the actions of tetracycline on acne

Article ID: WMC002714 2046-1690

The Action of Tetracycline on AcneCorresponding Author:Dr. Amin M Abdul Majid,Senior Lecturer, Discipline of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia -Malaysia

Submitting Author:Ms. Laila S Azman,Undergraduate student, School of Pharmaceutical Sciences, Universiti Sains Malaysia - Malaysia

Article ID: WMC002714

Article Type: Review articles

Submitted on:18-Dec-2011, 07:31:12 PM GMT Published on: 19-Dec-2011, 03:40:14 PM GMT

Article URL: http://www.webmedcentral.com/article_view/2714

Subject Categories:DERMATOLOGY

Keywords:Tetracycline, Acne, Pimple, Dermatology, Antibiotic, Action

How to cite the article:Azman L S, Rahim A A, Fan S K, Abd Kadir M H, Abdul Hamid N A, Muhammad S K,Wong A W, Abdul Majid A M. The Action of Tetracycline on Acne . WebmedCentral DERMATOLOGY2011;2(12):WMC002714

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The Action of Tetracycline on AcneAuthor(s): Azman L S, Rahim A A, Fan S K, Abd Kadir M H, Abdul Hamid N A, Muhammad S K, Wong A W,Abdul Majid A M

Abstract

There are few types of acne ranging from mild tosevere such as Acne Vulgaris, Acne Rosacea,Pyoderma Faciale, Gram-negative Folliculitis, AcneConglobata and the most severe one is AcneFulminans. Tetracycline can be used to treat acneproblems and is administered orally and topically.Generally, tetracycline is bacteriostatic but can bebactericidal if given in higher dose. It is widelydistributed throughout tissues and excretedunchanged via renal and biliary routes. The mostcommon side effects are nausea, headache andstaining of the teeth. Besides tetracycline, doxycyclineand minocycline are also used for treatment of acne ata lower dose. Tetracycline should not be given topatients having hypersensitivity to tetracycline,pregnant women and lactating mothers. It should notbe taken together with milk, antacids and oralcontraceptive.

Introduction

What is acne?

Acne is a common disorder affecting people of allraces and ages. It is a skin condition that causescomedones (blackheads and whiteheads) andinflamed red growths (papules, pustules, and cysts),formation of nodules (large papules) and possiblyscarring. It is also known as acne vulgaris or cysticacne (1, 2). Commonly, they are called pimples whichusually appear on the face but they can also developon the other parts of the body such as the back, theshoulders, neck and chest (3).Pustule is a red circle with a white or yellow centre. Asmall, red, tender bump with no head is called papule.Whereas cyst is a closed sac filled with fluid, pus, orother material. Whitehead is formed when the oilbreaks though to the surface. The oil changed fromwhite to black after being oxidized and result inblackhead (4).There are a few types of acne. The most common typeof acne is Acne Vulgaris, literally means “commonacne”. It is categorized as mild or moderate type. Thistype of acne is characterized by its different forms oflesions which include blackheads, whiteheads,

papules, pustules, nodules and cysts (5). It can betreated with some simple home remedies. Acne Rosacea usually affects people over the age of30. It frequently occurs in women but often moresevere when found in men. It looks similar to AcneVulgaris which leads to confusion however they havedistinct ways of treatment. It is manifested in the formof a red rash on the forehead, cheeks, nose and chin(6). The redness is often accompanied by bumps,pimples, and skin blemishes (5).Pyoderma Faciale is the other type of acne. It is alsoknown as Rosacea Fulminans. It is severe facial acneaffecting only females, usually between the ages of 20to 40 years old which comes with nodules, pustules aswell as sores and may leave permanent scarring. Itoccurs most often in women who have neverexperienced acne before and fortunately it does notlast longer than a year (5).The fourth type of acne called Gram-negativefolliculitis. It is a rare condition of bacterial infectionthat comes with long-term treatment of acne withantibiotics. It will result in pustules and cysts (7).Acne Conglobata is the most severe type of acne andmainly affects males. It is characterized by numerouslarge interconnected lesions on the face, chest, back,buttocks, upper arms, and thighs and can beaccompanied by numerous widespread blackheads. Itleads to severe psychological as well as physicalsuffering since it is extremely disfiguring. To makething worse, it causes damage to the skin andpermanent scarring (7).The last type of acne is known as Acne Fulminans. Itis an abrupt onset of acne conglobata-like symptomsaccompanied with fever and aching of the joints. Itnormally occurs in young men. Isotretinoin and oralsteroids are normally prescribed to get rid of it (5, 6).Causes of acneThe main culprit of acne is the excess production of anoily substance called sebum resulting in blockage ofhair follicles. The exact cause of acne is not fullyunderstood. However, the elements that influence itsdevelopment are known. It can be due to heredity, oilyskin or hair, hormonal imbalance, some prescriptionmedications and cosmetics that contain chemicals andvegetable oil, high stress, and possibly somenutritional deficiencies (8).Heredity or genetics is one of the factors that causeacne. Researchers believe that inheritance fromparents increase the tendency of their children to



