Lithium Flashcards by Hana Manuchar

Signs of intoxication require treatment withdrawal. What are the signs of lithium overdose?

Increasing GI disturbances (e.g. vomitting, diarrhoea)
Visual disturbances
Polyuria
Muscle weakness
Fine tremor, increasing to coarse tremor
CNS disturbances (e.g. confusion, drowsiness, stupor, lack of coordination)
Abnormal reflexes
Myoclonus (involuntary twitching/jerking of muscles)
Incontinence
Hypernatraemia

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What are signs of severe lithium overdose?

Seizures
Cardiac arrhythmias (including sinoatrial block, bradycardia, 1st degree heart block)
BP changes (hypotension)
Circulatory failure
Renal failure
Coma
Sudden death

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Most common reason for lithium intoxication

Most often due to complication of long term lithium therapy, caused by reduced excretion of the drug

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Factors that cause reduced excretion of lithium

Dehydration
Reduced renal function
Infection
Co-administration of drugs that interact e.g. diuretics and NSAIDs

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Why might you get delayed onset of symptoms (12 hours or more) with acute deliberate overdose?

Due to slow entry of lithium into tissues and continuing absorption from MR forms

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What is the therapeutic serum-lithium concentration range?

0.4-1mmol/litre

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Which concentration of serum-lithium is associated with serious toxicity? What might treatment consist of?

More than 2mmol/litre
May require haemodialysis if neurological symptoms or renal failure

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Why should lithium be prescribed by brand

Preparations can vary widely in bioavailability

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What are the two lithium salts available

Lithium carbonate & lithium citrate
They are NOT dose equivalent

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How to manage acute overdose

High serum-lithium concentrations may be present without features of toxicity
Usually just need to take measures to increase urine output (e.g. increase fluid intake but AVOID diuretics)
Otherwise, give supportive treatment and consider electrolyte balance, renal function, control of convulsions
Consider gastric lavage if appropriate
Consider whole-bowel irrigation for significant ingestion

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When is gastric lavage appropriate in managing acute overdose

Consider it if it can be performed within 1 hour of ingesting significant quantities of lithium

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Use of lithium salts in pregnancy

Avoid if possible, esp in 1st trimester (teratogenic risk including cardiac abnormalities)
Dose requirements increased during 2nd and 3rd trimester
Return abruptly to normal dose on delivery of baby
Close monitoring of serum-lithium concentration as risk of toxicity in neonate

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Use of lithium salts when breastfeeding

Avoid - present in milk & risk of toxicity in infant

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Use of lithium salts in renal impairment

Use with caution in mild-moderate impairment
Avoid in severe impairment

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How many hours post-dose should serum lithium concentrations be taken?

12 hours

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What is the serum lithium concentration that should be achieved, including the range for maintenance therapy & for elderly patients

0.4-1mmol/litre
Lower range of this for elderly & maintenance therapy

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What is the target serum lithium concentration that is recommended for acute episodes of mania & for patients who have previously relapsed or who have sub-syndromal symptoms

0.8-1mmol/litre

How often should serum lithium concentrations be taken

Weekly after initiation, and after each dose change until concentrations are stable
Then every 3 months for the 1st year
Then every 6 months thereafter

In which cases should serum lithium concentration be taken every 3 months?

65 and over
Taking drugs that interact (e.g. NSAIDs)
At risk of impaired renal or thyroid function
Increased calcium levels or other complications
Poor symptom control
Poor adherence
Last serum lithium conc was 0.8mmol/L or higher

When should additional measurements of serum lithium concentrations be taken

If pt developed significant intercurrent disease
Or if there is a significant change in pt sodium or fluid intake

Why is abrupt withdrawal of lithium not recommended?
What should you consider prescribing if lithium is to be stopped abruptly?

Increased risk of relapse
If stopped or discontinued abruptly, consider changing to atypical antipsychotic or valproate

If lithium is stopped, the dose should be gradually decreased over a period of….

At least 4 weeks
Preferably up to 3 months

Does treatment cessation cause withdrawal or rebound psychosis?

