Minocycline
249270
225689566
2008-07-14T22:29:47Z
Wolfkeeper
41690
/* Side effects */ unreferenced
{{drugbox
| 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<ref>[http://redpoll.pharmacy.ualberta.ca/drugbank/cgi-bin/getCard.cgi?CARD=APRD00547.txt DrugBank: DB01017 (Minocycline)<!-- Bot generated title -->]</ref>
| image = Minocycline structure.png
| CAS_number = 10118-90-8
| ATC_prefix = J01
| ATC_suffix = AA08
| ATC_supplemental = {{ATC|A01|AB23}}
| PubChem = 24960
| DrugBank = APRD00547
| C=23 | H=27 | N=3 | O=7
| molecular_weight = 457.477
| bioavailability = 100%
| protein_bound =
| metabolism = [[liver]]
| elimination_half-life = 11-22 hours
| excretion = mostly [[fecal]], rest [[renal]]
| pregnancy_AU = <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US = <!-- A / B / C / D / X -->
| pregnancy_category=
| legal_AU = S4
| legal_CA = <!-- / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK = <!-- GSL / P / POM / CD / Class A, B, C -->
| legal_US = <!-- OTC / Rx-only / Schedule I, II, III, IV, V -->
| legal_status =
| routes_of_administration = 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 [[blood plasma|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 [[American Cyanamid|Lederle Laboratories]] and marketed under the brand name ''Minocin''.<ref>[http://www.scripps.edu/chem/baran/images/grpmtgpdf/Lin_Mar_05revised.pdf]Lin, DW The Tetracyclines March 2005</ref>
==Indications==
[[Image:Minocycline-150.jpg|thumb|left|Minocycline 100 mg Capsules.]] It is primarily used to treat [[Acne vulgaris|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 (medical)|vertigo]]).
It may be used to treat certain strains of [[Methicillin-resistant Staphylococcus aureus|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 ([[Doxycycline]] excluded), minocycline may be used in renal impairment, but may aggravate [[systemic lupus erythematosus]].<!--
--><ref name="Note1">{{cite journal | author=Gough A, Chapman S, Wagstaff K, Emery P, Elias E | title=Minocycline induced autoimmune hepatitis and systemic lupus erythematosus-like syndrome | journal=BMJ | year=1996 | pages=169–72 | volume=312 | issue=7024 | pmid=8563540 |url=http://bmj.bmjjournals.com/cgi/content/full/312/7024/169}}</ref>
Also, more so than other tetracyclines, minocycline can cause the rare condition of [[idiopathic intra-cranial hypertension|secondary intracranial hypertension]] which has initial symptoms of headache, visual disturbances, and confusion. [[Cerebral edema]], as well as autoimmune [[rheumatoid arthritis]] are rare side effects to minocycline in some people.<!--
--><ref>{{cite journal|title=Minocycline-induced hypersensitivity syndrome presenting with meningitis and brain edema: a case report|author=Lefebvre N, Forestier E, Farhi D, ''et al.''|journal=Journal of Medical Case Reports|year=2007|volume=1|pages=22|doi= 10.1186/1752-1947-1-22}}</ref>
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.<ref>{{cite book |title=Drug Interactions in Infectious Diseases |last=Piscitelli |first=Stephen C. |coauthors=Keith Rodvold |year=2005 |publisher=Humana Press |isbn=1588294552 }}</ref>
In a recent news item in Science dated 23 November 2007, it has been mentioned that MINOCYCLINE in [[Amyotrophic lateral sclerosis|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 than those on the low doses. Science Vol 318, 1227, 2007.
==Side effects==
{{Unreferencedsection|date=July 2008}}
This medication may cause upset stomach, [[diarrhea]], [[dizziness]], unsteadiness, [[somnolence|drowsiness]], [[headache]] or [[vomiting]]. If these symptoms persist or worsen, one should notify their doctor. Minocycline increases [[photophobia|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]], [[jaundice|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).
== Uses ==
* [[Acne]]
* [[Amoebic dysentery]]
* [[Anthrax]]
* [[Cholera]]
* [[Gonorrhea]] (when [[penicillin]] cannot be given)
* Gougerot-Carteaud Syndrome ([[Confluent and Reticulated Papillomatosis]])
* [[Lyme Disease]]
* [[Bubonic plague]]
* Respiratory infections such as [[pneumonia]]
* [[Rocky Mountain spotted fever]]
* [[Syphilis]] (when penicillin cannot be given)
* [[Urinary tract infection]]s, rectal infections, and infections of the [[cervix]] caused by certain microbes
==Anti-inflammatory and neuroprotective==
Current research is examining the possible neuroprotective and anti-inflammatory effects of minocycline against progression of a group of [[neurodegenerative disorder]]s including [[multiple sclerosis]] (MS), [[rheumatoid arthritis]] (RA), [[amyotrophic lateral sclerosis]] (ALS), [[Huntington's disease]], and [[Parkinsons disease]],<!--
--><ref>{{cite press release |title= Preliminary Study Shows Creatine and Minocycline May Warrant Further Study In Parkinson’s Disease |publisher= National Institute of Health |date= February 23, 2006 |url=http://www.nih.gov/news/pr/feb2006/ninds-23.htm |format= |language= |accessdate=}} </ref> amongst others neurodegenerative diseases.<!--
--><ref name="Note2">{{cite journal | author=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 | title=Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease | journal=Nat Med | year=2000 | pages=797–801 | volume=6 | issue=7 | pmid=10888929 | doi=10.1038/80538}}</ref><!--
