Pharm renal

  1. Allopurinol, Febuxostat
    blocks xanthine oxidase. treats hyperuricemia
  2. Probenecid, Sulfinpyrazone
    blocks uric acid reabsorption at PCT
  3. Rasburicase
    uric oxidase. oxidizes uric acid --> decr levels of urate. Dramatic decrease in uric acid following first dose. Usually given 1 or 2 times per 24 hrs, 30 min iv infusion
  4. NSAIDs, Colchicine, Corticosteroids, ACTH
    inflamm drugs for hyperuricemia
  5. Enalapril
    ACE inhibitor prodrug
  6. Losartan
    Angiotensin receptor blocker
  7. acetazolamide
    carbonic anhydrase inhibitor. decr HCO3- absorption, decr Na reabsorption. treats hypertension
  8. Can also be used for Glaucoma, urine alkalinization, altitude sickness, Pulmonary edema. Depressed Respiration
  9. side effect of acetazolamide
    metabolic acidosis, renal stones
  10. Furosemide, Ethacrynic Acid, Bumetamidem
    [ascending] loop diuretic
  11. side effects of loop diuretics
    Hypokalemia, Alkalosis, Hypovolemia, Ototoxicity (Ethacrynic a.), Hyperuricemia, Hyperglycemia, Sulfa sensitivity – skin rash, nephritis (Furosemide, Bumet.)
  12. Hydrochlorothiazide and other thiazides
    Blocks Na-Cl symporter at DCT. Most useful in treating hypertension.
  13. side effect of thiazides
    Hypokalemia and alkalosis, Hyperuricemia (use cautiously in gout pt), Hyperglycemia, Hypercalcemia
  14. K sparing diuretics
    amiloride, triamterene, spirolactone (used when renin-angiotensin-aldosterone is high). work at collecting tube
  15. side effect of K sparing diuretics
    hyperkalemia & acidosis
  16. induces osmotic diuresis
  17. prodrug for ACE inhibitors
    Enalapril, Ramipril, Quinapril, Benazepril, Fosinopril
  18. side effect of ACE inhibitors
    Cough, angioedema (Bradykinin) Vasodilation, Hyperkalemia, hypotension (1st dose phenomenon), acute renal failure
  19. nephrotoxic antimicrobials (13)
    • Penicillins
    • Cephalosporins
    • Vancomycin
    • Sulfonamides
    • Fluoroquinolones
    • Tetracyclines
    • Aminoglycosides
    • Erythromycin
    • Amphotericin B
    • Rifampin
    • Pentamidine
    • Acyclovir
    • Foscarnet
  20. nephrotoxic antihyperlipidemics
    Lovestatin and other statins. Gemfibrozil
  21. nephrotoxic antihypertensive drugs
    All sartans (ARB), all ACE inhibitors, all diuretics
  22. nephrotoxic cancer drugs
    • Alkylating Agents – Renal tubule damage
    • Methotrexate – various toxicities
    • Cyclosporine, Tacrolimus – renal ischemia
    • Phosphamides – toxic acrolein is a metabolite, hemorrhagic cystitis, hematuria.
  23. what is the importance of MESNA?
    used w/ phosphamides. binds acrolein (toxic), to avoid damages like hemorrhage, cystitis, and hematuria
  24. nephrotoxicity of NSAIDs
    Blocks COX --> decr prostaglandin --> renal vasoconstriction --> renal blood flow insufficiency & hypertension
  25. Calculating Creatinine clearance
    • Male: [(140-age) x kg body wt]/ 72xserum creatinine
    • Female: multiple previous # by .85
  26. 1kg=
    2.2 lbs
  27. side effects of nitrates
    lack of sexual desire, headache, painful urination and increased bowel movements. HYPOtension
  28. drugs that can cause Glomerulonephritis
    Cyclosporine, corticosteroids, ACEI, and ARBs
  29. treatment of prostitis
    alpha 1 blockers (the -sins), NSAIDs, antibiotics (fluoroquinolones or sulfa)
  30. Diuretics that cause hyperuricemia
    • Loops – Ethacrynic Acid, Furosemide, Bumetanide
    • Thiazides – Hydrochlorothiazide, Indapamide, Metolazone
    • K Sparing - Amiloride
  31. Non-diuretic factors that cause hyperuricemia
    • Alcohol oxidation upsets NAD/NADH to favor production of lactate, which competes with uric acid for excretion sites.
