osteoporosis and gout Flashcards by J N

risk factors for osteoporosis

controllable: dec physical activity, low body wt, poor Ca and vitD intake, caffeine EtOH or tobacco, glucocorticoids and other meds
out of control: female, age, white Hispanic or Asian, personal or fam hx of fractures, premature menopause

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meds that may cause osteoporosis

CYP inducing anti-epileptics (inc vit D catabolism)
aromatase inhibitors, medroxyprogesterone (dec estrogen activity)
PPIs (dec Ca absorption)
GnRH agonists (dec estrogen and testosterone)
glitazones, glucocorticoids, heparin (dec bone formation, unclear MOA)

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effects of vitamin D

increases bone formation and resorption
inc synthesis CBP/calcibindin
increases absorption of Ca and P from gut
dec urine Ca and P
inhibits production of PTH
stimulates FGF23 release from bone

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effects of PTH

increase bone formation and resorption (stimulates osteoblasts and -clasts)
dec urine Ca
inc urine P
stimulates conversion from inactive to active vit D in kidney

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effects of calcitonin

decreases bone resorption (inactivates osteoclasts), promotes Ca deposition by blasts
inc urine Ca and P

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effects of FGF23

increases urine P

inhibits conversion of inactive to active vit D

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effects of RANKL, MCSF, and OPG

RANKL: activates osteoclasts
MCSF: activates osteoclasts
OPG: physiologic antagonist of RANKL prevents activation of osteoclasts

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calcium salts types and uses

calcium carbonate (needs acid for absorption), calcium citrate (more bioavailable)
use in hypocalcemic state, and prevention/tx of osteoporosis

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ADRs calcium salts

constipation
dec absorption ciprofloxacin, phenytoin, levothyroxine, tetracyclines
MI

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metabolism of vitamin D

sunlight: 7-DHC to cholecalciferol (D3) (also can be obtained in diet)
liver 25a-hydroxylase: D3 -> 25-hydroxy-D3
kidney 1a-hydroxylase: 25-H-D3 -> 1,25-DH-D3

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ergocalciferol

vitamin D2

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cholecalciferol

vitamin D3, synthesized in skin exposed to UV rays

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calcitriol

1,25-dihydroxy-vitamin D3

most active form of vitamin D

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calcifediol

25-hydroxycholecalciferol

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alfacalcidiol

a-hydroxycholecalciferol, a prodrug rapidly hydroxylated by liver to calcitriol

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teriparatide use, MOA, and ADR

recombinant human PTH for osteoporosis
short-term use only - stimulates osteoblasts > clasts
long-term stimulates osteoclasts
ADR: inc risk osteosarcoma w use >2 y

bisphosphonate names and MOA

“dronates” and “dronic acids”
analogues of pyrophosphate, replacing POP with PCP that is hydrolysis-resistant, stabilizing hydroxyapatite
also adsorb to hydroxyapatite, preventing resorption by inhibiting osteoclast activity

uses of bisphosphonates

osteoporosis, Paget’s disease, hypercalcemia, osteolytic bone lesions of metastatic cancer

ADRs of bisphosphonates

m/c: esophagitis, erosion (esp. alendronate; take while upright with water)
osteomalacia (eti- and pami-)
GI distress
osteonecrosis of jaw or other bones
atypical subtrochanteric fx

use of calcitonin

nasal spray
salmon calcitonin more potent and longer-acting than recombinant human calcitonin
tx of hyper-Ca states: post-meno osteoporosis, Paget’s dz
*short-term only (less than 6 h)

denosumab

IgG2 monoclonal antibody that binds and inactivates RANKL, mimics OPG
inactivates RANKL-RANK-NF-kB pathway, inhibiting gene expression for osteoclast fxn
ADR: worsened hypo-Ca

raloxifene

SERM that reduces risk of vertebral (? other) fractures, breast cancer, and coronary events
may worsen post-menopausal vasomotor sx

causes of gout

overproduction or underexcretion of uric acid, or 2’ to leukemia or lymphoma (tumor lysis syndrome d/t tx)

normal urinary excretion of uric acid

24 hours: ~750 mg

meds for tx of acute gout

NSAIDs (indomethacin, naproxen, sulindac) | colchicine

meds for tx of chronic gout

under-excretion: probenecid, rasburicase, lesinurad (SURI) | over-production: allopurinol, febuxostat

MOA of gout pain

urate crystals accumulate, cause inflammation, granulocytes migrate into joint space and phagocytose crystals, release lysosomes that cause inflammation and joint destruction

MOA of colchicine

decreases leukocyte activity primarily by inhibiting tubulin polymerization *not analgesic or anti-inflammatory, specifically suppresses gouty inflammation

ADRs of colchicine

diarrhea, BM suppression | GI pain, hematuria, alopecia, peripheral neuropathy

MOA and uses of probenecid

inhibiting tubular reabsorption of uric acid, promoting excretion and reducing blood levels use for chronic gout (under-excretors), tx of 2' hyperuricemia, prolongs action of penicillins and cephalosporins (competes for secretion = inc t1/2)

xanthine oxidase inhibitor MOA

decreases production of uric acid by preventing conversion of hypoxanthine to uric acid

uses of XO inhibitors

in chronic gout (over-producers), prevents acute gouts (but may worsen during acute gout), 2' hyperuricemia

drug interactions of XO inhibitors

inhibits azathioprine and 6-mercaptopurine elimination - must decrease doses up to 75% or severe toxicity

allopurinol

reversible XO inhibitor

febuxostat

irreversible XO inhibitor

rasburicase

synthetic urate oxidase (rodents) | converts uric acid to soluble allantoin, to dissolve uric acid and promote urinary excretion in resistant cases of gout

drugs to avoid during acute gout attack

XO inhibitors - can cause flares (reduce serum uric acid level so quickly -> release from tissue stores) ASA (dec urate excretion) diuretics (volume depletion -> inc urate conc in blood)