Lithium

INTRODUCTION:
  • Lithium acts by intefering with cell membrane ion transport and excitability, adenylate cyclase activation, neurotransmitter (norepinephrine) release, and Na., K+-ATPase activity. 
  • Lithium is not bound to plasma proteins.
  • Therapeutic serum levels are 0.6 to 1.2 mmol/L. 
  • Liver is not affected in lithium toxicity. 
  • Lithium should be stopped 48 hours before any major surgery because Lithium potentiates the action of non-depolarizing muscle relaxants
CLINICAL TOXICITY:
  • Effects begin 1 to 4 h after acute ingestion.
  • Gastrointestinal effects include nausea, vomiting, and diarrhea.
  • Polyuria is the commonest symptom. 
  • Neuromuscular effects include weakness, confusion, ataxia, tremors, fasciculations, myoclonus, choreoathetosis, coma, and seizures;
  • Cardiovascular effects include arrhythmias and hypotension.
  • Hyperthermia can occur.
  • Most common renal sequel of lithium toxicity is Nephrogenic DM
  • Leukocytosis, hyperglycemia, albuminuria, glycosuria, nephrogenic diabetes insipidus, and a falsely elevated serum chloride level (due to interference by lithium with its assays) resulting in a low anion-gap may be present.
  • ECG changes include sinus tachycardia or bradycardia, flattened or inverted T waves AV block, and a prolonged QT interval. 
  • Hypothyroidism is seen.
  • Prolonged or permanent encephalopathy and movement disorders can occur in patients with severe poisoning.
  • Neurological symptoms are:
  1. Tremors 
  2. Muscle weakness 
  3. Increased DTR 
  4. Convulsions 
  5. Drowziness progressing to coma.
DIAGNOSIS:
  • A serum level must be requested specifically.
INDICATION:
  • An appropriate pre-Lithium work-up includes Serum creatinine,thyroid function tests, and a complete blood count with differential,Serum electrolytes
  1. Acute Bipolar disorder 
  2. Vascular headache
  3. Neutropenia
  4. Major depression
  5. Drugs used In Bipolar MDP: Lithium, Valproate, Carbamazepine, Levothyroxine,40-
  6. DOC in Rapid Cycling MDP: Lithium + Levothyroxine
  7. DOC for acute mania: Lithium
  8. DOC for Prophylaxis of mania: Lithium
  9. Is a mood stabilizer
CONTRAINDICATIONS:
  • Contraindicated in pregnancy.
  1. Causes CVS defects 
  2. Causes diabetes insipidus
  3. Causes T wave inversions (MC)
  • The absolute Contraindication to lithium is Renal failure
INTERACTION OF LITHIUM:
  1. Diuretics (thiazide, furosemide) by causing Na+ loss promote proximal tubular reabsorption of Na+ as well as Li - Plasma level of lithium rises.
  2. Tetracyclines, NSAIDs and ACE inhibitors cause lithium retention.
  3. Lithium tends to enhance insulin/sulphonylurea induced hypoglycemia (lithium has insulin like action on glucose metabolism).
  4. Lithium inhibits the action of ADH on distal tubules --> causes nephrogenic DI.
  5. Lithium reduce thyroxine synthesis by interfering iodination of tyrosine
TERATOGENIC EFFECT:
  • Lithium carries the risk of teratogenesis if ingested during pregnancy, especially during first trimester.
  • The most commonly reported congenital malformations are cardiac abnormalities particularly Ebstein's anomaly.
  • Other congenital malformations have also been described and include neural tube defect, Talipes, Microtia, thyroid abnormalities
TREATMENT:
  • Amiloride is useful for lithium-induced nephrogenic diabetes insipidus because it blocks Li+ transport into the cells of the collecting tubules
  • Commonest side effect of lithium is tremors which can be treated by /3-adrenergic antagonist such as propranolol & primidone
  • Lithium toxicity is treated by increased hydration, Sodium bicarbonate & Hemodialysis
Exam Question
  • Amiloride is the drug of choice in lithium induced polyuria
  • Abnormality to check if lithium is given to a pregnant female Cardiac anomaly
  • Drug of choice in Bipolar MDP is lithium
  • Treatment of choice in acute Bipolar disorder Lithium
  • Lithium is the Drug of choice in Vascular headache,Neutropenia, Major depression
  • Lithium may produce Hypothyroidism
  • 0.8 – 1.2 meq/l is the theraputic level of Lithium in serum
  • An appropriate pre-Lithium work-up includes Serum creatinine,Thyroid-stimulating hormone (TSH),Serum electrolytes
  • The current agent of choice for treatment of bipolar affective (manic-depressive) disorder is Lithium carbonate
  • Commonest side effect of lithium is tremor 
  • Congenital Anomaly produced by lithium therapy is Heart Block
  • Ebstein's anomaly is caused by lithium toxicity
  • Most common cardiac adverse effect of lithium is Arrythmia
  • Lithium directly affects Sodium
  • Psoriasis is exacerbated by lithium
  • Lithium toxicity is treated by increased hydration, Sodium bicarbonate & Hemodialysis
  • The absolute Contraindication to lithium is Renal failure
  • Most common renal sequel of lithium toxicity is Nephrogenic DM
  • Lithium potentiates the action of non-depolarizing muscle relaxants so 2 days before administration of the muscle relaxant should lithium be stopped

Don't Forget to Solve all the previous Year Question asked on Lithium