develop acne (6). People with over-sensitive oil glandscause them keep on producing a higher level ofsebum. Hence, their oily complexions cause themmore prone to having acne (9). Fluctuation or imbalances of hormonal levels are oftenregarded as the main cause of acne. It can be seenwhen most people start to have acne when they reachpuberty which referred to teenage growth phase.During this stage, teenagers start to produceandrogens. It enlarges sebaceous glands and greateramounts of sebum are produced which mix with thedead skin cells or bacteria on the skin’s surface,resulting in the pores becoming blocked. Hence,inflammation starts to occur. Acne also appears whenwomen undergo menstruation whereby their hormonelevels are imbalanced (9, 10).In fact, dietary intake is closely related to hormonallevels. People who are more prone to acne breakoutswill have higher risks to get acne when they eat moreunhealthy food. This is because food with highercontent of chemicals and fat contributes to hormonalimbalance which will induce ailments such as acne(10).Besides, stress is also a factor that aggravates acne.When a person is under stress, more adrenalinehormones are produced and excessive hormones areresponsible for repeated acne breakouts by reducingthe nutrient-absorbing capacity of the body andimmediately attacking the skin. Stress actually slowsdown the healing process of both severe open woundsand small acne pustules since it affects the immunesystem of the body. In other words, adults are moreprone to stress-related acne as they at higher risk ofgetting stress (11).Deficiency of certain nutrient in body especially vitaminmay lead to acne aggravation. Acne development isclosed related to Vitamins A, B, C, E and zinc.Vitamins act as antioxidants that assist skin inelimination of toxins and harmful free radicals. Lack ofvitamins will increase the exposure of skin to toxinsand bacteria that may contribute to development ofacne(10). How acne can occur?There are many tiny holes on our skin surface calledpores. Each pore will grow a hair which known as hairfollicle. The hair follicles in our skin are connected withoil glands called sebaceous glands. The sebaceousglands produce sebum that helps to lubricate the skinby keeping the skin surface oily and protecting the skin.On the other hand, dead skin cells shed away from thepore lining whereas sebum is being distributed to theexterior surface of the skin (8, 12).In normal skin, the pore is open and the right amountof sebum secreted will come out on the skin surface.

However, when too much of oil/sebum is produced,the pores get clogged up. The blockage of pore alsocalled plug. The plug traps the dead skin cells, dirt anddebris within the hair follicles. This will prevent thesebum from leaving the pores which results in bacteriaas well as inflammatory cells building up underneaththe skin. Subsequently, the skin swells and red bumpsare formed. These indicate the formation of acne. Ifthe inflammation is deep in the skin, the pimples willenlarge to form cysts (1). The acne lesions we knowas whiteheads and blackheads are cal led“comedones”. Red, swollen, pus-filled lesions arecalled papules, nodules, and pustules (13). We canalso conclude that areas where a lot of sebaceousglands are present tend to have higher chance todevelop acne as the blockage of pores may occurfrequently.

Common Uses Of Tetracycline

Other than acne, tetracycline is widely used againstother bacterial infection because of its wide spectrumactivity such as infection caused by ticks, Lymedisease and Rocky Mountain spotted fever(RMSF)(14). Lyme disease is the most common tick-bornedisease caused by bacteria which belong to the genusof Borrelia. The RMSF caused by bacteria Rickettsiarickettsii is a lethal condition and tetracycline must begiven instantly. Doxycyline is usually used in treatmentof Lyme disease and RMSF (15).Tetracycline is also used in the treatment of urinarytract infection (UTI). Urinary tract infection is one of themost commonly found infection in developed countries,and it is eight or nine times more frequent amongwomen than men especially elderly women (16).Besides, sexual intercourse is also one of the riskfactor. The types of bacteria include E. coli, Klebsiella,Proteus, Pseudomonas, Serratia, and enterococcusbut rarely include anaerobes.In addition, tetracycline is widely used in the treatmentof Helicobacter pylori infections. It is a gram-negativebacterium found in human stomach which causesgastritis and gastric ulcers. In serious condition, it canlead to duodenal ulcers and stomach cancer.Tetracycline is usually combined with antacids,H2-antagonists or proton pump inhibitors to kill theHelicobacter pylori.Moreover, tetracycline is the preferred choice oftreatment for patients who develop resistance to thepenicillin such as Anthrax, Gonorrhea and Syphilis (17)

Some of the common uses of tetracycline are shownin Table 1.



