Drugs Flashcards
amphotercin B
nephrotoxic
pores in cell membrane and renal vasoconstriction
liposomal less toxic
Tx: volume expansion
VEGF inhibitors
nephrotoxic
interrupts fenestrated glomerular epithelium
results in HTN, proteinuria, thrombotic microangiopathy
EGFR inhibitors
nephrotoxic
hypomagnesemia and may inhibit P-gp
lithium
nephrotoxic
enters cell through ENaC
inhibits aquaporin 2 causing NDI
calcineurin inhibitors
nephrotoxic: difficult to tell in drug effect or transplant rejection
cisplatin
nephrotoxic and ototoxic
taken up by Ctr1 (copper) and OCT2
promotes cell death
calcium gluconate
IV: ~ 30 min
stabilizes membrane potential of myocardium
Tx: hyperkalemia
insulin
stimulates Na-H exchanger leading to a higher Na concentration to stimulate Na-K ATPase to take up K into cell
Tx: hyperkalemia
albuterol
Inhalation: B2 agonist
activates (phosphorylates) Na-K ATPase to take up K into cell
Tx: hyperkalemia
acetazolamide
PCT
carbonic anhydrase inhibitor: inhibits NaHCO3 reabsorption
effect: hyperchloremic systemic acidosis, alkaline urine, chloride reabsorption
Tx: glaucoma, cystinuria, seizure, mountain sickness
furosemide (Lasix)
loop diuretic
dilates veins: decrease LV filling pressure
SULFA drug
AE: ototoxicity, increase BUN, hyperglycemia, hyperuricemia, fluid and electrolyte imbalance, sialadentitis (inflammation of salivary glands)
DI: Lithium, indomethacin, probenecid, warfarin
secreted by organic acid transporter
bemtanide
loop diuretic
more POTENT than furosemide
useful with warfarin
torsemide
loop diuretic
vasodilator: lowers BP
longer T1/2
loop diuretics
block Na/K/2Cl transporter in TALH: high delivery of Na to distal nephron causing Na and H20 excretion
increase renal PG: increase RBF
stimulate renin release and maintain GFR
increase excretion: K, Ca, Mg, H (mild metabolic alkalosis)
Tx: edema, IV for acute pulmonary edema, hypercalcemia, protect against renal failure, washout toxins, HTN, SIADH
MOST POTENT diuretic
give NSAID to prevent resistance
thiazide diuretics
inhibit Na/Cl cotransporter in DCT: moderate Na/water excretion
Ca/Na counter transporter is more active: decrease Ca urinary excretion
increase Na to CD: increase K secretion
increase Mg excretion
Tx: edema, HTN, diabetes insipidus, hypercalciuria, osteoporosis, nephrogenic diabetes insipidus
AE: hypokalemia, hypomagnesia, hyperuricemia, hypercalcemia, hyperglycemia, lipid disorders, reduced GFR
GFR needs to be greater than 60 mL/min
K sparing diuretics
inhibits Na reabsorption and K secretion cortical collecting duct decrease Na to CD: decrease K secretion COMBINE with thiazides AE: hyperkalemia, megaloblastic anemia in patients with cirrhosis
spirinolactone
aldosterone antagonist
AE: gynecomastia, hirsutism, uterine bleeding
amiloride
K sparing: ENac inhibitor
triamterene
K sparing: ENac inhibitor
kayexelate
K resin: removal of K in GI
Tx: hyperkalemia
eplernone
aldosterone antagonist
ethacrynic acid
loop diuretic
mannitol
osmotic diuretic
hydrochlorothiazide
thiazide
metolazone
POTENT thiazide
GFR greater than 30 needed
chlorthalidone
thiazide
long T1/2
quinothazone
POTENT thiazide
arginine vasopressin
ADH
desmopressin
ADH like drug
