The Action of Tetracycline on Acne - WebmedCentral

38 Pages·2011·0.29 MB·English

Article ID: WMC002714 2046-1690
The Action of Tetracycline on Acne
Corresponding 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 DERMATOLOGY
2011;2(12):WMC002714
Copyright: This is an open-access article distributed under the terms of the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original
author and source are credited.
Source(s) of Funding:
None
Competing Interests:
None
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The Action of Tetracycline on Acne
Author(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 papules, pustules, nodules and cysts (5). It can be
treated with some simple home remedies.
Acne Rosacea usually affects people over the age of
30. It frequently occurs in women but often more
There are few types of acne ranging from mild to
severe when found in men. It looks similar to Acne
severe such as Acne Vulgaris, Acne Rosacea,
Vulgaris which leads to confusion however they have
Pyoderma Faciale, Gram-negative Folliculitis, Acne
distinct ways of treatment. It is manifested in the form
Conglobata and the most severe one is Acne
of a red rash on the forehead, cheeks, nose and chin
Fulminans. Tetracycline can be used to treat acne
(6). The redness is often accompanied by bumps,
problems and is administered orally and topically.
pimples, and skin blemishes (5).
Generally, tetracycline is bacteriostatic but can be
Pyoderma Faciale is the other type of acne. It is also
bactericidal if given in higher dose. It is widely
known as Rosacea Fulminans. It is severe facial acne
distributed throughout tissues and excreted
affecting only females, usually between the ages of 20
unchanged via renal and biliary routes. The most
to 40 years old which comes with nodules, pustules as
common side effects are nausea, headache and
well as sores and may leave permanent scarring. It
staining of the teeth. Besides tetracycline, doxycycline
occurs most often in women who have never
and minocycline are also used for treatment of acne at
experienced acne before and fortunately it does not
a lower dose. Tetracycline should not be given to
last longer than a year (5).
patients having hypersensitivity to tetracycline,
The fourth type of acne called Gram-negative
pregnant women and lactating mothers. It should not
folliculitis. It is a rare condition of bacterial infection
be taken together with milk, antacids and oral
that comes with long-term treatment of acne with
contraceptive.
antibiotics. It will result in pustules and cysts (7).
Introduction Acne Conglobata is the most severe type of acne and
mainly affects males. It is characterized by numerous
large interconnected lesions on the face, chest, back,
buttocks, upper arms, and thighs and can be
What is acne?
accompanied by numerous widespread blackheads. It
Acne is a common disorder affecting people of all
leads to severe psychological as well as physical
races and ages. It is a skin condition that causes
suffering since it is extremely disfiguring. To make
comedones (blackheads and whiteheads) and
thing worse, it causes damage to the skin and
inflamed red growths (papules, pustules, and cysts),
permanent scarring (7).
formation of nodules (large papules) and possibly
The last type of acne is known as Acne Fulminans. It
scarring. It is also known as acne vulgaris or cystic
is an abrupt onset of acne conglobata-like symptoms
acne (1, 2). Commonly, they are called pimples which
accompanied with fever and aching of the joints. It
usually appear on the face but they can also develop
normally occurs in young men. Isotretinoin and oral
on the other parts of the body such as the back, the
steroids are normally prescribed to get rid of it (5, 6).
shoulders, neck and chest (3).
Causes of acne
Pustule is a red circle with a white or yellow centre. A
The main culprit of acne is the excess production of an
small, red, tender bump with no head is called papule.
oily substance called sebum resulting in blockage of
Whereas cyst is a closed sac filled with fluid, pus, or
hair follicles. The exact cause of acne is not fully
other material. Whitehead is formed when the oil
understood. However, the elements that influence its
breaks though to the surface. The oil changed from
development are known. It can be due to heredity, oily
white to black after being oxidized and result in
skin or hair, hormonal imbalance, some prescription
blackhead (4).
medications and cosmetics that contain chemicals and
There are a few types of acne. The most common type
vegetable oil, high stress, and possibly some
of acne is Acne Vulgaris, literally means “common
nutritional deficiencies (8).