Mechanism of Action ofTetracycline

Tetracycline is generally bacteriostatic against mostorganisms, but high concentrations of tetracycline canbe bactericidal. The structure of tetracycline can beseen in the Figure 1. The antimicrobial action oftetracycline in acne occurs via protein synthesisinhibition. It acts by binding to the 30S subunit of themicrobial ribosome. Tetracycline gains access to theribosome after passive diffusion through porinchannels in the bacterial membrane. An activetransport process also exists in bacterial cells. Duringprotein biosynthesis, the new t-RNA with the aminoacid will try to bind to A-site of the ribosome. However,since the A-site is blocked by the tetracycline, theaminoacyl-tRNA cannot bind to it. Thus without thesequential attachment of the tRNA at the A-site,protein biosynthesis cannot occur. By inhibiting theprotein biosynthesis process, tetracycline will causecell death of the bacterial cell. This action is usuallyinhibitory and reversible upon withdrawal of the drug.Mammalian cells are not affected by tetracyclinebecause they do not contain 30S ribosomal subunit(18).Tetracycline, by targeting problematic surface bacteria,inhibits production of bacterial products that stimulateinflammation. Tetracycline will cause down-regulationof proinflammatory cytokines (ie,TNF-a, IL-1b, IL-6),production of anti-inflammatory cytokine (ie, IL-10)secretion and reduction in antibody production (19)

Mechanism of Resistance ofTetracycline

Tetracycline is a bacteriostatic agent which has a widespectrum of uses itherapeutically. In general, it acts onbacteria by stopping the protein synthesis to inhibit thegrowth of the bacteria. The use of this antibiotic is veryfamous since it has broad spectrum activity and lowtoxicity. However, the bacteria could evolve andbecome resistant to the antibiotic (20). The emergenceof tetracycline-resistant bacteria has resulted in thedecrease and limit of the therapeutic action oftetracycline. Indeed, tetracycline resistance in many

commensal and pathogenic bacteria has emergednow due to genetic achievement of tetracyclineresistance genes (21). Recently, three differencespecific mechanisms of tetracycline resistance arefound - tetracycline efflux, ribosome protection andtetracycline modification (22).Emergence of the tetracycline resistance is primarilydue to possession of genetically mobile tetracyclineresistance genes, which encode proteins that conferef?ux of tetracyclines, or ribosomal protection (21).These first two mechanisms are the most commonand most of their genes are usually attained viatransferable plasmids and/or transposons. Thepresence of both mechanisms in aerobic andanaerobic Gram-negative or Gram-positive bacteriaindicates their wide distribution among the bacterialkingdom (21).In tetracycl ine ef f lux, i ts genes code formembrane-associated proteins, which exporttetracyclines from the cell major facilitator superfamily(MFS) (23). Tetracycline efflux mechanism is anapproach to limit the access of tetracycline toribosome which can inhibit protein synthesis of thebacteria (22). The result from the export of tetracyclinewill reduce the intracellular drug concentration andthus, protects the ribosomes within the cell (23). Theresistance gene product is a cytoplasmic membraneprotein that is an energy-dependent tetracyclinetransporter (22).The other type of tetracycline resistance mechanism isribosomal protection protein. This is the least familiarmechanism, however it is probably more widespreadthan tetracycline efflux (24). The protein calledcytoplasmic protein interacts or associates with theribosome, making it insensitive to tetracyclineinhibition (21, 22). Ribosome protection is mediated bya soluble protein which shares homology with theGTPases participating in protein synthesis, namelyEF-Tu and EF-G (25, 26). At the N-terminal area, thegreatest homology is seen which contain theGTP-binding domain (25). Thus, the RPPs bind andhydrolyze GTP in a ribosome-dependent manner, andmaintenance of this activity is important for in vivoactivity (27). The mechanism of ribosomal protectionworks in vivo and in vitro, unlike the action of ef?uxproteins; which require intact membranes to function(21). On the other hand, the RPPs may beevolutionarily derived from the elongation factors, suchthat they lost their original function and have beenadapted to function in tetracycline resistance (27).The third mechanism of tetracycline resistance istetracycline modification. This reaction only works inaerobic environment, in the presence of both oxygenand NADPH and does not function in the natural host



