
Allopurinol (Zyloprim)
Xanthine oxidase inhibitor
Reduces uric acid levels in the blood can help dissolve stones
Most significant cause of UTI?
E Coli ~ 75% (Gram Negative)
Uncomplicated UTI vs. Complicated UTI
Uncomplicated
Occurs in an otherwise normal urinary tract
Involves only the bladder usually
Complicated UTI
Coexists with presence of..
Stones/obstruction
Catheters
Diabetes
Pregnancy
Recurrent infection
Antibiotics for treating UTI?
1st Line
Nitrofurantoin
Trimethoprim
Trimethoprim + sulfamethoxazole
Fosfomycin, Pivmecillinam
2nd Line
Fluoroquinolones
Beta Lactams
Nitrofurantoin MOA/Cover/Pharmicodynamics/Cautions/SEs
MOA
Inactivates bacterial ribosomal proteins
Bactericidal @ high doses, Bacteriostatic @ lower doses
Cover
Good gram ve cover, poor pseudomonas cover
Pharmacokinetics
Oral, well absorbed, metabolised in kidneys
Accumulated in urine good cover for cystitis
Cautions
Renal impairment, G6PD deficiency [hemolytic anaemia]
SEs
GI disturbance, pulmonary fibrosis, peripheral neuropathy
hypersensitivity reactions, cholestatic jaundice, hepatitis, erythema multiforme
Trimethoprim MOA/Cover/Pharmicodynamics/Cautions/SEs
MOA
Bactericidal
Binds to and Inhibits dihydrofolate reductase, thereby preventing folic acid production inhibits bacterial DNA synthesis
Cover
Good gram ve cover, NO pseudomonas cover
Pharmacokinetics
Oral, well absorbed, 20% renally excreted
Cautions
Dose adjust in renal impairment
SEs
GI disturbance, pruritus, Anti folate effects (megaloblastic anemia
Trimethoprim + Sulfamethoxazole MOA/SEs?
MOA
Bactericidal
Sulfamethoxazole binds to and inhibits dihydrofolate synthase, Trimethoprim binds to and Inhibits dihydrofolate reductase, thereby preventing folic acid production inhibits bacterial DNA synthesis
SEs
Stevens Johnson syndrome, N+V, CNS disturbance, vasculitis, transaminitis
Fluoroquinolones (e.g. ciprofloxacin, levofloxacin, moxifloxacin) MOA/Cover/Cautions/SEs?
MOA
Bactericidal
Inhibits bacterial DNA replication by binding to DNA gyrase and topoisomerase IV
Cover
Broad gram ve some gram -ve, Some pseudomonas cover
Caution
Renal dose adjustment Avoid in pregnancy
SEs
GI disturbance, headache, prolonged QT, Tendonitis (Statin), DILI drug-induced liver injury
Beta Lactams (e.g. Penicillin, cephalosporins, carbapenems) MOA/Cover/Cautions/SEs?
MOA
Bactericidal
Inhibit cell wall synthesis Target penicillin binding proteins
Cover
gram-positive, gram-negative and anaerobic organisms
SEs
N+V, Hypersensitivity, rash, cerebral irritation
