Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5265_Библиотеки_им_академика_М_И_Перельмана.pdf
Antibiotics 327
Dosage Forms:
➢ Oral solution (125 mg/5 ml)
➢ Capsules of 250 and 500 mg
The dosage for children is 50 to 100 mg/kg/day given as four equal doses, and the dosage for
adults is 1 to 2 g/day given as four equal doses.
Officials:
➢ Amoxycillin Sodium, I.P.
➢ Amoxycillin Sodium Injection, I.P.
➢ Amoxycillin Trihydrate Capsules, I.P.
➢ Amoxycillin Trihydrate Dispersible Tablet, I.P.
12.1.3 Cloxacillin
Brand Names: Cloxapen, Tegopen
Cloxacillin is a semi-synthetic beta-lactamase resistant penicillin antibiotic carrying a
3-(2-chlorophenyl)-5-methylisoxazole-4-carboxamido group at position 6. Cloxacillin, like other
penicillins, appears to be metabolized via breakage of the beta-lactam ring to form an inactive
penicilloic acid metabolite.
IUPAC Name: 2,2- dimethyl- 6β- ({[5- methyl- 3- (2- chlorophenyl) isoxazol- 4- yl]carbonyl}
amino)penam-3α-carboxylic acid.
Properties: Cloxacillin sodium is available as a white, crystalline, odorless, dry powder with
bitter taste. It is soluble in water, methanol, ethanol, pyridine, ethylene glycol; and slightly sol
in acetone and chloroform.
Uses:
➢ Cloxacillin is used to treat a wide variety of bacterial infections. It includes impetigo,
cellulitis, endocarditis, osteomyelitis, pneumonia, septic arthritis, and otitis externa.
➢ It is not effective for methicillin-resistant Staphylococcus aureus (MRSA). It works by
stopping the growth of bacteria.
Stability and Storage: Cloxacillin sodium capsules and powder for oral solution should be stored
in tight containers at a temperature less than 40°C, preferably between 15°C to 30°C. Upon
reconstitution, the resulting solution is stable for up to 24 hours at controlled room temperature
and 48 hours under refrigeration at 2°C to 8°C.
328 Text Book of Pharmaceutical Chemistry
Stability: Cloxacillin is relatively stable in gastric acid, stable in light and slightly hygroscopic.
Officials:
➢ Cloxacillin Sodium, I.P.
➢ Cloxacillin Sodium Capsules, I.P.
➢ Cloxacillin Sodium Syrup, I.P.
12.1.4 Streptomycin
Brand Name: Strycin (Bristol-Myers Squibb)
Streptomycin is a broad-spectrum aminoglycoside antibiotic derived from Streptomyces
griseus and has a broad-spectrum of antibacterial activity. It is effective with respect to most
gram-negative and a few gram-positive bacteria.
Chemically, it is a triacidic base and has an aldose sugar. The structure of Streptomycin
consists of three components called: Streptidine (I) (diguanidino compound), Streptose (II)
(aldose sugar) and N-methyl-L-glucosamine unit (III). These three units linked through glycosidic
linkages.
Properties: It occurs as white to light gray or pale buff hygroscopic powder with faint amine-like
odor. Streptomycin sulphate is available in the form of white to off-white powdery solid soluble
in water (50 mg/mL). Streptomycin (sulphate) is soluble in organic solvent such as DMSO and
dimethyl formamide, approximately 2 and 13 mg/mL respectively. The solubility of the sulfate
salt in water is greater than 20 g/1; in ethanol, the solubility is 0.35 g/1, and it is essentially
insoluble in ethyl ether.
Uses:
➢ Streptomycin (sulfate) is used for various diseases caused by microorganisms that are
sensitive to it in bacterial endocarditis, periotonitis, meningitis, infections of the urinary
tract, gastric infections, and so on.
➢ It is most effective for the chemotherapy of brucellosis, tularemia and yersinia infections.
➢ It is used to treat moderate to severe tuberculosis, pneumonia, E. coli, influenza, plague
and other infections caused by certain bacteria.