(Bacteroides) (21, 22). There is only one type of geneencodes the tetracycline resistance due to enzymaticalteration of tetracycline that is the tet(X) gene. Itsproduct is a 44-kDa cytoplasmic protein thatchemically modifies tetracycline (21). The tet(X) geneis classified according to the resistance gene whichshares amino acid homology with a number ofNADPH-requiring oxidoreductases, particularly in theregion containing the NADPH-binding site (22, 28).However, the clinical significance of tet(X) is stillunclear nor confer resistance on the Bacteroidesstrains in which it was originally found, but it requiressuch high levels of ventilation so it probably could notconfer meaningful levels of resistance in themicroaerophilic environment found in most sites on thehuman body (22).

Pharmacokinetics Profile ofTetracycline

Administration: Tetracycline can be given orally,periodontally, ophthalmic (eyes) or topically (29).However, in order to treat acne vulgaris, oraltetracycline is usually prescribed (30).Absorption: Oral tetracycline has relatively highabsorption in GIT which is 77-88% (30). It has highsolubility but quite poor permeability (30). Absorptionof tetracycline is reduced by administration with food,iron and milk (31). This is because iron, calcium,magnesium and aluminium will chelate tetracycline inGIT, hence reducing its absorption(30).Distribution: Tetracycline is widely distributedthroughout the tissues (30). However, since it is nothighly lipophilic, it may not optimally penetrate thefollicular unit (30). This is due to the fact that follicularunit contains high amounts of lipid-rich sebum (30).Metabolism: Tetracycline does not undergo anymetabolism(32).Excretion: Tetracycline is excreted unchanged viarenal and biliary routes (32). About 50% of the drug isexcreted through glomerular filtration (32).

Side Effects of Tetracycline

Every medication has its own side effect. The samegoes to tetracycline. If the side effect is severe, thenstop using the medication.The common mild side effects of using tetracycline arestinging, redness, burning, peeling, and itchiness. Anyallergic reaction towards tetracycline can beconsidered as severe side effects and its usageshould be stopped.

The other possible mild side effects of takingtetracycline include nausea, headache, stomachcramp, and vomiting (33). Indigestion, abdominalupset, gastrointestinal irritation (severe), rashes (rare,severe if they manifest), phototoxic reactions(oversensitivity to sunlight), the increased incidence ofcandidal valvovaginitis, severe headaches, hives,drug-induced hepatitis are also some of the sideeffects of using tetracycline. Skin, nails and eyes maybecome yellow or known as jaundice (34).The side effects are not similar to all the patients. It isdependent on the condition of a patient and how hisbody tolerates tetracycline.Results of a study done in 2004 indicated thattetracycline as well as other tetracycline derivativesmay well be responsible for staining of the teeth aswell as the oral cavity. Besides staining of the oralcavity and teeth, further research indicated that acnetreatments containing cyclones may also causeadverse drug reactions (36). Tetracycline should notbe used in children because it can cause permanentdiscoloration of the natural hue of the teeth(yellowing). The same goes to the pregnant women.They cannot use tetracycline during pregnancybecause the fetus may experience slower bone growth.Their teeth may also be affected once they are born(34).Tetracycline may also increase the risk of autoimmunedisorders, hypersensitivity syndromes and abnormalskin pigmentations. A reported released by auniversity in Germany indicates that side effectsrelated to the use of tetracycline may includecontraction of Sweet's syndrome. Sweet’s syndrome isa condition in which painful red nodules arise onvarious parts of the body and is also generallyaccompanied by fever and malaise (38).A study published by a hospital in France in May of2003 indicates that ‘adverse affects of cyclines mightbe serious and sometimes unknown.’ The reportfurther suggested that ‘long term treatment bytetracycline must be researched in patients presentingsuch symptoms.’ Symptoms related to adverse sideeffects in nearly 250 cases included autoimmunedisorders, hypersensitivity syndromes as well asabnormal skin pigmentations (37). A report released in February of 2000 indicated thattetracycline could also be responsible for the inductionof intracranial hypertension (39). Research indicates that patients who are consideringthe use of tetracycline to consider the risks associatedwith this acne treatment before proceeding withuse(35).



