Download ANTISEPSIS Aspects of history: Since the middle of XIX century the

ANTISEPSIS
Aspects of history:
Since the middle of XIX century the main what stopped the development
of surgery was the putridial complications of surgical wounds. These
complications about 80% caused sepsis and death of a patient.
Ancient Egyptians thought that it is useful to wash the wounds with a
water from silver plates.
Ancient Grecians washed the wounds with a rain water and wine.
In 1847 Semmelveis in a Hungarian clinic of obstetrics successfully used
chloride of lime in a hand preparation. This helped to decrease the
complications from 18% to 1,2%.
In France, in 1864 Pasteur announced the results of his scientific work,
that the cause of infection are small, alive subjects, able to multiple.
In 1867 in England D. Lister used 3-5% carbolic acid as antiseptic to disinfect contaminated wounds and he became the creator of antisepsis.
All these investments were achieved and their action verified in a surgical
practice during various wars.
Definition of antisepsis
An antiseptic is a chemical agent that either kills pathogenic
microorganisms or inhibits their growth so long as there is contact between
agent and microorganism.
The term "antiseptic" is reserved for agents applied to the body. The
antiseptic may actually be a disinfectant used in dilute solutions to avoid
damage to tissues.
A disinfectant is a germicidal, chemical substance used on inanimate
objects to kill pathogenic microorganisms but not necessarily all others,
especially the spores of microorganisms. These agents are usually used to
disinfect floors, fabrics and exreta in hospitals.
Antisepsis means to kill microorganisms, asepsis means the prevention
of the absence of microorganisms.
Hoverer, the first step in any process of biological decontamination
is through mechanical cleansing with soap or detergent and water to remove all
traces of blood, pus, proteins, and mucus before the antiseptic or disinfectant
is used.
The action of soap is double: first - mechanically cleans the surface
by emulgation of fats, and removes the microorganisms from the skin without
action on them; second - as other surface active agents, soaps changes the
osmotic pressure on the wall of microorganisms and leads them to "explosure".
Types of antisepsis:
- chemical antisepsis - when there are used various chemical substances with a bactericidal or bacteriostatic activity;
- physical antisepsis - when there are developed conditions
suppressing bacterial activity: cold, heat, wound dressings, drainage tubes,
physiotherapy.
- biological antisepsis - all methods that helps to raise the immune
activity of the organism and helps to maintain the physiology of the wound:
antibiotics, bacteriophages, serums, vaccines, immobization, rest of the
patient;
- mechanical antisepsis - all mechanical means directed to eliminate
the necrotic tissue, foreign bodies, to drain the secretion of the wound;
- prophylactic antisepsis - methods to avoid the development of
special selective and dangerous bacteria - such as tetanus and other;
The methods of antisepsis:
- superficial antisepsis - when wound dressings are flourished with
antiseptics, antiseptic baths, irrigation of wound with antiseptics;
when the
- deep antisepsis - when antiseptics are inserted into the tissue,
pathologic cavities are washed with antiseptics;
- haematogenic antisepsis - when antiseptics are used intravenously
or in to the arteries;
- local antisepsis;
- general antisepsis,
- mixed antisepsis.
I. TOPICAL AGENTS
Agents that can kill or inhibits the growth of microorganisms when applied
to living tissues without significant harm to the tissues. Antiseptics are
widely used but their efficacy and hazards are poorly understood.
PHENOLS:
Phenol /carbolic acid/ was first used in 1867 by Lister. A 1 to 2%
solution is effective against all nonsporulating bacteria and fungi, but
clinical usefulness is limited due to systemic toxicity manifested by CNS
stimulation with muscle tremors. HEXYLRESORCINOL in a 1:1000 concentration
allows effective penetration and spreading, but may cause skin irritation.
ALCOHOLS:
Ethyl alcohol /50 to 70% solution by weight/ and isopropyl alcohol
/70 to 90% solution by weight/ are both effective germicidal agents, but
isopropyl alcohol has the advantages of lower volatility, higher germicidal
activity and less potential for tissue corrosion.