Antibiotics 329
Preparations:
➢ Parenteral: For injection: 1 g (of Streptomycin)
➢ Generic Name: Streptomycin Sulfate for Injection.
Dosage Forms: Usual adult dose for tuberculosis: Streptomycin sulfate for intramuscular injection
is provided in 1 g single-injection vials. Dose in young is 15 mg/kg/day or 0.5 to 1 g daily to 1 g
twice weekly.
Storage and Stability: Dry powder should be stored under controlled room temperature between
15°C to 30°C. Streptomycin is stable under dry condition. It can be sealed from light for more
than four years with efficacy unchanged. The aqueous solution can be stored between pH 2 to 9
but degrades in strong acids alkalis and oxidizing agents. Its salts deliquesce on air but are
chemically not affected by air or light.
Officials:
➢ Streptomycin Sulphate, I.P.
➢ Streptomycin Injection, I.P.
➢ Streptomycin Sulphate Injection, I.P.
➢ Streptomycin Sulphate Tablet, I.P.
12.2 TETRACYCLINES
Brand Names: Sumycin, Panmycin, Achromycin V, Actisite
Tetracyclines are broad-spectrum bacteriostatic antibiotics produced by fermentation of
certain Streptomyces spp. Tetracyclines have a ring system characterized by a common octahydro
naphthacenes skeleton. Conventionally, tetracyclines can be classified into two types based on the
source and duration of action.
I. On the basis of sources:
➢ Naturally occurring – Tetracyclin, Chlortetracyclin, Oxytetracyclin and Demeclocyclin.
➢ Semi-synthetic – Doxycyclin, Lymecyclin, Meclocyclin, Methacyclin and Minocyclin.
II On the basis of duration of action:
➢ Short acting (half-life is 6-8 hours): Chlortetracycline, Oxytetracycline and
Tetracycline.
➢ Intermediate acting (half-life 12 hours): Demeclocyline and Methacycline.
➢ Long acting (half-life 16 hours): Doxycycline and Minocycline.
Tetracyclines are a large family of antibiotics, discovered in the form of chlortetracycline and
oxytetracycline (first members of tetracycline group) as natural products. Streptomyces
aureofaciens and S. rimosus are the sources of chlortetracycline and oxytetracycline, respectively.
It is amphoteric compounds, forming salts with either acids or bases. In neutral solution, this
substance exists mainly as zwitterions. The acid salts, which are formed through protonation of
the enol group on C-2, exist as crystalline compounds that are very soluble in water.
330 Text Book of Pharmaceutical Chemistry
IUPAC Name: (4S,4aS,5aS,6S,12aR)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-
3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide
Properties: Tetracycline and its hydrochloride salt occur as a clear, yellow, odorless powder with
melting point 175°C to 177°C. It is freely soluble in water; soluble in methanol and ethanol;
insoluble in ether and hydrocarbons; practically insoluble in chloroform and ether; very slightly
soluble in water; slightly soluble in alcohol; and very soluble in dilute hydrochloric acid and
alkali hydroxide solutions.
Uses:
➢ It is used to treat bacterial infections such as Rocky Mountain spotted fever, typhus fever,
tick fevers, Q fever, rickettsialpox and Brill-Zinsser disease.
➢ It may be used to treat infections caused by Chlamydiae spp, and upper respiratory
infections caused by typical (S. pneumoniae, H. influenzae) and atypical organisms.
➢ Tetracycline hydrochloride ointment is used in the prophylaxis of minor bacterial skin
infections and in the treatment of dermal ulcer.
➢ Their ointment preparation is indicated in the topical treatment of minor skin infections
caused by streptococci, staphylococci, and other susceptible organisms.
➢ Topical solution is indicated for the topical treatment of acne vulgaris.
➢ It is used in the treatment of sexually transmitted and gonococcal diseases, urinary tract
infections, and bronchitis.
