pharm - MSK info.txt

  1. biphosphonates structure
    similar to pyrophosphate (PPi), a natural circulating inhibitor of mineralization, just modified (carbon for oxygen) to better penetrate and attach to bone matrix.
  2. biphosphonates MOA
    two actions: first their structure allows for enhanced calcium binding, and they also prevent bone breakdown (via inhibition of osteoclast activity, mevalonate pathway).
  3. biphosphonate PK
    low oral bioavailability
  4. biphosphonate IND
    Paget's disease, osteoporosis
  5. biphosphonate CI
    hypocalcemia, vitamin D deficiency, hypoparathyroidism, severe renal insufficiency (monitor serum Cr)
  6. biphosphonate SE
    dysphasia, nausea, heartburn, esophageal irritation (to reduce, take first thing in the morning c 8oz H2O, NPO p x 30min, upright p x 30min). rare osteonecrosis of the jaw, atypical subtrochanteric/femoral shaft fracture (due to antiresorptive effects).
  7. alendronate (Fosamax) dosing
    70mg PO qwk
  8. risedronate (Actonel) dosing
    35mg PO qwk
  9. osteoporosis RF
    steroid use, low calcium intake (<1000 mg /d, 1200 if 50+), vitamin D deficiency (1000 U??), lifestyle (alcohol/tobacco)
  10. zolendronate (Reclast) info
    once-yearly treatment (every other year for prevention)
  11. vitamin D pathway
    typically skin produces cholecalciferol (D3), liver converts this to calcifediol (25-hydroxyvitamin D3), kidney converts this to calcitriol (1,25-dihydroxyvitamin D3 -- ACTIVE FORM).
  12. vitamin D MOA
    calcitriol is essential in the regulation of calcium and phosphorus (facilitates absorption, decreases excretion, regulates osteoclasts/osteoblasts, negative feedback loop c PTH).
  13. vitamin D IND
    osteoporosis/osteomalacia, hyperparathyroidism
  14. vitamin D monitoring
    measure calcifediol (25-hydroxyvitamin D3) -- less variables influence its levels, therefore its a more accurate indicator of intake/production
  15. calcitonin MOA
    hormone secreted by the thyroid gland that inhibits osteoclasts (and may also increase osteoblasts), in essence enhancing calcium retention in bone and "toning down" serum calcium levels
  16. parathyroid hormone MOA
    endogenous hormone that acts to increase serum calcium, decrease serum phosphate, and increase osteoclast activity via RANKL (increased bone remodeling, increased resorption). also stimulates calcitriol production in the kidney.
  17. parathyroid hormone IND
    severe osteoporosis
  18. parathyroid hormone SE
    long term tx (>2yrs) unknown. BBW for osteosarcoma.
  19. RANKL inhibitors MOA
    when RANKL binds to the RANK receptor on osteoclasts, there is increased bone breakdown/resorption. denosumab inhibits this.
  20. RANKL inhibitors PK
    SC. long T1/2 (dosed q6mo by health professional).
  21. RANKL inhibitors IND
    osteoporosis (Prolia -- not first line), bone mets of solid tumors (Xgeva)
  22. RANKL inhibitors CI
    hypocalcemia (correct prior to therapy)
  23. RANKL inhibitors SE
    skin reactions including eczema
  24. denosumab (Prolia) dosing
    60mg SC q6mo
  25. osteoporosis definition
    BMD > 2.5 SD below young adult mean. severe osteoporosis = osteoporosis + hx of fx.
  26. colchicine MOA
    binds microtubules, suppressing immune functions including decreased inflammatory mediators, decreased neutrophil adhesion/chemotaxis, and decreased phagocytosis of urate crystals by neutrophils.
  27. colchicine PK
    narrow TI (CYP3A4 / P-GP substrate)
  28. colchicine IND
  29. colchicine CI
    hepatic or renal impairment c concomitant CYP3A4 or P-GP inhibitor use (higher rates of toxicity)
  30. colchicine SE
    diarrhea, myelosupression, myopathy, neuropathy
  31. NSAIDs MOA
    block cyclooxygenase (COX) enzymes, which convert arachidonic acid to prostaglandins and leukotrienes, helping to reduce inflammation.
