Pharmacology

Question 1

What is the mode of action of lithium?

Answer 1

Several uncertain effects on biological systems (particularly at high conc), can substitite for Na/K/Ca/Mg and may have effect on cell membrane electrophysiology.

Interacts with cations inside cells including release of NT and 2nd messengers (e.g. adenylate cyclase, inositol 145 triphosphate, arachidonate, PKC, G proteins and calcium) - effectively BLOCKING ACTION OF NTs + HORMONES - also reduction in receptor up-regulation, perhaps explaining value as an adjunctive treatment

Question 2

Lithium increases the plasma concentration of…. ?

Answer 2

ACEIs / ARBs
Analgesics (esp. NSAIDs)
ADs (esp SSRIs)
Anti-epileptics
Anti-hypertensives (e.g. methyldopa), Antipsychotics (esp haloperidol)
Calcium-channel blockers
Diuretics
Metronidazole

Question 3

Lithium decreases the plasma concentration of…. ?

Answer 3

Antacids

Theophylline

Question 4

Lithium can specifically interact with…?

Answer 4

Antiarrhythmics e.g. amiodarone - increased risk of hypothyroidism

Antidiabetics (sometimes impairs glucose tolerance)

Antipsychotics (increased risk of EPSEs)

Muscle relaxants (enhanced effect)

Parasympathomimetics (antagonises neostigmine and pyridostigmine)

Question 5

Prior to starting lithium, what should be checked?

How should the dose be started?

Answer 5

Physical exam, FBC, U&E / GFR, TFTs, baseline BMI, if clinically indicated ECG and pregnancy test

Usually start 400-600mg at night, increased weakly depending on serum monitoring to maximum 2g (usual dose 800mg - 1.2g), actual dose depends on preparation used (molar availability varies even when mg are the sam)

Question 6

How should lithium be monitored?

Answer 6

Check level 7 days after starting and 7 days after each change of dose

Take blood samples 12 hours post-dose

Once therapeutic serum level established, check level and eGFR every 3 months

TFTs every 6 months

Monitor BMI and check for side effects

Question 7

How should lithium be stopped?

Answer 7

Reduce gradually over 1-3 months, particularly if pt has history of manic relapse (even if started on other anti-manic agent)

Question 8

What preparations of Lithium are available?

Answer 8

Camcolit (tablets) - lithium carbonate 250/400mg

Li-liquid (oral soltion) - lithium citrate 509mg/5mL

Liskonum (tablets) - lithium carbonate 450mg

Priadel (tablets) - lithium carbonate 200/400mg

Priadel (liquid) - lithium citrate - 520mg/5mL

Question 9

What are the main dose-related side effects of lithium?

Answer 9

Polyuria/dipsia (ADH antagonism)

Weight gain (carb metabolism and/or oedema)

Cognitive problems (e.g. dulling, impaired memory, poor concentration, confusion, mental slowness)

Tremor

Sedation or lethargy

Impaired co-ordination

GI distress (e.g. nausea, vomiting, dyspepsia, diarrhoea)

Hair loss

Benign leucocytosis

Acne

Oedema

Question 10

How are dose-related side effects of lithium managed?

Answer 10

Lowering dose or altering dose schedule or formulation

If side-effects persist, additional medications may be necessary e.g. B-blockers (tremor), thiazide or loop diuretics (polyuria, polydispia, oedema), topical Abx or retinoic acid (acne)

GI problems can be managed by administering lithium with meals or switching preparations e.g. lithium citrate

Question 11

What are cardiac conduction problems associated with lithium?

Answer 11

Usually benign ECG changes (e.g. T-wave changes, widening of QRS).

Rarely, exacerbation of existing arrhythmias or new arrhythmias due to conduction deficits at the SA or AV nodes (contraindicated in HF, sick sinus syndrome)

Question 12

What are the main long-term adverse effects of lithium?

Answer 12

Renal function (10-20% on long term therapy demonstrate morphological change e.g. interstitial fibrosis, tubular atrophy, sometimes glomerular sclerosis)

Subclinical / clinical hypothyroidism

Teratogenicity