Article: Minocycline

Minocycline
Systematic (IUPAC) name
2-(amino-hydroxy-methylidene)-4,7- bis(dimethylamino)-10,11,12a-trihydroxy-4a,5,5a, 6-tetrahydro-4H-tetracene-1,3,12-trione (synonym 7-Dimethylamino-6-demethyl- 6-deoxytetracycline)
Identifiers
CAS number	10118-90-8
ATC code	J01AA08
PubChem	24960
DrugBank	APRD00547
Chemical data
Formula	C23H27N3O7
Mol. weight	457.477
Pharmacokinetic data
Bioavailability	100% (oral)
Metabolism	liver
Half life	11-22 hours
Excretion	mostly fecal, rest renal
Therapeutic considerations
Pregnancy cat.	? (Aust)
Legal status	Schedule 4 (Aust)
Routes	oral

Minocycline hydrochloride, also known as minocycline, is a member of the broad spectrum tetracycline antibiotics, and has a broader spectrum than the other members. As a result of its long half-life it generally has serum levels 2-4 times that of most other tetracyclines (150 mg giving 16 times the activity levels compared to 250 mg of tetracycline at 24-48 hours).

It is marketed under several trade names, including Minomycin, Minocin, Arestin, and Dynacin.

Indications

It is primarily used to treat acne and rosacea as the once daily 100mg doasage is far easier for patients than the four times a day required with Tetracycline or Oxytetracycline.

Although minocycline's broader spectrum of activity, compared to other members of the group, includes activity against Neisseria meningitidis, its use as a prophylaxis is no longer recommended because of side effects (dizziness and vertigo).

It may be used to treat certain strains of MRSA infection and disease caused by drug resistant Acinetobacter.

For other uses of Minocycline see Tetracycline antibiotics and Oxytetracycline as the uses are much the same between Tetracyclines with only minor exceptions.

Cautions and Side effects

In addition to those common to the Tetracycline antibiotics group, minocycline may be used in renal impairment, but may aggrevate systemic lupus erythematosus.^[1]

Also, moreso than other tetracyclines, minocycline can cause the rare condition of secondary intracranial hypertension which has initial symptoms of headache, visual disturbances, and confusion.

Minocycline, like all Tetracyclines, becomes dangerous past its expiration date. While most prescription drugs lose potency after their expiration dates, tetracyclines are known to become toxic over time; expired tetracyclines can cause serious damage to the kidneys.

Minocycline's absorption is impaired if taken at the same time of day as calcium or iron supplements. Unlike some of the other tetracycline group antibiotics, it can be taken with calcium rich foods such as milk, although this does reduce the absorption slightly (by ~5%).

For further information, see below.

Possible additional indications

Current research is examining the possible neuroprotective effects of minocycline against progression of Huntington's Disease, an inherited neurodegenerative disorder.^[2][3] The neuroprotective action of minocycline may include its inhibitory effect on 5-lipoxygenase, ^[4] an inflammatory enzyme associated with brain aging.^[5] It also has been used as a last ditch treatment for toxoplasmosis in AIDS patients.

Even in the first decade of the 21st Century, many physicians in the UK still claimed to be completely unaware of the damage that Minocycline can cause [See Pediatrics 101(5):926-928, Archives of Dermatology 135(2):139-140 and 136(9):1143-1145, Archives of Internal Medicine 159(5):493-497 and Rheumatology 40(3):329-335 inter alia]. The deficiencies in the "Yellow Card" reporting system (and consequently in reference works, such as the British National Formulary) are well-known.

Thankfully, in most cases, the problems have been resolved, once the drug has been discontinued. Most of the conditions, caused by Minocycline, are auto-immune disorders [Rheumatoid Arthritis, Lupus, auto-immune hepatitis etc]. There is some suggestion that Minocycline has been responsible for a number of cases of chronic fungal infections, such as candidiasis, but more work remains to be done, in this area. One authority, Dr Neil McHugh of the Royal National Hospital for Rheumatic Diseases, in Bath, has noted that a number of patients, who had taken Minocycline, appeared to be suffering from a form of depression or Chronic Fatigue Syndrome. It is possible that these states are related to Lupus and benign intracranial hypertension.

Increased CSF pressure is also associated with the neuro-psychiatric phenomenon of derealisation, which has been noted in several Minocycline recipients [Southern Medical Journal 97:70-73].

Minocycline is known to cause a Serum-Sickness-Like Reaction. This is a type of delayed allergic reaction, in which the immune system interprets the antibiotic as a foreign threat, as if it were animal protein. The reaction is more likely to be severe, if the drug has been given to the patient, a number of times. Minocycline, which has passed its "use-by" date, can cause severe damage to the kidneys.

It is interesting to note that, following the publication of several articles in the British Medical Journal in the 1990s, the number of UK prescriptions [800 000 in 1993] for the drug stopped rising and then began to fall [BMJ 1998 316.72-73]. Such was the decrease in demand that the UK licence holder [Wyeth Laboratories] cut back on production and reduced the range of doses available.

One of the great advantages of Minocycline is the inability of bacteria to become resistant. Thus, although it was originally developed with Weil's Disease and Syphillus in mind, it came to be very popular with dermatologists, as a treatment for teenage acne. Even other antibiotics in the Tetracycline "family" have fallen victim to the problem of resistance.

Several types of antibiotic, including tetracyclines, work by inhibiting the action of enzymes, which bacteria need, in order to produce the proteins, from which new DNA is formed. Once these "building blocks" have been removed, the reproduction of bacteria is prevented. Over time, the existing bacteria will die but new cells won't be able to take their place and the bacterial "population" will dwindle.

It is likely, therefore, that Minocycline also inhibits the action of other enzymes, which have nothing to do with the reproduction of bacteria. This could explain why the drug is being used (in effect as an immuno-suppressant) to treat MS and arthritis and also to slow down degenerative brain conditions, by preventing the destruction of neurons.

Minocycline, licensed in 1973, was sold under the brand names "Minocin", "Minocin MR" and others. "MR" stands for "modified release": absorption was more efficient, when split between the stomach and the duodenum. During the 1990s, a switch was made from tablets to capsules.

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