  32. NSAIDs IND
    pain, inflammation, fever, acute gout
  33. NSAIDs INT
    NSAIDs + ASA (block antiplatelet effect -- give non-coated ASA 1 h prior to NSAID)
  34. NSAIDs CV risk
    naproxen lowest CV risk.
  35. NSAIDs SE
    CNS (HA, tinnitus, dizziness, confusion, hallucinations), GI (pain, dyspepsia, N/V, ulcers/bleeding), CV (fluid retention, HTN), renal dysfunction, pulmonary (asthma), rash
  36. ibuprofen dosing
    200-800 mg q4-6h, MDD 1200 fever, 2400 normal, 3200 osteoarthritis
  37. naproxen dosing
    375-500mg q12h
  38. meloxicam (Mobic) dosing
    7.5-15mg qd
  39. celecoxib dosing
    200mg qd
  40. COX1 vs COX2
    COX 1/TxA2 thought to play maintenance/protective role (stomach mucous), COX 2/PGI2 expressed primarily in inflammatory cells (selective blockade helps prevent inflammation while maintaining COX1 stomach protection). However, COX2 inhibits platelet aggregation while COX1 promotes it (so COX2 selective isn't always ideal, may lead to CV events).
  41. NSAIDs in renal pts
    COX2 selective may be safer for older pts c worry of renal injury (COX1 constricts AA)
  42. NSAIDs GI risk
    ketorolac highest GI risk. ibuprofen lowest GI risk.
  43. NSAIDs and HTN
    NSAIDs can increase BP (though effect varies widely) -- take in smallest dose for least amount of time. If on antihypertensive/diuretic and become uncontrolled, consider switch to CCB (least affected by NSAIDs).
  44. uricosurics MOA
    lower serum uric acid levels by increasing excretion (UA filtered freely at glomerulus, 90% reabsorbed in proximal tubule. probenecid competes with this transporter).
  45. uricosurics PK
    half life varies based on dosage (500mg = 3-8h, >500mg = 6-12h)
  46. uricosurics CI
    renal insufficiency, kidney stones, peptic ulcer, blood dyscrasias, age >60.
  47. uricosurics SE
    kidney stones (increased excretion of UA -- encourage hydration). also HA, GI, rash.
  48. probenecid dosing
    250mg BID x1wk, then increase to 500mg BID. continue up to MDD of 2-3g/d if needed (target sUA <6mg/dl)
  49. ULT
    begin 1-3wks post-acute attack. when initiating therapy, all uric acid-lowering therapies (ULTs) have the ability to actually increase gout flares (co-prescribe with colchicine 0.6mg qd/BID or low dose NSAIDs for prophylaxis -- begin 2-3 wks prior and continue for up to 6 months).
  50. xanthine oxidase inhibitors MOA
    xanthine oxidase converts typoxanthine to xanthine to uric acid. the inhibitors prevent this.
  51. xanthine oxidase inhibitors PK
    allopurinol half life T1/2 is 1-3h, but active metabolite T1/2 is 18-30h. hypouricemic effect onset 1-2 days, peak 1-2 wks, duration 1-3 wks.
  52. xanthine oxidase inhibitors IND
    gout, renal stones
  53. xanthine oxidase inhibitors INT
    febuxostat + azathioprine (inhibits metabolism, increases toxicity), febuxostat + mercaptopurine (inhibits metabolism, increases toxicity)
  54. xanthine oxidase inhibitors SE
    discontinue drug at the first sign of a rash! (could be start of severe hypersensitivity rxn such as SJS, TEN). febuxostat has higher rate of cardiovascular events than allopurinol.
  55. allopurinol dosing
    200-800mg/d qd-QID. adjust c renal impairment.
  56. febuxostat dosing
    40-80mg qd. do NOT need to adjust c renal impairment.
  57. xanthine oxidase bonus
    buildup of xanthine/hypoxanthine may cause feedback inhibition of purine synthesis (purines -> hypoxanthine).
  58. baclofen MOA
    muscle relaxant (but not a paralytic). binds to GABA-B receptors, opening K+ channels. K efflux results in hyperpolarization, inhibiting depolarization. (secondary mechanism = inhibiting calcium channels).
