PK

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Author:
ch.tyrrell
ID:
150799
Filename:
PK
Updated:
2012-04-28 22:02:10
Tags:
Psychotropics
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Description:
Psychotropics
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  1. What are the common uses of lithium?
    • treatment of bipolar disorder
    • adjunctive treatment of depression
  2. Is TDM of lithium necessary?
    • Classified by NCBOP as a NTI drug
    • Serious toxicity and death possible
    • Clear relationship between serum level and efficacy
  3. What formulations are lithium available in?
    • IR tablets and capsules
    • ER tablets
    • Syrup
  4. What is the absorption/bioavailability of lithium?
    • readily absorbed
    • 80-100%
    • monovalent cation
  5. What is the distribution of lithium?
    • widely distributed
    • does NOT bind to plasma proteins
    • crosses placenta and present in breast milk (category D)
  6. How does the Vd in elderly compare to adults?
    It decreases
  7. What is the metabolism of lithium?
    none
  8. Describe the elimination of lithium.
    • 1. Primarily eliminated as free ion (not metabolized)
    • **95% renal clearance
    • **biphasic
    • **half-life ~24 hours
    • 2. Renal clearance of lithium is approx 20% of CrCl
  9. How does the clearance of lithium of older adults compare to that of normal adults?
    clearance in older adults in ~2/3 of normal adults
  10. What is the therapeutic range of lithium for the treatment of acute mania?
    0.8 to 1.2 mEq/L
  11. What is the prophylaxis therapeutic range of lithium?
    0.5 to 0.8 mEq/L
  12. When should lithium serum levels be measured?
    12 hours post dose is generally recommended (for divided doses)
  13. What is moderate lithium toxicity?
    > 1.5 to 2.5 mEq/L
  14. What is severe lithium toxicity?
    > 2.5 mEq/L
  15. What are the side effects of lithium?
    • GI:N/V, anorexia, diarrhea, abdominal pain, tremor
    • Renal: polyuria, DI, interstitial nephritis, edema
    • Neuro/Cognitive: lethargy, fatigue, weakness, action tremor, cognitive slowing, memory disturbance
    • Neurologic toxicity: coarse tremor, ataxia, confusion, visual changes, dysarthria (severe = ataxia, seizures, hallucinations, delirium, coma, death)
    • Other: hypothyroidism, arrhythmias, acne, psoriasis, benign leukocytosis, weight gain
  16. What drug-drug interactions are there with lithium and what will they do to lithium levels?
    • thiazide diuretics, spironolactone, triamterene
    • NSAIDs, COX-2 inhibitors
    • metronidazole, tetracyclines
    • ACE inhibitors, ARBs

    They will increase lithium levels by 25-50%
  17. What happens to lithium levels when a person experiences dehydration?
    Lithium levels will go up 25-50%
  18. What is "ideal" dosing of lithium?
    QHS dosing
  19. What are the peak dose effects of lithium?
    nausea and tremor
  20. What is the typical dosing for a healthy young adult?
    1500mg/day + 300mg = 1.0 mEq/L
  21. What dose of lithium is given to a patient with a CrCl 10-50 ml/min?
    50% to 75% of normal dose
  22. What dose of lithium is given to a patient with a CrCl <10 ml/min?
    25% to 50% of normal dose
  23. What are the kinetic pearls of antidepressants (TCAs and SSRIs)?
    • Highly lipophilic, cross BBB
    • F~ 30% to 90%
    • Readily and completely absorbed but extensive 1st pass metabolism
    • Generally linear pharmacokinetics
  24. Discuss TCAs
    • Large Vd
    • Extensively bound to albumin and other proteins
    • Half-life = 6-88 hours [dosed daily]
  25. List TDM for Amitriptyline, Nortriptyline, Imipramine/Desipramine and Desipramine.
    • Amitriptyline 100 to 200 mcg/L
    • Nortriptyline 50 to 150 mcg/L
    • Imipramine and desipramine 180 to 350 mcg/L
    • Desipramine 100 to 200 mcg/L
  26. When should TCA levels be drawn?
    12 hours post-dose
  27. What is the half-life of SSRIs?
    • 15-33 hours (fluoxetine = 4-6 days)
    • Generally allows for once daily dosing
  28. What is the TDM of SSRIs?
    Does not exist with the exception of monitoring for adherence
  29. What are the pharmacodynamic considerations involving SSRIs?
    • Antidepressants and EtOH
    • Serotonin syndrome
  30. What are the drug-drug interactions involving SSRIs?
    fluoxetine and paroxetine - strong CYP2D6 inhibitors
  31. Give the ADME of atypicals/antipsychotics.
    • F= ~50-80%
    • Vd = large, highly bound to plasma proteins, can accumulate in tissues
    • Half-life 20-40 hours (usually dosed daily)
    • Higly lipophilic, crosses BBB
  32. Describe the TDM of antipsychotics (atypicals).
    • Not commonly done
    • For most, there does appear to be a threshold serum level needed for response and a serum level-response relationship
  33. What is the therapeutic range for clozapine?
    350-600 ng/mL

    **only antipsychotic that is really monitored**
  34. What is the therapeutic range for risperidone?
    20-60 ng/mL
  35. What is the therapeutic range for olanzapine?
    20-50 ng/mL
  36. What kind of drug interaction occurs with cigarettes and psychotropics?
    • 1A2 inducer
    • Olanzapine = need a lot more to get a good therapeutic dose
  37. What kind of drug interaction occurs with antidepressants and psychotropics?
    • 2D6 inhibitors
    • SSRI + antipsychotic = have to lower the dose of antipsychotic
  38. What kind of drug interaction occurs with St. John's Wort and psychotropics?
    • 3A4, 2D6 inducer
    • Will lower the levels of psychotropics (but not lithium)

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