HALOGENS:
Iodine is one of the oldest and most potent antiseptics. In a 1:20000
solution it is bactericidal after 1 min. and sporocidal after 15 min. There are
some disadvantages using iodine preparations: skin staining, tissue irritation,
hypersensitivity reactions, pain.
IODOPHORS:
Complexes of iodine usually with a surface active agent. Iodophors
such as povidone-iodine are less effective than the aqueous and alcoholic iodine
solutions, but may be less irritating and less toxic.
ACIDS:
Boric acid is weekly germicidal and nonirritating. But it is readily
absorbed if applied to large denuded areas, and can cause severe systemic
toxicity with gastrointestinal disorders, hypothermia, renal impairment,
vascular collapse, shock and death. It can be limitedly used only in
ophthalmology.
OXIDIZING AGENTS:
Hydrogen peroxide as 3% aqueous solution is weakly germicidal and
very unstable, but very useful for cleansing wounds. The antibacterial and high
mechanical activity is due to the rapid release of O.3% solution provides disinfection, 6% solution provides sterilization.
Potassium hypermangananatis is effective oxidizing and odorating
agent. 0,01- 0,05% provides disinfection, 2% provides burns.
ALDEHYDES:
Formaldehyde in a dilution of 1:200 is bactericidal after 6 to 12 h
but the solution is too irritating for clinical use. Methenamine can be used as
urinary antiseptic, but it should not be used in patients with hepatic
insufficiency.
HEAVY METALS:
Mercury compounds exert antibacterial action by reversible binding to
sulfhidryl enzymes in microorganisms. However, they are highly toxic to tissues,
and penetrate poorly. Mercuric oxide ointment 1%, amoniated mercury ointment,
thimerosal, nitromersol and merbromin.
Silver nitrate solution in a 1:1000 dilution rapidly destroys most
microorganisms. As a 0,5% solution it has been used extensively in the treatment
of burns to prevent infection. Prolonged use may cause an argyria,
methemoglobinemia. 1% silver nitrate ophthalmic solution is commonly used as
prophylaxis for gonorrheal ophthalmia neonatorum.
SURFACE ACTIVE AGENTS:
Antiseptic surfactants include both anionic and cationic compounds.
Most anionic surfactants are effective against gram-positive bacteria. The
cationic surfactants are effective against gram-positive and gram-negative
bacteria, as well as some fungi and viruses.
The advantages: rapid action, good tissue penetration and low
systemic toxicity.
The disadvantages: fast inactivation by soaps and the formation of
film on the skin under which some bacteria may survive.
FURANS:
Nitrofurazone is bactericidal against many gram-negative and positive
microorganisms in dilutions up to 1:75000. It is clinically useful as topical
antiseptic on surgical wounds and superficial skin lesions including burns,
ulcers, but systemic toxicity may result from absorption from large wound areas.
1:5000 furacilline kills only gram-positive bacteria.
MISCELLANEOUS AGENTS:
Mafedine acetate is a useful topical sulfonamide-like agent,
available as an 8,5 to 10% cream for applying to burns to prevent bacterial
invasion. It provides effective prophylaxis against both gram-positive and
negative bacteria, especially Pseudomonas aeruginosa. A disadvantage is severe
pain on application or removal.
Silver sulfadiazine is a topical antiseptic, effective against many
bacteria and fungi, but some microorganisms are resistant to its bacteriostatic
effect. It has been clinically useful for the treatment of burns, where it has
the advantages of prevention of Pseudomonas infections.
PAINTS:
Brilliant green 1-2% concentration ethyl alcohol solution.
Methylen blue 1-3% concentration ethyl-alcohol solution.
This antiseptic material is useful to contrast the pathological cavities of
human body, mostly these materials are effective against strepto - staphyllo
group of bacteria and their effectiveness is reduced in the presence of pus or
serum.
II. ANTIBACTERIAL AGENTS
An ideal antimicrobial agent exhibits selective toxicity, i.e.,
interferes, at concentrations tolerated by the host, with some metabolic and/or
synthetic process that exists only in the parasite and not in the host. At
present, the concept of true selective toxicity applies to the penicillins and
cefalosporins, which act only against bacteria.