  59. baclofen PK
    poor lipid solubility (so doesn't cross BBB -- intrathecal administration if needed there)
  60. baclofen IND
    muscle spasticity (MS, spinal cord lesions, CP)
  61. baclofen SE
    CNS (drowsiness, vertigo, slurred speech, ataxia), neuromuscular (weakness, hypotonia), cardiac (CP, dyspnea, palpitation, syncope), urinary.
  62. baclofen bonus
    avoid abrupt withdrawal due to severe spasticity, rhabdomyolysis, fever. OD can mimic brain death.
  63. alpha-2 agonists MOA
    central inhibition of neurotransmitter release (inhibition of presynaptic NE release via autoreceptor negative feedback loops)
  64. alpha-2 agonists PK
    clonidine oral/TD, dexmedetomidine IV
  65. alpha-2 agonists IND
    HTN (not first line), sedation, (glaucoma)
  66. alpha-2 agonists CI
    severe bradyarrhythmia, hypotension
  67. alpha-2 agonists INT
    alpha-2 agonists + MAOIs (MAOIs prevent NE breakdown, can lead to potentiation and extreme HTN)
  68. alpha-2 agonists SE
    oral use dry mouth, sedation, bradycardia, hypotension.
  69. inhaled anesthetics MOA
    binds to GABA-A receptors, opening chloride channels. Cl influx causes hyperpolarization, inhibiting depolarization.
  70. inhaled anesthetics PK
    newer drugs very low amount undergoes metabolism (route of elimination = exhalation). more vascular tissues quick to take up/release drug, less vascular the opposite (can act as a sink, prolong the anesthesia).
  71. inhaled anesthetics solubility
    solubility (as well as vascularity of tissue) has effects speed of onset: desflurane (lowest/fastest induction+elimination) < sevoflurane < isoflurane < halothane (highest/slowest induction+elimination).
  72. inhaled anesthetics IND
    general anesthesia, severe refractory status asthmaticus
  73. inhaled anesthetics CI
    family or personal hx of malignant hyperthermia (inhaled anesthetics are one of two triggers -- the other is succinylcholine)
  74. inhaled anesthetics SE
    hypotension, respiratory depression, halothane hepatic damage (very rare), sevoflurane kidney damage.
  75. goals of anesthesia
    maintenance of physiologic homeostasis, amnesia, analgesia, neuromuscular blockade.
  76. IV anesthetics MOA
    GABA mimetics bind to GABA-A receptors, opening chloride channels. Cl influx causes hyperpolarization, inhibiting depolarization. NMDA antagonists inhibit glutamate (excitatory NT) release by blocking glutamate's binding to NMDA receptors, inhibiting the subsequent calcium influx / cell depolarization.
  77. IV anesthetics PK
    fast onset (begin working within one "arm to brain" circulation time). however, vessel-rich organs also quickly uptake drugs reducing their levels in the blood (and therefore the brain) in a matter of minutes. therefore, termination action of single bolus is more the result of redistribution than metabolism/elimination.
  78. IV anesthetics IND
    induction/maintenance of general anesthesia, sedation, intubation
  79. IV anesthetics SE
    hypotension (best indicator of oversedation), respiratory depression, addiction. propofol/etomidate pain on injection, etomidate adrenal suppression (use as single bolus only).
  80. IV anesthetics dosing by population
    larger doses needed for alcoholics (even as little as one drink/day), children (greater mg/kg needed). lower doses for elderly, sick, those taking opioids.
  81. IV anesthetics GABA mimetics vs NMDA antagonists
    GABA mimetics do not have analgesic properties, cause apnea, and lower cerebral blood flow / ICP. NMDA antagonists do have analgesic properties, do not cause apnea, and increase cerebral blood flow / ICP (bad for those with brain injury).
  82. most common IV anesthetic
    propofol (favorable recovery profile, short elimination half life, less prolonged sedation/nausea then pentothal).
  83. fospropofol
    water-soluble prodrug, causes less injection site irritation than propofol though suffers from lack of familiarity/comfort among practitioners.
  84. etomidate
    preferred when vasodilation and cardiac depression are undesirable (least risk of hypotension -- use with severe cardiac disease or acute trauma/blood loss). higher rates of postoperative nausea.
