Infectious diseases: Pharmacology - Tetracyclines

Question 1

Bacteriostatic or bactericidal?

Answer 1

Bacteriostatic

Question 2

Mechanism of action of tetracyclines

Answer 2

Bind reversibly to ribosomal 30S subunit to inhibit bacterial protein synthesis

Question 3

Examples of tetracyclines

Answer 3

Doxycycline
Minocycline
Tetracycline

Question 4

Coverage of tetracyclines

Answer 4

Broad-spectrum
Gram positive and negatives including Rickettsiae, Chlamydiae, Mycoplasma, some protozoas
Anaerobes

Question 5

Major indications for tetracyclines

Answer 5

Mycoplasma pneumoniae
Chlamydiae
Rickettsiae (Lyme disease, typhus)
Some spirochetes (including Treponema pallidum)
In combination regimens for H. pylori
Stops shedding of vibrios in cholera (although facing increasing rates of resistance)

Question 6

Why are tetracyclines no longer used in gonococcal disease?

Answer 6

Due to increasing rates of resistance

Question 7

Other indications for tetracyclines

Answer 7

Acne vulgaris
Exacerbation of bronchitis
CAP
Leptospirosis

Question 8

Three mechanisms of resistance to tetracyclines

Answer 8

1. Decreased intracellular accumulation due to impaired influx or increased efflux via active transport protein pump (encoded on plasmid)
2. Ribosome protection due to production of proteins that impair binding of tetracycline to ribosome
3. Enzymatic inactivation of erythromycin

Question 9

How do doxycycline and minocycline retain some activity against bacteria which have developed active transport protein pump to increase efflux of tetracyclines?

Answer 9

Less rapidly pumped than other tetracyclines

Question 10

Describe the pharmacokinetics of tetracyclines

Answer 10

Absorption: good oral absorption but impaired by food, various ions (Ca2+, Mg2+, Fe2+, Al3+), alkaline pH
Distribution: widely distributed except into CSF
Excretion: predominantly bile and urine (except doxycycline - does not need renal adjustment), some in faeces

Question 11

Six adverse reactions to tetracyclines

Answer 11

1. GIT upset (nausea, vomiting, diarrhoea) and disruption of normal flora
2. Deposited in growing teeth and bones (causes discolouration, growth inhibition, deformity; avoid use in <8yo)
3. Liver, kidney and local tissue toxicity
4. Photosensitisation
5. Vestibular reactions (vertigo)
6. Crosses placenta