Renal and Endocrine Flashcards
Vaptans
Collecting Duct Diuretics V2 antagonists Drugs: - conivaptan - tolvaptan - satavaptan Use: - resolves hyponatremia
Desmopressin
V1 and V2 agonist ADH analog - DDAVP Actions: - vasoconstriction - releases vWF from endothelial cells - helps pts reabsorb water Indications: - diabetes insipidus - sleep enuresis - hemophilia and vWF disease
Acetazolamide
Carbonic Anhydrase inhibitor - others: dorzolamide, zonisamide Weak diuretic - limited by GT balance activation Bicarbonaturia - makes you acidic, metabolic acidosis Not used for volume overload Indications: - glaucoma - epilepsy - altitude sickness - metabolic alkalosis - hyperK/hypoK periodic paralysis Side effects: - drowsiness - dizziness - headache - fatigue
Mannitol
Osmotic diuretic
- induce convective movement of water into lumen (more than solutes)
- huge aquaresis
Not effective for IV contrast nephropathy
Indications:
- decreases intracranial pressure
- induce forced diuresis - rhabdomyolysis
- free radical scavenger
Side effects:
- initial ECF volume expansion before water loss
Furosemide
Loop diuretic - blocks Na K 2Cl transporter in TALH - weak carbonic anhydrase inhibitor - vasodilation Large volume natriuresis Isosthenuria Minimum amount needed to achieve effect, with a maximal level of effectiveness 6 hours Variable oral bioavailability Sulfonamide moiety - anaphylaxis can occur Indications: - edema - 1st line for CHF - edema, other - acute pulm edema (immediately vasodilates), cirrhosis, nephrotic syndrome - HTN - hypercalcemia - induces Ca loss - forced diuresis Side effects: - excess volume depletion - hypoK - leading to cardiac arrhythmias - hypoCa - hypoMg - ototoxicity Other use: - tumor lysis syndrome with normosaline to increase loss of uric acid - accelerate Na turnover, give with normosaline
Loop diuretics
Furosemide Torsemide - sulfa - high bioavailable Bumetanide - sulfa - high bioavailable Ethacrynic acid - no sulfa - high bioavailable
HCTZ
Thiazide diuretics - block NCC in DCT - moderate volume natriuresis Cannot produce maximally dilute urine - can't lose electrolyte free water (no hypotonic urine) Ineffective if GFR less than 40 Direct vasodilator Usual dose not over 25 Contraindicated if hyponatremia Uses: - nephrogenic DI - induces Na depletion, increases collecting duct water reabsoprtion Indications: - HTN - first line - edema - nephrogenic DI - hypercalciuria - risk factor for kidney stones - dose over 25 Side effects: - hyponatremia - hypoK - hyperlipidemia - hypercalcemia - hyperuricemia - azotemia - glucose intolerance
Metolazone
Thiazide diuretic - significant proximal tubular effects - partial carbonic anhydrase inhibitor - increased natriuresis Contraindicated if hyponatremia
Amiloride
K sparing diuretic - blocks ENaC - reduce K excretion Small to moderate diuresis Indications: - cirrhosis - combination with HCTZ - blocks hypoK from thiazides Side effects: - hyperK - potentiated by NSAIDs and ACE-I - hypotension
Spironolactone
K sparing diuretic - block aldo - inhbits K excretion Small to moderate diuresis Long half-life Indications: - cirrhosis - CHF - hyperaldosteronism - 1st line Side effects: - hyperK - hypotension - gynecomastia - erectile dysfnx
Eplerenone
K sparing diuretic - block mineralocorticoid receptor - inhibits K excretion Small to moderate diuresis Indications: - CHF - cirrhosis? Side effects: - hyperK - hypotension
Triamterene
K sparing diuretic - blocks ENaC - reduce K excretion Small to moderate diuresis Indications: - cirrhosis - combination with HCTZ - blocks hypoK from thiazides Side effects: - hyperK - potentiated by NSAIDs and ACE-I - hypotension
