Drugs for bipolar disorder Flashcards
What are the main mood stabilising drugs?
Lithium
Carbamazepine
Valproate/sodium valproate
Lamotrigine
What are the indications for lithium?
Prevention of manic or depressive episodes in bipolar disorder
Treatment of acute mania
Adjunct therapy for schizophrenia and treatment-resistant depression
Used in treatment of SIADH
Is lithium more effective in treating manic or depressive episodes?
Lithium is better at treating manic episodes
Discuss the MOA of lithium
Uncertain, little to no psychotropic effects in euthemic individuals
Proposed action = act via ion transport (Na+ substitute) > inhibits DA release > inc 5HT release (bad for mania, good for depression)> dec formation of inositol triphosphate
Down regulates kidney’s ADH response
What is the hypothesis behind Lithium use?
In mania, there is inc neurotransmitters utilising DAG/IP3 2nd messenger –> inc 5HT
Lithium reduced the response produced by these overactive NT
Discuss the metabolism of lithium
It is not metabolised, excreted unchanged by kidneys
Excessively reabsorbed from renal tubules, renal clearance is about 20% of glomerular filtration rate
Na will compete with lithium for tubular reabsorption
What type of drug kinetics apply to lithium?
Lithium is biphasic, this means that half of the oral dose will be excreted by the kidneys in the first 12 hours
the rest will be excreted over the next 1-2 weeks
It also requires regular dosing over 2+ weeks before a steady state is reached
Discuss some drug/condition interactions associated with lithium
Antithyroid drugs or iodides = enhance hypothyroid goitrogenic (suppressant) effect of lithium
NSAIDs (COX2 blocking PGE2)/Diuretics = both dec blood pressure > dec GFR > accumulation of lithium due to inc reabsorption as Na dec
Dehydration/vomiting/diarrhoea = inc lithium levels
neuroleptics = cause more severe EPS > lithium non-selectively blocks DA > causing inc contraction due to Ach
Discuss some ADRs associated with lithium
Common = metallic taste, diarrhoea (toxicity), epigastric discomfort, vertigo, tremor, nephrotoxicity, hypothyroidism, hypercalacemia, hyperparathyroidism, benign T wave changes on EC
Infreq = memory impairment, hair loss
Rare = arrhythmias, hyperthyroidism, nystagmus (repetitive eye movement)
What are the symptoms of mild-to-moderate lithium toxicity?
Blurred vision, muscle weakness, drowsiness, apathy, ataxia, flu-like illness
Dec Na = inc diarrhoea, nausea, vomiting
What are the symptoms of severe lithium toxicity?
Inc muscle tone, hyperreflexia, myoclonic jerk
psychosis, seizures, coma
What are some things to monitor with lithium use?
It is a NTI drug
Take blood 8-12 hrs after administration to assess concentration, measure again 5-7 days after, then after each dose change, and then every 3 months
Steady state -74 days to reach
Monitor frequently during illness = diet, temp, preg, mania/depression, concomitant meds
Toxicity is possible in lower concentrations = organic neurological or other CNS illnesses
What is the prophylactic dose for lithium?
0.4-1.0 mmol/L
What is the lithium dose for acute mania?
0.8-1.2 mmol/L
What increases lithium levels?
Renal dysfunction, D/V, fluid/ salt loss, diuretics/dehydration, excessive sweating, high fever, NSAIDs or ACEi, low salt diet
