Anti-Manic Drugs Lecture#1

Antimanic agents
OR
Mood Stabilizers
Dr. Muhammad Tariq

Lecture Contents
1.Introduction of Anti-manic drugs

2.Classification of Antimanic drugs
3.Lithium
4.Mechanism of Action of Lithium Salts
5.Pharmacokinetic
6.Adverse Rection
7.Clinical uses
8.Book References 2
Antimanic drugs
• Anti-manic drugs or mood stabilizers are used in
the treatment of mania both to control acute
attacks and to prevent their recurrence
• For bipolar disorder

• In mood cycling, but are not effective in treating
depression
• Treatment of some cases of schizophrenia

3
Classification of Antimanic drugs
1- Lithium salts: Lithium carbonate
2- Anticonvulsants
• Carbamazepine [Tegretol]
• Valproic acid [Depakote]
• Lamotrigine [Lamictal]
3- Atypical antipsychotics
• Olanzapine
• Risperidone
• Clozapine
4- Benzodiazepines (BZs)
4
Lithium
 Lithium ion, Li+, is the oldest and best known mood stabilizing drug
 Lithium salts (carbonate, citrate) are the most commonly prescribed
 60-80% success in reducing acute manic and hypomanic states
It reduces the risk of suicide related to bipolar disorder
1- Prophylaxis and treatment of mania
2- Prophylaxis of and maintenance treatment of bipolar disorders
3- Lithium augmentation
Prophylaxis of recurrent depression in unipolar depression and schizophrenic patients
who don't respond to treatment
5
Proposed Mood Stabilising Mechanism of Action of
Lithium Salts
Neurotransmitter Receptor
Lithium carbonate
X
IP3 formation
Hormone-induced cAMP production
(but not thought to be a significant
mechanism in brain)
Signalling events involving
other receptors
6
 Effect of lithium on the IP3 and DAG second-messenger system.
 The schematic diagram shows the synaptic membrane of a neuron. (PIP2, phosphatidylinositol-4,5-
bisphosphate; PLC, phospholipase-C; G, coupling protein; Effects, activation of protein kinase C,
mobilization of intracellular Ca2+, etc.).
 Lithium, by inhibiting the recycling of inositol substrates, may cause depletion of the second-messenger
source PIP2 and therefore reduce the release of IP3 and DAG.
7
Pharmacokinetics
• Completely absorbed from GIT

• Long plasma half-life (20 hr)
• Not bound to plasma proteins
• Not metabolized in the body
• Distributed in all body fluids
• Slow entry into intracellular compartment.
• Its concentration can be detected in plasma, saliva, urine
8
Pharmacology of Lithium Salts
• no effect in normal person
• stabilizes mood in affective disorder
• low therapeutic index
• toxicity: correlated with plasma concentration; fine tremors, ataxia,
confusion, delirium, convulsions, cardiac arrhythmias
• treatment should be under normal Na+ intake
and normal cardiac and renal function
9
Lithium Carbonate
• Lithium is clinically effective at plasma concentration of 0.5-1 mM.

• Above 1 mm, it produces a variety of toxic effects, therefore, monitoring of plasma
concentration is essential.
• After the drug is started, 7-10 day must be elapsed before the antimanic effect is
reached.
• Lithium causes depletion of membrane phosphatidylinositol and accumulation of
intracellular inositol phosphate.
• Hormone-mediated cAMP production is reduced.
10
Lithium Carbonate
Adverse effects
• Anorexia (loss of appetite) , diarrhoea , hypothyroidism , seizures (Convulsion and
death if plasma concentration reaches 3-5 Mm).
• Leukocytosis , nephrotic syndrome and polyuria , impotence (lacking of power).
• A toxic drug ; adverse reactions are dose-and concentration-dependent .
• Edema is a frequent adverse effect of lithium treatment and may be related to some
effect of lithium on sodium retention.
• Patients receiving lithium should avoid dehydration and the associated increased
concentration of lithium in urine. Periodic tests of renal concentrating ability should be
performed to detect changes.
11
Cardiac Adverse Effects
The bradycardia-tachycardia
 "sick sinus”syndrome is a definite contraindication to the use of lithium
because the ion further depresses the sinus node. T wave flattening is often
observed on the ECG but is of questionable significance
Enlargement of thyroid gland with decreased function (hypothyroidism)
12
Use During Pregnancy
Lithium is transferred to nursing infants through breast milk, in which it has a

concentration about one-third to one-half that of serum. Lithium toxicity in
newborns is manifested by lethargy, cyanosis, poor suckling and perhaps
hepatomegaly.
The issue of dysmorphogenesis is not settled but the most recent data suggest
that lithium carries a relatively low risk of teratogenic effects.
13
Drug Interactions
• Renal clearance of lithium is reduced about 25% by thiazide diuretics

(hydrochlorothiazide, chlorothiazide) and doses may need to be reduced by a
similar amount.
• A similar reduction in lithium clearance has been noted with several of the newer
nonsteroidal anti-inflammatory drugs that block synthesis of prostaglandins
(Ibuprofen, Indomethacin). This interaction has not been reported for either
aspirin or acetaminophen.
• All neuroleptics tested to date, with the possible exception of clozapine and the
newer antipsychotics, may produce more severe extrapyramidal syndromes when
combined with lithium.
14
Summary
Book References
1. Whalen, K., Lippincott illustrated reviews: pharmacology. 2018: Lippincott Williams & Wilkins.
2. Tripathi, K., Essential of Medical Pharmacology; 2008. New Delhi, 2008: p. 235-236.
3. Katzung, B.G., Basic and clinical pharmacology. 2012: Mc Graw Hill.
4. Brenner, G.M. and C.W. Stevens, Brenner and Stevens’ Pharmacology E-Book. 2017: Elsevier Health Sciences.
5. Shanbhag, T., S. Shenoy, and V. Nayak, Pharmacology. 2017: Elsevier Health Sciences.
15
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Antimanic agents

Dr. Muhammad Tariq

1.Introduction of Anti-manic drugs

• For bipolar disorder

• Treatment of some cases of schizophrenia

• Completely absorbed from GIT

• Lithium is clinically effective at plasma concentration of 0.5-1 mM.

Enlargement of thyroid gland with decreased function (hypothyroidism)

Lithium is transferred to nursing infants through breast milk, in which it has a

• Renal clearance of lithium is reduced about 25% by thiazide diuretics

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