At the cellular and subcellular level, most antimicrobial agents
function in one of four major ways:
1. Inhibition of cell wall synthesis (Bacitracin, Cephalosporins,
Cycloserine, Penicillins, Ristocetin, Vancomycin).
2. Alteration of cell membrane permeability (Amphotericin B,
Nystatin, Polymixins).
3. Inhibition of protein synthesis [i.e., inhibition of transcription
of genetic material and translation] -(Chloramphenicol, Eritromycins,
Lincomycins, Tetracyclins, Aminoglicosides).
4. Inhibition of nuclein acid synthesis (Nalidixic acid, Novobiocin,
Perymethamine, Sulfonamides, Trimetoprim, Rifampin).
The choice of antibacterial agent for the treatment depends on:
generalized,
operation);
-
the localization of infectious process on the human body;
type of the infectious process (localized, spread out destructive);
the purpose of antibacterial effect (prophylaxis or treatment);
the spectrum of antibacterial action of the drug;
time when the antibiotic was administered (before or after the
type of the action of the drug (bactericidal or bacteriostatic);
pharmacokinesis of antibiotics (the ways to the body and out);
the way of administration;
the dosage of the antibiotics;
the time of administration;
an interaction with other drugs.
Resistance to antimicrobial drugs:
1. Microorganisms produce enzymes which destroy the active drug.
2. Microorganisms change their permeability to the drug.
3. Microorganisms develop an altered structural target (receptor) for
the drug.
4. Microorganisms develop an altered metabolic pathway that bypasses
the reaction inhibited by the drug.
5. Microorganisms develop an altered enzyme, which can still perform
its metabolic function but is much less affected by the drug than the enzyme in
the susceptible organism.
Penicillins:
microbiology, pharmacology, clinical use.
Penicillin was isolated from Penicillium notatum by Fleming in 1928,
but it was not until 1940 that Florey and Sir William Dunn School of Pathology
began to work out the properties of the compound.
Penicillin V (phenoximethyl penicillin) is an oral form of antibiotic
(adult dose 125-500 mg/kg/day - 4 doses.
Penicillin G is an antibiotic of higher activity used orally, i/m or
i/v (25.000-500.000 units/kg/day - 6 doses) .
Later in 1950 due to the development of penicillin G resistant
Staphylococcus aureus, was started to product semisinthetic penicillins:
- methicillin, oxacillin, active against beta-lactamase producing S.
aureus (100-200 mg/kg/day -4 doses);
- ampicillin, active against selected gram-negative bacilli (100-200
mg/kg/day - 4 doses);
- carbenicillin and ticarcillin, active against Pseudomonas
aeruginosa (50-100 mg/kg/day - 4 doses),
Penicillins are well distributed and active (bactericidal) in the
most areas of the body, such as lung, liver, kidneys, muscle, bone and placenta.
The activity of penicillins against microbes have been decreased due
to the changes in structural protein components of the outer membrane due to
mutations cause organisms to become more resistant to penicillins. But in
increased daily doses they are still in use against many gram-positive and gramnegative aerobes and anaerobes.
Cephalosporins
In 1945 Professor Giuseppe Brotzu in fungus Cephasporium acremonium
found the substance capable of inhibiting the growth of pathogenic gram-positive
and gram-negative microorganisms.
In 1964 cephalothin (Keflin) became the first cephalosporin
antibiotic introduced in clinical practice, and later many derivates were
investigated - cephaloridine (Loridine) in 1966; cephaloglucin (Kafocin) in
1970; cephalexin (Keflex) in 1971; cefazolin (Kefzol) in 1973; cefadroxil
(Duricef) in 1979; and many others. The interest in cephalosporins is increasing
and today there are known few generations of cephalosporins used in treatment
and prophylaxis of infectious diseases.
Most important differences are not in microbiologic activity,
therapeutic effectiveness, or toxicity, but in pharmacokinetics and cost (still
very expensive).