    • Anticancer alkylating agents: Cisplatin, Vincristine and cyclophosphamide.
    • Immunosuppressant Cyclosporine.
    • Antiparkinson’s: L-Dopa
    • Bronchodilator Theophylline
    • Antifungal Ketoconazole
    • Anti-TB Pyrazinamide, Ethambutol
  32. Indomethacin
    NSAIDs antiflamm for hyperuricemia.
  33. The NSAID not used for treating hyperuricemia
    Never aspirin due to renal effects. When metabolised, aspirin causes decreased urate excretion via partial competitive block of active organic acid secretion by salicylic acid, a weak organic acid, like uric acid
  34. Triamcinolone
    corticosteroid given intra-articularly.
  35. Anti inflammatory properties are specific for gouty arthritisBinds to tubulin- inhibits granulocyte motility
  36. Drug of choice for relief of inflamm in acute phase of gouty arthritis. Prophylactic doses may prevent/reduce intensity of acute attacks.Should be taken w/in 1st 12 hrs, relief w/in 48 hrs
  37. Side effects of diarrhea, N&V, ab pain. Alopecia, bone marrow depression, peripheral neuritis. Hemorrhagic gastroenteritis, vascular damage, nephrotoxicity and ascending paralysis of the CNS. DIC
  38. Very effective in rapid resolution of inflammatory symptoms, one-half day in many cases.An alternative to NSAIDS and Colchicine in patients with GI or renal toxicity
  39. Side effects: N&V , diarrhea, peripheral neuritis, bone marrow depression, hepatic toxicity, interstitial nephritis. Hypersensitivity
  40. Drug intxn: inhibits oxidation of 6-mercaptopurine and azathioprine and dosages must be decreased. Inhibits metabolism of anticoagulants and probenecid
  41. Xanthine oxidase inhibitor. Used for long-term control of urate load. Extensive liver metabolism. Newer drug in this class.
  42. No need for dose adjustment in patients with kidney problems. Most commonly nausea, joint pain and rash
  43. Reduction of Urate Pool. Used to retain certain antibiotics like penicillin cephalosporin, fluoroquinolones which are excreted via the proximal tubule and benefit from extended duration
    Probenecid and sulfinpyrazone
  44. Side effects: With incr uric acid excretion there is incr likelihood of renal stone precipitation Must maintain high urinary output at alkaline pH
    Probenecid & sulfinpyrazone
  45. May extend use of limited world supply of Oseltamivir (Tamiflu)
    Probenecid & sulfinpyrazone
  46. Salicylates decrease the effectiveness of __________ because they compete for the same secretion sites
  47. side effects: GI distress. Give with food or milk. May aggravate or reactivate ulcers. Anemia, leucopenia, agranulocytosis, thrombocytopenia
  48. Cancers likely to produce tumor lysis syndrome
    Burkitt's lymphoma, lymphoblastic lymphoma, T-cell acute lymphoblastic leukemia (ALL), and acute myeloid leukemia (AML) – Rapid proliferation, sensitive to chemotherapy.Also, bulky solid tumors, including germ cell, breast, and small cell lung tumors, and neuroblastoma
  49. Sx of tumor lysis syndrome
    hyperuricemia, hyperkalemia, hypocalcemia, hyperphosphatemia, oliguric renal failure.
  50. __________ is More Effective Than Allopurinol in Lowering Acute Urate
  51. PCT recovers
    HCO3- & Na
  52. Ascending loop recovers...
  53. DCT recovers
    Na & Ca
  54. collecting tubules
    Aldosterone recovers Na+ -vs- K+ and H+ . Also recovers HOH via ADH
  55. drugs that work at collecting tubules
    K sparing (spirolactone, amiloride, triameterene). Spirolactone is also aldosterone antagonist. Others block Na influx.
