Pharmacology for Dentistry

96 Section 2/ Drugs Acting on CNS

PHENOTHIAZINES

PHARMACOLOGICAL ACTIONS

a. Action on CNS: Effects differ in nor-
mal and psychotic individuals.

1. Sedation: They produce sedation
   which does not progress to anaesthesia.
   They decrease the agitation, anxiety and
   aggressiveness in psychotic patient without
   affecting wakefulness.


2. Antipsychotic effect: In schizophrenic
   patients, they improve thought disorders,
   blunted affect, withdrawal and self centered
   behaviour. They also improve the halluci-
   nations and delusions.

They produce neuroleptic syndrome
which consists of motor retardation and
emotional quietening.

In animal studies, they reduce the spon-
taneous motor activity and produce cata-
lepsy (state of rigidity and immobility).

3. Action on CTZ: Chlorpromazine de-
   presses the chemoreceptor trigger zone
   (CTZ) and acts as a powerful antiemetic
   agent.


4. Effect on hypothalamus: They produce
   hypothermia by acting on temperature
   regulating centre. They also produce
   central sympathoplegia resulting in
   miosis and failure in ejaculation.
   They produce parkinsonism like reac-
   tion by increasing the spontaneous firing of
   dopaminergic neurons of basal ganglia.

b. Effect on CVS: Chlorpromazine may

produce orthostatic hypotension prob-

ably due to inhibition of centrally me-

diated pressor reflexes. It also causes

prolongation of QT interval in ECG.

c. Effect on endocrine system: They can

produce amenorrhoea and galactor-

rhoea due to increase in serum prolac-

tin level in females. It also blocks the

release of growth hormone, ADH and

gonadotrophin secretion.

d. Local anaesthetic: Chlorpromazine has

a potent local anaesthetic action.

e. ANS: They have varying degree of a

adrenergic blocking activity. They also

have weak anti-cholinergic, H 1 -

antihistaminic and anti 5-HT actions as

well.

They also cause blockade of postsynap-

tic monoaminergic (including 5-HT, norad-

renaline and dopamine) transmission in the

brain resulting in decrease in central sym-

pathetic activity.

Pharmacokinetics

Phenothiazines are well absorbed after

oral and parenteral administration. They are

distributed in all the body tissues and

metabolised in liver by hydroxylation and

glucuronide conjugation and demethylation.

The metabolites are excreted in urine and bile

for long period of time even after discontinu-

ing the drug.

Adverse Reactions

CNS side effects include lethargy,

drowsiness, increase in REM sleep, restless-

ness, excitement and impaired psychomo-

tor functions.

The other side effects include epileptic

seizures, disturbances in body temperature

regulation. ANS side effects include tachy-

cardia, difficulty in micturition, inhibition

of ejaculation, postural hypotension,

blurring of vision (with thioridazine), con-

stipation, nasal stuffiness etc.