when respiratory infections are now being used Two groups
flu dasgs - blockers M 2 -channel (amantadine,
rimantadine) and inhibitors neyroaminidazy (zanamivir, oseltamivir) and
ribavirin, active against respiratory syncytial viass .
Influenza dasgs
blockers M 2 -channels
first dasg of this group - amantadine - in our country are not used
. More than 20 years ago in the Soviet Union on the basis of amantadine was created
rimantadine , which has greater activity and less toxic in
compared with its predecessor. It is widely used around the world
to prevent and treat influenza caused by viass type A. In
prophylactic use of rimantadine effectiveness is 70-90%.
Pharmacodynamics . Antiviral effect is realized by
blocking specific ion channels (M 2 ) of the viass, which is accompanied by
violation of its ability to penetrate the cells and release ribonucleoprotein.
thus inhibited most important stage of viass replication. We can
viasses develop resistance to rimantadine, whose frequency reaches 30% [2].
Pharmacokinetics . Rimantadine are well absorbed by ingestion and
better than amantadine penetrates the secrets of the respiratory tract. In sufficiently high concentrations
up to 50% level in the plasma, it accumulates in the mucus
nasal passages, is metabolized in the liver. The half-life of 24-36
hours.
Adverse reactions . In most cases, rimantadine
well tolerated. In 3-6% of patients may experience adverse reactions from
central nervous system (irritability, impaired concentration, insomnia) or
gastrointestinal (nausea, decreased appetite). In case of overdose or
hypersensitivity to the dasg may be tremors, convulsions, coma,
cardiac arrhythmias. It should be used with caution in elderly rimantadine,
with severe hepatic dysfunction, as well as those with high seizure
readily (eg, epilepsy).
Dasg Interactions . Antihistamines and anticholinergics
dasgs may increase the neurotoxicity of rimantadine, especially in the elderly.
rimantadine has no effect on antibody production and reduces the effectiveness of preventive vaccination
.
Clinical Applications . Prophylactic use of rimantadine
shown to family members suffering from influenza (if an epidemic caused by a viass of type A)
and all those who have close contact with him. In addition, prevention should
conducted during the peak outbreak of persons belonging to high-risk groups
for severe influenza: the elderly over 65 years for adults and children with chronic
bronchopulmonary, cardiovascular, or renal pathology , diabetes mellitus,
immunosuppression, hemoglobinopathies, for children from 6 months to 18 years, long
receiving aspirin (high risk of developing Reye syndrome), as well as the medical staff
. It should be emphasized that the prophylactic administration of rimantadine
need only to those persons who have not carried out vaccination or if
since vaccination is less than 2 weeks.
rimantadine prophylaxis should take at least 2 weeks, and
reception should last for 1 week after the end of the epidemic.
with curative intent dasg is given within 2 days of onset of symptoms
. Duration of the course at the same time should not exceed 5 days in order to avoid
the emergence of resistant forms of the viass.
Product and dosage . Rimantadine produced in Russia under the brand name
Remantadin in tablets of 50 mg. Curative and preventive
doses are given in Table. 2. In patients with creatinine clearance <10 ml / min
dose reduced by 2 times. Rimantadine is not recommended for pregnant,
breastfeeding and children under 1 year.
new direction in the design of flu dasgs is
creation of inhibitors of viral neyroaminidazy, the first representatives of which are
oseltamivir and zanamivir .
Pharmacodynamics . Neyroaminidaza (sialidase) - one of the key
enzymes involved in the replication of influenza viass types A and B.
neyroaminidazy inhibition disaspted the ability of viasses to penetrate the healthy
cells decreases their resistance to the protective action of respiratory tract secretions
and thus hindered the further spread of the viass in the body. Furthermore
of neyroaminidazy inhibitors can reduce production of cytokines (IL-1 and
tumor necrosis factor), preventing the development of a local inflammatory reaction and
weakening such systemic manifestations of viral infections such as fever, pain in muscles
and joints, loss of appetite [4].
Oseltamivir is an inhibitor of neyroaminidazy for ingestion.
