•ANTIMANIACS

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•
•Mania → excessive desire, too much of
euphoria.

•bipolar manic depressive psychosis.

•Genetic predisposition

•drugs that reduce DA or NE activity relieve

mania.

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•Lithium is a small monovalent cation like Na+ or
K+.

•Evidence of Li+ efficacy for treating MDP was a

chance discovery.

•In 1940, lithium chloride was introduced as a Na+

free table salt for use by hypertensive patients.

•1960 to 1970 → importance of maintaining its

therpeutic range of plasma level was realised

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*
•
•In mania the neuronal circuits become
overactive and start producing more IP3 and
DAG, and in turn inositol

•Lithium selectivley inhibit signal

transduction in overactive neurons by
blocking conversion of IP2 to IP1 and of IP1
to inositol.

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•As a result the supply of free inositol to
regenerate PIP2, in the hyperactive
neurons, is interrupted and ultimately the
release of IP3 and DAG is also reduced.

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OTHER MECHANISMS:

1. may uncouple receptors from their G-

protein.

2. alterations of PKC mediated signaling,

alter gene expression as well as the
production of proteins implicated in long
term mood stabilization.

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PHARMACOKINETICS:

•Lithium is readily absorbed from GIT. Distribution

→ no protein binding or metabolism.

•The elimination half life is 24 hrs but the does are

given at 8 hourly interval.

•It is excreted primarily through kidney (96% ) but

through saliva and sweat (4%) as well.

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•Na+ loading enhances Li+ clearance ➔
explains the appearance of Li+ toxicity
associated with diuretics and diarrhoea.

• Since Li+ has a low margin of safety and a

narrow therapeutic window (0.5 – 1.5
mEq/L), the frequent measurement of serum
steady state concentration are essential.

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•Because of biphasic elimination rate, Li+
plasma conc. Are usually determined 12
hours after the last dose.

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•THERAPEUTIC USES:

--- Lithium is used as lithium carbonate as it

is less hygroscopic and less GIT irritant than
lithium chloride.

--- starting dose is 300 – 600 mg TDS.

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Manic depressive bipolar psychoses
•Lithium is the first line therapy

•65-70% cases → improve

•“rebound effect”

•Because the therapeutic actions of lithium

take 10-15 days to develop, it is generally
used in combination with other drugs.

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•Benzodiazepines such as lorazepam or
clonazepam are indicated as adjuvants for
short term management of agitation usually
associated with mania.

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OTHER USES:
•Leucocyte count is increased with lithium
therapy. This property of lithium is utilised to
treat cancer chemotherapy induced
leukopenia and agranulocytosis.

•Lithium is occasionally used to treat cluster

headache and as an adjuvant to tricyclic
antideprssants in recurrent unipolar
depression.

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ADVERSE EFFECTS:

1. Fine tremors (controlled by propranolol ),

confusion and slurred speech may be seen
even at therapeutic conc.

2. subclinical hypothyroidism → on long

term use

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3. long term use some patients develop
nephrogenic diabetes insipidus,.

resistant to ADH but responds to the

potassium sparing diuretic amiloride.

4. Diarrhoea

5. oedema
Folliculitis
Leukocytosis

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6. renal clearance of Li+ increases during
pregnancy but decrease immediately after
delivery. Dose adjustments are thus needed
accordingly.

➔ avoided in lactating mothers.

•a very low risk of teratogenicity.

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 DRUG INTERACTION
Phenothiazine Increase risk of extrapyrmidal side effects
butyrophenone

Thiazide , loop diuretics Rise in Li+ plasma conc.

NSAIDS (except aspirin, Reduce renal clearance of Li+

PCM)

Insulin / sulfonylurea Increase risk of hypoglycemia

Succinyl choline or d- Increase muscle relaxation

tubocurarine

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• ALTERNATIVE DRUGS TO LITHIUM

• With lithium → 50% response

1. VALPROIC ACID
-- Alone or in combination with lithium
-- Frequent adjustment of doses between
750 mg /day to 2000 mg / day

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2. CARBAMAZEPINE

-- Alone or in combination with lithium

-- Starting dose → 200 mg BD

3. Newer anticonvulsant
-- gabapentin, topiramate
-- Lamotrigine → in cyclic episode of MDP,
minimal risk of inducing mania.

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4. Atypical antipsychotics
Olanzapine, risperidone, quetiapine →
adjuvant to Li+ → for acute mania and bipolar
disorder