Like penicillins, the cephalosporins are usually bactericidal in
action, and resistance of bacteria to the cephalosporins can be attributed to
the ability of organism to disrupt these critical structural properties or to
prevent the antibiotics from reaching their site in action.
The cephalosporins penetrate well through inflamed skin, synovial,
pleural, peritoneal, and pericardial surfaces.
An average doses of therapeutic activity generally varies from 250 mg
to 2 g every 4-6hours.
The major use of cephalosporins is related with the prophylaxis of
infectious complications. And due to the investment of new types of
cephalosporins they are used also in treatment of nonclostridial anaerobic and
gram-negative infections.
Aminoglycosides
The bactericidal activity of the aminoglycoside antibiotics against
gram-negative aerobes has led to their increasing use throughout the world. In
many instancies they have been used in combination with penicillins or
cephalosporins.
An inhibition of protein synthesis is the main action of
aminoglycosides. They are poorly absorbed orally, and usually are administered
intramuscularly,
Streptomycin is active against tuberculosis bacteria, but is not
active against many gram-negative microorganisms. Dosages of 0.5 g twice daily
or 1 g every day for 90 days to treat tuberculosis. Also in the same doses (two
week administration) it can be used for treatment of nonspecific infections.
Neomycin generally is used locally irrigating the infected places in
a cases of peritonitis, septic arthritis, or osteomyelitis, and perorally to
prepare the intestines for colon surgery.
Kanamycin was isolated in Japan in 1957. It's broad-spectrum
aminoglycoside against many gram-negative microorganisms. It easy penetrates
into body liquids including synovial, pleural, peritoneal, bile. Usual dosage is
0.5-1 g - 2 times daily.
Amikacin is semisinthetic derivate of kanamycin with a wide range of
antibacterial activity against most strains resistant to other aminoglycosides.
It's more concentrated in adipose tissue.
Gentamycin and tobramycin are broad spectrum of action aminoglycosides, what are easy penetrating into the most of body tissues. Dosage 80 mg x
3 times daily.
Sisomicin and netilmicin are more new aminoglycosides with less
amount of side affects (nephrotoxicity and ototoxicity).
Clinical indications: pneumonia, meningitis, bacterial endocarditis,
burns, intraabdominal infection, malignant external otitis.
Adverse reactions of aminoglycosides generally are high nephrotoxicity and ototoxicity, and prolonged neuromuscular block after general
anesthesia with myorelaxation.
Polymyxins, Colistin, Vancomycin and Bacitracin
Polymyxins and Colistin.
Polymyxins were discovered in the late 1940, and have been of medical
interest largely because of their high activity against Pseudomonas aeruginosa.
The polymyxins are a group of five related antibiotics identified as
A, B, C, D, E. because of the lesser toxicity, only polymyxins B and E
(Colistin) are on market today.
Polymyxin B sulfate is given in a dose of 2.5-3 mg/kg/day every 12
hours.
The main side effect is neurotoxic action (weakness, drowsiness,
ataxia). Persons injected with the polymyxins should not be advised to drive
automobiles.
Clinical indications all infections related with Ps. aeruginosa.
Vancomycin.
Vancomycin is active against of staphylococci, hemolytic streptococci, pneumococci, enterococci, gonococci. Gram-negative organisms are
resistant.
Vancomycin is not absorbed from gastrointestinal tract, and the oral
route is used in the treatment of enterocolitis.
Dosage usually 0.5 g intravenously every 6 hours.
Adverse reactions: may cause eighth nerve damage - decreased hearing
function; also superinfections with gram-negative bacteria and fungi may appear.
Bacitracin.
Bacitracin is produced from the culture of Bacillus subtilis. It's
active against gram-positive cocci, corynebacteria, neisseriae, Treponema
pallidum, and clostridia. It acts on bacteria by interference with synthesis of
the cell wall.
Dosage: it's not recommended for systemic use. For topical
application, bacitracin is usually recommended with polymyxin, neomycin for
treatment of superficial skin or mucous membranes infections.
Adverse reactions. systemic administration is associated with a high
risk of renal failure owing to tubular and glomerular necrosis. In topical
application an allergic sensitization can occur.
