pharm neuro info.txt

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pharm neuro info.txt
2012-09-28 20:56:29
pharm neuro info

pharm neuro info.txt
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  1. dopamine replacement MOA
    l-dopa is a dopamine precursor. its adadministered with the peripheral decarboxylase inhibitor carbidopa (otherwise metabolized prior to crossing BBB, incerases SE incl N/V, ortho hypo). also allows for lower doses of levodopa (75%) and more rapid/even titration.
  2. dopamine agonists MOA
    mimic dopamine.
  3. dopamine replacement PK
    l-dopa has short plasma T1/2 (1-3h), competes for absorption c its inactive metabolite. however therapeutic effect is often extended by neuron's ability to store dopamine. full therapeutic effect w/i weeks-months.
  4. dopamine replacement metabolism
    metabolized by COMT (more peripherally), MAO (more centrally).
  5. dopamine agonists IND
    parkinsons. pramipexoke restless leg syndrome. parlodel/cabergoline (ergots) endocrine (acromegaly, amenorrhea-galactorrhea, prolactin-secreting adenoma).
  6. dopamine replacement IND
  7. dopamine agonists CI
    pergolide/cabercoline (ergots) should no longer be used due to risk of valvular heart disease.
  8. dopamine agonists INT
    l-dopa/DA + phenothiazine antiemetics (prochlorperazine/metoclopramine -- they are dopamine receptor blockers)
  9. dopamine agonists SE
    more common in DA than l-dopa. nausea, peripheral edema, ortho hypotension, hallucinations/vivid dreams. serious sudden sleep onset (driving?). ergots require slower titration due to N/V, fatigue, hypotension.
  10. apomorphine
    most effective SC dopamine agonist -- onset 3-20 min, duration 90 min. used in combo c l-dopa to reduce dose/minimize off time
  11. levadopa
    always administered with the peripheral decarboxylase inhibitor carbidopa (otherwise metabolized prior to crossing BBB, incerases SE incl N/V, ortho hypo). also allows for lower doses of levodopa (75%) and more rapid/even titration.
  12. dopamine replacement vs dopamine agonists
    advantages of dopamine agonists over l-dopa include no need for enzymatic conversion, longer duration of action, and they avoid potential neurodegeneration associated c conversion of l-dopa to free radicals
  13. pergolide
    improves glycemic control in type 2 DM
  14. COMT
    catechol-o-methyl transferase
  15. COMT inhibitors MOA
    COMT breaks down l-dopa. these drugs inhibit this. (other l-dopa breakdown pathway is via dopa decarboxylase. product of breakdown is 3-OMD, which competes with L-dopa at BBB transporters -- therefore full effect of l-dopa achieved with coadministration of COMT and DDC inhibitors)
  16. COMT inhibitors PK
    T1/2 similar to l-dopa. entacapone prolongs T1/2 of l-dopa 50%. entacapone does not cross BBB, tolcapone does.
  17. COMT inhibitors IND
    parkinsons adjunct (decreased wearing off)
  18. COMT inhibitors CI
    hx of neuroleptic malignant syndrome, rhabdomyolysis, pheochromocytoma. tolcapone liver disease/LFT 2xlimit.
  19. COMT inhibitors INT
    COMT inhibitors + MAOI w/i 14 days (too much E/NE = tachy, htn, arrhythmias).
  20. COMT inhibitors SE
    dopamine-related (N/V, ortho hypotension, dyskineasia, vivid dreams/hallucinations). also discoloration of urine (dark yellow - reddish brown)
  21. amantidine
    NMDA antagonist -- relatively weak antiparkinsonian drug with low toxicity that is most useful in treating patients with early or mild PD and perhaps later when dyskinesia becomes problematic
  22. benztropine
    anticholinergic -- should be reserved for younger patients in whom tremor is the predominant problem. Their use in older or demented individuals and those without tremor is strongly discouraged.
  23. trihexyphenidyl
    anticholinergic -- should be reserved for younger patients in whom tremor is the predominant problem. Their use in older or demented individuals and those without tremor is strongly discouraged.
  24. MAOIs
    nonselective MAOIs often contraindicated. MAO-B selective MAOIs become nonselective at higher doses, so caution with them as well.
  25. parkinsons -- what is it?
    loss of dopaminergic neurons in substantia nigra. Balance between D1 pathway (enables movement) and D2 pathway (inhibits movement) is disrupted in this disease (low DA levels lead to greater D2 activation).
