LITHIUM

• Understand the PK and toxicological profile of lithium.

Structure/Class	Monovalent cation
Pharmacodynamics	Functions by inhibiting IP3 and GSK-3, which is a multifunctional protein kinase. Overall acts to reduce α-adrenergic and muscarinic transmission. Also inhibits adenylyl cyclase and second messenger systems, therefore causing hypothyroidism and Nephrogenic DI.
Absorption/administration	PO Absorption is virtually complete in 6-8 hours.
Distribution	Initially distributed in TBW, with Vd ~0.5L/kg, rising to 0.7 to 0.9L/kg. No protein binding, but some sequestration in bone.
Metabolism	Nil
Excretion	Virtually entirely in urine. Clearance is ~20% of creatinine clearance. Long T ½ – about 20 hours.
Indications	Bipolar affective disorder (especially manic phase) Depressive disorders Schizophrenia
Contraindications
Special precautions	Pregnancy – renal clearance increases during pregnancy and clearance decreases post-partum.
Interactions	Thiazide diuretics reduce clearance of lithium by 25%. Clearance also reduced by NSAIDs. Use of anti-psychotics may produce more severe extrapyramidal symptoms with lithium.
Adverse events	Neurological Very common. Tremor, ataxia and dysarthria are common. May also cause new psychiatric disturbances (mental confusion) Endocrinology Hypothyroidism Renal Nephrogenic DI à causes polyuria and polydipsia Cardiac Depresses SA node (CI in SSS and tachy-brady syndrome) Pregnancy and post-partum Lithium causes Ebstein’s anomaly May also cross breast milk – results in lethargy, poor suck and poor reflexes. Idiosyncratic Acne, leukocytosis.
Dosing/administration
Toxicology	Therapeutic ODs are more common than intentional/accidental OD, due to changes in the patient’s status (that is ,decreased serum Na, increased diuretic use or fluctuating renal function) Treatment is dialysis or supportive care.
Withdrawal syndrome
Special notes