Macrolides:
Erythromycin and Troleandomycin
Erythromycin.
Erythromycin is the most important of the macrolide ("large ring")
antibiotic. It passes readily into all most tissue of the body, except
cerebrospinal fluid.
Indications for use: Acne vulgaris; amebiasis; chlamydia; diphtheria;
erythrasma; Legionnaires disease; mycoplasma pneumoniae; pertussis; otitis
media; pneumonia; skin and soft tissue infections; streptococcal
tonsilopharyngitis; syphilis and gonorrhea.
Dosage: various preparations of erythromycin are known. Dosage
depends on the form and type of medication. (usually it's 0.5 g x 4 times
daily).
Adverse reactions. Gastrointestinal disorders (vomiting nausea,
abdominal pain, jaundice).
Troleandomycin.
Troleandomycin is semisynthetic derivate of oleandomycin, a macrolide
produced by species of Streptomyces antibioticus. Although similar to
erythromycin in chemical structure and spectrum of antimicrobial activity, it's
less active against gram-positive organisms.
Dosage is oral, counted according to the commercial type of drug.
Adverse reactions. a number of gastrointestinal disorders have been
reported after oral administration. The most serious is cholestatic jaundice,
which occurs most commonly on the seventh to tenth day of administration.
Lincomycin and Clindamycin
Lincomycin.
Lincomycin is an antibiotic produced by Streptomyces lincolnensis. It
was isolated from soil near Lincoln, Nebraska in 1962. It's a broad spectrum
antibiotic of bacteriostatic action.
Clindamycin is a derivate of lincomycin, which has an increased
antibacterial (bacteriostatic) activity, an increased rate of absorption from
gastrointestinal tract and low order of toxicity.
Despite that these antibiotics are of low activity against many gramnegative microorganisms, an effective action against aerobic and facultatively
anaerobic bacterial pathogens is important for the clinical use.
In humans, significant concentrations were observed in bile,
peritoneal, pleural fluids, eye, brain, bone, bone marrow, joint capsule, and
synovial fluid.
These medications can be used:
Lincomycin orally (250-500 mg) or i/m injections solution containing
300 mg/ml - three times daily for treatment of variety of ear, nose, throat,
respiratory, dental, skin and soft tissue, bone and joint, and septicemic
infections caused by staphylococci, streptococci, and pneumococci.
Clindamycin capsules containing 75-150 mg., or 150 mg of clindamycin
base per each ml., administered according to the weight of patient. Clinical
use of clindamicin is the same as lincomycin, but it's more broad for the
treatment of the intraabdominal infection (an activity against anaerobes).
Adverse reactions are: prolonged neuromuscular block after general
anesthesia with myorelaxation; hypotension, if these preparations were
administered rapidly intravenously; specific colitis.
The Tetracyclines
This group of antibiotics was introduced in 1948 by Duggar.
The tetracyclines diffuse well into most body tissues and fluids.
They are present in the milk of most lactating women and pass through the
placenta to the fetus. They appear in saliva, cornea, sclera, iris,
gastrointestinal tract. Tetracyclines have an affinity for fast growing tissues,
liver, tumors, and areas of new bone formation.
The tetracyclines are incompletely absorbed from the gastrointestinal
tract, but the absorption can be impaired when tetracyclines are taken with milk
products or with products containing calcium, magnesium, or aluminium.
Clinical indications because of very broad spectrum of action are:
acne; malignant pleural effusion, Whipple's disease; mycobacterium Marinum,
pelvic inflammatory disease, chronic bronchitis and brochiectasis.
Side effects and toxicity are related with:
- allergic reactions including rash, urticaria, angioneurotic edema,
asthma, anaphylactic reactions;
- gastrointestinal side effects - nausea and diarrhea;
- hepatic toxicity - abnormal liver function;
- skin - rash, phototoxity;
- renal - azotemia, fanconi syndrome;
- hematologic - anemia, neutropenia, eosinophylia;
- teeth - staining, dysgenesis, fluorescence;
- miscellaneous - bulging fontanelle - meningeal irritation,
increased intracranial pressure, vertigo;
- superimposed infections - monilia, gram-negative infections,
fungal, staphylococcal infections.
