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What are the common uses of lithium?
- treatment of bipolar disorder
- adjunctive treatment of depression
Is TDM of lithium necessary?
- Classified by NCBOP as a NTI drug
- Serious toxicity and death possible
- Clear relationship between serum level and efficacy
What formulations are lithium available in?
- IR tablets and capsules
- ER tablets
What is the absorption/bioavailability of lithium?
- readily absorbed
- monovalent cation
What is the distribution of lithium?
- widely distributed
- does NOT bind to plasma proteins
- crosses placenta and present in breast milk (category D)
How does the Vd in elderly compare to adults?
What is the metabolism of lithium?
Describe the elimination of lithium.
- 1. Primarily eliminated as free ion (not metabolized)
- **95% renal clearance
- **half-life ~24 hours
- 2. Renal clearance of lithium is approx 20% of CrCl
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
What is the therapeutic range of lithium for the treatment of acute mania?
0.8 to 1.2 mEq/L
What is the prophylaxis therapeutic range of lithium?
0.5 to 0.8 mEq/L
When should lithium serum levels be measured?
12 hours post dose is generally recommended (for divided doses)
What is moderate lithium toxicity?
> 1.5 to 2.5 mEq/L
What is severe lithium toxicity?
> 2.5 mEq/L
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
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%
What happens to lithium levels when a person experiences dehydration?
Lithium levels will go up 25-50%
What is "ideal" dosing of lithium?
What are the peak dose effects of lithium?
nausea and tremor
What is the typical dosing for a healthy young adult?
1500mg/day + 300mg = 1.0 mEq/L
What dose of lithium is given to a patient with a CrCl 10-50 ml/min?
50% to 75% of normal dose
What dose of lithium is given to a patient with a CrCl <10 ml/min?
25% to 50% of normal dose
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
- Large Vd
- Extensively bound to albumin and other proteins
- Half-life = 6-88 hours [dosed daily]
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
When should TCA levels be drawn?
12 hours post-dose
What is the half-life of SSRIs?
- 15-33 hours (fluoxetine = 4-6 days)
- Generally allows for once daily dosing
What is the TDM of SSRIs?
Does not exist with the exception of monitoring for adherence
What are the pharmacodynamic considerations involving SSRIs?
- Antidepressants and EtOH
- Serotonin syndrome
What are the drug-drug interactions involving SSRIs?
fluoxetine and paroxetine - strong CYP2D6 inhibitors
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
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
What is the therapeutic range for clozapine?
**only antipsychotic that is really monitored**
What is the therapeutic range for risperidone?
What is the therapeutic range for olanzapine?
What kind of drug interaction occurs with cigarettes and psychotropics?
- 1A2 inducer
- Olanzapine = need a lot more to get a good therapeutic dose
What kind of drug interaction occurs with antidepressants and psychotropics?
- 2D6 inhibitors
- SSRI + antipsychotic = have to lower the dose of antipsychotic
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)