  26. cholinesterase inhibitors PK
    rivastigmine available TD (compliance)
  27. cholinesterase inhibitors IND
    Alzheimer's, NNB reversal, postoperative intestinal ileus, urinary retention. neostigmine/pyridostigmine myasthenia gravis.
  28. cholinesterase inhibitors CI
    neostigmine, pyridostigmine, physostigmine, edrophonium less selective for CNS, therefore CI in bronchial asthma, urinary/GI obstruction.
  29. cholinesterase inhibitors SE
    SLUDGE: salivation, lacrimation, urination, defecation, GI distress, emesis.
  30. irreversible cholinesterase inhibitors
    sarin gas and pesticides
  31. ergot alkaloids MOA
    agonists at 5HT-1B and alpha1, result in vasoconstriciton. also agonists at 5HT-1B and 5HT-1D autoreceptors that are thought to decrease pain transmitter release.
  32. ergot alkaloids PK
    low oral bioavailability, T1/2 2 h (extensive first pass metabolism) though biologic activity lasts > 24 h. ergotamine PO/SL/PR, dihydroergotamine SC/NS. ergonovine and methylergonovine are absorbed fastest (peak plasma levels < 90 min).
  33. ergot alkaloids metabolism
  34. ergot alkaloids IND
    ergotamine/dihydroergotamine acute migraine. ergonovine/methylergonovine PP hemorrhage.
  35. ergot alkaloids CI
    CAD, HTN, PVD, pregnancy
  36. ergot alkaloids INT
    ergots + triptans w/i 24 h (addative effects).
  37. ergot alkaloids SE
    N/V/D, paresthesias, angina, HTN. do not give ergotamine IV (excessive vasoconstriction / hypertension risk)
  38. triptans MOA
    agonist at 5HT-1B (BUT NOT ALPHA-1), result in vasoconstriciton. also agonists at 5HT-1B and 5HT-1D autoreceptors that are thought to decrease pain transmitter release.
  39. triptans PK
    sumatriptan fastest, reaches peak plasma concentrations 12 min p SC. frovatriptan/naratriptan longest acting. sumatriptan/zolmitriptan also available as nasal sprays.
  40. triptams metabolism
    metabolism often by MAO-A (frovatriptan CYP1A2, eletriptan CYP3A4 / PGP).
  41. triptans CI
    CAD, HTN.
  42. triptans INT
    triptan + triptan (addative). triptan + MAOI w/i 14 d. rizatriptan + propranolol.
  43. triptans SE
    paresthesias, chest/jaw/neck tightness/pain/pressure. weight gain (except topiramate which is weight loss).
  44. migraine combos
    1. increase GABA activity, 2. vasoconstrictor, 3. CNS depressor
  45. topirimate MOA
    unknown. possibly Na or Ca channel blocking, GABA potentiation, NMDA antagonism, or inhibition of carbonic anhydrase.
  46. topirimate monitoring
    do not need to monitor levels. do check Cr, bicarb, mental health.
  47. topirimate IND
    migraine, epilepsy.
  48. topirimate CI
    pregnancy (cat D, cleft palate in 1T)
  49. topirimate INT
    topirimate + OCPs (decreased efficacy)
  50. topirimate SE
    significant cognitive impairment, fatigue, paresthesias, taste changes, weight loss.
  51. Qsymia
    phentermine + ER topirimate, marketed for weight loss.
  52. female hormones
    progesterone is a natural anticonvulsant, while estrogen has proconvulsant activity.
  53. phenytoin MOA
    Sodium channel inhibitor, slowing recovery from inactivated state. Selectively targets channels that are opening/closing rapidly. May also enhance GABA release, inhibit glutamate release, block Ca channels.
  54. phenytoin monitoring
    Therapeutic levels = 10-20 mcg/mL total, 1-2 mcg/mL free. dental exam q3months.
  55. phenytoin PK
    highly protein bound. ER formulations contain 8% less drug than IR -- monitor closely when switching.
  56. phenytoin metabolism
    CYP2C9,2C10,2C19. Exhibits saturation kinetics: at low concentrations, first order kinetics (certain % per unit time) -- at high concentrations, zero-order kinetics (certain amount per unit time) due to saturation of pathways.
  57. phenytoin IND
  58. phenytoin CI
    pregnancy (cat D)
  59. phenytoin INT
    phenytoin + OCPs (decreased efficacy). CPY P450 enzyme inducer, may also saturate metabolic pathways used by other drugs.
  60. phenytoin SE
    gingival hyperplasia, coarsening of facial features in women. BBW for cardiovascular risk c rapid infusion (>50 mg/min, >150mg PE/min).