Chloramphenicol
Chloramphenicol is produced by Streptomyces venezuelae, and was
synthesized in 1948. It has unique properties of lipid solubility and is active
against a number of important microbial pathogens, but awfully for a long period
of time it was used without any order and irrationally. due to that the side
effects were more found that the gross advantages of that drug.
Chloramphenicol is a broad-spectrum antimicrobial with variable
activity against gram-positive and gram-negative aerobic bacteria, and also
against anaerobic bacteria, rickettsiae, chlamydia, and mycoplasma.
Dosage is available for systemic administration by the oral and
intravenous routes. Intramuscular administration should not be administered
owing to incomplete hydrolysis of the succinate ester to active drug. The usual
dose is 50-100 mg/kg/day in 4 divided doses.
Chloramphenicol is widely distributed through the body, and has
excellent possibility to penetrate into the brain tissue.
Toxicity:
- hematologic - bone marrow suppression (non-dose-related aplastic
anemia);
- gastrointestinal side effects - nausea, vomiting, perineal
irritation, stomatitis and diarrhea;
- superinfections (candida, Ps aeruginosa; S. aureus)
- neurologic complications include optic neuritis, peripheral
neuritis, delirium, mental confusion.
Clinical indications generally are: typhoid fever and other salmonelloses,
central nervous system infections, anaerobic infections, rickettsial diseases.
Sulfonamides:
Trimethoprim - Sulfamethoxazole,
Nalidixic acid Oxolinic
acid,
Methenamine, and Nitrofurans
Sulfonamides and Trimethoprim.
The first chemical moiety responsible for the curative effect, known
as sulfanilamide was synthesized in 1908. Now there are thousands of derivates
known by this name.
Trimetoprim was synthesized as a pat of research program into
antimetabolities in 1942.
Sulfonamides are still active against most of the bacteria that
usually cause urinary tract infection
Trimetoprim is inhibitory to many pathogenic bacteria on other areas
of body.
These medications can be used orally, because are easy absorbed by
the gut, and are excreted in the urine in high concentrations.
Clinical usage: for long-term prophylaxis of urinary tract
infections, Nocardia and Haemophilus influenzae infections.
Side effects:
- crystalluria and urinary stone formation;
- skin rashes, erythema;
- nausea, vomiting.
Nalidixic acid and oxolinic acid.
Nalidixic acid was first reported in 1962 and oxolic acid was
reported 6 years later.
Nalidixic acid is dispensed in 500 mg tablets, the dosage being two
tablets every 6 hours (4 g daily). It's more active against gram-negative rods
than gram-positive cocci.
Oxolinic acid (Prodoxol) is available in 750 mg tablets, one being
taken every 12 hours (1.5 g daily). It's more intrinsically active, and inhibits
E.Coli, Proteus, Klebsiella, Ps. aeruginosa and Enterobacter.
Both are well absorbed after oral administration, and about 80% of
active substance can be accounted from the urine.
Clinical use - treatment of acute urinary tract infections.
Side effects are often found:
- gastrointestinal (nausea, vomiting);
- stimulating of CNS (headache, restlessness, insomnia, nervousness).
Methenamine
It's known more than 100 years. For medical purposes is usually known
as methenamine or hexamine, and are used as the cheapest compounds for treatment
of urinary tract infections.
Clinical indications are for treatment of acute urinary tract
infections or to "cover" during prostatectomy and instrumentation.
Dosage: 2-4 g daily.
Side reaction - disuria.
Nitrofurans
Nitrofurantoin and furazolidone are known and used from 1939.
Clinical indications: acute or chronic urinary tract infections. Also
it can be used in a presence of kidney impairment for long term treatment.
Dosage: 100 mg every 6 hours in acute urinary infections and 50 mg at
night for prophylaxis. it can be given i/m or i/v as the combination with sodium
salt.