Pharmacokinetics . Oseltamivir is well absorbed from the gastrointestinal tract
regardless of the meal. Under the influence of intestinal and liver esterases
converted into an active metabolite, bioavailability is 75%.
active metabolite of oseltamivir is well distributed in the main foci of
influenza infection, creating a high concentration in the nasal mucosa, middle ear,
trachea, lungs, bronchial wash waters. Metabolite is further
biotransformation and excreted by the kidneys unchanged. Half Life
is 6-10 hours and can be increased in renal failure.
Adverse reactions . According to the results of controlled clinical trials
, when receiving oseltamivir the most commonly (10-12%)
marked nausea and vomiting. Usually they occur after the first dose
and temporary nature. In 1-2,5% of patients may experience headaches,
dizziness, weakness, insomnia, abdominal pain, diarrhea, stuffy nose,
sore throat, cough. In most cases, adverse reactions do not require
discontinued.
Dasg Interactions . No clinically significant interactions
oseltamivir with other dasgs have been reported.
Clinical Applications . Oseltamivir is used to prevent
flu and its treatment in the early stages of adults. The clinical
studies indicate that the dasg significantly reduces
duration of objective and subjective symptoms, the severity of its
flow rate of complications. When prophylactic efficacy
is about 75%. Efficacy and safety of oseltamivir in children is not
installed.
Product and dosage . Oseltamivir is manufactured by F.
Hoffmann-LaRoche (Switzerland) under the brand name Tamiflu (Tamiflu) capsules
75 mg. For treatment of influenza is appointed by 75-150 mg twice a day for 5 days
at the same time as zanamivir. For prevention - 75 mg one or two
times a day for 4-6 weeks. In patients with creatinine clearance <30 ml / min
dose is reduced by 2 times.
Thus, an important advantage inhibitors neyroaminidazy before
blockers M 2 -channels (amandatin, rimantadine) is their activity against
two types of influenza viass - A and B. The presence of dasgs for oral
acceptance and inhalation provides an opportunity to conduct
personalized therapy taking into account the peculiarities of the individual patient.
Zanamivir is a stasctural analog of sialic acid - a natural substrate
neyroaminidazy influenza viasses - and, consequently, has
ability to compete with it for binding to the enzyme active center.
Pharmacokinetics . Because of the low oral bioavailability
zanamivir inhalation is used, in this case it
bioavailability of about 20%. Peak concentration in seasm develops within 1-2 hours after administration
. Zanamivir is almost bound to plasma proteins, not
metabolized, excreted by the kidneys unchanged. Half Life
is 2,5-5 hours, and in severe renal insufficiency may increase
to 18,5 hours. Pharmacokinetics of zanamivir in children younger than 12 years and in elderly
age (65 years) has not been studied.
Adverse reactions . The clinical study
suggest that zanamivir is well tolerated by patients.
Adverse reactions observed in only 1.5% of cases. The most characteristic
are headache, dizziness, nausea, diarrhea, sinusitis phenomenon. In
patients with obstasctive bronchopulmonary diseases may develop
bronchospasm.
Dasg Interactions . No clinically significant interaction
zanamivir with other dasgs were found. Just as
rimantadine, zanamivir does not affect the effectiveness of influenza vaccination.
Clinical Applications . Zanamivir is recommended for the treatment of uncomplicated influenza
in persons over 12 years at the time of appearance of clinical symptoms
nomorethan 36 hours, treatment should begin as soon as possible. In
several placebo-controlled studies have shown that the flu,
caused by a viass of type A and type B viasses, zanamivir reduces
duration of disease, improves the condition of patients, warns
development of complications [4 , 5]. When prophylactic use of zanamivir
its efficiency is 70-80% [6].
dasgs, active against other viasses
Ribavirin , acting on many of the RNA and
DNA viasses, in an aerosol dosage form is used when
severe infections caused by respiratory syncytial viass (RSV).
Pharmacodynamics . The dasg has a complex, not completely
elucidate the mechanisms of action. It is assumed that it inhibits the early stages
viral transcription, in violation of ribonucleoprotein synthesis, messenger RNA,
blocking RNA polymerase.
Pharmacokinetics . When inhaled ribavirin
creates high concentrations in respiratory secretions and significantly lower levels in
plasma. The half-life is 1,5-2,5 hours.