  61. fosphenytoin
    prodrug, dosed in phenytoin equivalents (PE) to avoid need for conversion. it is better tolerated, safer, and leads to quicker therapeutic levels but is more expensive.
  62. lamotrigine MOA
    inhibits Na channels (slows recovery from inactive state). May also inhibit Ca channels and glutamate release.
  63. lamotrigine monitoring
    do not need to monitor levels
  64. lamotrigine metabolism
    at high doses, produces auto-induction.
  65. lamotrigine IND
    epilepsy, bipolar disorder
  66. lamotrigine INT
    reduces levels = phenytoin, carbamazepine, phenobarbital, OCPs. increases levels = valproate (can be used additively, but increases chances of skin rxns)
  67. lamotrigine SE
  68. lamotrigine CI
    okay-ish in pregnancy (cat C)
  69. carbamazepine MOA
    sodium channel blocker. may also have effects on adenosine receptors (inhibiting NE), GABA, and glutamate.
  70. carbamazepine PK
    T1/2 is variable because they are autoinducers (T1/2 between 12 and 65 hrs reported, decreases with repeated dosing).
  71. carbamazepine monitoring
    therapeutic levels = 4-12 mcg/mL
  72. carbamazepine IND
    epilepsy, trigeminal neuralgia, bipolar disorder.
  73. carbamazepine CI
    porphyria, hypersensitivity to TCAs, pregnancy (Cat D)
  74. carbamazepine INT
    carbamazepine + MAOI w/i 14 days
  75. carbamazepine SE
    hyponatremia due to ADH secretion. BBW for serious dermatologic reactions with the HLAB1502 allele (Asian pts) and for aplastic anemia / agranulocytosis.
  76. oxcarbazepine
    a less potent analogue of carbamazepine that attempts to maintain efficacy but avoid autoinduction (fails in both departments, may have slightly less interactions).
  77. GABA analogues MOA
    unknown. postulated that they inhibit calcium influx at synaptic terminal, decreasing glutamate release. also might enhance synthesis of GABA.
  78. GABA analogues metabolism
    does not undergo metabolism, excreted unchanged.
  79. GABA analogues IND
    epilepsy, neuralgia, fibromyalgia
  80. GABA analogues SE
    peripheral edema
  81. Horizant
    gabapentin enacarbil (prodrug) is indicated for restless leg syndrome. It is more expensive, but isn't any more effective than off-label gabapentin.
  82. Gralise
    an ER formulation of gabapentin indicated for post-herpetic neuralgia -- but its a brand so more expensive!
  83. barbiturates MOA
    increase the binding of GABA to GABA-A receptors, increasing the influx of Cl (CNS depressants). also potentiate the binding of benzos.
  84. barbiturates PK
    redistribution effect if administered IV. They are also autoinducers (induce the same enzymes that metabolize it, resulting in increased dose requirements over time).
  85. barbiturates INT
    liver enzyme inducer (CYP2A + CYP3A)
  86. barbiturates IND
    epilepsy, sedation. antiseizure effects occur at a lower dose than sedation, however the therapeutic index difference between the two is small. phenobarbital is more selective for antiseizue than sedation, so it is the most common.
  87. barbiturates CI
    porphyria (can exacerbate accumulation of porphyrins)
  88. barbiturates SE
    sedation, addiction/tolerance, hypotension (especially IV use)
  89. barbiturate toxicity
    resembles alcohol intoxication (sedation, slurred speech, lack of coordination/ataxia, nystagmus, hypotension, respiratory depression)
  90. barbiturate withdrawal
    resembles alcohol withdrawal (agitation, sleep disturbances/hallucinations, seizures, tachy/HTN, sweating).
  91. valproate MOA
    sodium channel blocker. may also promote synthesis/inhibit breakdown of GABA, block glutamate, inhibit Ca channels.
  92. valproate metabolism
    phase II enzyme metabolism, however it is a CYP2C9 inducer (substrates = phenytoin, phenobarbital).
  93. valproate IND
    epilepsy, bipolar disorder, migraine prophylaxis
  94. valproate CI
    hepatic disease, pregnancy
  95. valproate SE
    GI (N/V). serious, rare hepatotoxicity (though LFT elevation relatively common), pancreatitis. carnitine supplementation may help mitigate risk
  96. phenobarbital monitoring
    therapeutic range = 15-40 ug/mL
  97. divalproex sodium
    SR form of VPA (more commonly used)
  98. valproate monitoring
    therapeutic range = 50-125 mcg/mL