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Minocycline



Minocycline
Systematic (IUPAC) name
(2E,4S,4aR,5aS,12aR)-2-(amino-hydroxy-methylidene)-4,7-bis(dimethylamino)-10,11,12a-

trihydroxy-4a,5,5a,6-tetrahydro-4H-tetracene-1,3,12-trione[1]

Identifiers
CAS number 10118-90-8
ATC code J01AA08 A01AB23
PubChem 24960
DrugBank APRD00547
Chemical data
Formula C23H27N3O7 
Mol. mass 457.477
Pharmacokinetic data
Bioavailability 100%
Metabolism liver
Half life 11-22 hours
Excretion mostly fecal, rest renal
Therapeutic considerations
Pregnancy cat.

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Legal status

Prescription Only (S4)(AU)

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. It is a bacteriostatic antibiotic. 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). Minocycline was originally discovered by Lederle Laboratories and marketed under the brand name Minocin.[2]

Additional recommended knowledge

Contents

Indications

It is primarily used to treat acne and other skin infections as well as lyme disease as the one pill twice daily 100 mg dosage 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

Contrary to all the other tetracycline antibiotics (Doxycyclin excluded), minocycline may be used in renal impairment, but may be aggravating systemic lupus erythematosus.[3]

Also, more so than other tetracyclines, minocycline can cause the rare condition of secondary intracranial hypertension which has initial symptoms of headache, visual disturbances, and confusion. Meningitis and cerebral edema are rare side effects of minocycline.[4]

Minocycline, like all tetracyclines, becomes dangerous past its expiration date. While most prescription drugs lose potency after their expiration dates, tetracyclines were known to become toxic over time due to the breakdown of certain chemicals present in the manufactured capsules. This is not a present concern in drugs manufactured in first world countries. Expired tetracyclines, as previously manufactured, 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.[5] In a recent news item in Science dated 23rd November 2007, it has been mentioned that MINOCYCLINE in ALS is harmful. Patients on minocycline declined more rapidly than those on placebo. At present the mechanism of this side effect is unknown. According to the researcher from Columbia University the effect does not seem to be dose dependent because the patients on high doses did not do worse that those on the low doses. Science Vol 318, 1227, 2007.

Side effects

This medication may cause upset stomach, diarrhea, dizziness, unsteadiness, drowsiness, headache or vomiting. If these symptoms persist or worsen, one should notify their doctor. Minocycline increases sensitivity to sunlight. It has also been linked to cases of lupus, although rarely. Prolonged sun exposure should be avoided. Wear protective clothing and use a sunscreen if needed. Very unlikely but should be reported: fever, yellowing of the eyes or skin, stomach pain, sore throat, vision changes and mental changes.

In those cases where this drug must be used for extended periods, blue-gray skin discoloration may occur. In the unlikely event one has an allergic reaction to this drug, immediate medical attention should be sought. Symptoms of an allergic reaction include rash, itching, swelling, severe dizziness, trouble breathing. This drug has also been reported to cause Idiopathic intracranial hypertension (Pseudotumor Cerebri). Other effects not listed above should be reported to the doctor or pharmacist.

Uses

Anti-inflammatory and neuroprotective

Current research is examining the possible neuroprotective and anti-inflammatory effects of minocycline against progression of a group of neurodegenerative disorders including multiple sclerosis (MS), rheumatoid arthritis (RA), amyotrophic lateral sclerosis (ALS), Huntington's disease, and Parkinsons disease,[6] amongst others neurodegenerative diseases.[7][8][9]

The neuroprotective action of minocycline may include its inhibitory effect on 5-lipoxygenase,[10] an inflammatory enzyme associated with brain aging, and is being studied for use in Alzheimer's disease patients.[11] It also has been used as a "last ditch" treatment for toxoplasmosis in AIDS patients. Minocycline is neuroprotective in mouse models of amyotrophic lateral sclerosis (ALS) and Huntington's disease and has been recently shown to stabilize the course of Huntington's disease in humans over a 2-year period.

As an anti-inflammatory, minocycline inhibits apoptosis (cell death) via attenuation of TNF-alpha, downregulating pro-inflammatory cytokine output. This effect is mediated by a direct action of minocycline on the activated T cells and on microglia, which results in the decreased ability of T cells to contact microglia which impairs cytokine production in T cell-microglia signal transduction .[12] Minocycline also inhibits microglial activation, through blockade of NF-kappa B nuclear translocation.