acne”. It is categorized as mild or moderate type. This
Heredity or genetics is one of the factors that cause
type of acne is characterized by its different forms of
acne. Researchers believe that inheritance from
lesions which include blackheads, whiteheads,
parents increase the tendency of their children to
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develop acne (6). People with over-sensitive oil glands However, when too much of oil/sebum is produced,
cause them keep on producing a higher level of the pores get clogged up. The blockage of pore also
sebum. Hence, their oily complexions cause them called plug. The plug traps the dead skin cells, dirt and
more prone to having acne (9). debris within the hair follicles. This will prevent the
Fluctuation or imbalances of hormonal levels are often sebum from leaving the pores which results in bacteria
regarded as the main cause of acne. It can be seen as well as inflammatory cells building up underneath
when most people start to have acne when they reach the skin. Subsequently, the skin swells and red bumps
puberty which referred to teenage growth phase. are formed. These indicate the formation of acne. If
During this stage, teenagers start to produce the inflammation is deep in the skin, the pimples will
androgens. It enlarges sebaceous glands and greater enlarge to form cysts (1). The acne lesions we know
amounts of sebum are produced which mix with the as whiteheads and blackheads are called
dead skin cells or bacteria on the skin’s surface, “comedones”. Red, swollen, pus-filled lesions are
resulting in the pores becoming blocked. Hence, called papules, nodules, and pustules (13). We can
inflammation starts to occur. Acne also appears when also conclude that areas where a lot of sebaceous
women undergo menstruation whereby their hormone glands are present tend to have higher chance to
levels are imbalanced (9, 10). develop acne as the blockage of pores may occur
In fact, dietary intake is closely related to hormonal frequently.
levels. People who are more prone to acne breakouts
Common Uses Of Tetracycline
will have higher risks to get acne when they eat more
unhealthy food. This is because food with higher
content of chemicals and fat contributes to hormonal
imbalance which will induce ailments such as acne Other than acne, tetracycline is widely used against
(10). other bacterial infection because of its wide spectrum
Besides, stress is also a factor that aggravates acne. activity such as infection caused by ticks, Lyme
When a person is under stress, more adrenaline disease and Rocky Mountain spotted fever(RMSF)
hormones are produced and excessive hormones are (14). Lyme disease is the most common tick-borne
responsible for repeated acne breakouts by reducing disease caused by bacteria which belong to the genus
the nutrient-absorbing capacity of the body and of Borrelia. The RMSF caused by bacteria Rickettsia
immediately attacking the skin. Stress actually slows rickettsii is a lethal condition and tetracycline must be
down the healing process of both severe open wounds given instantly. Doxycyline is usually used in treatment
and small acne pustules since it affects the immune of Lyme disease and RMSF (15).
system of the body. In other words, adults are more Tetracycline is also used in the treatment of urinary
prone to stress-related acne as they at higher risk of tract infection (UTI). Urinary tract infection is one of the
getting stress (11). most commonly found infection in developed countries,
Deficiency of certain nutrient in body especially vitamin and it is eight or nine times more frequent among
may lead to acne aggravation. Acne development is women than men especially elderly women (16).
closed related to Vitamins A, B, C, E and zinc. Besides, sexual intercourse is also one of the risk
Vitamins act as antioxidants that assist skin in factor. The types of bacteria include E. coli, Klebsiella,
elimination of toxins and harmful free radicals. Lack of Proteus, Pseudomonas, Serratia, and enterococcus
vitamins will increase the exposure of skin to toxins but rarely include anaerobes.
and bacteria that may contribute to development of In addition, tetracycline is widely used in the treatment
acne(10). of Helicobacter pylori infections. It is a gram-negative
How acne can occur? bacterium found in human stomach which causes
There are many tiny holes on our skin surface called gastritis and gastric ulcers. In serious condition, it can
pores. Each pore will grow a hair which known as hair lead to duodenal ulcers and stomach cancer.
follicle. The hair follicles in our skin are connected with Tetracycline is usually combined with antacids,
oil glands called sebaceous glands. The sebaceous H2-antagonists or proton pump inhibitors to kill the
glands produce sebum that helps to lubricate the skin Helicobacter pylori.
by keeping the skin surface oily and protecting the skin. Moreover, tetracycline is the preferred choice of
On the other hand, dead skin cells shed away from the treatment for patients who develop resistance to the
pore lining whereas sebum is being distributed to the penicillin such as Anthrax, Gonorrhea and Syphilis (17)
exterior surface of the skin (8, 12). Some of the common uses of tetracycline are shown
In normal skin, the pore is open and the right amount in Table 1.
of sebum secreted will come out on the skin surface.