Formulations of Tetracycline

The oral dose of tetracycline for treating acne is from125mg to 500mg depending to the severity of the acne.Beside tetracycline, doxycycline and minocycline arealso used for treatment of acne at a lower dose (40).Table 2.1 shows a list of tetracycline, minocycline anddoxycycline product available in Malaysia. While Table2.2 shows the international listing of tetracycline,minocycline and doxycycline brand name.Most oral tetracycline is formulated into capsule ortablet form which gives tetracycline a better stability tothe tetracycline when taken orally. This is becausetetracycline degrades to epitetracycline due toepimerization in protic solvent which cause thetetracycline to be inactive (40). Besides that, therelease of tetracycline is controlled when it is given intablet or capsule form over its solution form (40).Beside oral route, tetracycline is also formulated fortopical route. The dosage forms used are cream,ointment and gel (40). The topical form of tetracyclineis mostly applied to a small area affected by acnebecause usage over a larger area has been proven tobe awkward (40). Besides that, topical application oftetracycline could avoid the gastrointestinaldisturbance caused by the drug and drug interactionswhich may occur if taken orally. The first stable topicaltetracycline produced was in ointment form becausetetracycline is relatively stable in the ointment base(40). However for cosmetic use, the oily formulation isless desirable thus the formulation of a less greasycream was created. Finally the gel formulation oftetracycline was created which is stable, non-greasy,less irritating and soft for the skin (40).

Drugs Interactions AndContraindications

Tetracycline is contraindicated in patients known tohave tetracycline hypersensitivity (47).Tetracycline is bacteriostatic. So, tetracycline must notbe given in conjunction with penicillin or otherbactericidal antibiotics because it may disturb thebactericidal action of penicillin (49). Bacteriostatic andbactericidal antibiotics should not be used togethersince the bactericidal agents, for example, penicillinsmay be inhibited by the bacteriostatic agent too (48).Treatment with tetracycline can alter the normal floraof the colon and allow overgrowth of Clostridiumdifficile. Hence, the patient may suffer from diarrheaduring treatment. Symptomatic of Clostridium

difficile-associated disease, pseudomembranouscolitis, may also occur in the initial weeks of thefollowing treatment. If patient is suspected to havepseudomembranous colitis, tetracycline should bestopped immediately and the patient should be treatedwith supportive and specific treatment without delay.Any products that inhibit peristalsis are contraindicatedin this clinical situation (47).There are some compounds that may interfere withthe bioavailability of tetracycline antibiotics. Theseinclude antacids; sucralfate; magnesium salicylate;magnesium citrate; polysaccharide-iron complex;quinapril (tablets contain magnesium); andmultivitamins that contain iron, calcium, manganese,or zinc. Laxative preparations containing magnesiumare also contraindicated. So, tetracycline should notbe given with or within 4 hours of any of the abovedrugs. Besides, calcium salts and magnesium saltsthat are contained in food and dairy products can formchelates with tetracycline and decrease the absorption.Administration of tetracycline at least one hour prior toor two hours after a meal and/or milk will reduce theeffect (47).Warfarin has shown a clinically significant interactionwith tetracycline because the action of warfarin andother oral anticoagulants are increased by eitherimpairing prothrombin utilization or decreasingproduction of vitamin K (48).Tetracycline should not be used with acitretin,isotretinoin, strontium, and tretinoin that are takenorally because very serious interactions may occur.Zinc can affect tetracycline because it can attach totetracycline in the stomach. This reduces the amountof tetracycline absorbed. Thus, it will decrease theeffectiveness of tetracycline too (49).Tetracycline may chelate the divalent or trivalentcations, forming insoluble compounds (50).Tetracycline bioavailability may be decreased bydidanosine, due to the buffering agents in didanosinetablets or powder. Some antidiarrheals that compriseof cations will form chelated compounds too (50).Concurrent use of tetracycline with oral contraceptivesmay make the oral contraceptives less effective (50).This is due to stimulation of estrogen metabolism or adecline in estrogen enterohepatic circulation viachanges in gastrointestinal flora (48).Topical tetracycline preparations contain sodiumsulfites while oral dosage forms may contain tartrazinedye. More precaution steps should be consideredwhen dealing with patients with a known sulfitehypersensitivity or tartrazine dye hypersensitivity.Sensitivity reactions are prone to have happen inasthmatic than in non-asthmatic patients (50).If a pregnant mother wants to use the tetracycline, she



