Tetracycline is an antibiotic that fights bacteria in the body. Tetracycline is used to treat many different bacterial infections, such as urinary tract infections, acne, gonorrhea, Chlamydia, and others. Tetracycline may also be used for other purposes not listed in this medication guide.
Tetracycline is used to treat bacterial infections, including pneumonia and other respiratory tract infections; acne; infections of skin, genital and urinary systems; and the infection that causes stomach ulcers (Helicobacter pylori). It also may be used as an alternative to other medications for the treatment of Lyme disease and for the treatment and prevention of anthrax (after inhalational exposure). Tetracycline is in a class of medications called tetracycline antibiotics. It works by preventing the growth and spread of bacteria. Antibiotics will not work for colds, flu, or other viral infections.
Presently, the name “tetracycline” refers to a number of antibiotics of either natural, or semi-synthetic origin, derived from a system of four linearly annelated six-membered rings (1,4,4a,5,5a,6,11,12a-octahydronaphthacene) with a characteristic arrangement of double bonds. The tetracycline molecule possesses five asymmetric centers: C-4, -4a, -5a, -6, and -12a. A determination of the crystal structure of aureomycin hydrochloride has clearly defined the relative stereochemistry of these centers . 1H NMR studies [23,24], especially as applied to 5-hydroxytetracycline, have established independently the proton topology . The determination of its complete structure, involving a sagacious use of IR and UV spectroscopy, has been named a masterpiece in the field of structural analysis .
Figure 2.2.1Three Dimensional Structure of Tetracycline
Tetracycline Hydrochloride occurs as yellow, small hygroscopic crystals or crystalline powder. Tetracycline Hydrochloride soluble in dilute acid and slightly soluble in water having the molecular weight of 444.44. its melting point is 170-173oC.
2.2.Properties of Tetracycline
2.2.1. Physical Properties
- Name: 2-Naphthacenecarboxamide, 4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-, [4S(4a,4aa,5aa,6b,12aa)]-
- Molecular weight: 444.44
- Molecular formula: C22H24N2O8
- Melting Point: 170-173°C (with decomposition)
- Colour/Crystalline: cr (+3w)
- Specific Rotation: [a]25/D -239° (MeOH)
2.2.2. Chemical properties
The reactions that tetracyclines undergo are generally of a sophisticated nature, dictated by the complex functionality and the sensitivity of the molecules to mild reaction conditions (acid, base, heat) .
- Acidic conditions
When exposed to dilute acid conditions, tetracycline undergoes dehydration to yield anhydrotetracycline. Anhydroterramycin suffers further cleavage and lactonization to apoterramycin:
Diluted acid promotes epimerization at C-4 as well.
- Basic conditions
Mild alkali attacks 11a carbon of tetracycline, which is transformed to isotetracycline:
- Formation of complexes
Tetracycline possesses a great tendency to form complexes with a number of chemical
It complexes most readily with Fe3+, Fe2+, Cu2+, Ni2+, Co2+, Zn2+, Mn2+, Mg2+, Ca2+, Be2+, Al3+ among metal ions, phosphates, citrates, salicylates, p-hydroxybenzoates, saccharin anion, caffiene, urea, thiourea, polivinylpyrrolidone, serum albumin, lipoproteins, globulins, and RNA .
2.1.1. Antimicrobial properties
In the 1950s, when most of the tetracyclines were discovered, their antimicrobial spectrum was broader than of any othen antibiotic then known. Tetracyclines are characterized by their exceptional chemotherapeutic efficacy against a wide range of Gram positive and Gram negative bacteria, richettsia, spirochetes, and large viruses, such as members of the lymphogranuloma group . The main indications for the use of tetracyclines are infections due to Escherichia coli and Haemophilus influenzae, infections of the bile duct, bacterial respiratory disorders including bronchitis prophylaxis, mixed infections arising from the mouth, pharynx, or intestinal tract, brucellosis, tularemia, plague and other pasteurelloses, leptospirosis, lymphogranuloma inguinale, cholera, and rickettsiosis . Because of the development of strains of microorganisms resistant to the tetracyclines, these antibiotics have lost some of their usefulness. They are no longer the drugs of first choice for treatment of staphylococcal, streptococcal, or pneumococcal infections. The individual tetracyclines differ less in their potency that in pharmacokinetic properties such as resorption, tissue diffusion, and elimination
2.2. How used this medicine
Tetracycline comes as a capsule and suspension (liquid) to take by mouth. It was usually taken two to four times daily. Tetracycline were been taken on an empty stomach, at least 1 hour before or 2 hours after meals or snacks. A full glass of water was drunk with each dose of tetracycline. Must be avoided tetracycline with food, especially dairy products such as milk, yogurt, cheese, and ice cream. Followed the directions on prescription label carefully, and asked the doctor or pharmacist to explain any parts that do not understand. Tetracycline taken exactly as directed. Did not take more or less of it or took it more often than prescribed by the doctor.
Shaken the liquid well before each used to mix the medication evenly.
Before taking tetracycline,
- If patients were allergic to tetracycline, minocycline, doxycycline, sulfites, or any other medications.
