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Venlafaxine (Effexor)

Mode of action: it slows down the reuptake of 5-hydroxytryptamine and norepinephrine, to a small extent – dopamine. Mode of action stipulates an ability of the medicine to enhance the transmission of nerve impulses into the central nervous system.

Venlafaxine absorbs and metabolizes well after the ingestion in the liver. Meal does not influence much on absorption and biotransformation of venlafaxine. It takes out from the organism with the help of the gemmae. 

Indications 

Treat for depression with attending anxiety, secondary prophylaxis and depressive disorder (in hospital or in the community setting).

Side effects

There are the groups of side effects that depend on frequency of emergence: frequent – more than 1%, infrequent - 0.1-1%, seldom - 0.01-0.1%, very seldom – less than 0.01%.


Nervous system: frequent - headache, asthenia, debilitation,
insomnia, nightmares, nervosism, paresthesia, muscle hypertonia, tremor, sedation; infrequent - apathy, hallucinations, myoclonus, faintness; seldom - spasms, mania, neuroleptic malignant syndrome.


CVS: frequent - elevation of arterial tension, hyperemia of skin integument; infrequent - drop of arterial tension, postural hypotension, tachycardia.


Digestive system: frequent - reduction of appetite, sickness, vomiting, infrequent - bruxism (unintentional           teeth-grinding), hepatic transaminitis; seldom - hepatitis.


Urogenital system: frequent - decreased interest, erection disorder and/or ejaculation disorder , anorgasmia, menorrhagia, acraturesis; infrequent - uroschesis, women orgastic dysfunction.


Sensory organs: frequent - accommodation disorder, mydriasis, vision impairment; infrequent - taste perception disorder.


Hemopoietic system (for capsule): frequency unknown - agranulocytosis,
ŕďëŕńňč÷ĺńęŕ˙ anaemia, hypogranulocytosis, pancytopenia.


Hypersensitivity reaction: infrequent - eruption, photosensitization; anaphylactic reaction.
Lab values: infrequent - thrombocytopenia; seldom – rising             bleeding time, hyponatremia; by long-term use of high doses - hypercholesterinemia.
Others: frequent - body weight loss, hyperspiration (including at night); infrequent - ecchymosis, body weight gain; seldom - syndrome of inappropriate secretion of antidiuretic hormone (SIADH), when intake  capsules - serotonin syndrome (sickness, vomiting, abdominal pains, diarrhea, meteorism, psychomotor agitation, tachycardia, hyperthermia, muscular rigidity, spasms, myoclonus, hyperhidrosis,            impairment of consciousness from delirium to semicoma and coma with  fatality).


With the origin of withdrawal state: dizziness, headache, asthenia, tirednesssleep disturbance (changing the type of dreams, sleepiness or insomnia, sleep-onset insomnia), anxiety, nervosism, mental confusion, paresthesia, hyperhidrosis, xerostomia, reduction of appetite, sickness, vomiting, diarrhea (majority of these reactions represent insignificantly and do not need to be cure).

Contraindications:

Hypersensibility, polypharmacy with inhibitors of  monoamine oxidase, pregnancy, service period, under 18 years of age. With precaution. Recently old myocardial infarction, unstable angina, arterial hypertension, tachycardia, spasms in anamnesis, ocular hypertension, narrow-angle glaucoma, mania in anamnesis, hyponatremia, hypovolemia, dehydration, simultaneous dose of diuretics, suicidal tendencies, predisposition to  bleeding  from the part of skin  and mucous membrane, nephatony orhypohepatia.

Special instructions:

The prescription of  venlafaxine is possibly only  not until 14 days from the moment of treatment cessation with inhibitors of monoamine oxidase and has to be stopped not less than 7 days before the beginning of taking any inhibitor of  monoamine oxidase (possibly development or increase of giddiness, sickness, vomiting, hyperperspiration, hyperemia of skin, tremor,     myoclonia, hyperthermia, signs, that are similar to neuroleptic malignant syndrome, spasms, up to fatal outcome).
During curing you should control blood pressure. Remember that at the beginning of curing you can have the desire to commit a suicide. For decrease the probability of overdosage it is important to give the patient minimum of the drug at the beginning of curing.
Hyponatremia and/or syndrome of inappropriate secretion of antidiuretic hormone could be developed during treatment at the patients associated with oligemia or dried (including elderly patients, who taking diuretics).
The bleeding of skin and mucous membrane can be increased during curing with venlafaxine that is why it is necessary to be very careful when it is used by patients with predisposition to bleeding.
If venlafaxine has been used directly before labor or shortly before childbirth, it is important to take into account the possibility of development of withdrawal state at a newborn.
The medicine practically does not influence on the speed of healthy volunteers’ psychomotor actions, their cognition and mixed behavioral response. Nevertheless, taking into consideration the possibility of appearance significant side effects from the part of CNS, during treatment it is necessary to be careful when driving a car and doing potential dangerous kind of activity, those require heightened attention focusing and quickness of psychomotor actions.
It is recommended not to take ethanol during treatment.

 

Interaction:

It raises anticoagulant impact of warfarin.
It enhances influence of ethanol on psychomotor actions.
Cinamet restrains metabolism of the venlafaxine’s first undergoing and does not influence on pharmacokinetics.
It increases AUC risperidone 32%, but does not influence essential on total disposition profile of active pharmaceutical ingredients.
Does not integrate with preparations that including lithium.