Rifampin
Rifampin is a semisynthetic animirobial drug with an unique mexanism
of action. Alone it's effective in prophylaxis of meningococcal infections, and
in combination with another drugs, it's effective in treatment of tuberculosis,
and ultimately may prove to be useful in therapy of a variety of other
infectious diseases.
It has broad spectrum of antimicrobial activity against most gramnegative and gram-positive activity.
Rifampin is well absorbed from the gastrointestinal tract, except
immediately after a meal.
Dosage 600 - 900 mg daily.
Adverse reactions:
- immunosuppression by the drug - suppresses secretion of migrationinhibition factor by lymphocytes; response of lymphocytes to stimulation by
nonspecific mitogens;
- immunologic reactions to the drug production of antibody by
cultured lymph node cells;
- direct tissue toxicity to the kidneys;
- interactions with other drugs - induces of liver drug metabolizing
enzymes.
Clinical indications: treatment of tuberculosis, gonorrhea, and for
nasopharingeal carriers of Neisseria meningitidis.
Antifungal agents:
Amphotericin B, flucytosine, Grisefulvin, Imidazoles
These four antimicrobial agents are grouped as antifungals, but these
are not only one with a selective action against fun
gi.
Amphotericin B.
Amphotericin B usually is given intravenously is of broad spectrum
activity against many fungal microorganisms.
Dosage: to the 50 mg vial of the commercial preparation, 10 ml of
sterile water is added shaken for 3 minutes and diluted in 5% glucose solution
for i/v usage. The dosage of drug is increased daily or every other day by 5-10
mg increments. The total dose is of 1.5 - 2.5 g administered in approximately 6
weeks period.
Indications: most of types of severe systemic mycoses.
Toxicity: fever, chills, sweating, anorexia, nausea, vomiting,
malaise, headache, depression. Sometimes it can be prevented by use of
antihistamines or aspirin.
Flucytosine
Flucytosine is a fluorinated pyrimidine. Despite the relative
insolubility in water, flucytosine is well absorbed from gastrointestinal tract
after oral administration.
Dosage - 150 mg/kg/day divided into 4 doses. drug for administration
is available in 250-500 mg tablets.
Indications: with a few exceptions it is proper to use flucytosine
preferentially to amphotericin B in any patient who can take the drug orally and
who is infected with a suspected fungus. The spectrum of action is little
smaller than amphotericin B.
Griseofulvin.
Griseofulvin is derivated from Penicillium seofulvum dierckx. It
produces readily detectable shrinking and stunting of newly developing hyphae
such that is was originally termed the curling factor. It seems to exert these
effects by impairing synthesis of protein and nucleic acids and by breaking down
intracellular organelle membranes.
Griseofulvin is supplied in capsules of 125 mg, in tablets of 125,
250, or 500 mg, or as an oral suspension of 250 mg/5 ml. the daily dose for
infants is 10 mg/kg, for children 125-500 mg, for adults 500-1000 mg. It has
customary to give these amounts in 4 equally divided doses at 6-hours intervals.
Indications; epidermophytoses involving skin, hair, or nails due to
species of Microsporum, Trichophyton, and Epidermophyton.
Toxicity: headache, peripheral neuritis, lethargy, fatigue can
develop.
Imidazoles.
They causes thickening of fungal cell walls and proliferation of the
plasmalemma. Two main members of this group are widely used in clinical
practice: clotrimazole and miconazole.
Dosage:
Clotrimazole is available for topical use as a 100 mg vaginal tablet,
a 1% solution, or 1% cream.
Miconazole is available for topical use as a 2% skin cream, 2%
lotion, or 2% vaginal cream. For systemic therapy miconazole is supplied in 20
ml ampules as a sterile preparation. This ampule should be diluted in at least
200 ml of either 0.9% sodium chloride or 5% glucose injectable solution. The
drug has also been given intrathecally at various sites and for washing of urine
bladder in a dose of 200 mg in diluted solution.
Indications: treatment of dermatophytoses, and skin, nail, oral, or
vaginal forms of Candida infections.
Toxicity: Itching and burning when applied on mucous membranes;
thrombophlebitis after i/v injections; nausea, vomiting; leukopenia and
thrombocytopenia.
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