  56. Acetazolamide, Methazolamide
    orally available carbonic anhydrase inhibitor
  57. Dorzolamide, Brinzolamide
    carbonic anhydrase inhibitor. Topical application for glaucoma
  58. Sulfonamide with Thiazide action
  59. Amiloride, Triamterene
    K sparing drugs that are sodium influx blockers.
  60. spirolactone, eplerenone
    K sparing drug that acts as aldosterone antagonist
  61. mechanism for acetazolamide use for altitude sickness
    decr HCO3 reabsorption --> metabolic acidosis --> compensatory respiratory alkalosis
  62. Inhibit Na+, K+, Cl- co-transporter. This site is responsible for recovering 30% of filtered Na+.Also lose Ca++, Mg+, plus HOH.
    Ascending loop. Furosemide, bumetanide, torsemide are sulfonamides. Ethacrynic acid
  63. Side effects: Hypokalemia and Alkalosis. Hypovolemia, thirst, hyponatremia. Hyperuricemia. Hyperglycemia Ototoxicity (_________). hypersensitivity – (_________)
    Loop diuretics. Ototoxicity w/ ethacrynic acid. Hypersensivity w/ sulfa based drugs (furosemide, bumetamide, torsemide)
  64. Digoxin causes...
    hypokalemia. Contraindicated for use w/ loop diuretics and thiazides
  65. drugs w/ cross hypersensitivity
    • Sulfa antibiotics
    • Carbonic anhydrase inhibitors (Acetazolamide, Dorzolamide)
    • Loop diuretics (Furosemide, and others, but not Ethacrynic acid)
    • Thiazides (Hydrochlorothizide, Indapamide)
  66. drugs w/ usefulness in CHF, Hypertension, Nephrogenic diabetes insipidus (direct stimulus of ADH site), Reduce formation of calcium stones, benefit osteoporosis
    thiazides (DCT)
  67. hyponatremia can result from compensatory mechanism against _______
    rapid diuresis (which leads to hypovolemia)
  68. ADH action at V1 receptor
    arterial constriction
  69. ADH action at V2
    collecting duct water recovery
  70. Desmopressin induces
    V2 receptor (collecting duct water recovery)
  71. Li+ MOA
    blocks V2 at collecting duct (water recovery).
  72. Li-induced diabetes insipidus is treated w/ _______ and not _______
    desmopressin. ADH
  73. Vasodilators decrease perfusion pressure
    Hydralazine, Minoxidil, Nitroprusside
  74. Alpha blockers decrease perfusion pressure
    Prazosin, phenoxybenzamine
  75. Phosphodiesterase inhibitors, caffeine and methylxanthines cause mild diuresis via...
    blocked Na+ recovery in the tubule (also caffeine blocks ADH release from posterior pituitary)
  76. ACE inhibitors and ARBs cause high renin due to...
    Angiotensin II exerts a negative feedback against further release of renin.It acts directly at juxtaglomerular cells. ACE inhibitors and ARBs interrupt this feedback
  77. AT1 receptor
    activated by Angiotensin II. Signalling involves Gq and PLCSmooth muscle contraction – vasoconstriction
  78. AT1 receptor actions (all effects can be blocked by ACE inhibitors and ARBs)
    • Vasoconstriction
    • Aldosterone synthesis and secretion
    • increased vasopressin (ADH) secretion
    • Cardiac hypertrophy
    • Vascular smooth muscle cell proliferation
    • Augmentation of peripheral SANS activity
    • Renal renin inhibition
  79. aldosterone actions
    • Na+ reabsorption at DCT and cortical collecting tubule
    • Hypokalemia, Alkalosis, hypertension, Increased plasma volume
  80. ACE is a...
    Peptidyl Dipeptidase (PDP), also known as kininase II, the enzyme that converts bradykinin, a powerful vasodilator, to inactive fragments
  81. actions of bradykinin
    • Vasodilator actions at Bradykinin II (B2) receptor; causes NO release. Also PGE2, PGI2
    • Proinflammatory – Due to B1 receptor; mediates pain, swelling, & angioedema.