- Specially prescription and nonprescription medicines, such as vitamins, nutritional supplements, and herbal products were taking or plan to taken, especially antacids, anticoagulants (‘blood thinners’) such as warfarin (Coumadin), and penicillin. Tetracycline might be decreased the effectiveness of some oral contraceptives; another method of birth control might be used while taking this drug.
- Be awared that antacids, calcium supplements, iron products, and laxatives containing magnesium interfere with tetracycline, making it less effective. Taken tetracycline 1 hour before or 2 hours after antacids (including sodium bicarbonate), calcium supplements, and laxatives containing magnesium. Take tetracycline 2 hours before or 3 hours after iron preparations and vitamin products that contain iron.
- If patients have or have ever had diabetes, allergies, asthma, hay fever, hives, or kidney or liver disease.
- If patients were pregnant, plan to become pregnant, or were breast-feeding. If patients become pregnant while taking tetracycline, called doctor immediately. Tetracycline could harm the fetus.
- If patients were having surgery, including dental surgery, told the doctor or dentist that they were taking tetracycline.
- Planed to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Tetracycline made skin sensitive to sunlight.
2.4.Action taken when forget a dose
The missed dose was taken as soon as remembered it. However, if it was almost time for the next dose, skipped the missed dose and continued regular dosing schedule. Did not take a double dose made up for a missed one.
There are mainly two types of dosage forms available in the local market of tetracycline hydrochloride, such as-
v Tetracycline hydrochloride capsule
v Tetracycline hydrochloride suspension
Tetracycline may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- upset stomach
- itching of the rectum or vagina
- sore mouth
- redness of the skin (sunburn)
- changes in skin color
Some side effects can be serious. If you experience any of these symptoms, call your doctor immediately:
- severe headache
- blurred vision
- skin rash
- difficulty breathing or swallowing
- yellowing of the skin or eyes
- dark-colored urine
- light-colored bowel movements
- loss of appetite
- upset stomach
- stomach pain
- extreme tiredness or weakness
- joint stiffness or swelling
- unusual bleeding or bruising
- decreased urination
- pain or discomfort in the mouth
- throat sores
- fever or chills
If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA)
2.7.Contraindication of Tetracycline
Antibiotic medicines caused diarrhea, which might be a sign of a new infection. If patients were have diarrhea that was watery or has blood in it, called doctor. Any medicine did not used to stop the diarrhea unless the doctor has told.
Avoided exposure to sunlight or artificial UV rays (sunlamps or tanning beds). Tetracycline made skin more sensitive to sunlight and sunburn may result. A sunscreen (minimum SPF 15)was used and wear protective clothing if you must be out in the sun. Iron supplements, multivitamins, calcium supplements, antacids, or laxatives were not taken within 2 hours before or after taking tetracycline.
2.8.Storage conditions are needed for this medicine
Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom). Throw away any medication that is outdated or no longer needed. Talk to your pharmacist about the proper disposal of your medication.
|2.9.Toxiticity of tetracycline’s towards bacteria|
The least concentration of a tetracycline completely inhibiting growth of bacteria [mg per ml]
2.1.Mechanism of action of Tetracyclines
Tetracyclines inhibit a lot of enzyme reactions essential for the vital processes of bacterial cells. The most sensitive biochemical reaction that is inhibited is the synthesis of proteins . Tetracycline works by binding specifically to the 30S ribosome of the bacteria, preventing attachment of the aminoacyl tRNA to the RNA-ribosome complex. It simultaneously inhibits other steps of the protein biosynthesis. Tetracycline can also alter the cytoplasmic membrane and this in turn causes leakage of nucleotides and other compounds out of the cell. This does not directly kill the bacteria but instead inhibit it.
2.2. List of Tetracycline Hydrochloride Capsule Available in the Market of Bangladesh.
Tetracycline Hydrochloride available in the market both in the form of capsule as well as suspension. In Bangladesh more than fifty manufacturing companies manufacture tetracycline hydrochloride as single ingredient capsules. Name of some of the brand and manufacturing company mentioned below.
Table2.14.1: List of Tetracycline HCl capsules available in the market.
ACME Laboratories Ltd.
Medicon Laboratories Ltd.
Beximco Pharma Ltd.
Jayson Pharma Ltd.
Amico Pharma Ltd.
Novertis Pharma Ltd.
Apex Pharma Ltd
Doctor,s Pharma Ltd
TETRACYCLINE CHEMIST LAB
Chemist Laboratories Ltd
Opsonin Chemical Ltd.
Renata Pharma Ltd.
Incepta Pharma Ltd
Globe Pharma Ltd.
General Pharma Ltd.
IBN Sina Pharma Ltd.
Asiatic Laboratories Ltd.
Square Pharma Ltd.
Pacific Pharma Ltd.
Albion Laboratories ltd.
Modern Pharma Ltd.
North Benggal Lab Ltd.
Indo Bangla Lab Ltd.
Quality Pharma Ltd.
Belsen Pharma Ltd.
Zenith Pharma Ltd.
2.3. Collection of samples for this study
Total 10 brands of tetracycline HCl capsule of different manufacturers were purchased from the retail shops for this analytical study. The selection of brands was done by random sampling from the list of finished products available in the market. During the collection of samples, the batch number and expiry date was properly checked. The samples were then coded for analysis; as shown in the following table.
Table2.15.1: List of collected samples with their batch number and expiry date.