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Clonazepam is a derivative of benzodiazepine. This group of drugs is usually used as anxiolytics and sedatives; some of them incl. Clonazepam, however, is also used as anticonvulsants.
Clonazepam is a drug with long-lasting anticonvulsants and anti-anxiety effects. It is used to treat epilepsy in adults and children, both in treating generalized seizures (akinetic, myoclonic, tonic-clonic seizures), absences, and partial (focal) seizures.
The mechanism of the anticonvulsant action of Clonazepam is probably based on synaptic inhibition associated with gamma-aminobutyric acid (GABA) receptors, benzodiazepine receptors, and chloride channels, resulting in an influx of chloride ions into the interior of the nerve cell and suppression of continuous neuronal stimulation in the central nervous system. Since the drug directly inhibits cortical and subcortical epileptic lesions, it prevents the generalization of a seizure.
In addition, it shortens the duration of seizures. Therefore, in parenteral form (intravenous or intramuscular), it is used as the drug of choice (i.e., the most reliable, reliable treatment method) for all types of status epilepticus.
In the oral form, the indications for use are most clinical forms of epilepsy in infants and children, especially typical and atypical forms of absence seizures (Lennox-Gastaut syndrome), primary and secondary generalized tonic-clonic seizures, and juvenile myoclonic epilepsy. It can be used to treat epilepsy in adults, especially partial seizures.
It is also used in the treatment of mental disorders, in panic disorder, as a drug supporting the treatment of patients agitated in psychoses (mania, reactive psychosis, organic disorders), in sleep disorders, dyskinesias (uncoordinated, involuntary movements of the whole body or parts of it, e.g., limbs), tics, tremors, myoclonus (short-term contractions of muscles or individual muscle fibers), and neuralgia (neuralgia).
Clonazepam is rapidly and completely absorbed from the gastrointestinal tract. After oral administration, the maximum concentration in the blood serum is reached after 1–4 h. Bioavailability is approx 90%. It is 85% bound to plasma proteins. After oral administration of 2 mg clonazepam, the effect starts within 30-60 minutes and lasts for 6-8 hours in children and 8-12 hours in adults.
After intravenous administration, the effect starts immediately and lasts for 2-3 hours. Biologically the half-life is 30–40 hours. After that, it is metabolized in the liver. The main metabolite has shown little anticonvulsant activity in experimental studies.
Within 4–10 days, 50–70% of an orally administered dose is excreted in the urine, 10–30% in the feces as free or conjugated metabolites, and only 0.5% is found unchanged in the urine. The elimination of the drug from plasma may be slower in newborns, the elderly, and patients with renal or hepatic impairment. The drug crosses the placenta and into human milk.
The dosage and duration of treatment are determined individually for each patient and depend on the disease entity, age, body weight, and concomitant diseases.
Oral administration: Swallow the tablets whole with a little water.
Treatment should be started with the lowest possible effective dose, up to 3 times a day at equal intervals. The starting dose should not exceed 1.5 mg per day. Then, it should be increased gradually, depending on the patient's response, until an appropriate maintenance dose has been established, usually between 4 and 8 mg per day.
For children, both the starting and maintenance doses depend on body weight. Therefore, the daily dose should be divided into 3-4 doses given at equal intervals.
Clonazepam solution for injection is administered to terminate all clinical forms of status epilepticus.
It is given by slow infusion or injection into a vein. Dosage and treatment duration are determined individually. The usual dose is 0.5 mg of Clonazepam for children and 1 mg for adults.
In an emergency, if intravenous administration is not possible, the clonazepam solution can also be administered intramuscularly. The drug should not be discontinued suddenly. Instead, it is necessary to reduce the dose gradually.
The most common side effects include drowsiness, headache, tiredness, flu, depression, dizziness, irritability, insomnia, difficulty coordinating movement or walking, loss of balance, nausea, and difficulty concentrating—also the possibility of mental and physical dependence. With prolonged use, tolerance to the drug may develop, and the effectiveness of the treatment may decrease.
In addition, Clonazepam can cause physical and psychological dependence and cause epileptic seizures in rapid sequence when used excessively and incorrectly.
Several disorders have also been reported with the use of this drug:
Immune system: allergic reactions and very few cases of anaphylaxis;
Endocrine system: isolated, reversible cases of incomplete precocious puberty in children;
Psychiatric: amnesia, hallucinations, hysteria, changes in sexual appetite, insomnia, psychosis, suicide attempt, depersonalization, dysphoria, emotional instability, organic disinhibition, lamentations, decreased concentration, restlessness, confusional state and disorientation, excitability, irritability, aggressiveness, agitation, nervousness, anxiety and sleep disturbances;
Nervous system: drowsiness, slowness, muscle hypotonia, dizziness, ataxia, difficulty in articulating speech, incoordination of movement and gait, abnormal eye movement, forgetting recent facts, behavior change, increased seizures in certain forms of epilepsy, loss of voice, coarse and uncoordinated movements, coma, tremor, loss of strength on one side of the body, light-headed sensation, lack of energy and tingling, and altered sensitivity in the extremities.
Eyepieces: double vision, “glassy eye” appearance;
Cardiovascular: palpitations, chest pain, heart failure, including cardiac arrest;
Respiratory system: pulmonary and nasal congestion, hypersecretion, cough, shortness of breath, bronchitis, rhinitis, pharyngitis, and respiratory depression;
Gastrointestinal: loss of appetite, furred tongue, constipation, diarrhea, dry mouth, fecal incontinence, gastritis, liver enlargement, increased appetite, sore gums, abdominal pain, gastrointestinal inflammation, toothache.
Skin: hives, itching, rash, transient hair loss, abnormal hair growth, swelling of the face and ankle;
Musculoskeletal: muscle weakness, frequent and usually transient, muscle pain, back pain, traumatic fracture, neck pain, dislocations, and tensions; Urinary disorders: difficulty urinating, urinary loss during sleep, nocturia, urinary retention, urinary tract infection.
Reproductive system: menstrual cramps, decreased sexual interest;
Clonazepam is contraindicated in patients with allergies to benzodiazepines or any other ingredients in the formula and patients with severe lung or liver disease or acute narrow-angle glaucoma.
The use of Clonazepam in case of pregnancy, breastfeeding, kidney, lung, or liver diseases, porphyria, galactose intolerance or lactase deficiency, cerebellar or spinal ataxia, regular use, or acute intoxication by alcohol or drugs should only be done under the guidance of a doctor.
Overdose of Clonazepam is suspected with the following symptoms: hypotension, bradycardia, severe weakness, somnolence, confusion, decreased reflexes, paradoxical agitation, tremor, nystagmus, dysarthria, ataxia, shortness of breath or shortness of breath, respiratory depression, and heart failure. Gastric lavage and intake of the sorbent - activated charcoal - are prescribed as treatments. Symptomatic treatment is also recommended to maintain respiratory function and stabilize blood pressure. Hemodialysis is ineffective.
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Clonazepam is thought to be effective in epilepsy, muscle hypertension, West syndrome, and seizures. However, some patients report that treatment is accompanied by drowsiness, addiction, and other side effects. Therefore, always start the treatment under your doctor's guidance.