Pharmacology for Dentistry

32 Section 1/ General Principles of Pharmacology

into sulfonamide, which was the first
antimicrobial agent in treating the systemic
bacterial infections.

HYDROLYSIS

It is a cleavage of drug molecule by
taking up a molecule of water. The most
hydrolytic enzymes are found outside the
endoplasmic reticulum, and in higher
concentrations in liver, kidney and plasma.
The metabolism of an ester by an enzyme
esterase results in the formation of an acid
and alcohol. The examples are meperidine,
procaina-mide, pethidine and lidocaine etc.
Meperidine is catalyzed by esterases to be
changed into meperidinic acid and
procainamide is catalyzed by amidases.

CONJUGATION REACTION (STAGE II
OR SYNTHETIC REACTIONS)

The conjugation reaction involves the
chemical combination of the reactive group
with a molecule provided by the body e.g.
glucuronic acid, sulfate, glycine. This
conjugation reaction decreases the drug
activity to give a pharmacologically inactive
compound, which is highly water soluble,
that increases the rate of drug excretion.

Glucuronide Conjugation
This is the most common single
metabolic reaction undergone by drugs,
which occurs in the liver. These reactions are
catalyzed by a family of enzymes known as
uridine diphosphate (UDP) glucuronyl
transferases. These enzymes are present in
liver, kidney, intestine and lungs.

The compounds with a hydroxyl or
carboxylic acid groups are easily conjugated
with glucuronic acid which is derived from
glucose.

The examples are aspirin, phenacetin,

morphine, chloramphenicol, metronidazole,

steroidal hormones etc.

Sulfate Conjugation

Sulfate conjugation is catalyzed by a fam-

ily of enzymes known as ‘sulfotransferases’,

which are present in the cell cytoplasm of

liver and other organs. Example are chloram-

phenicol and sex steroids etc.

Acetylation

This reaction is catalyzed by enzymes

‘N-acetyltransferases’ that utilize acetyl-

CoA as a cofactor, and are present in the cell

cytoplasm of the liver, intestine, kidney and

lung.

Examples:

Isoniazid



   

 





N-acetylisoniazid

Other examples are sulfonamides, PAS

etc.

Methylation

This reaction is catalysed by enzyme

‘methyl-transferases’ (catechol-o-methyl-

transferase) and generally uses S-

adenosylmethionine as a methyl donor.

Examples are conversion of norepi-nephrine

into normetanephrine, which has less than

one percent of the vasoconstrictor activity

of the parent compound.

Glutathione Conjugation

It is an important pathway in the

detoxification of a large variety of chemical

toxic substances. Forming a mercapturate is

normally a minor pathway like naphthalene