Use and
Dosage:

Intake with food. It is advisable to take it at the regular hours, not chewing and taking some water with it. Pills: recommended beginning dose is 37.5 mg twice a day. If warranted the dosage interval can be increased not less than 4 days at 75 mg per day. Recommended dose if you have moderate depression is 225 mg per day at 3 stages, if you have hard depression - maximum permissible daily dose is 375 mg at 3 stages.
Capsules (do not divide, do not powder and do not dissolve in water): recommended beginning dose is 75 mg once per day; if warranted the dosage interval can be increased not less than 4 days up to 2 weeks and more. Maximum daily dose is 225 mg.
The patients, who has been getting pills, can be transferred to take capsules at the similar doses.
Gradual withdrawal will help to avoid withdrawal state: if the course of treatment consists of 6 weeks and more the period gradual withdrawal of the medicine should have not less than 2 weeks and depends on dosage, duration of therapy and patient’s individual peculiarities (in clinical testing of capsules the dose was reduced by 75 mg once per week).
With renal disorder (the speed of glomerular filtration is 10-70 ml/min) the daily dose has to be reduced by 25-50%.
With hemodialysis the daily dose has to be reduced by 50%, you should take the medicine after ending the treatment of hemodialysis.
The daily dose of patients with
ń moderate hypohepatia has to be reduced by 50% and more.

Escilopram (Lexapro)

Antidepressant, the mechanism of action is based on selective serotonin reuptake inhibitors.

Escitalopram’s pharmacokinetics is linear and depends proportionally on the dose in the range of 10–30 mg daily. The maximum concentration in the blood plasma is attained during 5 hours after taking the medicine inside.  Escitalopram’s absorption does not depend on the simultaneous meal. Bioavailability (for citalopram) is about 80%.  The volume of distribution (for citalopram) is 12 l/kg of weight.  

Approximately 56% of escitalopram are chemically bound with blood plasma proteins. When taking once daily the equilibrium state is achieved in average in 1 week. 

Major depressive disorders; generalized anxiety disorder. Escitalopram’s biotransformation is principally done inside the liver. Escitalopram’s major metabolites,  S-demetiltsitalopram  and  S- didemetiltsitalopram , do not have an important pharmacological activity.  Elimination half-life is 27–32 h. Escitalopram is excreted in the urine, about 8% in the form of escitalopram and 10% — in the form of  S-demetiltsitalopram.

 

Use

The starting dose is 10 mg once daily. The dose may be increased to 20 mg once daily after 1 week. It is taken once daily (in the morning or evening), with or without food. The dose for patients having a hepatic failure and patients of advanced age should not be over 10 mg/daily. Escitalopram’s dose correction is not necessary for patients having moderate hepatic failure.
In case of
major depressive disorder a maintenance therapy is carried out in the dose of
10–20 mg daily during several months (taking into account the clinical situation). 
The duration of treatment in case of
generalized anxiety disorder is ordinary up to 8 weeks.

Contraindications

Hypersensitivity to escitalopram or citalopram, simultaneous use of Mao inhibitors.

 

Side effects

The most common side effects associated with escitalopram are nausea, ejaculatory delay, difficulty sleeping or drowsiness, excessive tiredness, sweating.

 

Special instructions

Generally escitalopram does not have negative effect on the psychomotor activity,

however you should avoid driving transport vehicles and working with potentially dangerous mechanisms before finding individual reaction on the treatment.  

Prescription of the drug in the period of pregnancy is possible only if the expected therapeutic effect for the mother exceeds potential risk for the fetus. Racemic citalopram is excreted in the breast milk.

 

Interactions

The drug does not potentiate effects of alcohol on the central nervous system, however alcohol is not recommended during escitalopram treatment period.
While using the drugs with
acetylsalicylic acid, other non-steroidal, anti-inflammatory and other grugs with antiaggregatory effect, the risk of development of gastro-intestinal bleeding increases.  While using selective serotonin reuptake inhibitors with sumatriptan isolated cases of weakness, hyperreflexia and discoordination are known; in case of such kind of treatment the patient has to be under medical supervision
.

The combined use with ketoconazole may occur a reduced concentration of ketoconazole in the blood plasma.

 

Overdose

Cases of overdose with escitalopram’s treatment at the dose to 600 mg are discribed; any symptoms of the intoxication were not observed.  The overdose of escitalopram in the dose of 2 g did not lead to death. The lethal outcome is possible is case of a more important overdose, mainly when combined other psychotropic drugs or alcohol.
The main complications caused by e
scitalopram’s overdose are dizziness, sweating, nausea, vomiting, tremor, drowsiness, sinus tachycardia, convulsions. Amnesia, mental confusion, koma, hyperventilation, cyanosis, rhabdomyolysis, cardiogram changes are rarely observed.  In order to maintain an adequate ventilation and oxygenation it is necessary to provide the patency of the upper respiratory tract, control B.P., ECG and the external respiration.
There is no specific antidote; the treatment is supporting and symptomatic. Because of a big volume of e
scitalopram’s distribution forced diuresis, dialysis, hemoperfusion and exchange blood transfusion  have little effect.

 

 



 

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