--><ref name="Note3">{{cite journal | author=Tikka TM, Koistinaho JE | title=Minocycline provides neuroprotection against N-methyl-D-aspartate neurotoxicity by inhibiting microglia | journal=J Immunol | year=2001 | pages=7527–33 | volume=166 | issue=12 | pmid=11390507 |url=http://www.jimmunol.org/cgi/content/full/166/12/7527}}</ref><!--
--><ref>{{cite journal |author=Nirmalananthan N, Greensmith L |title=Amyotrophic lateral sclerosis: recent advances and future therapies |journal=Curr. Opin. Neurol. |volume=18 |issue=6 |pages=712–9 |year=2005 |pmid=16280684|doi=10.1097/01.wco.0000187248.21103.c5}}</ref>
The neuroprotective action of minocycline may include its inhibitory effect on [[5-lipoxygenase]], <ref name="Note4">
{{cite journal | author=Song Y, Wei EQ, Zhang WP, Zhang L, Liu JR, Chen Z | title=Minocycline protects PC12 cells from ischemic-like injury and inhibits 5-lipoxygenase activation | journal=Neuroreport | year=2004 | pages=2181–4 | volume=15 | issue=14 | pmid=15371729 | doi=10.1097/00001756-200410050-00007}} </ref>
an inflammatory enzyme associated with brain aging, and is being studied for use in [[Alzheimer's disease]] patients.<!--
--><ref name="Note5">{{cite journal | author=Uz T, Pesold C, Longone P, Manev H | title=Aging-associated up-regulation of neuronal 5-lipoxygenase expression: putative role in neuronal vulnerability | journal=FASEB J | year=1998 | pages=439-49 | volume=12 | issue=6 | pmid=9535216 |url=http://www.fasebj.org/cgi/content/full/12/6/439}}</ref>
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 [[apoptotic|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]] .<!--
--><ref>{{cite journal |author=Giuliani F, Hader W, Yong VW |title=Minocycline attenuates T cell and microglia activity to impair cytokine production in T cell-microglia interaction |journal=J. Leukoc. Biol. |volume=78 |issue=1 |pages=135–43 |year=2005 |pmid=15817702 |doi=10.1189/jlb.0804477}}</ref>
Minocycline also inhibits microglial activation, through blockade of [[NF-kB|NF-kappa B]] nuclear translocation.
It is thought that minocycline exerts neuroprotective effects independent of its anti-inflammatory properties.<!--
--><ref name="Maier">{{cite journal |author=Maier K, Merkler D, Gerber J, Taheri N, Kuhnert AV, Williams SK, Neusch C, Bähr M, Diem R |title=Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation |journal=Neurobiol. Dis. |volume=25 |issue=3 |pages=514–25 |year=2007 |pmid=17239606 |doi=10.1016/j.nbd.2006.10.022}}</ref>
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 [[Blood vessel|vascular]] [[cell adhesion molecule|cell adhesion molecule-1]] ([[VCAM-1]]). The activity of [[matrix metalloproteinase|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.<!--
--><ref>{{cite journal |author=Zabad RK, Metz LM, Todoruk TR, Zhang Y, Mitchell JR, Yeung M, Patry DG, Bell RB, Yong VW |title=The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study |journal=Mult. Scler. |volume=13 |issue=4 |pages=517–26 |year=2007 |pmid=17463074 |doi=10.1177/1352458506070319}}</ref><!--
--><ref>{{cite journal |author=Zemke D, Majid A |title=The potential of minocycline for neuroprotection in human neurologic disease |journal=Clinical neuropharmacology |volume=27 |issue=6 |pages=293–8 |year=2004 |pmid=15613934|doi=10.1097/01.wnf.0000150867.98887.3e}}</ref><!--
--><ref name="Maier">{{cite journal |author=Maier K, Merkler D, Gerber J, Taheri N, Kuhnert AV, Williams SK, Neusch C, Bähr M, Diem R |title=Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation |journal=Neurobiol. Dis. |volume=25 |issue=3 |pages=514–25 |year=2007 |pmid=17239606 |doi=10.1016/j.nbd.2006.10.022}}</ref><!--
--><ref>{{cite journal |author=Popovic N, Schubart A, Goetz BD, Zhang SC, Linington C, Duncan ID |title=Inhibition of autoimmune encephalomyelitis by a tetracycline |journal=Ann. Neurol. |volume=51 |issue=2 |pages=215–23 |year=2002 |pmid=11835378|doi=10.1002/ana.10092}}</ref>
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.<!--
--><ref name="pmid17909152">{{cite journal |author=Lampl Y, Boaz M, Gilad R, ''et al'' |title=Minocycline treatment in acute stroke: an open-label, evaluator-blinded study |journal=Neurology |volume=69 |issue=14 |pages=1404–10 |year=2007 |pmid=17909152 |doi=10.1212/01.wnl.0000277487.04281.db}}</ref>
==Trade names and availability==
Minocycline is no longer covered by patent and is therefore marketed under several trade names:
*'''Minomycin'''
*'''Minocin'''
*'''Minoderm'''
*'''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==
{{reflist|2}}
==External links==
*[[New Zealand]] [http://www.medsafe.govt.nz/profs/Datasheet/m/Minotabtab.htm Datasheet] May 2002
*[http://www.drugs.com/minocycline.html Minocycline on drugs.com]
*[http://www.medicinenet.com/minocycline-oral/article.htm Minocycline on medicinenet.com]
* Minocycline to Treat Childhood Regressive Autism [http://clinicaltrials.gov/ct2/show/NCT00409747]
{{Stomatological preparations}}
{{TetracyclineAntiBiotics}}
[[Category:Tetracycline antibiotics]]
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