Dosage Forms:
➢ Capsule/tablet: 250 mg, 500 mg
➢ Syrup: 125 mg/5 ml, 5 mg
Storage and Stability: Stored in the freezer and protected from light and moisture. The product
will darken in moist air when exposed to strong sunlight. Stable in air, but exposure to strong
sunlight causes it to darken.
Antibiotics 331
Officials:
➢ Tetracycline, I.P.
➢ Tetracycline, Oral suspension, I.P.
➢ Tetracycline Hydrochloride, I.P.
➢ Tetracycline Hydrochloride Capsules, B.P., I.P.
➢ Tetracycline Hydrochloride Eye Ointment, I.P.
➢ Tetracycline Intravenous Infusion, B.P.
➢ Tetracycline, B.P., I.P.
12.2.1 Doxycycline
Brand Names: Doryx, Doryx MPC
Doxycycline is a semi-synthetic, tetracycline in which the 5-beta-hydrogen is replaced by
a hydroxy group, while the 6-alpha-hydroxy group is replaced by hydrogen. The structural
formula for Doxycycline is:
IUPAC Name: (4S,4aR,5S,5aR,6R,12aR)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-
methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide.
Properties: Doxycycline occurs as a yellow crystalline powder. It is very slightly soluble in
water; sparingly soluble in alcohol; freely soluble in dilute acid and alkali hydroxide solution;
practically insoluble in chloroform and ether; soluble in methanol; and sparingly soluble in
ethanol.
Uses: Doxycycline is used in the treatment of bacterial infections in different parts of the body
such as:
➢ It is used in the treatment of chest and lung infections, in sexually transmitted
infections (STIs).
➢ It is used in the treatment of nose and throat infections.
➢ It is used in urinary tract infections (UTIs), skin infections, pimples and abscesses
(usually on the face) known as acne rosacea.
➢ It is also used to prevent malaria and to treat anthrax infection.
➢ It is used in intestinal infections, respiratory infections, eye infections, gonorrhea,
chlamydia, syphilis, periodontitis (gum disease), and others.
332 Text Book of Pharmaceutical Chemistry
Dosage Forms and Strengths:
➢ Capsules: 50 mg (Monodox, generic), 75 mg (Monodox), 100 mg (Monodox,
Vibramycin, generic), 150 mg (Adoxa).
➢ Tablets: 20 mg (generic), 50 mg (Adoxa, generic), 75 mg (Acticlate, Adoxa, generic),
100 mg (Adoxa, generic), 150 mg (Acticlate, generic).
➢ Syrup: 50 mg/5 mL (Vibramycin)
➢ Oral Suspension: 25 mg/5 mL (Vibramycin, generic).
Storage and Stability: It should be stored at 20°C to 25°C. It should be protected from sunlight
and artificial light. It should be retained in carton until time of use. Doxycycline is stable for 48
hours in solution when diluted with sodium chloride injection, USP, or 5% Dextrose Injection,
U.S.P., to concentrations between 1 mg/mL and 0.1 mg/mL and stored at 25°C. Doxycycline in
these solutions is stable under fluorescent light for 48 hours, but must be protected from direct
sunlight during storage and infusion.
Official:
➢ Doxycycline Hydrochloride, I.P.
12.2.2 Minocycline
Brand Names: Amzeeq, Arestin, Dynacin, Minocin, Minolira, Solodyn, Ximino, Zilxi, Vectrin,
Myrac
Minocycline is a second-generation tetracycline antibiotic and was first reported in 1966. It is
active against gram-negative and gram-positive bacteria. It is an analogue of tetracycline having a
dimethylamino group at position 7 and lacking the methyl and hydroxy groups at position 5.
It was patented in 1961 and came into commercial use in 1971. Its structural formula is:
IUPAC Name: (4S,4aS,5aR,12aR)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-
dioxo-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide
Uses:
➢ Minocycline is used to treat different types of bacterial infections, such as urinary tract
infections, pneumonia, respiratory infections, skin infections and severe acne.
