Discuss the possible mechanisms of action of lithium.

• Mediated by Li+
• Influences IP3 and DAG 2nd messenger systems by decreasing various enzymes which are very important for conversion and re-circulation of membrane phosphoinositides.
• IP3 and DAG is important in monoamine and cholinergic neurotransmission.

What is the therapeutic index of lithium and what is its clinical significance?

• 0.5 - 1.5 mM
• >2mM is toxic
• Plasma levels is very important and therapeutic drug monitoring should be executed.

When is lithium used as single drug and in which cases and with which type of drugs is lithium combined? 

• Clonazepam and lorazepam is used in combination with lithium.
• Tradition APD's worsen EPS in combination with lithium, therefore it will then be used in mono therapy.

Name 3 clinically significant interactions lithium may have with other drugs. Illustrate your answer with suitable examples of drugs.

• Neurotoxic combination with carbamazepine, calcium channel blockers, losartan, etc.
• Traditional APD (chlorpromazine, periciazeine, etc.) worsen EPS in combination with lithium
• Diuretics, such as thiazides increases Li+ which can result in toxicity.
• Theophylline and caffeine increases renal excretion of lithium

Name the major side effects of lithium.

• Tremors, sedation, ataxia, aphasia
• Muscle weakness, fatigue
• Polidypsia, Poliuria, Nocturia
• Nephrogenic diabetes insipidus
• Thyroid enlargement

What is the status of the use of lithium during pregnancy and lactation?

Given the very high risk of relapse in the postpartum period, a high target therapeutic lithium level is recommended. Most clinical guidelines discourage breastfeeding in women treated with lithium.

Name three other important indications for lithium.

• Anxiety
• OCD
• Prophylactic use can prevent mood swings between mania and depression
• Hypomania and mania