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Paroxetine - an antidepressant from hell?

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Paroxetine, also known by the trade names Aropax, Paxil, Pexeva, Seroxat, Sereupin and Brisdelle, was first marketed in 1992. Effective for major depression and various anxiety disorders, it has quickly gained a significant share of the antidepressant prescription market. However, by the late 1990s, paroxetine became frequently associated with serious drug interactions and side effects. When Paxil (paroxetine) was first approved, it was called "a much-needed and welcome addition to the antidepressant/hypnotic arsenal."

Mechanisms of action of paroxetine

In addition to being a serotonin reuptake inhibitor, it also had mild to moderate noradrenergic effects through norepinephrine reuptake inhibition (NRI or NARI) and could activate, which often helped depressed patients with lethargy.

Indications for the use of paroxetine

Paroxetine has been effective in the treatment of generalized anxiety, panic, post-traumatic stress, social phobia, premenstrual dysphoric disorder and obsessive-compulsive spectrum disorders

Side effects and complications from paroxetine therapy

Paroxetine has been reported to affect male fertility, birth defects, gestational hypertension, QT prolongation in infants, hyperprolactinemia, cognitive impairment in the elderly, autism, sexual side effects, weight gain and suicidality, aggression and akathisia in children and adolescents. Paroxetine has the highest known affinity for the serotonin transporter (0.13 nanomolar) of any antidepressant currently used.

Sexual disorders

Patients may be willing to tolerate some side effects, such as sexual dysfunction, early in treatment, but they are likely less willing to tolerate side effects that reduce their quality of life during ongoing treatment.

Paroxetine may cause cancer

By the early 1990s, animal studies showed that antidepressants increased the incidence and growth of breast cancer in mice. The researchers hypothesized that this increase in tumor incidence and growth may have been associated with inhibition of enzymes (eg, CPY450 2D6 isoenzyme) that are involved in the metabolism of carcinogens and estrogens, resulting in increased concentrations and serum levels of carcinogens and estrogens that are associated with breast cancer Another cause of tumorigenesis is increased inhibition of dopamine release in pituitary lactotrophs, leading to disinhibition. prolactin production and its increased level.

Between 2001 and 2006, several groups of researchers published case-control studies and reviews of antidepressant and breast cancer studies. Some have concluded that there is no association between antidepressant use and breast cancer, while others have concluded that there is an association and/or that a possible association between antidepressants and breast cancer risk has not been ruled out and more research is needed. In a 2006 study, Chien et al. concluded that there is limited evidence that ever use of antidepressants is associated with overall breast cancer risk. However, they found that SSRIs may increase the risk of progesterone receptor-negative (PR-), estrogen receptor-negative, and progesterone receptor-negative (ER+/PR-) tumors, although further research is needed to confirm this association. 33% (20 of 61) of studies reported a positive association between antidepressants and cancer. 67% (41/61) of studies reported no association or antiproliferative effect. It was concluded that preclinical and clinical data are mixed in demonstrating an association between antidepressant use and breast and ovarian cancer.

Paroxetine has the highest inhibition constant for the P450 2D6 isoenzyme of all antidepressants (Ki = 0.065–4.65 μmol). This high affinity explains its high inhibitory interaction profile with 2D6 substrates. The potent inhibition of 2D6 by paroxetine also means that there is significant inhibition of the metabolism of carcinogenic 2D6 substrates, implying an increased likelihood of tumorigenesis. Paroxetine was associated with a 620% increase in the risk of breast cancer in women who took it over a four-year period. A Canadian epidemiological study of antidepressant use and breast cancer found that paroxetine had an odds ratio (OR) for breast cancer in women treated for depression and/or anxiety over a four-year period of 7.2. This was several times higher OR than any other antidepressant or class of antidepressants in this study, including tricyclic antidepressants (TCAs), which were found to have a median OR of 2.0.

Through 2D6 inhibition, the metabolism of tamoxifen is inhibited, which increases the risk of death from breast cancer over a five-year period in women taking both drugs. Paroxetine is also a potent 3A4 inhibitor with multiple interactions with 3A4 substrate.

conclusions

1) Do not use paroxetine as first-line therapy in antidepressant-naïve patients with a family history of breast cancer; 2) If a woman with no history of breast cancer responds well to paroxetine, continue paroxetine; 3) If the woman has a strong family history of breast cancer (mother, sisters, grandmothers or aunts) or tests positive for BRCA1 or BRCA2, after consultation with a gynecologist, stop taking paroxetine and prescribe another drug; 4) Always gradually reduce the dose of paroxetine before stopping and/or cross-tap slowly when being treated with another drug

Reviews

Mikhail M .: “I took paroxetine for three months. The drug helped me, there were no special side effects. For the holiday I decided to drink a little alcohol, but I didn’t stop taking the pills. Despite the fact that I used to tolerate alcohol well, this time after drinking alcohol, my stomach on the right began to hurt. Doctors diagnosed me with hepatitis, it turned out that this medicine cannot be taken with alcohol.”