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commensal and pathogenic bacteria has emerged
Mechanism of Action of
now due to genetic achievement of tetracycline
Tetracycline
resistance genes (21). Recently, three difference
specific mechanisms of tetracycline resistance are
found - tetracycline efflux, ribosome protection and
Tetracycline is generally bacteriostatic against most tetracycline modification (22).
organisms, but high concentrations of tetracycline can Emergence of the tetracycline resistance is primarily
be bactericidal. The structure of tetracycline can be due to possession of genetically mobile tetracycline
seen in the Figure 1. The antimicrobial action of resistance genes, which encode proteins that confer
tetracycline in acne occurs via protein synthesis ef?ux of tetracyclines, or ribosomal protection (21).
inhibition. It acts by binding to the 30S subunit of the These first two mechanisms are the most common
microbial ribosome. Tetracycline gains access to the and most of their genes are usually attained via
ribosome after passive diffusion through porin transferable plasmids and/or transposons. The
channels in the bacterial membrane. An active presence of both mechanisms in aerobic and
transport process also exists in bacterial cells. During anaerobic Gram-negative or Gram-positive bacteria
protein biosynthesis, the new t-RNA with the amino indicates their wide distribution among the bacterial
acid will try to bind to A-site of the ribosome. However, kingdom (21).
since the A-site is blocked by the tetracycline, the In tetracycline efflux, its genes code for
aminoacyl-tRNA cannot bind to it. Thus without the membrane-associated proteins, which export
sequential attachment of the tRNA at the A-site, tetracyclines from the cell major facilitator superfamily
protein biosynthesis cannot occur. By inhibiting the (MFS) (23). Tetracycline efflux mechanism is an
protein biosynthesis process, tetracycline will cause approach to limit the access of tetracycline to
cell death of the bacterial cell. This action is usually ribosome which can inhibit protein synthesis of the
inhibitory and reversible upon withdrawal of the drug. bacteria (22). The result from the export of tetracycline
Mammalian cells are not affected by tetracycline will reduce the intracellular drug concentration and
because they do not contain 30S ribosomal subunit thus, protects the ribosomes within the cell (23). The
(18). resistance gene product is a cytoplasmic membrane
Tetracycline, by targeting problematic surface bacteria, protein that is an energy-dependent tetracycline
inhibits production of bacterial products that stimulate transporter (22).
inflammation. Tetracycline will cause down-regulation The other type of tetracycline resistance mechanism is
of proinflammatory cytokines (ie,TNF-a, IL-1b, IL-6), ribosomal protection protein. This is the least familiar
production of anti-inflammatory cytokine (ie, IL-10) mechanism, however it is probably more widespread
secretion and reduction in antibody production (19) than tetracycline efflux (24). The protein called
cytoplasmic protein interacts or associates with the

ribosome, making it insensitive to tetracycline
inhibition (21, 22). Ribosome protection is mediated by
a soluble protein which shares homology with the
GTPases participating in protein synthesis, namely

EF-Tu and EF-G (25, 26). At the N-terminal area, the
Mechanism of Resistance of greatest homology is seen which contain the
Tetracycline GTP-binding domain (25). Thus, the RPPs bind and
hydrolyze GTP in a ribosome-dependent manner, and
maintenance of this activity is important for in vivo
activity (27). The mechanism of ribosomal protection
Tetracycline is a bacteriostatic agent which has a wide
works in vivo and in vitro, unlike the action of ef?ux
spectrum of uses itherapeutically. In general, it acts on
proteins; which require intact membranes to function
bacteria by stopping the protein synthesis to inhibit the
(21). On the other hand, the RPPs may be
growth of the bacteria. The use of this antibiotic is very
evolutionarily derived from the elongation factors, such
famous since it has broad spectrum activity and low
that they lost their original function and have been
toxicity. However, the bacteria could evolve and
adapted to function in tetracycline resistance (27).
become resistant to the antibiotic (20). The emergence
The third mechanism of tetracycline resistance is
of tetracycline-resistant bacteria has resulted in the
tetracycline modification. This reaction only works in
decrease and limit of the therapeutic action of
aerobic environment, in the presence of both oxygen
tetracycline. Indeed, tetracycline resistance in many
and NADPH and does not function in the natural host
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(Bacteroides) (21, 22). There is only one type of gene The other possible mild side effects of taking
encodes the tetracycline resistance due to enzymatic tetracycline include nausea, headache, stomach
alteration of tetracycline that is the tet(X) gene. Its cramp, and vomiting (33). Indigestion, abdominal
product is a 44-kDa cytoplasmic protein that upset, gastrointestinal irritation (severe), rashes (rare,
chemically modifies tetracycline (21). The tet(X) gene severe if they manifest), phototoxic reactions
is classified according to the resistance gene which (oversensitivity to sunlight), the increased incidence of
shares amino acid homology with a number of candidal valvovaginitis, severe headaches, hives,
NADPH-requiring oxidoreductases, particularly in the drug-induced hepatitis are also some of the side
region containing the NADPH-binding site (22, 28). effects of using tetracycline. Skin, nails and eyes may
However, the clinical significance of tet(X) is still become yellow or known as jaundice (34).
