Lithium and its complications

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

Metabolism NoneExcretion 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-PhenytoinAnalgesics : -Nonsteroidal Anti-Inflammatory AgentsEg,Ibuprofen, Diclofenac Na* Aspirin and Sulindac do not affect!! ;

Decreased lithium level-Theophylline derivative usage-Na bicarbonate-Na citrate

Conditions affecting lithium clearanceDehydrationHyponatremiaRenal impairment

ComplicationsCan beAcuteChronic

Has a propensity to affect multiple systems

Acute poisoning featuresMildsymptoms 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 characterizeTHE GI AND CNS AND CARDIAC SYSTEMS ARE AFFECTED

Chronic complicationsRenal

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 1Few 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 releaseTreatment 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 tachycardiaUnmask underlying abnormalities like brugada syndrome

Anorexia, nausea and vomiting

Metallic taste, weight gain

Xerostomia and excessive salivation both are possible Gastrointestinal complications

Central nervous systems effectsHeadache, confusion, sedation, coma

Seizures

Extrapyramidal signs can occur

Movement disorders Restlessness, tics, dystonia

Autoimmune disorders Drug induced Systemic lupus erythematosus

Myasthenia gravis

ManagementStop LiOffending agentStabilize and secureAirwayMonitor Moderate to severe poisoning patients should be monitored adequately, HDU setting

InvestigateLithium levelsElectrolytesECGS.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> CRRTWhen severe toxicity, renal failure , deterioration seen

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