    • Bronchoconstrictor. Gq, PLC
  82. side effect of ACE inhibitors
    • Angiotensin II absence: Hypotension (1st-Dose Phenomenon). Acute renal failure.
    • Aldosterone absence: Hyperkalemia
    • Bradykinin presence: Cough (Captopril Cough), bronchial hyperresponsiveness, angioedema
  83. indirect decrease in renin
    • Clonidine, CNS-active Alpha-2 agonist, decreases SANS, --> decr Beta-1 agonist action of NE at the JGA to release renin.
    • Beta-blockers antagonize NE at the B-1 receptor of the JGA
  84. first direct renin inhibitor
  85. Binds renin. Renin, a peptidase, is unable to convert Angiotensinogen to Angiotensin I. Therefore, no A II
  86. Aliskiren Usefulness
    Diuretics, ACE Inhibitors and ARBs reduce BP, but incr renin release. Adding a direct renin blocker may suppress renin increase
  87. combo used in first line defense for hypertension
    Aliskiren and Amlodipine (Dihydropyridine type calcium channel blocker)
  88. Aliskiren toxicity
    • Same pregnancy caution as ACEIs and ARBs. Mild diarrhea. Allergy.
    • Also with Hydrochlorothiazide: cough, dizziness
    • With Valsartan or Amlodipine: dizziness
  89. effects of bradykinin
    Vasodilation. Bronchoconstriction. Proinflamm (pain, swelling, angioedema)
  90. Benefits of ACE inhibitors
    Antihypertensive. Chronic renal failure pts experience improved renal hemodynamics. Esp important in diabetic pts. Post-MI pts benefit from fewer arrhythmias, due to less SANS activity driven by Angiotensin II
  91. direct acting ACE inhibitors
    Captopril & Lisinopril
  92. ACE inhibitor prodrugs
    Enalapril, Ramipril, Quinapril, Benazepril, Fosinopril, Moexipril, Perindopril
  93. active ACE inhibitor metabolites given directly
    Enalaprilat, Ramiprilat
  94. ACE inhibitors side effects
    • Angiotensin absence: Hypotension (First-Dose Phenomenon). Acute RF. Aldosterone absence: Hyperkalemia
    • Bradykinin presence: Cough (Captopril Cough), respiratory irritability, angioedema
  95. 1st dose hypotension in ACE inhibitors can be overcome by...
    using partial doses and incrementally, one to two weeks, increasing the dose to full maintenance dose
  96. angioedema induced by ACE inhibitors is difficult/dangerous due to...
    airway restriction
  97. ACE inhibitor contraindications
    • K Supplements and K Sparing Diuretics potentiate Hyperkalemia.
    • NSAIDs and Aspirin counteract anti-BP benefits of ACEI (Bradykinin needs PGE)
    • 2nd, 3rd term pregnancy–fatal fetal malformation, hypotension, nephrotox
  98. ACE inhibitor that is first, least potent, shortest t1/2 (2 hrs, needs to be given 3-4x/day), most toxic
  99. Longest half life (12 hrs, given once a day) ACE inhibitor
  100. Enalaprilat half life
    11 hours. Active metabolite of ACE inhibitor. Can be used directly.
  101. Block the AT-1 receptor at arterioles, adrenal cortex and SANS
    • Valsartan (DIOVAN), Losartan (COZAAR)
    • Candesartan(ATACAND) superior blood pressure lowering
    • Eprosartan, Telmisartan, Olmesartan
  102. side effects/contraindications of ARBs
    • Angiotensin absence: Hypotension (First-Dose Phenomenon). Acute RF.
    • Aldosterone absence: Hyperkalemia
    • K Supplements and K Sparing Diuretics potentiate Hyperkalemia. NSAIDs and Aspirin counteract anti-BP benefits of ACEI (Bradykinin needs PGE)
    • 2nd/3rd term pregnancy–fatal fetal malform, hypotension, nephrotox
  103. Drug induced nephrotoxicity
    • Aminoglycosides
    • Amphotericin B
    • ACEIs and ARBs
    • Intratubular Obstruction
    • Allergic Nephritis
    • Diuretics and Mannitol
    • Contrast Media
    • ASA and NSAIDs
  104. acute tubular necrosis commonly caused by
    aminoglycosides, contrast media, cisplatin, amphotericin B, foscarnet, and mannitol
  105. hemodynamically mediated kidney injury, which results from a decrease in GC hydrostatic pressure, is caused by...