unclear nor confer resistance on the Bacteroides The side effects are not similar to all the patients. It is
strains in which it was originally found, but it requires dependent on the condition of a patient and how his
such high levels of ventilation so it probably could not body tolerates tetracycline.
confer meaningful levels of resistance in the Results of a study done in 2004 indicated that
microaerophilic environment found in most sites on the tetracycline as well as other tetracycline derivatives
human body (22). may well be responsible for staining of the teeth as
well as the oral cavity. Besides staining of the oral
Pharmacokinetics Profile of
cavity and teeth, further research indicated that acne
Tetracycline
treatments containing cyclones may also cause
adverse drug reactions (36). Tetracycline should not
be used in children because it can cause permanent
Administration: Tetracycline can be given orally, discoloration of the natural hue of the teeth
periodontally, ophthalmic (eyes) or topically (29). (yellowing). The same goes to the pregnant women.
However, in order to treat acne vulgaris, oral They cannot use tetracycline during pregnancy
tetracycline is usually prescribed (30). because the fetus may experience slower bone growth.
Absorption: Oral tetracycline has relatively high Their teeth may also be affected once they are born
absorption in GIT which is 77-88% (30). It has high (34).
solubility but quite poor permeability (30). Absorption Tetracycline may also increase the risk of autoimmune
of tetracycline is reduced by administration with food, disorders, hypersensitivity syndromes and abnormal
iron and milk (31). This is because iron, calcium, skin pigmentations. A reported released by a
magnesium and aluminium will chelate tetracycline in university in Germany indicates that side effects
GIT, hence reducing its absorption(30). related to the use of tetracycline may include
Distribution: Tetracycline is widely distributed contraction of Sweet's syndrome. Sweet’s syndrome is
throughout the tissues (30). However, since it is not a condition in which painful red nodules arise on
highly lipophilic, it may not optimally penetrate the various parts of the body and is also generally
follicular unit (30). This is due to the fact that follicular accompanied by fever and malaise (38).
unit contains high amounts of lipid-rich sebum (30). A study published by a hospital in France in May of
Metabolism: Tetracycline does not undergo any 2003 indicates that ‘adverse affects of cyclines might
metabolism(32). be serious and sometimes unknown.’ The report
Excretion: Tetracycline is excreted unchanged via further suggested that ‘long term treatment by
renal and biliary routes (32). About 50% of the drug is tetracycline must be researched in patients presenting
excreted through glomerular filtration (32). such symptoms.’ Symptoms related to adverse side
effects in nearly 250 cases included autoimmune
Side Effects of Tetracycline
disorders, hypersensitivity syndromes as well as
abnormal skin pigmentations (37).
A report released in February of 2000 indicated that
Every medication has its own side effect. The same tetracycline could also be responsible for the induction
goes to tetracycline. If the side effect is severe, then of intracranial hypertension (39).
stop using the medication. Research indicates that patients who are considering
The common mild side effects of using tetracycline are the use of tetracycline to consider the risks associated
stinging, redness, burning, peeling, and itchiness. Any with this acne treatment before proceeding with
allergic reaction towards tetracycline can be use(35).
considered as severe side effects and its usage
should be stopped.
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Formulations of Tetracycline difficile-associated disease, pseudomembranous
colitis, may also occur in the initial weeks of the
following treatment. If patient is suspected to have
pseudomembranous colitis, tetracycline should be
The oral dose of tetracycline for treating acne is from
stopped immediately and the patient should be treated
125mg to 500mg depending to the severity of the acne.
with supportive and specific treatment without delay.
Beside tetracycline, doxycycline and minocycline are
Any products that inhibit peristalsis are contraindicated
also used for treatment of acne at a lower dose (40).
in this clinical situation (47).
Table 2.1 shows a list of tetracycline, minocycline and
There are some compounds that may interfere with
doxycycline product available in Malaysia. While Table
the bioavailability of tetracycline antibiotics. These
2.2 shows the international listing of tetracycline,
include antacids; sucralfate; magnesium salicylate;
minocycline and doxycycline brand name.
magnesium citrate; polysaccharide-iron complex;
Most oral tetracycline is formulated into capsule or
quinapril (tablets contain magnesium); and
tablet form which gives tetracycline a better stability to
multivitamins that contain iron, calcium, manganese,
the tetracycline when taken orally. This is because
or zinc. Laxative preparations containing magnesium
tetracycline degrades to epitetracycline due to
are also contraindicated. So, tetracycline should not
epimerization in protic solvent which cause the
be given with or within 4 hours of any of the above
tetracycline to be inactive (40). Besides that, the
drugs. Besides, calcium salts and magnesium salts
release of tetracycline is controlled when it is given in
that are contained in food and dairy products can form
tablet or capsule form over its solution form (40).
chelates with tetracycline and decrease the absorption.