➢ It is used in chlamydia, tick fever and certain other infections such as eye, lymphatic,
intestinal and genital.
Antibiotics 333
➢ It is also used for gonorrhea, syphilis, and other infections as a second-line drug in those
with a penicillin allergy.
➢ Oral minocycline is indicated in the treatment of asymptomatic meningococcal carriers to
eliminate Neisseria meningitidis from the nasopharynx.
➢ Systemic minocycline is used in the treatment of atypical mycobacterial infections.
Properties: Minocycline occurs as bright yellow-orange amorphous solid, odorless with slightly
bitter taste. It is slightly hygroscopic, sensitive to light and bright yellow-orange amorphous solid.
It is soluble in solution of alkali hydroxides and carbonates; and practically insoluble in
chloroform and ether.
Storage and Stability: Minocycline should be stored at controlled room temperature 20°C to
25°C. It is stable at least 3-4 years when stored at room temperature. It is stable in air when
protected from light and moisture
Official:
➢ Minocycline Tablet, B.P.
12.3 MACROLID ANTIBIOTICS
Macrolides are group of antibiotics derived from Saccharopolyspora erythraea (originally
called Streptomyces erythreus). They are natural products composed of a large macrocyclic
lactone ring and one or more deoxy sugars, generally cladinose and desosamine. The most
frequently used macrolide antibiotics are erythromycin, azithromycin, clarithromycin, and
roxithromycin, commonly used to treat both acute and chronic infections.
Macrolides mainly affect gram-positive cocci and intracellular pathogens such as
mycoplasma, chlamydia, and legionella. They act by inhibiting protein synthesis in bacteria by
reversibly binding to the P site of the 50S unit of the ribosome. Primarily, their actions are
bacteriostatic but may be bactericidal at high concentrations, or depending on the type of
microorganism.
12.3.1 Erythromycin
Brand Names: Erythrocin, Aktipak, Apo-Erythro-S, Benzamycin, Ery, Ery-tab, Eryc, Erygel,
Eryped, Erythro, Erythrocin, Erythrocin Stearate
Erythromycins are macrolide antibiotic and were first isolated in 1952 from the culture liquid
of microorganisms of the type Streptomyces erytherus. The structure of erythromycin is complex
and consists of a 14-membered lactone ring along with ten asymmetric centers and two sugars,
L-cladinose and D-desosamine. Erythromycin comes in four forms: Erythromycin A, B, C and D.
Erythromycin A is known for being the most antibacterial with B, C and D following
respectively.
334 Text Book of Pharmaceutical Chemistry
Properties: It appears as fluffy colorless or white to faint yellow, practically odorless, bitter,
powder. It is slightly soluble in ethanol, ethyl ether; insoluble in water; freely soluble in acetone
and chloroform.
Mechanism of Action: It inhibits bacterial protein synthesis by binding to bacterial 50S
ribosomal subunits. Binding inhibits peptidyl transferase activity and interferes with the
translocation of amino acids during the translation and assembly of proteins. Erythromycin may
be bacteriostatic or bactericidal depending on the organism and drug concentration.
Uses: Erythromycin is used to prevent and treat infections in many different parts of the body
such as:
➢ It is used topically in the treatment of acne vulgaris.
➢ It used in respiratory tract infections, skin infections and diphtheria.
➢ It is used as an alternative agent in the treatment of anthrax.
➢ It is used in intestinal amebiasis and acute pelvic inflammatory disease.
➢ It is generally effective in the treatment of mild to moderate inflammatory acne.
➢ It is used in Legionnaire’s disease, pertussis, and syphilis.
➢ It is also used to prevent recurrent attacks of rheumatic fever in patients who have had an
allergic reaction to penicillin or sulfa drugs.
Storage and Stability: Erythromycin topical solutions and gels should be stored at 15°C to 30°C;
exposure to heat or open flames should be avoided. The topical ointment should be stored at a
temperature less than 27°C. It should be stored in tight container as defined in the USP-NF.