should know that all tetracyclines have a harmful effecton the skeletal development and bone growth of thefetus or child. Therefore, tetracycline should not beused in the second half of pregnancy unless there aremore benefits from treatment to the mother comparedto the risk of fetus, but their use should be consideredonly with extreme caution (47).Although tetracycline can form non absorbablecomplexes with the calcium in breast milk, tetracyclineis distr ibuted into breast milk. Therefore,breast-feeding mothers should not use tetracyclineantibiotics because risks o) teeth discoloration, enamelhypoplasia, inhibition of linear skeletal growth, oral andvaginal thrush, or photosensitivity reactions canhappen in the nursing infant (47).Dosage and frequency of tetracycline must beadjusted if given to patients with severe renal diseasebecause some of the tetracycline is excreted inunchanged in the urine (47).Dose adjustment may berequired in patients with hepatic disease too becausesome tetracycline is excreted via bile. The excretionprocess can be delayed in these patients (47).It hasbeen reported that fatal renal toxicity can occur withthe concurrent use of tetracycline and methoxyflurane(50).

Conclusion

Tetracycline is one of the antibiotics that can treatacne and it can be given orally or topically. All the do’sand don’ts of tetracycline must be followed to ensurethe effectiveness of the antibiotic. The number ofbacteria in and around the follicle can be decreased byusing the antibiotic. Antibiotic can also decrease theirritating chemicals produced by white blood cells andreduce the concentration of free fatty acids in thesebum, thus reducing the inflammatory response (51).Finally this results in fewer pimples and less redness.If left untreated, acne can lead to a number ofproblems such as pain, infections, and scarring (52).

Acknowledgement

We would like to acknowledge and extend our heartfeltgratitude and appreciation to the following personswho have made the completion of this report possibleto be done successfully. Special thanks to Dr. AminMalik Shah bin Abdul Maj id, Discipl ine ofPharmacology, School of Pharmaceutical Sciences,Universiti Sains Malaysia for his vital encouragementand support throughout the period of time as oursupervisor.Not only that, we thankful for the constant

reminders and much motivation from him.Besides, we also want to thank all of FAR 241Antimicrobial Therapy lecturers; which they taught usthe concept of antimicrobial therapy in pharmacy fieldand special thanks to Lydia Pang Kai Tsan for helpingus checked the grammatical errors in our report.We would also like to forward our thanks to thosecontributed accidentally or in-accidentally throughoutthis report. On top of that, we would like to express ourappreciation to all group members that fullycontributed and committed in making this reportsucceed.

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45. National Pharmaceutical Control Bureau.Minocycline. [database on the Internet]. 2011 [cited2011 Nov 17]. Available from:http://portal.bpfk.gov.my/product_search.cfm46. National Pharmaceutical Control Bureau.Doxycycline. [database on the Internet]. 2011 [cited2011 Nov 17]. Available from:http://portal.bpfk.gov.my/product_search.cfm47. Tetracycline Contraindications and Precautions.RX-s.net Online pharmacy. [homepage on theInternet]. No date [cited 2011 Nov 10]. Available from:http://rx-s.net/weblog/more/tetracycline_contraindications_precautions/48. Tetracycline Interactions. RX-s.net Onlinepharmacy. [homepage on the Internet]. No date [cited2011 Nov 10]. Available from:http://rx-s.net/weblog/more/tetracycline_interactions/49. Zinc. Medline Plus. [monograph on the Internet].No date [cited 2011 Nov 10]. Available from:http://www.nlm.nih.gov/medlineplus/druginfo/natural/982.html50. Tetracycline (tetracycline Hydrochloride) -Warnings and Precautions. Drug Lib.com. [homepageon the Internet]. No date [cited 2011 Nov 10].Available from:http://www.druglib.com/druginfo/tetracycline/warnings_precautions/51. Heather L. Brannon. Antibiotics Used to TreatAcne. [homepage on the Internet]. 2008 [cited 2011Dec 10]. Available from:http://dermatology.about.com/cs/antibiotics/a/acneabx.htm52. Monson K, Schoenstadt A. Tetracycline for Acne.[homepage on the Internet]. January 2010 [cited 2011Dec 10]. Available from:http://antibiotics.emedtv.com/tetracycline/tetracycline-for-acne.html.



