Allopurinol, Febuxostat
blocks xanthine oxidase. treats hyperuricemia
Probenecid, Sulfinpyrazone
blocks uric acid reabsorption at PCT
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
NSAIDs, Colchicine, Corticosteroids, ACTH
inflamm drugs for hyperuricemia
Enalapril
ACE inhibitor prodrug
Losartan
Angiotensin receptor blocker
acetazolamide
carbonic anhydrase inhibitor. decr HCO3- absorption, decr Na reabsorption. treats hypertension
Can also be used for Glaucoma, urine alkalinization, altitude sickness, Pulmonary edema. Depressed Respiration
acetazolamide
side effect of acetazolamide
metabolic acidosis, renal stones
Furosemide, Ethacrynic Acid, Bumetamidem
[ascending] loop diuretic
side effects of loop diuretics
Hypokalemia, Alkalosis, Hypovolemia, Ototoxicity (Ethacrynic a.), Hyperuricemia, Hyperglycemia, Sulfa sensitivity � skin rash, nephritis (Furosemide, Bumet.)
Hydrochlorothiazide and other thiazides
Blocks Na-Cl symporter at DCT. Most useful in treating hypertension.
side effect of thiazides
Hypokalemia and alkalosis, Hyperuricemia (use cautiously in gout pt), Hyperglycemia, Hypercalcemia
K sparing diuretics
amiloride, triamterene, spirolactone (used when renin-angiotensin-aldosterone is high). work at collecting tube
side effect of K sparing diuretics
hyperkalemia & acidosis
induces osmotic diuresis
mannitol
prodrug for ACE inhibitors
Enalapril, Ramipril, Quinapril, Benazepril, Fosinopril
side effect of ACE inhibitors
Cough, angioedema (Bradykinin) Vasodilation, Hyperkalemia, hypotension (1st dose phenomenon), acute renal failure
nephrotoxic antimicrobials (13)
PenicillinsCephalosporinsVancomycinSulfonamidesFluoroquinolonesTetracyclinesAminoglycosidesErythromycinAmphotericin BRifampinPentamidineAcyclovirFoscarnet
nephrotoxic antihyperlipidemics
Lovestatin and other statins. Gemfibrozil
nephrotoxic antihypertensive drugs
All sartans (ARB), all ACE inhibitors, all diuretics
nephrotoxic cancer drugs
Alkylating Agents � Renal tubule damageMethotrexate � various toxicitiesCyclosporine, Tacrolimus � renal ischemiaPhosphamides � toxic acrolein is a metabolite, hemorrhagic cystitis, hematuria.
what is the importance of MESNA?
used w/ phosphamides. binds acrolein (toxic), to avoid damages like hemorrhage, cystitis, and hematuria
nephrotoxicity of NSAIDs
Blocks COX --> decr prostaglandin --> renal vasoconstriction --> renal blood flow insufficiency & hypertension
Calculating Creatinine clearance
Male: [(140-age) x kg body wt]/ 72xserum creatinineFemale: multiple previous # by .85
1kg=
2.2 lbs
side effects of nitrates
lack of sexual desire, headache, painful urination and increased bowel movements. HYPOtension
drugs that can cause Glomerulonephritis
Cyclosporine, corticosteroids, ACEI, and ARBs
treatment of prostitis
alpha 1 blockers (the -sins), NSAIDs, antibiotics (fluoroquinolones or sulfa)
Diuretics that cause hyperuricemia
Loops � Ethacrynic Acid, Furosemide, Bumetanide Thiazides � Hydrochlorothiazide, Indapamide, Metolazone K Sparing - Amiloride
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-DopaBronchodilator TheophyllineAntifungal KetoconazoleAnti-TB Pyrazinamide, Ethambutol
Indomethacin
NSAIDs antiflamm for hyperuricemia.
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
Triamcinolone
corticosteroid given intra-articularly.
Anti inflammatory properties are specific for gouty arthritisBinds to tubulin- inhibits granulocyte motility
Colchicine
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
Colchicine
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
Colchicine
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
ACTH
Side effects: N&V , diarrhea, peripheral neuritis, bone marrow depression, hepatic toxicity, interstitial nephritis. Hypersensitivity
Allopurinol
Drug intxn: inhibits oxidation of 6-mercaptopurine and azathioprine and dosages must be decreased. Inhibits metabolism of anticoagulants and probenecid
Allopurinol
Xanthine oxidase inhibitor. Used for long-term control of urate load. Extensive liver metabolism. Newer drug in this class.