    ACE inhibitors, ARBs and NSAIDs. Will result in decr urine output
  106. Signs of PCT injury
    metabolic acidosis with bicarbonaturia; and reductions in serum phosphate, uric acid, potassium, and magnesium as a result of increased urinary losses
  107. signs of DCT injury
    polyuria from failure to maximally concentrate urine, metabolic acidosis from impaired urinary acidification, and hyperkalemia from impaired sodium recovery and potassium excretion
  108. clinical presentation of aminoglycoside toxicity
    Gradual rise in Serum Creatinine and decrease in Cr CL after 6-10 days of therapy
  109. clinical presentation of Amphotericin B Toxicity
    K, Na and Mg wasting. Impaired urine concentrating ability. Distal tubular acidosis due to leak of H+ out of tubular lumen. Decrease in RBF and GFR leading to rise in SCr and BUN
  110. Patients at risk of developing nephrotoxicity from these agents are hospitalized pts w/ CHF, Chronic Kidney Disease & diabetic nephropathy
    ARBs and ACE inhibitors
  111. intratubular obstructions are caused by
    HMG-CoA Reductase Inhibitors (Statins), Acyclovir, Triamterene, Foscarnet, protease inhibitor (Indinavir)
  112. mechanism of statin intratubular obstruction
    Rhabdomyolosis – intratubular precipitation of myoglobin can cause acute, severe kidney injury. Risk is increased if co-administered with gemfibrozil, niacin, or inhibitors of the CYP3A4 metabolic pathway (e.g., erythromycin and itraconazole)
  113. mechanism of intratubular obstruction w/ Acyclovir
    relatively insoluble at physiologic urine pH and is associated with intratubular precipitation in dehydrated oliguric patients
  114. Mechanism of intratubular obstruction w/ Triamterene
    may precipitate in renal tubules and cause kidney injury
  115. intratubular obstruction in Foscarnet
    complexes with Ca to form foscarnet-Ca crystals in renal glomeruli causing glomerulonephritis and tubular necrosis
  116. Intratubular obstruction in protease inhibitor Indinavir
    causes crystalluria, crystal nephropathy, dysuria, urinary frequency, back and flank pain, or nephrolithiasis in approximately 8% of treated patients
  117. Clinical signs of acute allergic interstitial nephritis
    5-14 days after drug therapy: fever, maculopapular rash, eosinophilia, sterile pyuria and hematuria, low-level proteinuria, and oliguria. hyperkalemia, hyponatremia, polyuria, hypouricemia, low HCO3, metabolic acidosis
  118. Causative agents of acute allergic interstitial nephritis
    Acyclovir, AG, Ampho B, β-lactams, Erythromycin, Rifampin, Sulfonamides, Tetracyclines, Vancomycon, Trimethoprim-sulfamethoxazole, Acetazolaminde, Amiloride, Chlorthalidone, Loop diuretics, Triamterene, Thiazide diuretics
  119. Nephrotoxicity of furosemide
    hypokalemia, alkalosis, high urate, hyponatremia, azotemia (high BUN, creatinine)
  120. nephrotoxicity of hydrochlorthiazide
    hypokalemia, alkalosis, high urate, hyponatremia, hypercalcemia
  121. nephrotoxicity of Triamterene
    Hyperkalemia, acidosis (less potent and more toxic than amiloride), triamterene precipitation in nephron
  122. contrast media nephrotoxicity
    renal ischemia and direct toxic effects on renal tubular cells
  123. Prevent Contrast Media Nephrotoxicity
    Identify pts at risk. 4 hrs before contrast medium injection & for at least 12 hrs afterward, inject small dose of contrast medium & maintain continuous saline infusion. Desensitization & hydration. Effective in reducing incidence of CMN
  124. Candesartan
    superior ARBs in BP lowering
Card Set
Pharm renal
Pharm renal