  85. ketamine
    dysphoric (produces unpleasant sensations/hallucinations -- commonly coadministered c benzodiazepine), causes a dissociative state, SNS activation (incr. HR/BP therefore less hypotension risk), and bronchodilation (good for intubation of pts c severe bronchospasm like asthma)
  86. local anesthetics MOA
    bind voltage-gated sodium channels, inhibiting AP propagation. work on the intracellular side so must be able to cross cell membrane (increased lipid solubility = bigger/faster/longer effect).
  87. local anesthetics nerve differences
    large-diameter nerves and myelinated nerves both more difficult to block, require higher doses and are blocked for shorter durations (autonomic smallest/nonM therefore easiest, motor largest/M therefore hardest, sensory intermediate however have higher basal rate so signaling actually blocked earlier than motor).
  88. local anesthetics SE
    CNS toxicity (numbness/tingling, tinnitus, blurred vision, AMS, seizure, coma), CV toxicity (heart block, VT, VF especially bupivacaine) -- both more common with accidental intravascular injection. pain on injection (initially activated Na channels). intraneural injection nerve damage.
  89. local anesthetics PK
    onset time/duration of action both dose dependent. can also be improved by low-dose epinephrine (also reduces bleeding, but additional risk of tachycardia/HTN)
  90. local anesthetics bonus
    local anesthetics are weak bases, so acidic environments (abscess/infection) ionize drug and make anesthetizing more difficult.
  91. NONdepolarizing neuromuscular blockers MOA
    cause muscle relaxation/paralysis. the NONdepolarizers competitively antagonize ACh at the NMJ. partial blockade decreases strength (vs complete). selective for skeletal muscle (no effect on smooth/cardiac muscle -- also do not affect consciousness).
  92. NONdepolarizing neuromuscular blockers IND
    paralysis (surgery, intubation)
  93. NONdepolarizing neuromuscular blockers CI
    conscious patient
  94. NONdepolarizing neuromuscular blockers INT
    nondepolarizing muscle relaxants + inhaled anesthetics (prolonged effects). mixing nondepolarizing muscle relaxants (synergistic effects).
  95. NONdepolarizing neuromuscular blockers SE
    mivacurium hypotension (due to histamine release). pancuronium tachycardia (due to vagolytic effects).
  96. NONdepolarizing neuromuscular blockers bonus
    degree of paralysis can be measured with nerve stimulator -- partial = small twitch c TOF fade, compete = no contraction. zero contractions with train of four test will not respond to reversal medication, will only cause side effects (bradycardia, salivation/mucous, bronchospasm, N/V/D, urination -- also OD causes paradoxical reparalyzes!)
  97. DEpolarizing neuromuscular blockers MOA
    cause muscle relaxation/paralysis. DEpolarizers irreversibly bind postsynaptic ACh receptors, locking sodium channels open / depolarization (contraction not held b/c sarcoplasmic reticulum sucks up internal Ca after initial contraction/fasciculation). this also results in an efflux of potassium, typically raising sK levels 0.5-1 mEq/L (normal 3.5-5).
  98. DEpolarizing neuromuscular blockers PK
    shortest acting paralytic drug currently available (onset 45 sec, duration 4-5 min). metabolized by pseudocholinesterase (can't be reversed with anti-cholinesterases -- rarely someone is pseudocholinesterase deficient, and duration of action can be >12h!)
  99. DEpolarizing neuromuscular blockers IND
    intubation, ECT
  100. DEpolarizing neuromuscular blockers CI
    conscious patient, risk of hyperkalemia (renal failure) or hyperresponders (esp burn pts, spinal cord paralysis pts, muscular dystrophy pts), myotonic dystrophy (prolonged effect), malignant hyperthermia (c volatile anesthetics)
  101. DEpolarizing neuromuscular blockers SE
    hyperkalemia, muscle pain (due to transient fasciculations), bradycardia (more pronounced in kids, if concerned prevent by pretreatment c atropine)
  102. DEpolarizing neuromuscular blockers bonus
    degree of paralysis can be measured with nerve stimulator -- partial = small twitch c NO TOF fade (not competitively bound -- does fade with phase 2 blockade / multiple doses), compete = no contraction.