Dutasteride
5 alpha reductase inhibitor - blocks conversion of testosterone to DHT - reduces size of prostate in BPH - reduces urinary symptoms in BPH Takes 6 mo for action Side effects: - sexual dysfnx - gynecomastia - increased hair growth
Finasteride
5 alpha reductase inhibitor - blocks conversion of testosterone to DHT - reduces size of prostate in BPH - reduces urinary symptoms in BPH Takes 6 mo for action Side effects: - sexual dysfnx - gynecomastia - increased hair growth
Mifepristone
Anti-progesterone - disrupts endometrium - softens cervix - lowers progesterone in body Abortion bill
Flutamide, Bicalutamide, Nilutamide
Anti-testosterone
- 2nd line for prostate cancer
Clomiphene
Selective estrogen receptor modulator - stimulates ovulation - used for infertility Mechanism: - binds to estrogen receptors in hypothalamus and anterior pituitary - inhibits negative feedback of estrogen - increases FSH production - has pro-estrogenic effects in ovary
Tamoxifen
Selective estrogen receptor modulator - breast cancer rx and prevention Antagonist on breast tissue Agonist on endometrium Agonist on bone - reduced osteoporosis Side effects: - endometrial hyperplasia - heavy periods - endometrial polyps - DVT and VTE - strokes - hot flashes - cataracts
Raloxifene
Selective estrogen receptor modulator - breast cancer rx and prevention Antagonist on breast Antagonist on endometrium - no endometrial hyperplasia Agonist on bone - reduced osteoporosis Side effects: - DVT and VTE - hot flashes - MSK Contraindications: - clotting disorders
Ospemifene
Selective estrogen receptor modulator
- rx of postmenopausal symptoms
Aromatase inhibitors
Drugs: - letrozole - anastrazole - exemastane Use: - rx and prevention of breast cancer If premenopausal women, must suppress ovaries Side effects: - vasomotor symptoms - like menopause - MSK complaints - vaginal dryness - HTN
Oral Contraceptive Pills
Progesterone and Estrogen Regular menses Lighter menses Improvement of premenstrual syndrome Improvement in acne Decreased libido - cuz decreased testosterone from increased sex binding hormone globulin (binds free T)
Emergency contraception
Morning after pill
High dose progesterone
- inhibits LH surge
- only effective if used before LH surge
Estrogen therapy
For hormone replacement in menopause
- approved for hot flashes
Progesterone therapy
For hormone replacement in menopause
- only for endometrial protection due reduce endometrial growth in women with uterus
Vaginal estrogen
For vaginal dryness in menopause
Trastuzumab
Anti-HER2/neu Use: - HER+ breast cancer Side effects: - CHF/cardiotoxicity
Anthracyclines for breast cancer
Doxorubicin/adriamycin
Mechanism:
- topo II inhibitor (stabilizes double strand DNA break)
- intercalate btw DNA base pairs to block synthesis
- oxygen free radical production via Fe
Side effects:
- CHF/cardiotoxic
Rx for acromegaly
Somatostatin analogs: - octreotide - lanreotide GH antagonist: - pegvisomant
Rx for hyperprolactinemia
Dopamine agonists:
- cabergoline
- bromocriptine
Bisphosphonates
Drugs: - alendronate - best choice - risedronate - ibandronate - zoledronic acid Mechanism: - inhibits osteoclast activity and prevents osteoblast apoptosis Use: - rx of choice for osteoporosis - increase BMD, reduce all fx - rx of Paget's disease of bone - IV zoledronic acid - acute symptomatic hypercalcemia - IV zoledronic acid Ibandronate does not reduce hip fx Side effects: - iriis - bone pain - flu symptoms - osteonecrosis of the jaw - atypical subtrochanteric femur fx Contraindications: - renal failure - severe reflux - for oral - gastrectomy - for oral
Denosumab