Tx: central diabetes insipidous, bleeding disorders, nocturnal enurisis
conivaptan
IV V2R antagonism less selective for V2R than tolvaptan Tx: hyponatremia CYP3A4 metabolism AE: numerous, infusion site rxn
tolvaptan
V2R antagonism
CYP3 metabolism
AE: hyplerglycemia, GI, clotting
osmotic diuretic
inhibit Na/H2O reabsorption in PCT: decrease medullary tonicity impair ability of thin segments of LOH
increase excretion: urine, Na, K, Cl excretion
initially increase BP
Tx: dialysis disequilibrium syndrome, reduce intracranial and intraocular pressure
AE: volume overload
CI: cardiac failure
aldosterone antagonist
late DT and CD
reduce ENac: increase Na excretion and reduce K
Tx: diuretic with thiazide, CHF, cirrhosis
ADH like drug
V2R agonist
increase water permeability in CD
Tx: ADH-sensitive diabetes insidious, nephrogenic diabetes insipidous
vaptans
VR2 antagonist
Tx: SIADH
demeclocycline
V2R antagonist
Tx: SIADH
terlipressin
IV; restricted use
V1R agonist: smooth muscle contration
Tx: ileus, reduce bleeding in esophageal varices and acute hemorrhagic gastritis
renal cancer Tx in children
majority curable
classic cytotoxic agents in combination
renal cancer Tx in adults
targeted drugs
TKI first, then mTOR inhibitor
standard Wilm’s tumor or clear cell sarcoma in childrenTx
nephrectomy
radiation
vincristine, dactinomycin +/- doxorubicin
OR
vincristine, doxorubicin, cyclophosphamide, etoposide
recurrent Wilm’s tumor Tx
alternate
- vincristine, doxorubicin, cyclophosphamide
- etoposide, cyclophosphamide
recurrent clear cell sarcoma Tx in children
cyclophosphamide and carboplatin if not used initially
brain involvement: ICE: ifosfamide, carboplatin, etoposide
surgical resection and/or radiation
Tx for rhabdoid and neuroepithelial tumor in children
none
carboplatin
intrastrand DNA links
cyclophosphamide
inter and intra-strand links
AE: hemorrhagic cystitis
doxorubicin
intercalate, Topo-II inhibition, radicals
AE: cardiotoxic
dactinomycin
intercalate, DNA dependent RNA synthesis inhibition; single strand breaks: free radical, topo-II
AE: hepatic dysfunction, extravasional necrosis
etoposide
topo-II inhibitor
AE: hematologic, BP instability
ifosfamide
inter and intrastrand links
AE: hemorrhagic cystitis
vincristine
blocks tubulin polymerization
AE: peripheral neuropathy: “stocking glove”
MESNA
give with cyclophosphamide
Tx hemorrhagic cystitis
VEGF inhibitors
clear cell renal carcinoma bevacizumab axitinib sunitinib sorafenib pazopanib: EGFR inhibitor all TKI: PDGFR inhibitor AE: HTN
mTOR inhibitors
bind FKBP12: inhibit immune, cell cycle, angiogenesis; promote apoptosis
Tx: clear cell renal carcinoma
CYP3A4 substrate
AE: maculopapular rash, mucosistis, anemia, fatigue, pulmonary infiltrates, blood dyscrasia
-nib
oral
tyrosine kinase inhibitors
conserved ATP binding domain
resistance: ATP binding domain, and up regulation of mTOR2
metabolized by CYPs: CYP3A4
AE: hepatic, proteinuria
CV: HTN, QT, thromosis, hemorrhage, blood dyscrasia
endocrine: thyroid, adrenal, glucose need to monitor
aldesleukin (IL-2)
T cell GF
activates JAK/STAT
AE: capillary leak syndrome (hypotension, tachycardia, hematoligic toxicity, pulmonary edema, renal toxicity); potential for sepsis
Tx: clear cell renal carcinoma