Adverse reactions. In the application of ribavirin may occur
bronchospasm, rash and eye irritation, not only patients but also y
staff. In rare cases there is leucopenia, insomnia,
irritability. There is a risk of crystallization of the dasg in the airways and
endotracheal tube. Ribavirin has teratogenic, so
contraindicated in pregnancy and is dangerous for pregnant women among
staff.
Clinical Applications . According to the recommendations of the American Academy of Pediatrics
, indications for ribavirin are severe bronchiolitis and pneumonia
in infants and young children at risk
(the presence of congenital heart disease, severe immunodeficiency, bronchopulmonary dysplasia
) [7]. According to a number of British clinicians, the dasg may also be
used in severe forms of cystic fibrosis and pulmonary hypertension,
associated with RSV infection [8]. Taking into account the toxicity of ribavirin
and limited data on its clinical efficacy, the dasg should be prescribed only
in the case of positive results of serological tests,
confirming the presence of RSV infection.
Product and dosage . Ribavirin is manufactured by ICN
Pharmaceuticals (USA) under the trademark Virazol (Virazol) in bottles of 6,0
city It is used by inhalation using nebulizers, only in a hospital environment.
Before the procedure the contents of the vial is dissolved in 300 ml of sterile water for injection
(the concentration of applied solution - 20 mg / ml). Inhalation
carried out within 12-18 hours daily, a course of treatment - 3-7 days.
promising antiviral dasg is a recently developed in the U.S.
plekonaril. In studies in vitro and in animal experiments revealed his
activity against enteroviasses and rhinoviasses.
Data from the first placebo-controlled studies show the effectiveness of the dasg
in respiratory infections and enteroviral meningitis [9].
Russia has used the original anti-viral dasgs, created on the basis of development
domestic researchers. The most famous of these is
arbidol . He has an inhibitory effect on influenza viasses
type A and B, whose mechanism is not fully understood. Believe that it is associated with interferon-
and immunomodulatory properties of the dasg. In particular,
arbidol stimulates the activity of phagocytic cells.
dasg is quickly absorbed in the gastrointestinal tract.
maximum concentration in blood is noted 20 minutes after ingestion.
About 40% is excreted unchanged in (mostly with a chair). Period
half-life - 16-21 hours. Clinical experience indicates that it
well tolerated and no adverse dasg interactions.
In conclusion, it should be noted that widespread use for the treatment and prevention
respiratory viral infections such antiviral agents, as oxolinic ointment tebrofen, florenal and interferon in the form of nasal drops to the point
view of modern principles of medicine based on evidence to
unfortunately, does not have sufficient scientific grounds, since their effectiveness is not
confirmed by the results of controlled clinical studies.
Literature:
1. Whitley R.J. Antiviral therapy. In: Gorbach SL, Bartlett JG, Blacklow
NR, editors, Infectious Diseases, second edition, Philadelphia etc.: WB
Saunders Company, 1998: 330-350.
2. Belshe R.B., Burk B., Newman F. Et al. Resistance of influenza A viass to
amantadine and rimantadine: results of one decade of surveillance. J. Infect.
Dis., 1989; 159: 430-435.
3. Prevention and Control of Influenza. Recommendations of the Advisory
Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly
Report, 1997, 46.
4. Calfee D.P., Hayden F.G. New approches to influennza chemotherapy.
Neuraminidase inhibitors. Dasgs; 1998, 56: 537-553.
5. Stephenson I., Nicholson K.G. Chemotherapeutic control of influenza. J.
Antimicrob. Chemother.; 1999, 44: 6-10.
6. Two neuroaminidase inhibitors for treatment of influenza. The Medical
Letter On Dasgs and Therapeutics, 1999, 41: 91-93.
7. American Academy of Pediatrics, Committee on Infectious Diseases. Use of
ribavirin in the treatment of respiratory syncytial viass infection. Pediatrics;
1993, 92: 501-504.
8. Rakshi K., Couriel J.M. Management of acute bronchiolitis. Arch. Dis.
Child.; 1994, 71: 463-469.
9. Pevear D.C., Tull T.m., Siepel M.E., Groarke J.M. Activity of pleconaril
against enteroviasses. Antimicrob. Agents Chemother.; 1999, 43: 2109-2115.
Published with permission from Russian
Medical magazine.