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Lithium
lithium
16
Accounting
Pre-School
10/13/2014

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Term
Lithium Indications
Definition

Acute mania

Prevention of recurrent bipolar affective illness, especially manic episodes (not good for rapid cycling or mixed 

 

Other uses: recurrent depression, can be combined with antipsychotics to treat psychosis, unipolar depression who don't respond to antidepressants because they might actually be bipolar

Term
Lithium absorption and distribution
Definition

Almost completely absorbed from GI tract (available in extended release tablet to prolong action) and distributed in extracellular fluid with gradual accumulation in various tissues to different degrees 

 

Final volume of distribution approaches that of body water

 

Lithium passes slowly through BBB so 40% CSF concentrations 

Term
Lithium Excretion
Definition

95% of single dose is eliminated in urine (t1/2 = 20-24 hours)

Repeated administration will increase half life to 2.4 days; also increases in geriatric patients and those with impaired renal function

 

Considerable pharmacokinetic variations with patients - can only be used safely in patients that can be regularly monitored 

Term
Optimal serum levels of Lithium
Definition

.6 - 1.3 meq/L

Titration to higher doses should be done under very close supervision 

 

Avoid dehydration, this will up lithium concentrations

 

Excess sodium will enhance the elimination of sodium 

Term
Sodium levels and Lithium
Definition

Excess sodium will enhance elimination of sodium


Decreased sodium will decrease the elimination of sodium 

Term
Mechanism of Action of Lithium
Definition

Inhibits inositol monophosphatase

Inhibition of GPCRs

Inhibits growth factor pathways 

Term
Inhibition of Inositol Monophosphatase
Definition

Lithium inhibits inositol monophosphatase -- which depletes IP3 and DAG formation 

 

Mania might be associated with a state of neuronal hyperactivity and thus lithium may selectively inhibit these pathways 

Term
Inhibition of GPCRs
Definition

Lithium inhibits NE stimulated adenylate cyclase 

Major -- decreased ADH --> polyuria

Minor -- inhibition of TSH --> subclinical hypothyroidism 

Term
Inhibition of Growth Factor Pathways
Definition

Growth factors act through an enzyme called glycogen synthase kinase 3 to promote cell death 

 

Lithium inhibits this cell enzyme which can lead to neuroprotective effects and long term plasticity 

Term
Lithium: CNS toxic effects
Definition

Symptoms can occur at therapeutic doses, but if they are severe or there is more than one, indication of toxicity

 

Tremor (frequent), sedation, decreased cognition, incoordination 

Term
Lithium - Thyroid effects
Definition

Lithium concentrated in thyroid gland and causes decreased thyroid function in most patients, but effects are reversible 

 

Monitor TSH levels every 6-12 months 

Term
Lithium - Polydipsia and Polyuria and Treatment
Definition

Nephrogenic diabetes insipidus 

Inhibition of adenylate cyclase leads to decreased aquaporin 2 channels in apical membrane of collecting tubule of kidney; resistant to vasopressin 

 

Rx: amiloride and thiazide diuretics can be used to treat polyuria -- MOA: due to decrease in ECF and increased reabsorption of sodium and water in proximal tubule; may also increase aquaporin 2 levels 

Term
Lithium other side effects
Definition

Tubulointerstitial nephropathy (chronic LI treatment), n/v/d/weight gain, dermatitis, exacerbation of psoriasis, hair loss, and acne, reversible increase in PMN leukocytes (can be exploited to treat low WBC states), may be used in pregnancy but has been associated with Ebstein's anomaly 

 

Possible alternative would be a typical antipsychotic; clearance of lithium increases during pregnancy 

Term
Lithium overdose
Definition

Symptoms: convulsions, coma, confusion, coarse hand tremor, muscle rigidity, fasiculations, ataxia 

 

Therapeutic overdose is due to lithium accumulation due to reduced sodium levels that may happen through use of diuretics

 

Values of 2 meq/L can induce potential toxicity 

Term
Treatment of Overdose
Definition

Hemodialysis is effective if toxicity is severe with significant CNS effects and renal impairment

 

In more mild toxicity treat with fluids 

Term
Drug Interactions of Lithium
Definition

Lithium often used in combo with haloperidol -- may produce more EPS (use atypicals instead)

 

NSAIDs, ACEi, and diuretics may decrease clearance of Lithium 

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