Pharmacology for Dentistry

(Mode of Action of Drugs)

PharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamicsPharmacodynamics

ChapterChapter

5.3 Prostaglandins and Leukotrienes

Prostaglandins

and

Leukotrienes

EICOSANOIDS – PROSTAGLANDINS AND

LEUKOTRIENES

In 1935, von Eular demonstrated a substance
present in the extracts of human seminal
fluid, which caused contraction of the isolated
intestine and uterine muscle. This substance
was named as ‘prostaglandin’ (PG) because
of its probable origin from the prostate gland.
In 1962, the structure of two prostaglandins
namely PGE 1 & PGF2a were elucidated and
in 1964, PGE 2 was biosynthesized.

Biosynthesis and Metabolism

Prostaglandins (PG’s) and leukotrienes
(LT’s) are biologically active derivatives of
20 carbon atom polyunsaturated essential
fatty acids, which contains 3, 4 or 5 double
bonds (e.g. 5, 8, 11, 14-eicosatetraenoic acid
i.e., arachidonic acid).

In human being, arachidonic acid is the
most important precursor for the
biosynthesis of eicosanoids. Arachidonic
acid is formed from linoleic acid in most
mammalians by desaturation and carbon
elongation to dihomog-linolenic acid and
subsequent desaturation.

Inhibitors of Eicosanoid Biosynthesis

Salicylates and related non-steroidal

anti-inflammatory drugs inhibit

cyclooxygenase, thus all the PG’s formed by

this pathway i.e. PGG 2 , PGE 2 , PGD 2 , PGF2a,

TXA 2 and prostacyclin can not be

synthesized.

Pharmacological Actions

Uterus: Uterine smooth muscle from

pregnant women are uniformly contracted

by PGF’s. PGI 2 and high concentrations of

PGE 2 produce relaxation. While, nonpreg-

nant human uterus are contracted by PGF’s

but relaxed by PGE’s.

Bronchial muscle: Bronchial and

tracheal muscle are contracted by PGF’s &

PGD 2 and relaxed by PGE’s. Asthmatic

patients are sensitive to PGF2a and PGE 1 &

PGE 2 causes bronchodilatation. LTC 4 &

LTD 4 are bronchoconstrictors.

Gastrointestinal tract: Longitudinal

muscle is contracted by PGE 2 & PGF2a, while

circular muscle is contracted by PGI 2 &

PGF2a and relaxed by PGE 2.