IFN-alpha 2b
SC
activates JAK/STAT
AE: neuropsychiatric, infectious disorders, autoimmune, ischemic
less common AE: xerostomia, dysguesia, diaphoresis, cough, dizziness
Tx: clear cell renal carcinoma
temsirolimus
mTOR inhibitor
IV weekly
metabolize to sirolimus
everolimus
mTOR inhibitor
daily oral drug
TKI with Steven Johnson syndrome
hypersensitivity
sorafenib
suntinib
bevacizumab
IV infusion
VEGF inhibitor Ab
AE: thrombosis, HTN, CHF, proteinuria, blood dyscrasia, hemorrhage, GI perforation
WOUND HEALING complications
renal cancer drugs that cause renal damage
carboplatin
ifosfomide
IL-2
targeted Tx not including mTOR inhibitors
Drugs that induce hyperkalemia
- block Na channel in distal nephron: K sparing diuretics, trimethoprim, pentamidine
- block aldosterone production: ACEI/ARBs, NSAIDs, Heparin, tacrolimus
- block aldosterone receptors (spironolactone, eplerenone)
- block Na/K ATPase in distal nephron: cyclosporine
- extrarenal: digoxin, B2 blockers, somatostatin (inhibits insulin)
- K release from injured: tumor lysis syndrome, rhabdomyolysis, depolarizing paralytic agents
drugs that induce hypokalemia
DIURETICS, ANTI-INFECTIVE agents
- increased excretion: diuretics, foscarnet, laxatives
- increased uptake: B2 agonist, dextrose, insulin, levothyroxine, theophylline
- misc: amphotericin B, caspofungin, corticosteroids, itrconazole
- 2 to hypomagnesemia: aminoglycosides, amphotericin B, cisplatin, cyclosporine, loop diuretics
hypokalemia with low Mg
occludes ROMK channel
low Mg: K leaves cell and is excreted
MUST CORRECT to Tx hypokalemia
NSAIDs (kidney injury)
AIN
inhibit PG: maintain adequate renal perfusion
chronic use: hyponatremia, hyperkalemia and metabolic acidosis, HTN
ACEI/ARB (kidney injury)
inhibit renal auto-regulation of GFR
bilateral renal artery stenosis, volume depletion
hyperkalemia, acute renal injury
aminoglycosides (kidney injury)
ATN
proximal tubule accumulation resulting in cell death
decrease K, Mg, Ca
accumulation in DT and CD can impair concentrating abilities
Tx: expand volume, limit dose
SMX-TMP (kidney injury)
ATN, AIN
inhibits ENac; increased Cr without GFR effect
Tx: hydrate and alkalinize urine
amphotericin B (kidney injury)
pores in cell membrane
renal tubular acidosis
renal vasoconstriction
tx: fluids
VEGF inhibitors (kidney injury)
VEGF maintenance of fenestrated glomerular epithelium
HTN, proteinuria, thrombotic microangiopathy
EGFR Ab (kidney injury)
cetuximab
hypomagnesemia
inhibit P-gp
lithium (kidney injury)
ENac
dysregulation of AQP-2 and develop NDI
calcineurin inhibitors (kidney injury)
cyclosporine, tacrolimus
interstitial fibrosis
inhibit transfer of NF-AT to nucleus
cisplatin (kidney injury)
ATN
promote cell death
TNF-alpha production in tubular cells
acute interstitial nephritis (AIN)
onset: 10-14 d Sx: fever, rash, eosinophilia UA: WBC casts, hematuria, proteinuria, eosinophiluria Tx: stop drug, corticosteroids Dx: biopsy
acute tubular necrosis (ATN)
onset: 7-10 d uremic Sx UA: granular casts, renal epithelial cast, oliguria Dx: Hx, exam, labs initiation, maintenance, recovery proximal straight tubule, TALH hypoprefusion + casts and debris collect in tubule; ATP depleted Tx: discontinue contrast