Mechanism: - anti-RANKL - reduce activation of osteoclast precursor Use: - reduce all fx Sid effects: - increased risk of eczema - osteonecrosis of the jaw - atypical femur fx - risk of hypocalcemia in ESRD Can use in ESRD
Calcitonin
Mechanism: - inhibits osteoclast fnx Effects: - BMD increase - decrease spine fx - no reduction in hip fx Use: - osteoporosis - not very effective, not 1st line - acute symptomatic hypercalcemia to inhibit bone breakdown Side effects: - nasal irritation - lightheadedness
Teriparatide
Directly stimulates bone formation Mechanism: - stimulates osteoblast fnx Effects: - increase BMD - reduce all fx Risks: - rare hypercalcemia - lightheadedness from low BP - osteosarcoma in rats
Cinacalcet
Calcium sensor receptor agonist
- binds to Ca sensing receptor on parathyroid cells
- inhibits PTH release
Use:
- primary and secondary hyperparathyroidism
Levothyroxine
First line for thyroid hormone replacement
T4 replacement
Liothyronine
T3 replacement Fast action, short half-life More potent than T4 IV used for myxedema coma - give with hydrocortisone for prophylactic stress dose in case of polyendocrine syndrome
Liotrix
4:1 ratio T4:T3
Thyroid desiccated USD
Animal source
Allergenicity
Methimazole
Anti-thyroid thioamide Mechanism: - inhibit thyroid peroxidase - block iodine organification - block coupling of iodotyrosines Slow onset cuz blocks synthesis, not release 1st line
Propylthyiouracil
Anti-thyroid thioamide Mechanism: - inhibit thyroid peroxidase - block iodine organification - block coupling of iodotyrosines - PTU also blocks T4 to T3 conversion Slow onset cuz blocks synthesis, not release Use: - use in 1st trimester of pregnancy cuz less placenta crossing - or if allergy to methimazole Can precipitate fulminant liver failure
Perchlorate
Antithyroid anion inihbitor
Mechanism:
- block uptake of iodine via competitive inhibition of Na/I cotransporter
Thiocyanate
Antithyroid anion inihbitor
Mechanism:
- block uptake of iodine via competitive inhibition of Na/I cotransporter
Iodide
Antithyroid iodide
Mechanism:
- block organification
- inhibit thyroglobulin proteolysis so blocks hormone release
- decrease size and vascularity of hyperplastic gland
Take before surgery to reduce size of gland
Rapid improvement in thyrotoxicosis symptoms
Disadvantages:
- increases intraglandular iodine stores
- prevents use of radioactive iodine for wks
- cannot use alone - gland escapes the block, get withdrawal toxicosis
Radioactive iodine I-131
Destruction of thyroid parenchyma witihn a few wks due to selective uptake by thyroid
Don’t give to pregnant or nursing
Get some thyroid hormone release as thyroid is destroyed
B-blockers
For hyperthyroid
- block symptoms of thyrotoxicosis cuz mimic symp stimulation
Use propranolol
- blocks peripheral T4 to T3 conversion
Thyroid storm Rx
Iodine - immediate help BBs - propranolol Steroids PTU/methimazole but these take a while Rx the underlying cause Can do plasmapheresis, peritoneal dialysis, cholestyramine, lithium Acetaminophen, not ASA
Myxedema coma Rx
IV thyroxine big bolus, then lower doses daily
Prophylactic hydrocortisone
Sulfonylureas
First gen - tolbutamide - chlorpropamide - tolazamide - acetohexamide Second gen - glyburide - glipizide - glimepiride
Glyburide, glipizide, glimepiride
Mechanism: - block KATP channel - no efflex - depolarizes beta cell - increased insulin secretion Big A1c reduction - 1-2% Side effects: - nausea - skin rxns - photosensitivity - abnormal LFTs - weight gain Can lead to hypoglycemia
Glinides
Drugs: - repaglinide - nateglinide Mechanism: - stimulate insulin secretion Short acting Big A1c reduction - 1-2% Side effects: - URI - headache - weight gain No sulfur - can be used when allergic to sulfur or sulfonylureas