Tetracycline in bacterial infection

Lyme disease

Rocky Mountain spotted fever

Typhus fever

Tick fever

Conjunctivitis (pink eye)

Chlamydia

Certain types of pneumonia and other respiratory infections

Urinary tract infections (UTIs)

Plague

Cholera

Skin infections

Illustrations

Illustration 1

Table 1: Some of the common uses of tetracycline



Gram Positive Gram Negative

Streptococcus pyogenes

Streptococcus pneumoniae

Enterococcus group

Neisseria gonorrhea

Haemophilus influenzae

Vibrio cholera

Brucella

Escherichia coli

Klebsiella

Enterobacter

Shigella

Other Microorganisms

Borrelia

Treponema pallidum

Fusobacterium

Actinomyces species



FIGURE 1: The 4 rings of the basic tetracycline structure.

Illustration 2

Figure 1



Product name Company name Active

ingredient

Dosage

form

Reference

MYCIN CAPSULE 2470 MG KCK PHARMACEUTICAL

INDUSTRIES SDN. BHD.

T e t r a c y c l i n e

HCL

Capsule 44

VEMYCLIN CAPSULE

2470MG

IDAMAN PHARMA

MANUFACTURING


HCL

Capsule 44

BETACYCLINE TABLET

2470

UPHA PHARMACEUTICAL

MFG. (M) SDN BHD


HCL

Tablets 44

PHARMYCIN CAPSULE

2470MG

M A L A Y A N

P H A R M A C E U T I C A L

INDUSTRIES SDN BHD


HCL

Capsule 44

Illustration 3

TABLE 2.1: List of tetracycline, minocycline and doxycycline product available in Malaysia



TETRACYCLINE MC

CAPSULE 2470MG

KOMEDIC SDN BHD T e t r a c y c l i n e

HCL

Capsule 44

TETRA CAPSULE 2470MG ROYCE PHARMA

MANUFACTURING SDN BHD


HCL

Capsule 44

T E T R A C Y C L I N E

OINTMENT 3% W/W

HOE PHARMACEUTICAL

SDN. BHD.


HCL

Ointment 44

TRIOMYCIN CAPSULE

2470MG

Z O N T R O N

PHARMACEUTICALS SDN.

BHD.


HCL

Capsule 44

DHATRACIN TABLET

2470MG

ASCENT PHARMAHEALTH

MALAYSIA SDN. BHD.


HCL

Tablets 44



AXCEL TETRACYCLINE

CAPSULES

KOTRA PHARMA (M) SDN

BHD


HCL

Capsule 44

TETRACYCLINE CAPSULE

2470MG

DYNAPHARM (M) SDN SHD T e t r a c y c l i n e

HCL

Capsule 44

TETRACYCLINE TABLET

2470MG

DYNAPHARM (M) SDN SHD T e t r a c y c l i n e

HCL

Tablets 44

TETRACAP 2470 CAPSULE HOVID BERHAD T e t r a c y c l i n e

HCL

Capsule 44

TETRACAP CAPSULE

4700MG

HOVID BERHAD T e t r a c y c l i n e

HCL

Capsule 44



P H A R M A N I A G A

TETRACYCLINE CAPSULE

2470MG


MANUFACTURING BERHAD


HCL

Capsule 44

BORYMYCIN CAPSULE

470MG

Y.S.P. INDUSTRIES (M) SDN

BHD

Minocycline Capsule 45

BORYMYCIN CAPSULE Y.S.P. INDUSTRIES (M) SDN

BHD


A P O - M I N O C Y C L I N E

470MG

P H A R M A F O R T E

(MALAYSIA) SDN. BHD.


XIDOX CAPSULE 100MG IDAMAN PHARMA

MANUFACTURING SDN BHD

Doxycycline Capsule 46



ASIDOXYN CAPSULE 100

MG

ROYCE PHARMA

MANUFACTURING SDN.

BHD


MEDOMYCIN CAPSULE

100MG

KOMEDIC SDN BHD Doxycycline Capsule 46

VIBRAMYCIN TABLET

100MG

PFIZER (MALAYSIA) SDN.

BHD.

Doxycycline Tablets 46

DOXYCILLIN TABLET

100MG

UPHA PHARMACEUTICAL

MFG. (M) SDN BHD




DOXYCYCLA CAPSULE

100MG




DOXYCAP 100MG HOVID BERHAD Doxycycline Capsule 46

DOXYMYCIN CAPSULE Y.S.P. INDUSTRIES (M) SDN

BHD


DOXYCYCLINE TABLET

100MG

DYNAPHARM (M) SDN BHD Doxycycline Tablets 46

DOXYCYCLINE CAPSULE

100MG

DYNAPHARM (M) SDN BHD Doxycycline Capsule 46



DOLINE 100 TABLET MERCK SDN. BHD. Doxycycline Tablets 46

VIBRAMYCIN TABLET

100MG

PFIZER (MALAYSIA) SDN.