Febuxostat
No need for dose adjustment in patients with kidney problems. Most commonly nausea, joint pain and rash
Febuxostat
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
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
May extend use of limited world supply of Oseltamivir (Tamiflu)
Probenecid & sulfinpyrazone
Salicylates decrease the effectiveness of __________ because they compete for the same secretion sites
probenecid
side effects: GI distress. Give with food or milk. May aggravate or reactivate ulcers. Anemia, leucopenia, agranulocytosis, thrombocytopenia
sulfinpyrazone
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
Sx of tumor lysis syndrome
hyperuricemia, hyperkalemia, hypocalcemia, hyperphosphatemia, oliguric renal failure.
__________ is More Effective Than Allopurinol in Lowering Acute Urate
Rasburicase
PCT recovers
HCO3- & Na
Ascending loop recovers...
everything
DCT recovers
Na & Ca
collecting tubules
Aldosterone recovers Na+ -vs- K+ and H+ . Also recovers HOH via ADH
drugs that work at collecting tubules
K sparing (spirolactone, amiloride, triameterene). Spirolactone is also aldosterone antagonist. Others block Na influx.
Acetazolamide, Methazolamide
orally available carbonic anhydrase inhibitor
Dorzolamide, Brinzolamide
carbonic anhydrase inhibitor. Topical application for glaucoma
Sulfonamide with Thiazide action
Indapamide
Amiloride, Triamterene
K sparing drugs that are sodium influx blockers.
spirolactone, eplerenone
K sparing drug that acts as aldosterone antagonist
mechanism for acetazolamide use for altitude sickness
decr HCO3 reabsorption --> metabolic acidosis --> compensatory respiratory alkalosis
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
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)
Digoxin causes...
hypokalemia. Contraindicated for use w/ loop diuretics and thiazides
drugs w/ cross hypersensitivity
Sulfa antibioticsCarbonic anhydrase inhibitors (Acetazolamide, Dorzolamide)Loop diuretics (Furosemide, and others, but not Ethacrynic acid)Thiazides (Hydrochlorothizide, Indapamide)
drugs w/ usefulness in CHF, Hypertension, Nephrogenic diabetes insipidus (direct stimulus of ADH site), Reduce formation of calcium stones, benefit osteoporosis
thiazides (DCT)
hyponatremia can result from compensatory mechanism against _______
rapid diuresis (which leads to hypovolemia)
ADH action at V1 receptor
arterial constriction
ADH action at V2
collecting duct water recovery
Desmopressin induces
V2 receptor (collecting duct water recovery)
Li+ MOA
blocks V2 at collecting duct (water recovery).
Li-induced diabetes insipidus is treated w/ _______ and not _______
desmopressin. ADH
Vasodilators decrease perfusion pressure
Hydralazine, Minoxidil, Nitroprusside
Alpha blockers decrease perfusion pressure
Prazosin, phenoxybenzamine
Phosphodiesterase inhibitors, caffeine and methylxanthines cause mild diuresis via...
blocked Na+ recovery in the tubule (also caffeine blocks ADH release from posterior pituitary)
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
AT1 receptor
activated by Angiotensin II. Signalling involves Gq and PLCSmooth muscle contraction � vasoconstriction
AT1 receptor actions (all effects can be blocked by ACE inhibitors and ARBs)
VasoconstrictionAldosterone synthesis and secretion increased vasopressin (ADH) secretion Cardiac hypertrophyVascular smooth muscle cell proliferationAugmentation of peripheral SANS activityRenal renin inhibition
aldosterone actions
Na+ reabsorption at DCT and cortical collecting tubuleHypokalemia, Alkalosis, hypertension, Increased plasma volume
ACE is a...