Psychiatrist : “Many patients suffering from anxiety and depression look for solutions to their problems “at the bottom of the bottle.” Before starting treatment with paroxetine, we warn them that either take medication and become a healthy person, or continue to drink alcohol, but this may end badly. Patients who try to combine both cause significant harm to their health, and sometimes end up in intensive care.”

Content

Consequences of using paroxetine with alcohol

With the simultaneous use of paroxetine and alcohol, a certain symptom complex develops. Its manifestations may be:

Nausea and vomiting;
Migraine-type headache;
Pathological drowsiness;
Impaired consciousness up to coma;
Psychotic states with hallucinations and delusions;
Decreased visual acuity;
Acute hepatitis.

All of these conditions develop if sufficient time has not passed between taking alcohol and paroxetine. In order to avoid consequences, it is necessary to stop drinking alcohol at least three days before starting treatment with paroxetine. You can drink alcohol again no less than a week after the end of treatment.

Serrata (Serox) 10 mg tab. intestinal/solvent N30 - Instructions

Compound

The active element is serratiopeptidase.
The composition also includes additional components in the form of sodium starch glycolate, magnesium carbonate, lactose monohydrate, magnesium stearate and corn starch.

Release form

The medicine is produced in tablets. Supplied in packs of 30 per pack.

pharmachologic effect

The drug may have anti-inflammatory and antifibrinolytic effects.

Serratiopeptidase is an enzyme derived from intestinal bacteria such as Serratia E15. These non-pathogenic substances and substances that exhibit proteolytic activity are part of the drug, which quickly destroys bradykinin, fibrin and other inflammatory mediators. They also have anti-inflammatory and anti-inflammatory effects. This effect causes the release of amine due to the pain present in the inflamed tissue.

The use of this drug promotes the lysis of necrotic tissues and their decomposition products. Its active agent reduces nasal congestion and accelerates the action and absorption of various antibiotics.

The active substance for the breakdown of bradykinin, serotonin and histamine reduces capillary permeability and reduces their expansion. In addition, it leads to inhibition of plasmin blockers, thereby improving their fibrinolytic effect.

Pharmacokinetics

Absorption of the drug occurs in the intestines. It should also be noted that the substances contained in the drug are not broken down in the stomach; the maximum amount of the active substance is determined after an hour. Usually the medication is excreted by the kidneys.

Indications for use

Serrata is prescribed for the treatment of various diseases:

in otolaryngology: sinusitis, otitis media and other inflammations are accompanied by increased mucus secretion and production of working sputum. This drug is also used to improve the absorption of antibiotics;
in surgery and traumatology: for cracks, sprains, dislocations and other injuries. In addition, tablets are used for edema;
in dermatology: acute dermatoses that occur with pain;
in plastic surgery - to reduce swelling and growth of microdermabrasion to prevent possible rejection.

Contraindications

The absolute restrictions are:

allergy to the composition of the medicine;
pathological conditions that can lead to problems with the risk of blood clots and bleeding.

Side effects

In rare cases, this drug may cause vomiting, nausea, and abdominal pain.

People receiving this medication may often experience nosebleeds.

Sometimes the drug in question provokes allergic reactions: itching or rash and hives.

Drug interactions

The combination of anticoagulants and serratiopeptidase may cause primarily increased effects. If these drugs must be taken simultaneously, the patient should be under the strict supervision of a physician, who will be able to adjust the dosage of the anticoagulant if necessary.

Application and dosage

The medication is prescribed one tablet per day in three divided doses.

Drug adjustment depends on the severity of the daily dose and the type of disease. A specialist should determine the minimum effective dosage based on the specific situation and duration of taking the drug.

Overdose

Excessive doses of Serrata may cause increased side effects. In some cases, an overdose can cause internal bleeding.

If such pathological conditions occur, you should stop taking medications and symptomatic treatment.

special instructions

This drug affects the blood clotting process. In this regard, anticoagulants should be used with extreme caution, especially in combination with blood coagulation pathology and patient sensitivity to blood.

People with problems with the liver or kidneys need to be under the supervision of a specialist.

Use during pregnancy and breastfeeding

Appointment is not recommended.

Impact on the ability to drive vehicles and operate machinery

No special precautions are required.

Terms of sale

As prescribed by a doctor.

Storage conditions

The medication must be stored in a temperature range from 15 to 25 degrees Celsius, in a dark place out of reach of children.