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79 Cards in this Set
- Front
- Back
ANDROGENS
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what cells do FSH, and LH, respectively, stimulate in the testis?
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FSH --> sertoli cells; LH --> leydig cells
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what cells release testosterone in the testes?
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leydig cells
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what genetic element initiates sexual differentiation in males?
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TDF on Y chromosome
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what if there is no TDF?
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baby will be female (have ovaries)
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in early fetal development, what is necessary for internal male genitalia to form, and where does it come from?
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mullerian inhibiting hormone - comes from sertoli cells
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what if there is no mullerian inhibiting hormone?
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female internal genitalia
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what is necessary for external male genitalia?
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DHT
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what is necessary for external female genitalia?
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lack of testosterone
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what needs to happen for there to be DHT?
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conversion of testosterone to DHT by 5-alpha-reductase
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where is type 1, and type 2 5-alpha-reductase found?
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type 1 - liver and skin; type 2 - urogenital tract and liver
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what can deficiencies of type 2 5-alpha-reductase result in?
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ambiguous gender idnetification at birth, usually female
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what can be done about this?
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dramatic reversal at puberty, as testosterone is converted by type 1 5-alpha-reductase, resulting in male gender assignment
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hyperplasia/carcinoma of the prostate is treated by inhibiting what androgen(s)?
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DHT
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acne is treated by inhibiting what androgen(s)?
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T
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male pattern baldness is treated by inhibiting what androgen(s)?
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T, DHT
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precocious puberty in boys is treated by inhibiting what androgen(s)?
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T
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sex drive in sex offenders is treated by inhibiting what androgen(s)?
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T
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what is the Kd for the androgen receptor with DHT compared to T?
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DHT 1000> T
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what feature of AR gene increases sensitivity to androgens?
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lesser amount of glutamine repeats (12-32 normal - if over 40, spinal/bulbar muscular atrophy)
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what are the indications for giving testosterone (2) and how is it given?
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given as skin cream for: 1) congenital or acquired hypogonadalism in men; 2) breast carcinoma in posmenopausal women
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what drug must we know that is used for prostate cancer, precocious puberty, uterine leiomyoma, and endometriosis?
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leuprolide
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what type of drug is it, and what is its MOA?
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GnRH agonist - continued exposure disrupts pulsatility of gonadotrophs, inhibiting FSH and LH secretion
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what are its adverse effects (4)?
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1) short term rise in serum testosterone; 2) decreased libido; 3) negative effects on mood; 4) osteoporosis
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what is a non-FDA approved use for ketoconazole?
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prostate cancer
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what are its adverse effects (4)?
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1) short term rise in serum testosterone; 2) decreased libido; 3) negative effects on mood; 4) osteoporosis - same as leuprolide
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what drug is used for metastatic prostate cancer and BPH, and what type of drug is it?
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flutamide - nonsteroidal anti-androgen - directly blocks androgen receptor
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what are its adverse effects (4)?
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1) short term rise in serum testosterone; 2) decreased libido; 3) negative effects on mood; 4) osteoporosis - same as leuprolide
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what is flutamide most effective in combination with?
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leuprolide
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what drug is used for prostate cancer, BPH, and alopecia, and what is its class/MOA?
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finasteride - 4-aza analog of T that acts as competitive, specific inhibitor of type II 5-alpha-reductase
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what does finasteride block, and not block?
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blocks actions of DHT but not T in prostate, seminal vesicles, hair follicles, epididymis
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what are the adverse effects of finasteride like?
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generally better tolerated than flutamide
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what is a non-FDA approved use of testosterone?
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to improve libido in both women and men
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GOUT
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what decreases local pH in gouty attacks, and what leads to that?
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increased lactate production, from inflammatory response
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what exacerbates inflammatory response?
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increased synovial phagocytosis of crystallized uric acid
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why is there more crystallized uric acid?
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drop in local pH (all of these create a vicious cycle)
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what are treatment goals of gout (3)?
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1) relieving gouty attacks; 2) preventing recurring gouty episodes; 3) preventing urate lythiasis
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what drug is a diagnostic indicator of gout, and what type of drug is it?
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colchicine - a plant alkaloid - diagnostic because it is only effective against gout - dramatically relieves pain and inflammation of gouty arthritis in 12-24 hours
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what is the MOA of colchicine?
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inhibits tubulin polymerization, leading to inhibition of leukocyte and phagocyte migration and phagocytosis of crystals in joints
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why are NSAIDS often used?
