A Textbook of Clinical Pharmacology and Therapeutics

Mechanism of action

Macrolides bind to bacterial 50S ribosomes and inhibit protein
synthesis.

Pharmacokinetics

Well absorbed orally and distributed adequately to most sites
except the brain, macrolides are inactivated by hepatic
N-demethylation, 15% being eliminated unchanged in the
urine. Food delays absorption but may reduce gastro-intestinal
side effects.

Adverse effects

Erythromycinis remarkably safe and may be used in pregnancy
and in children. Nausea, vomiting, diarrhoea and abdominal
cramps are the most common adverse effects reported, related to
direct pharmacological actions rather than allergy. Cholestatic
jaundice has been reported following prolonged use.
Intravenous administration frequently causes local pain and
phlebitis.

Drug interactions

Erythromycininhibits cytochrome P450 and causes accumu-
lation of theophylline,warfarinandterfenadine. This can
result in clinically important adverse effects.

AZITHROMYCIN AND CLARITHROMYCIN

Each of these has greater activity than erythromycinagainst
H. influenzae.Azithromycinis less effective against Gram-
positive bacteria than erythromycin, but has a wider spectrum
of activity against Gram-negative organisms. Clarithromycin
is an erythromycinderivative with slightly greater activity
than the parent compound; tissue concentrations are higher
than with erythromycin. It is given twice daily.
Azithromycinandclarithromycinare more expensive than
erythromycin, but cause fewer gastro-intestinal side effects.

TETRACYCLINES

Uses

Tetracyclines (e.g. tetracycline,oxytetracycline,doxycycline)
have a broad range of antibacterial activity covering both
Gram-positive and Gram-negative organisms and, in addition
organisms such as Rickettsia,ChlamydiaandMycoplasma. They
are used in atypical pneumonias and chlamydial and rick-
ettsial infections, and remain useful in treating exacerbations
of chronic bronchitis or community-acquired pneumonia.
They are not used routinely for staphylococcal or streptococ-
cal infections because of the development of resistance.
Tetracyclines are used in the long-term treatment of acne
(Chapter 51).

Mechanism of action

Tetracyclines bind to the 30S subunit of bacterial ribosomes
and prevent binding of the aminoacyl-tRNA to the ribosome
acceptor site, thereby inhibiting protein synthesis.

Adverse effects

These include:

1. nausea, vomiting and diarrhoea (pseudomembranous
   colitis due to Clostridium difficilereported occasionally);
   2.hypersensitivity reactions (including rash, exfoliative
   dermatitis, Stevens–Johnson syndrome, urticaria,
   angioedema, anaphylaxis, pericarditis);
   3.worsening of renal failure;
   4.hepatotoxicity (rare);
   5.discoloration and damage of the teeth and bones of the
   fetus if the mother takes tetracyclines after the fifth month
   of pregnancy, and of children; they should therefore be
   avoided in pregnancy and children under 12 years.

Pharmacokinetics

Tetracyclines are well absorbed orally when fasting, but their

absorption is reduced by food and antacids. They undergo

elimination by both the liver and the kidney. The half-life

varies between different members of the group, ranging from

six to 12 hours. The shorter-acting drugs are given four times

daily and the longer-acting ones once daily. Doxycyclineis

given once daily, can be taken with food and is not contraindi-

cated in renal impairment.

Drug interactions

Tetracyclines chelate calcium and iron in the stomach, and

their absorption is reduced by the presence of antacids or

food.

SODIUM FUSIDATE

Uses

Fusidic acidis combined with other drugs to treat staphylo-

coccal infections, including penicillin-resistant strains. It pen-

etrates tissues (including bone) well. It is normally used in

conjunction with flucloxacillin for serious staphylococcal

infections. It is also available as eyedrops for the treatment of

bacterial conjunctivitis.

Mechanism of action

It inhibits bacterial protein synthesis.

Adverse effects

Adverse effects are rare, but include cholestatic jaundice.

Pharmacokinetics

When administered either orally or intravenously, its half-life

is four to six hours and it is excreted primarily via the liver.

VANCOMYCIN

Uses and antibacterial spectrum

Vancomycinis valuable in the treatment of resistant infections

due to Staphylococcus pyogenes. It is also rarely used to treat

COMMONLYPRESCRIBEDANTIBACTERIALDRUGS 329