Beside oral route, tetracycline is also formulated for
Administration of tetracycline at least one hour prior to
topical route. The dosage forms used are cream,
or two hours after a meal and/or milk will reduce the
ointment and gel (40). The topical form of tetracycline
effect (47).
is mostly applied to a small area affected by acne
Warfarin has shown a clinically significant interaction
because usage over a larger area has been proven to
with tetracycline because the action of warfarin and
be awkward (40). Besides that, topical application of
other oral anticoagulants are increased by either
tetracycline could avoid the gastrointestinal
impairing prothrombin utilization or decreasing
disturbance caused by the drug and drug interactions
production of vitamin K (48).
which may occur if taken orally. The first stable topical
Tetracycline should not be used with acitretin,
tetracycline produced was in ointment form because
isotretinoin, strontium, and tretinoin that are taken
tetracycline is relatively stable in the ointment base
orally because very serious interactions may occur.
(40). However for cosmetic use, the oily formulation is
Zinc can affect tetracycline because it can attach to
less desirable thus the formulation of a less greasy
tetracycline in the stomach. This reduces the amount
cream was created. Finally the gel formulation of
of tetracycline absorbed. Thus, it will decrease the
tetracycline was created which is stable, non-greasy,
effectiveness of tetracycline too (49).
less irritating and soft for the skin (40).
Tetracycline may chelate the divalent or trivalent
Drugs Interactions And cations, forming insoluble compounds (50).
Contraindications Tetracycline bioavailability may be decreased by
didanosine, due to the buffering agents in didanosine
tablets or powder. Some antidiarrheals that comprise
of cations will form chelated compounds too (50).
Tetracycline is contraindicated in patients known to
Concurrent use of tetracycline with oral contraceptives
have tetracycline hypersensitivity (47).
may make the oral contraceptives less effective (50).
Tetracycline is bacteriostatic. So, tetracycline must not
This is due to stimulation of estrogen metabolism or a
be given in conjunction with penicillin or other
decline in estrogen enterohepatic circulation via
bactericidal antibiotics because it may disturb the
changes in gastrointestinal flora (48).
bactericidal action of penicillin (49). Bacteriostatic and
Topical tetracycline preparations contain sodium
bactericidal antibiotics should not be used together
sulfites while oral dosage forms may contain tartrazine
since the bactericidal agents, for example, penicillins
dye. More precaution steps should be considered
may be inhibited by the bacteriostatic agent too (48).
when dealing with patients with a known sulfite
Treatment with tetracycline can alter the normal flora
hypersensitivity or tartrazine dye hypersensitivity.
of the colon and allow overgrowth of Clostridium
Sensitivity reactions are prone to have happen in
difficile. Hence, the patient may suffer from diarrhea
asthmatic than in non-asthmatic patients (50).
during treatment. Symptomatic of Clostridium
If a pregnant mother wants to use the tetracycline, she
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should know that all tetracyclines have a harmful effect reminders and much motivation from him.
on the skeletal development and bone growth of the Besides, we also want to thank all of FAR 241
fetus or child. Therefore, tetracycline should not be Antimicrobial Therapy lecturers; which they taught us
used in the second half of pregnancy unless there are the concept of antimicrobial therapy in pharmacy field
more benefits from treatment to the mother compared and special thanks to Lydia Pang Kai Tsan for helping
to the risk of fetus, but their use should be considered us checked the grammatical errors in our report.
only with extreme caution (47). We would also like to forward our thanks to those
Although tetracycline can form non absorbable contributed accidentally or in-accidentally throughout
complexes with the calcium in breast milk, tetracycline this report. On top of that, we would like to express our
is distributed into breast milk. Therefore, appreciation to all group members that fully
breast-feeding mothers should not use tetracycline contributed and committed in making this report
antibiotics because risks o) teeth discoloration, enamel succeed.
hypoplasia, inhibition of linear skeletal growth, oral and
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Illustrations
Illustration 1
Table 1: Some of the common uses of tetracycline
Tetracycline in bacterial infection
 Lyme disease
 Rocky Mountain spotted fever
 Typhus fever
 Tick fever
 Conjunctivitis (pink eye)
 Chlamydia
 Certaintypes of pneumoniaand other respiratory infections
 Urinary tract infections(UTIs)
 Plague
 Cholera
 Skininfections
WebmedCentral > Review articles Page 10 of 38