Lithium and its

complications

Phamacokinetics

Absorption
standard release preparations, 6-8 hours with peak
plasma levels occurring within 4 hours.
Slow release preparations reach peak levels up to 12
hours
Distribution
Total body water with slow entry into tissue
compartments including the central nervous system.
No plasma protein binding.

Metabolism
None
Excretion
Almost entirely renally excreted
Excretion is dependent on creatinine
clearance
Elimination half-life is 24 hours

Therapeutic window
- Narrow, 0.8 and 1.2 mmol/L
- If having difficulty tolerating consider 0.6
mmol/L
- Check level one week after changing dose
- Check 12 hours after last dose, usually
morning before dosing
- Levels above 1.5mmol/L show mild toxcity
- Levels above 2.5 mmol/L are emergencies

Common situations that affect

lithium levels
Increased levels of lithium are seen in when
combined with
Antihypertensive:
- ACE Inhibitors
- Angiotensin II Receptor Blockers
- Calcium Channel Blockers
(Nondihydropyridine)
- Diuretics - thiazide and loop

Neurological medications
-Carbamazepine,
-Topiramate,
-Fosphenytoin
-Phenytoin
Analgesics :
-Nonsteroidal Anti-Inflammatory Agents
Eg,Ibuprofen, Diclofenac Na
* Aspirin and Sulindac do not affect!!
;

Decreased lithium level

-Theophylline derivative usage
-Na bicarbonate
-Na citrate

Conditions affecting lithium

clearance
- Dehydration
- Hyponatremia
- Renal impairment

Complications
Can be
Acute
Chronic
Has a propensity to affect multiple systems

Acute poisoning features

Mild symptoms include nausea, vomiting, lethargy,
tremor, and fatigue.
Moderate intoxication are confusion, agitation,
delirium, tachycardia, occasional heart blocks, and
hypertonia.
Severe intoxication Coma, seizures, hyperthermia
and hypotension characterize
THE GI AND CNS AND CARDIAC SYSTEMS ARE AFFECTED

Chronic complications
Renal
Endocrine
Cardiac

Renal complications
- Nephrogenic diabetes insipidus
- Renal tubular acidosis
- Nephrotic syndrome
-Chronic kidney disease

Nephrogenic diabetes insipidus

-The tubules lose their response to ADH due to
lithium
-Suspect when patient on lithium has new
onset nocturnal micturition and polyuria
-Confirm with water depravation test
-Ideally stop lithium
-If cannot stop add amiloride

Renal tubular acidosis

-Usually develop distal renal tubular acidosis
-That's type 1
Few complications include hypokalemia
Increased urinary stone formation

Nephrotic syndrome
- Possible mechanism include minimal change
disease and FSGS
- Exact mechanism is unknown
-Some still query whether there is a definitive
association and if these associations were
incidental

Chronic kidney disease

- Possible risk of CKD exists as does the risk of ESRD
- Mechanism is attributable to chronic interstitial
nephritis
- Risk include prolonged duration, advanced age, DM,
HTN
- Presents as renal insufficiency
- But rarely exceeds 2mg/dl unless lithium is continued
Renal biopsy maybe required

Endocrine complications
Thyroid dysfunction

Parathyroid dysfunction

Thyroid dysfunction
- Always screen thyroid functions before
starting lithium and post lithium every 6 months
for several years
- Goitre is commonly seen, usually within two
years of treatment, IGF
-Hypothyroidism occurs and is more
complicated by seen in women

- Again most are seen within two years

- Mechanism is due to increased iodine content
in thyroid gland by lithium
- It reduces T4, T3 production and release
Treatment is with thyroxine replacement and
frequent monitoring

Autoimmune thyroiditis, whether lithium is a

cause for auto immune thyroiditis is still unsure,
but anti thyroid antibodies are seen in higher
incidence in those with lithium induced
hypothyroidism

Hyperthyroidism, observation reveals the

incidence of hyperthyroidism is generally higher
than general population in those taking lithium

Parathyroid dysfunction can occur

-Increased PTH secretion results in
hyperparathyroidism
- Thus calcium levels will be elevated and
abnormal
-Take an endocrine opinion

Cardiac dysfunction
Commonly causes rhythm abnormalities
ST T segment changes
Sick sinus syndrome.
Chronic inappropriate bradycardia
Sinus pauses or arrest
Alternating Bradycardia and tachycardia
Unmask underlying abnormalities like brugada
syndrome

Gastrointestinal complications
Anorexia, nausea and vomiting
Metallic taste, weight gain
Xerostomia and excessive salivation both are
possible

Central nervous systems effects

Headache, confusion, sedation, coma
Seizures
Extrapyramidal signs can occur
Movement disorders Restlessness, tics,
dystonia

Autoimmune disorders
Drug induced Systemic lupus erythematosus
Myasthenia gravis

Management
Stop
Li
Offending agent
Stabilize and secure
Airway
Monitor
Moderate to severe poisoning patients
should be monitored adequately, HDU setting

Investigate
-Lithium levels
-Electrolytes
-ECG
-S.Creatinine

Detoxify
if conscious and rational and within 1hr of
presentation, can attempt lavage
Rx
-Hydrate with normal saline- Will aid in reducing
continued reabsorption by kidney
-Renal replacement therapy. HD> CRRT
When severe toxicity, renal failure , deterioration seen

Symptomatic Management
- Seizure- Benzodiazepine, Barbiturates
- Hyperthermia- Tepid sponging and PCM