It is thought that minocycline exerts neuroprotective effects independent of its anti-inflammatory properties.[13]

A recent study reported the impact of the antibiotic minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in MS patients over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment relapse rate in patients in the study prior to treatment, no relapses occurred between months 6 and 24. The only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of interleukin-12 (IL-12), which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1 (VCAM-1). The activity of matrix metalloproteinase-9 was decreased by treatment. Clinical and MRI outcomes in this study were supported by systemic immunological changes and call for further investigation of minocycline in MS.[14][15][13][16]

A recent study (2007) found that patients taking 200 mg of minocycline for 5 days within 24 hours of an ischemic stroke showed an improvement in functional state and stroke severity over a period of 3 months compared with patients receiving placebo.[17]

Trade names and availability

Minocycline is no longer covered by patent and is therefore marketed under several trade names:

  • Minomycin
  • Minocin
  • Arestin
  • Akamin
  • Aknemin
  • Solodyn
  • Dynacin
  • Sebomin
  • Mino-Tabs

StoneBridge Pharma also markets Minocycline as Cleeravue-M in combination with SteriLid eyelid cleanser in the treatment of rosacea blepharitis.

References

  1. ^ [1]
  2. ^ [2]Lin, DW The Tetracyclines March 2005
  3. ^ Gough A, Chapman S, Wagstaff K, Emery P, Elias E (1996). "Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome". BMJ 312 (7024): 169-72. PMID 8563540.
  4. ^ Lefebvre N, Forestier E, Farhi D, et al. (2007). "Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report". Journal of Medical Case Reports 1: 22.
  5. ^ Piscitelli, Stephen C.; Keith Rodvold (2005). Drug Interactions in Infectious Diseases. Humana Press. ISBN 1588294552. 
  6. ^ National Institute of Health (February 23, 2006). "Preliminary Study Shows Creatine and Minocycline May Warrant Further Study In Parkinson’s Disease". Press release.
  7. ^ Chen M, Ona VO, Li M, Ferrante RJ, Fink KB, Zhu S, Bian J, Guo L, Farrell LA, Hersch SM, Hobbs W, Vonsattel JP, Cha JH, Friedlander RM (2000). "Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease". Nat Med 6 (7): 797-801. PMID 10888929.
  8. ^ Tikka TM, Koistinaho JE (2001). "Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia". J Immunol 166 (12): 7527-33. PMID 11390507.
  9. ^ Nirmalananthan N, Greensmith L (2005). "Amyotrophic lateral sclerosis: recent advances and future therapies". Curr. Opin. Neurol. 18 (6): 712-9. PMID 16280684.
  10. ^ Song Y, Wei EQ, Zhang WP, Zhang L, Liu JR, Chen Z (2004). "Minocycline protects PC12 cells from ischemic-like injury and inhibits 5-lipoxygenase activation". Neuroreport 15 (14): 2181-4. PMID 15371729.
  11. ^ Uz T, Pesold C, Longone P, Manev H (1998). "Aging-associated up-regulation of neuronal 5-lipoxygenase expression: putative role in neuronal vulnerability". FASEB J 12 (6): 439-49. PMID 9535216.
  12. ^ Giuliani F, Hader W, Yong VW (2005). "Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction". J. Leukoc. Biol. 78 (1): 135-43. doi:10.1189/jlb.0804477. PMID 15817702.
  13. ^ a b Maier K, Merkler D, Gerber J, Taheri N, Kuhnert AV, Williams SK, Neusch C, Bähr M, Diem R (2007). "Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation". Neurobiol. Dis. 25 (3): 514-25. doi:10.1016/j.nbd.2006.10.022. PMID 17239606.
  14. ^ Zabad RK, Metz LM, Todoruk TR, Zhang Y, Mitchell JR, Yeung M, Patry DG, Bell RB, Yong VW (2007). "The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study". Mult. Scler. 13 (4): 517-26. doi:10.1177/1352458506070319. PMID 17463074.
  15. ^ Zemke D, Majid A (2004). "The potential of minocycline for neuroprotection in human neurologic disease". Clinical neuropharmacology 27 (6): 293-8. PMID 15613934.
  16. ^ Popovic N, Schubart A, Goetz BD, Zhang SC, Linington C, Duncan ID (2002). "Inhibition of autoimmune encephalomyelitis by a tetracycline". Ann. Neurol. 51 (2): 215-23. PMID 11835378.
  17. ^ Lampl Y, Boaz M, Gilad R, et al (2007). "Minocycline treatment in acute stroke: an open-label, evaluator-blinded study". Neurology 69 (14): 1404–10. doi:10.1212/01.wnl.0000277487.04281.db. PMID 17909152.
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Minocycline". A list of authors is available in Wikipedia.
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