Erythromycin (base) capsules and tablets should be stored in tight containers at room temperature
(15°C to 30°C).
Antibiotics 335
Officials:
➢ Erythromycin, I.P.
➢ Erythromycin Tablet, I.P.
➢ Erythromycin Estolate Capsules, I.P.
➢ Erythromycin Estolate Tablets, I.P.
➢ Erythromycin Stearate Tablets, I.P.
12.3.2 Azithromycin
Brand Names: Azasite, Azithromycin, Day Dose Pack, Zithromax, Zithromax TRI-PAK,
Zithromax Z-Pak, Zmax
Azithromycin is a broad-spectrum, semi-synthetic antibiotic.
Chemical Structure: Azithromycin belongs to the azalide derived from erythromycin and a
member of a subclass of macrolide antibiotics. The 15-membered lactone ring is derived from
erythromycin, upon incorporation of a methyl-substituted nitrogen atom (bold).
Properties: Azithromycin appears as white crystalline powder with melting point 113°C to
115°C. It is soluble in ethanol and DSMO, and minimally soluble in water.
Mechanism of Action: Azithromycin reversibly binds to the 23S rRNA of the 50S ribosomal
subunit of the bacterial ribosome of susceptible microorganisms, thereby inhibiting the
translocation step of protein synthesis by preventing the assembly of the 50S ribosomal subunit.
This inhibits bacterial protein synthesis, inhibits cell growth and causes cell death.
Uses:
➢ Azithromycin is used to treat a wide variety of infections caused by bacteria, such as
respiratory infections, skin infections, ear infections, eye infections, and sexually
transmitted diseases.
➢ This is also used in middle ear infections, strep throat, pneumonia, traveler’s diarrhea,
and certain other intestinal infections, urinary tract infections and sinusitis.
➢ It is used orally in children for the treatment of acute otitis media (AOM).
➢ It is used in the treatment of pharyngitis and tonsillitis caused by Streptococcus pyogenes.
336 Text Book of Pharmaceutical Chemistry
Dosage Forms and Strengths: Azithromycin comes as a tablet, an extended-release (long-
acting) suspension (liquid), and a suspension (liquid) to take by mouth.
➢ Injection: 500 mg/vial
➢ Tablet: 250 mg, 500 mg
➢ Oral Suspension: 100 mg/5 ml, 200 mg/5 ml
Storage and Stability: Azithromycin 250 mg or 500 mg tablets should be stored at controlled
room temperature between 15°C to 30°C. Reconstituted suspension: store at 5°C and 30°C.
Azithromax for injection: Stable for 24 hours at or below 30°C, or for 72 hours if stored under
refrigeration (5°C). Discard any unused portion after use.
12.4 MISCELLANEOUS
12.4.1 Chloramphenicol
Brand Names: Chloroptic, AK-Chlor, Chloromycetin Ophthalmic, Ocu-Chlor
Chloramphenicol is a semi-synthetic, broad-spectrum antibiotic produced initially by
Streptomyces venezuelae. It is a bacteriostatic antibiotic but may be bactericidal in high
concentrations or when used against highly susceptible organisms. It is active against gram-
positive and negative bacteria, rickettsiae, mycoplasma, chlamydia). It is an organo chlorine
compound that is dichloro-substituted acetamide containing a nitrobenzene ring, an amide bond
and two alcohol functions. Since it has two chiral centres, four isomers are possible. The D-(–)
threo is the biologically active form.
IUPAC Name: 2,2-dichloro-N-[(1R, 2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl] acetamide
Properties: Chloramphenicol occurs as white or grayish-white or yellowish-white crystalline,
bitter taste powder or fine crystals with melting point 150.5°C to 151.5°C. It is slightly soluble in
water; soluble in alcohol and propylene glycol; soluble in propylene glycol; very soluble in
methanol, ethanol, butanol, ethyl acetate and acetone; fairly soluble in ether; and insoluble in
benzene, petroleum ether and vegetable oils.