BHD.



DOXYCYCLINE CAPSULE

100 MG




DOXYMYCIN CAPSULE Y.S.P. INDUSTRIES (M) SDN

BHD




DOXYCILLIN CAPSULE

100 MG

CCM PHARMACEUTICALS

SDN. BHD.


DOMYCIN TABLET 100

MG

DUOPHARMA (M) SDN. BHD. Doxycycline Tablets 46

TETRADOX CAPSULES

100 MG

RANBAXY (MALAYSIA)

SDN. BHD.




Name Active ingredient Reference

Abramycin Tetracycline 43

Abricycline Tetracycline 43

Achromycin Tetracycline 43

Achromycin V Tetracycline 43

Actisite Tetracycline 43

Agromicina Tetracycline 43

Illustration 4

TABLE 2.2: International listing of tetracycline, minocycline and doxycycline brand name



Ambramicina Tetracycline 43

Ambramycin Tetracycline 43

Amycin Tetracycline 43

Bio-Tetra Tetracycline 43

Biocycline Tetracycline 43

Bristaciclin Tetracycline 43



Bristaciclina Tetracycline 43

Bristacycline Tetracycline 43

Cefracycline Tetracycline 43

Ciclibion Tetracycline 43

Copharlan Tetracycline 43

Criseociclina Tetracycline 43



Cyclopar Tetracycline 43

Cytome Tetracycline 43

Democracin Tetracycline 43

Deschlorobiomycin Tetracycline 43

Dumocyclin Tetracycline 43



Enterocycline Tetracycline 43

Hostacyclin Tetracycline 43

Lexacycline Tetracycline 43

Limecycline Tetracycline 43

Liquamycin Tetracycline 43



Medocycline Tetracycline 43

Mericycline Tetracycline 43

Micycline Tetracycline 43

Neocycline Tetracycline 43

Oletetrin Tetracycline 43



Omegamycin Tetracycline 43

Orlycycline Tetracycline 43

Panmycin Tetracycline 43

Polycycline Tetracycline 43

Polyotic Tetracycline 43



Purocyclina Tetracycline 43

Resteclin Tetracycline 43

Retet Tetracycline 43

Robitet Tetracycline 43

Roviciclina Tetracycline 43



SK-Tetracycline Tetracycline 43

Solvocin Tetracycline 43

Sumycin Tetracycline 43

TAC Tetracycline 43

Tetra-CO Tetracycline 43



Tetrabon Tetracycline 43

Tetrachel Tetracycline 43

Tetracycl Tetracycline 43

Tetracycline II Tetracycline 43

Tetracyn Tetracycline 43

Tetradecin Tetracycline 43



Tetrafil Tetracycline 43

Tetramed Tetracycline 43

Tetraverine Tetracycline 43

Tetrex Tetracycline 43

Topicycline Tetracycline 43



Tsiklomistsin Tetracycline 43

Tsiklomitsin Tetracycline 43

Veracin Tetracycline 43

Vetacyclinum Tetracycline 43

Alti-Minocycline Minocycline 42



Apo-Minocycline Minocycline 42

Arestin Minocycline 42

Dynacin Minocycline 42

Gen-Minocycline Minocycline 42

Klinomycin Minocycline 42

Minociclina Minocycline 42

Minocin Minocycline 42

Minocyclin Minocycline 42

Minocycline HCl Minocycline 42

Minocyclinum Minocycline 42



Minocyn Minocycline 42

Minomycin Minocycline 42

Novo-Minocycline Minocycline 42

Solodyn Minocycline 42

Vectrin Minocycline 42



Alti-Doxycycline Doxycycline 41

Apo-Doxy Doxycycline 41

Atridox Doxycycline 41

Doryx Doxycycline 41

Doxy 100 Doxycycline 41

Doxy-Caps Doxycycline 41

Doxy-Lemmon Doxycycline 41

Doxychel Doxycycline 41



DoxychelHyclate Doxycycline 41

Doxycin Doxycycline 41

Doxylin Doxycycline 41

Doxytec Doxycycline 41

Jenacyclin Doxycycline 41

Monodox Doxycycline 41



Novo-Doxylin Doxycycline 41

Nu-Doxycycline Doxycycline 41

Oracea Doxycycline 41

Periostat Doxycycline 41

Supracyclin Doxycycline 41

Vibra-Tabs Doxycycline 41

Vibramycin Doxycycline 41



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