Peptidyl Dipeptidase (PDP), also known as kininase II, the enzyme that converts bradykinin, a powerful vasodilator, to inactive fragments
actions of bradykinin
Vasodilator actions at Bradykinin II (B2) receptor; causes NO release. Also PGE2, PGI2Proinflammatory � Due to B1 receptor; mediates pain, swelling, & angioedema. Bronchoconstrictor. Gq, PLC
side effect of ACE inhibitors
Angiotensin II absence: Hypotension (1st-Dose Phenomenon). Acute renal failure.Aldosterone absence: HyperkalemiaBradykinin presence: Cough (Captopril Cough), bronchial hyperresponsiveness, angioedema
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
first direct renin inhibitor
Aliskiren
Binds renin. Renin, a peptidase, is unable to convert Angiotensinogen to Angiotensin I. Therefore, no A II
Aliskiren
Aliskiren Usefulness
Diuretics, ACE Inhibitors and ARBs reduce BP, but incr renin release. Adding a direct renin blocker may suppress renin increase
combo used in first line defense for hypertension
Aliskiren and Amlodipine (Dihydropyridine type calcium channel blocker)
Aliskiren toxicity
Same pregnancy caution as ACEIs and ARBs. Mild diarrhea. Allergy. Also with Hydrochlorothiazide: cough, dizzinessWith Valsartan or Amlodipine: dizziness
effects of bradykinin
Vasodilation. Bronchoconstriction. Proinflamm (pain, swelling, angioedema)
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
direct acting ACE inhibitors
Captopril & Lisinopril
ACE inhibitor prodrugs
Enalapril, Ramipril, Quinapril, Benazepril, Fosinopril, Moexipril, Perindopril
active ACE inhibitor metabolites given directly
Enalaprilat, Ramiprilat
ACE inhibitors side effects
Angiotensin absence: Hypotension (First-Dose Phenomenon). Acute RF. Aldosterone absence: HyperkalemiaBradykinin presence: Cough (Captopril Cough), respiratory irritability, angioedema
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
angioedema induced by ACE inhibitors is difficult/dangerous due to...
airway restriction
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
ACE inhibitor that is first, least potent, shortest t1/2 (2 hrs, needs to be given 3-4x/day), most toxic
Captopril
Longest half life (12 hrs, given once a day) ACE inhibitor
Lisinopril
Enalaprilat half life
11 hours. Active metabolite of ACE inhibitor. Can be used directly.
Block the AT-1 receptor at arterioles, adrenal cortex and SANS
Valsartan (DIOVAN), Losartan (COZAAR) Candesartan(ATACAND) superior blood pressure lowering Eprosartan, Telmisartan, Olmesartan
side effects/contraindications of ARBs
Angiotensin absence: Hypotension (First-Dose Phenomenon). Acute RF.Aldosterone absence: HyperkalemiaK 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
Drug induced nephrotoxicity
AminoglycosidesAmphotericin BACEIs and ARBsIntratubular ObstructionAllergic NephritisDiuretics and MannitolContrast MediaASA and NSAIDs
acute tubular necrosis commonly caused by
aminoglycosides, contrast media, cisplatin, amphotericin B, foscarnet, and mannitol
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
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
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
clinical presentation of aminoglycoside toxicity
Gradual rise in Serum Creatinine and decrease in Cr CL after 6-10 days of therapy
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
Patients at risk of developing nephrotoxicity from these agents are hospitalized pts w/ CHF, Chronic Kidney Disease & diabetic nephropathy
ARBs and ACE inhibitors
intratubular obstructions are caused by
HMG-CoA Reductase Inhibitors (Statins), Acyclovir, Triamterene, Foscarnet, protease inhibitor (Indinavir)
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)
mechanism of intratubular obstruction w/ Acyclovir
relatively insoluble at physiologic urine pH and is associated with intratubular precipitation in dehydrated oliguric patients
Mechanism of intratubular obstruction w/ Triamterene
may precipitate in renal tubules and cause kidney injury
intratubular obstruction in Foscarnet
complexes with Ca to form foscarnet-Ca crystals in renal glomeruli causing glomerulonephritis and tubular necrosis
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
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
Causative agents of acute allergic interstitial nephritis
Acyclovir, AG, Ampho B, ?-lactams, Erythromycin, Rifampin, Sulfonamides, Tetracyclines, Vancomycon, Trimethoprim-sulfamethoxazole, Acetazolaminde, Amiloride, Chlorthalidone, Loop diuretics, Triamterene, Thiazide diuretics
Nephrotoxicity of furosemide
hypokalemia, alkalosis, high urate, hyponatremia, azotemia (high BUN, creatinine)
nephrotoxicity of hydrochlorthiazide
hypokalemia, alkalosis, high urate, hyponatremia, hypercalcemia
nephrotoxicity of Triamterene
Hyperkalemia, acidosis (less potent and more toxic than amiloride), triamterene precipitation in nephron
contrast media nephrotoxicity
renal ischemia and direct toxic effects on renal tubular cells
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
Candesartan
superior ARBs in BP lowering