No clear evidence of this. However stopping lithium abrupt increases the risk of relapse

Lithium: important interactions with drugs that alter renal function e.g.

ACEi
ARBs
NSAIDs
Diuretics

Can lithium be taken with ACEi e.g. ramipril, enalapril, perindopril

Severe interaction: predicted to increase concentration of lithium; monitor and adjust dose Also increases risk of nephrotoxicity

Can lithium be taken with ARBs e.g. candesartan, olmesartan, losartan, valsartan

Severe Interaction: potentially increased conc of lithium; monitor conc and adjust dose

Can lithium be taken with NSAIDs e.g. naproxen, ketoprofen, meloxicam, celecoxib?

Severe interaction: increased conc of lithium; monitor conc and adjust dose

Can lithium be taken with diuretics e.g. chlortalidone, eplerenone, indapamide, bendroflumethiazide, metolazone, spironolactone, furosemide

Severe interaction: increases conc of lithium; monitor conc and adjust dose

Can lithium be taken with serotonergic drugs e.g. MAOis, SSR agonists like almotriptan, citalopram, fluoxetine, dexamfetamine, fentanyl, ondansetron?

AVOID - increased risk of serotonin syndrome

Can lithium be taken with TCAs e.g. lofepramine, amitriptyline, nortriptyline, clomipramine, dosulepin?

Use with caution - increased risk of neurotoxicity

Can lithium be taken with methotrexate

Increased risk of nephrotoxicity - but no recommendations, so can be used

Which class of antibiotics should be avoided, or the dose adjusted, in patients taking lithium? What is the interaction?

- The tetracyclines e.g. oxytetracycline, lymecycline, doxycycline, minocycline - Increased risk of lithium toxicity

Which antibiotics interact severely with lithium (one class of abx + one type)

Tetracyclines - increased risk of lithium toxicity. Avoid or adjust dose. Metronidazole - increased conc of lithium. Avoid or adjust dose.

Indications for lithium

- Treatment and prophylaxis of: ○ Mania ○ Bipolar disorder ○ Recurrent depression ○ Aggressive or self-harming behaviour

Dose of lithium

- Adjusted according to serum-lithium concentration - Doses initially divided throughout the day - Once daily administration is preferred when serum-lithium concentration is stabilised

Lithium is contraindicated in

Addison's disease Cardiac disease associated with rhythm disorder Cardiac insufficiency Dehydration FHx or PHx Brugada syndrome Low sodium diet Untreated hypothyroidism

Caution for lithium salts in long term use

○ Associated with thyroid diseases and mild cognitive & memory impairment ○ Only undertake with careful assessment of risk and benefit ○ Monitor thyroid function every 6 months (more often if evidence of deterioration) ○ Need for continued therapy should be assessed regularly and pt should be maintained after 3-5 years only if benefit persists

Patient and carer advice for all pt on lithium salts

- Report any signs and symptoms of lithium toxicity, hypothyroidism, renal dysfunction (e.g. polyuria, polydipsia) and benign intracranial hypertension (persistent headache and visual disturbance) - Maintain adequate fluid intake and avoid dietary changes which reduce or increase sodium intake - Lithium treatment packs on initiation (PIL, lithium alert card, record book for serum-lithium conc) - May impair performance of skilled tasks e.g. driving and operating machinery

Monitoring of pt parameters

- Assess renal, cardiac and thyroid function before treatment initiation ECG recommended if CVD or risk factors for it - Body weight/BMI, serum electrolytes, eGFR and thyroid function every 6 months during treatment (more often if evidence of impaired renal/thyroid function or raised calcium levels) - Monitor cardiac function regularly

Cautions for lithium

- Avoid abrupt withdrawal (risk of relapse) - Cardiac disease - Concurrent ECT (may lower seizure threshold) - Diuretic treatment (risk of toxicity) - Elderly (reduce dose) - Epilepsy (may lower seizure threshold) - Myasthenia Gravis - Psoriasis (risk exacerbation) - QT interval prolongation - Review dose as necessary in diarrhoea, vomiting, and intercurrent infection (esp if sweating profusely) - Surgery - Long term use