2. Specifics

Question 1

what is the MOA of llithium?

Answer 1

Li is a mood stabilizer. Its MOA is increasing GABA and serotonin activity

increase in GABA inhibits over-excitation in the brain= stabilizes the mood

Question 2

with lithium, what is the onset of action?

Answer 2

5 days, and at the point, one must check its level.

Question 3

So with lithium, before you prescribe it to the patient, what investigations should you do?

Answer 3

Prior to starting a patient on Li, they need their renal, CVS and thyroid functions checked

Question 4

how long does it take Lithium to reach therapeutic dose?

Answer 4

It takes 20-40 days to reach therapeutic dose.

You’re aiming for:
Acute: 0.8-1
Maintenance: 0.6-0.8
Toxicity is experienced >1.2
Need to check Li level on day 5, and then once at optimal dose, do weekly for 4-6 weeks.

Question 5

With lithium, you give it to the patient, what doses are you looking out fore?

Answer 5

You’re aiming for:
Acute: 0.8-1
Maintenance: 0.6-0.8
Toxicity is experienced >1.2

Question 6

How often do you need to check lithium levels in a patient?

Answer 6

Need to check Li level on day 5, and then once at optimal dose, do weekly for 4-6 weeks.

Question 7

how is lithium excreted?

Answer 7

renaly

and because is it minimally protein bound, it is freely filtered at a rate
depending on the GFR

Hence patients with renal dysfunction are at greater risk of toxicity and need
dose adjustments.

Question 8

what type of patients might reach lithium toxicity sooner?

Answer 8

Hence patients with renal dysfunction are at greater risk of toxicity and need
dose adjustments.

lithium is excreted renaly

Question 9

so you give a patient lithium, what are the less severe side effects of lithium that you’re expecting?

Answer 9

Less severe
● Polyuria, polydipsia and dry mouth
● Shakiness/tremor
● Confusion

● Transient GI Sxs
● Dizziness/vertigo
● Leukocytosis (increased WCC)

● Headache
● Muscle weakness
● Acne
● Cognitive dulling

Question 10

so you give a patient lithium, what are the more severe side effects of lithium that you’re expecting?

Answer 10

More severe
● Hypothyroidism
● Nephrogenic diabetes insipidus (competes with ADH receptors and increases renal water
output)

● Kidney injury
● Aplastic anaemia

Question 11

you give your patient lithium and they come back with acute lithium toxicity, how are they presenting?

Answer 11

Acute: Predominantly GI Sxs such as N/V, cramping and diarrhoea. Progression of acute toxicity can
involve neuromuscular signs like dystonia, hyperreflexia, ataxia. Rarely can get cardia dysrhythmias (like
T wave flattening). Acute exposure can also cause leukocytosis.

Question 12

what medication precipitates lithium toxicity?

Answer 12

● Loop and thiazide diuretics
● NSAIDs especially aspirin
● ACE inhibitors

Question 13

you give your patient lithium and they come back with acute-on-chronic lithium toxicity, how are they presenting?

Answer 13

These are patients who take Li regularly and recently took a larger-than-usual dose.

Usually have both GI and neuro symptoms.

Question 14

you give your patient lithium and they come back with chronic lithium toxicity, how are they presenting?

Answer 14

Chronic: Usually precipitated by introduction of a new medication that impairs excretion of Li or induces
a hypovolemic state.

Sxs mainly neurological such as altered mental state, coma, seizures (in severe
cases). Also nystagmus, tremor, ataxia and hyperreflexia. Can develop SILENT (syndrome of irreversible
Li-effectuated neurotoxicity) characterised by cognitive impairment, sensorimotor peripheral neuropathy and cerebellar dysfunction.

Renal toxicity is also common with chronic Li therapy- can get nephrogenic diabetes insipidus, renal tubular acidosis, nephrotic syndrome or chronic tubulointerstitial nephritis.

Chronic toxicity can also result in hypothyroidism.

Li is avidly taken up by thyroid cells and block TH release from thyroglobulin.

Chronic exposure can also result in aplastic anaemia.

Question 15

how do you manage lithium toxicity?

Answer 15

STOP LITHIUM IMMEDIATELY.
ABC
Fluid therapy is mainstay of Tx:

If mild, can give N saline drip.

If more severe, we give 5g Na Bicarb 2x/day.

If severe (level >3): dialyze and
admit to ICU.

Supportive therapy is the mainstay of Mx of Li toxicity.

Airway protection and prevention of aspiration are NB.

Seizures can be controlled with benzos/phenobarb/propafol.

Occasionally in cases of OD, gastric lavage can be done.

Whole bowel irrigation can be done in
extended-release Li.

Question 16

what is the MOA of sodium valproate (epilim)?

Answer 16

blockade of voltage-gated Na channels and increases levels of GABA

(which decreases overexcitation and stabilizes mood).

Mostly metabolised in the liver by CYP450 enzymes.

Question 17

How is Na Valproate metabolised?

Answer 17

Mostly metabolised in the liver by CYP450 enzymes.

Question 18

You give your patient Na Valproate, what kind of monitoring/ investigations do you need to do every time they come in?

Answer 18

Monitoring: FBC, LFTs and renal function 6 monthly.

Question 19

you give your patient Na Valproate, what other medication are you hesitant about giving them together?

Answer 19

Levels are increased by other antiepileptics, aspirin and erythromycin.

Levels decreased by
carbapenem antibiotics and COC.

Question 20

you wanna give your patient Na Valproate, what contraindications would stop you?

Answer 20

severe liver impairment (and things that increase hepatic risk like urea cycle d/os and mitochondrial disease), pregnancy, kids <2, porphyria, pancreatitis.

Question 21

you give your patient Na Valproate, what less severe side effects are you expecting?

Answer 21

● Nausea and vomiting
● GI upset: abdo cramps and diarrhoea
● Dizziness

● Diplopia/blurred vision
● Weakness
● Drowsiness

● Thrombocytopenia/pancytopenia
● Tremor
● Alopecia
● Confusion

Question 22

you give your patient Na Valproate, what more severe side effects are you expecting?

Answer 22

● Weight gain and PCOS risk (or change in menstrual periods)
● Severe pancreatitis

● Hepatotoxicity
● Teratogenicity (severe NTDs)
● SIADH and hypoNa

Question 23

with one of the lithium toxicity side effects, what is Ebstein anomaly

Answer 23

In this condition, your tricuspid valve is in the wrong position and the valve’s flaps (leaflets) are malformed.