Biguanide
Metformin 1st line: - reduces diabetes related end points - reduces diabetes related deaths - reduces all cause mortality - MI reduction Mechanism: - decreases hepatic gluconeogenesis - lowers fasting glucose - increases insulin mediated glucose utilization in muscle/liver Big A1c reduction - 1-2% Side effects: - diarrhea, nausea, anorexia - lactic acidosis - vit B12 deficiency Weight loss No hypoglycemia Contraindications: - renal dysfnx - concurrent liver disease or alcohol abuse - heart failure - past hx of lactic acidosis - decrease tissue perfusion or hemodynamic instability
Thiazolidinediones
Drugs: - rosiglitazone - pioglitazone Mechanism: - PPAR y modulators - increase sensitivity of muscle, fat, and liver to insulin by increasing glucose transporter expression GLUT4 - modulate protein expression - do not work instantly - takes 4-6 wks for protein expression to be seen - inhibit hepatic gluconeogenesis A1c reduction good 1-1.5% Side effects: - large weight gain - fluid retention - peripheral edema - CHF - bladder cancer - pioglitazone - osteoporosis Contraindications: - heart failure
Alpha glucosidase inhibitors
Drugs: - acarbose, miglitol Mechanism: - competitively inhibit alpha glucosidase enzymes at enterocyte brush border - reduce rate of polysaccharide absorption in proximal small intestine - lower post-prandial glucose levels - effect only on post-prandial glucose, not fasting Minor A1c reduction - 0.5-0.8% Side effects: - GI discomfort - flatulence, diarrhea Weight neutral Use this when run out of options
GLP 1 inhibitor
Drugs: - exenatide - liraglutide - albiglutide - dulaglutide Mechanism: - potentiates glucose stimulated insulin secretion - suppresses glucagon secretion and slows gatric motility Good A1c reduction - 1% Side effects: - nausea, vomit - diarrhea - risk of pancreatitis - C cell thyroid tumors/hyperplasia - liraglutide Big weight loss
DPP4 inhibitors
Drugs: - sitagliptin - saxagliptin - linagliptin - alogliptin Mechanism: - inhibits DDP4 - increase endogenous GLP-1 A1c reduction okay - 0.6-0.9% Not as good as GLP1 agonist Side effects: - increased risk for URI and UTI - pancreatitis - C cell hyperplasia Weight neutral
SGLT2 inhibitors
Drugs: - canagliflozin - dapagliflozin - empagliflozin Mechanism: - selective inhibitor of SGLT2 - increases urinary glucose excretion by inhibiting glucose reabsorption A1c reduction okay - 0.5-0.7% Side effects: - hypotension - induces osmotic diuresis - hyerpkalemia - yeast infxn - UTI - DKA - can trigger in type 1 DM Good weight loss Reduce BP
Glucagon
Hyperglycemic hormone - causes rise in blood sugar Mechanism: - catabolism of stored glycogen and increase in gluconeogenesis and ketogenesis - increase in blood glucose Side effects: - transient nausea/vomit Clinical use: - reversal of hypoglycemia
Insulin analogs
Ultra short acting: - lispro - aspart - glulisine Long acting no peak: - glargine Long acting: - detemir NPH - old long acting Regular - old short acting
Ketoconazole
Blocks androgen and cortisol synthesis
Use:
- adrenal carcinoma, hirsutism, prostate cancer
Side effects:
- liver toxicity
- adrenal insufficiency - headache, sedation, fatigue, decreased appetite, N/V
- hypoandrogenism - gynecomastia, decreased libido, impotence
Mitotane
Inhibits CYP11B1 (11 B OHase)
Use:
- adrenal carcinoma
- medical adrenalectomy
Metyrapone
Blocks 11 B OHase
Use:
- hypercortisolism
Mifepristone
GC receptor antagnoist - rx Cushing related hyperglycemia
PR antagonist - don’t use in pregnancy women
- abortion pill
Fludrocortisone
Aldo replacement Side effects: - HTN - hypoK - heart failure