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decreased side effects
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what is colchicine indicated for?
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prophylaxis of recurrent episodes of gouty arthritis
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what are adverse effects of colchicine?
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diarrhea, N/V, abdominal pain, hair loss, bone marrow suppression, peripheral neuritis, myopathy
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what is the normal dosing of colchicine for an acute attack, and what should be avoided?
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2mg is given as a single dose IV - not to exceed 4 mg, not to be repeated within 7 days
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how much is lethal?
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8mg/24 hours
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what NSAID is used in gout, and how does it help besides being anti-inflammatory?
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indomethacin - inhibits urate crystal phagocytosis
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what NSAID is better than others at lowering serum uric acid, and what is the problem?
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oxaprozin may be better at this, but its use, like other uricosuric agents, is not recommendeed in patients with uric acid stones
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what drug is effective for treatment of primary uricemia caused by antineoplastic therapy, and what is its MOA?
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allopurinol - competitive inhibitor of xanthine oxidase - inhibits urate synthesis
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what is the main use of allopurinol?
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effective for treatment of primary hyperuricemia and that secondary to antineoplastic therapy
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what are other indications for allopurinol?
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reserved for more severe forms of gout - high urinary urate (600-700), gouty nephropathy, recurrent renal sotnes, elevated serum urate
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allopurinol is used in situations when what two drugs are contraindiicated?
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sulfinpyrazone, probenecid
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why is probenecid contraindicated with allopurinol?
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allopurinol increases the half life of probenecid, which itself increases clearance of oxypurinol (an active allopurinol metabolite)
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what problem may allopurinol induce in the short term, and how?
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gouty arthritis - as serum levels of uric acid fall, crystal previously phagocytosed by synovocytes will be released, initiating gouty attack
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what may be required during initial treatment?
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coadministration of colchicine, sulfinpyrazone, or probenecid
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what are other adverse effects of allopurinol (5)?
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1) depression of bone marrow; 2) hepatic toxicity; 3) interstitial nephritis; 4) allergic skin reactions; 5) cataracts
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what is the name of agents used to increase the rate of uric acid excretion, and what two must we know?
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uricosuric agents - used to increase rate of uric acid secretion - 1) probenecid; 2) sulfapyrazone
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what treatment course does probenecid have?
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should begin with goal of lifelong treatment (like allopurinol)
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what is probenecid mainly used for?
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to decrease the bodies pool of urate in patients with increasingly frequent gouty attacks
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what is probenecid not effective in doing?
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relieving acute gouty attack (may exacerbate)
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what is the MOA of probenecid and where does it act?
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potent inhibitor of uric acid reabsorption at renal tubules
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what drugs inhibit the actions of probenecid and sylfinpyrazone?
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salicylates
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what happens when probenecid and sulfinpyrazone are used together?
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their effects are additive
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what AE is associated with probenecid, and who should it not be used in?
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uric acid stones - avoid in patients with nephrolithiasis, and with caution in patients with high serum urate levels
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what is the primary complication of probenecid?
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precipitation of acute gouty attack
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what is the toxicity of sulfinpyrazone?
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gastric distress/peptic ulcers
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what drug interaction was mentioned for sulfinpyrazone?
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can increase hepatic toxicity of acetaminophen
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what are the primary agents for managing acute gouty attacks?
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NSAIDs, colchicine, and other anti-inflammatory agents (allopurinol and uricosuric agents do not alter course, and actually increase gouty attacks)
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what drug is used to reduce frequency of gouty attack during early chronic treatment?
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colchicine
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what NSAIDS are DOC for acute gouty attacks (2)?
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indomethacin, naproxen
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how do salicylates affect gout?
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they elevate serum urate concentration and antagonize probenecid and sulfinpyrazone
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what things minimize intrarenal deposition of uric acid (2), why, and when is this essential?
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since pKa is 5.6, and solubility of undissociated form is low, maintaining plasma volume, alkaline urine minimizes its intrarenal deposition - this is important in first few weeks of therapy
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what are the adverse effects of allopurinol in the chart (4)?
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1) skin rash; 2) N/V; 3) kidney abnormalities; 4) diarrhea
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what are the main adverse effects of colchicine (2)?
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1) GI distress; 2) bone marrow depression
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what are the side effects/toxicity of probenecid?
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1) increase risk of stones; 2) may cause attacks during early treatment
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what are often the first line drugs in gout, and what are they used in conjunction with?
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NSAIDS - used in conjunction with uricosurics
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