  103. analine analgesics MOA
    has analgesic and antipyretic effects but no antiplatelet/antiinflammatory effects, most likely through inhibition of PGE2 centrally and COX enzymes peripherally
  104. analine analgesics PK
    CYP2E1 enzyme pathway basis for acetaminophen toxicity (CYP2E1 metabolizes APAP to NAPQI, which is toxic. typically reduced by glutathione/GSH, however when GSH stores are depleted injury can occur).
  105. analine analgesics IND
    pain, fever
  106. analine analgesics SE
    increased risk for asthma
  107. NSAIDs vs APAP
    APAP more selective for CNS, different COX binding (NSAIDs act at COX site, APAP acts at peroxidase site), APAP inhibited by hydroperoxide (produced by macrophages/platelets, likely why it has no antiinflammatory/antiplatelet effects)
  108. acetaminophen OD
    toxic dose 10x greater than therapeutic dose. tx targeted at replenishing GSH stores by giving NAC, a precursor.
  109. acetaminophen at risk
    Chronic alcoholism -> increased 2E1 activity -> faster generation of NAPQI. Low GSH stores due to young age or malnutrition. Reduced liver conjugation leaving more to be metabolized by 2E1.
  110. opioids MOA
    bind to opioid receptors (G-protein coupled) located in the brain and spinal cord. The main opioid receptor is the Mu receptor, of which there is over 100 polymorphisms (variation in response! -- may also be incomplete cross tolerance between opioids)
  111. opioids IND
    pain, cough, diarrhea, dyspnea
  112. opioids CI
    decreased LOC, elderly, hepatic/renal impairment, addiction hx
  113. opioids INT
    opioids + sedatives (respiratory depression)
  114. opioids SE
    respiratory depression, NV, pruritis, urinary retention/constipation, miosis, truncal rigidity, sphincter of Oddi spasm.
  115. Vicodin dosing
    hydrocodone/acetaminophen, 2.5-10mg hydrocodone PO q4-6h PRN
  116. Percocet dosing
    oxycodone/acetaminophen, 2.5-10mg oxycodone PO q6h PRN
  117. Oxycontin dosing
    ER oxycodone, 10mg PO q12h
  118. Ultram dosing
    tramadol, 50-100mg PO q4-6h PRN
  119. opioid OD
    apnea/hypoventilation/hypoxia, miosis, decr LOC, track marks
  120. opioid WD
    rhinorrhea/lacrimation, yawning, chills/piloerection, hyperventilation, hyperthermia, mydriasis, muscular aches, V/D, anxiety/hostility
  121. methylnaltrexone
    does not cross BBB, so useful for peripherally mediated SE (like constipation) w/o reducing analgesic effects
  122. Mu1 vs. Mu2
    Mu1 = sedation, analgesia, euphoria. Mu2 = constipation, respiratory depression.
  123. short-acting opioids
    hydrocodone, hydromorphone, morphine, oxycodone
  124. long-acting opioids
    fentanyl TD, ER morphine, ER oxycodone, methadone
  125. opioid ER formulations
    ONLY FOR CONTINUOUS PAIN CONTROL FOR AN EXTENDED PERIOD (not PRN). do not cut/crush/chew/dissolve tablets (risk of OD due to faster release -- alcohol can also speed release from capsules).
  126. morphine
    "gold standard" -- metabolites include morphine-6-glucoronidate (more potent, renally cleared so adjust dose if needed).
  127. codeine
    pro-drug metabolized to morphine by 2D6 (genetic variability / interactions). don't use in kids (URMs)
  128. opioids strength
    morphine 1, hydromorphone 10, fentanyl 80
  129. tramadol
    BBW seizures, serotonin storm. Nucynta (tapentadol) is a more potent version that is not metabolized by glucuronidation and does not mess with CYP450 enzymes.
  130. methadone
    titrate slowly to effect (full effect takes 3-5 days). BBW pts tolerant to opioids may be incompletely tolerant to methadone, QT prolongation.
  131. Hoffman degredation
    spontaneous breakdown (no hepatic/renal needed). atracurium and cisatracurium (NNBs -- mivacurium pseudocholinesterase-metablized).
  132. APAP osteoarthritis
    300-800mg TID-QID
  133. APAP pain
    400mg q4-6h PRN
  134. APAP fever
    200-400mg q4-6h PRN
  135. APAP anti-inflammatory
    600mg QID x 7-14d
Card Set
pharm - MSK info.txt
pharm - MSK info.txt