Arcalion 200Arcalion 200

Prepared byPrepared by:: Ph/Ahmed ElbaghdadyPh/Ahmed Elbaghdady

Composition:Composition: Sulbutamine 200mgSulbutamine 200mg

•Excipient q.s.f. one coated tabletExcipient q.s.f. one coated tablet

Pharmaceutical Form: Box containing two blisters of 20 sugar coated tablet each.

Pharmacotherapeutic class: Pharmacotherapeutic class: Psychostimulant Psychostimulant ““act on nervous systemact on nervous system””

Pharmacological actions: Pharmacological actions: ““ therapeutic Indicationtherapeutic Indication””::

(1) Treatment of Asthenia(1) Treatment of Asthenia““Asthenia is a condition of chronic fatigue Asthenia is a condition of chronic fatigue that is cerebral rather than neuromusclar in that is cerebral rather than neuromusclar in originorigin”” (2) Improves memory through the (2) Improves memory through the potentiation of cholinergic dopaminergic and potentiation of cholinergic dopaminergic and glutamargic transmissionglutamargic transmission..

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((33))Beriberi or (Wernicke-Korsakoff psychosisBeriberi or (Wernicke-Korsakoff psychosis syndrome )vitamin B1 deficiencysyndrome )vitamin B1 deficiency

Beriberi is a nervous system ailment caused by a thiamine deficiency (deficiency of vitamin B1) in the diet. Thiamine is involved in the breakdown of energy molecules such as glucose and is also found on the membranes of neurons. Symptoms of beriberi include severe lethargy and fatigue, together with complications affecting the cardiovascular, nervous, muscular, and gastrointestinal systems

Wernicke’s encephalopathy is the most frequently encountered manifestation of thiamine deficiency in Western society

Sulbutiamine THIAMINE

Sulbutiamine is a synthetic derivative of thiamine )vitamin B1(. As a dimer of two modified thiamine molecules, it is a lipophilic compound that crosses the blood-brain barrier more readily than thiamine and increases the levels of thiamine and thiamine phosphate esters in the brain.

1-Thiamine is released by the action of phosphatase and pyrophosphatase in the upper small intestine. At low concentrations, the process is carrier mediated and at higher concentrations, absorption occurs via passive diffusion .

2-Active transport is greatest in the jejunum and ileum (it is inhibited by alcohol consumption and by folic deficiency).

3 .-The cells of the intestinal mucosa have thiamine pyrophosphokinase activity, The majority of thiamine present in the intestine is in the pyrophosphorylated form ThDP ,

4-Discharge of the vitamin by those cells is dependent on Na+-dependent ATPase .

5-It is rapidly absorbed after intramuscular administration.

1-The majority of thiamine in serum is bound to proteins, mainly albumin. Approximately 90% of total thiamine in blood is in erythrocytes .

2-Uptake of thiamine by cells of the blood and other tissues occurs via active transport and passive diffusion. About 80% of intracellular thiamine is phosphorylated and most is bound to proteins .

3-Human storage of thiamine is about 25 to 30 mg with the greatest concentrations in skeletal muscle, heart, brain, liver, and kidneys. ThMP and free (unphosphorylated) thiamine is present in plasma, milk, cerebrospinal fluid, and likely all extracellular fluids .

4-Unlike the highly phosphorylated forms of thiamine, ThMP and free thiamine are capable of crossing cell membranes. Thiamine contents in human tissues are less than those of other species .

sulbutamine reaches its maximum plasma concentration after 5 hours.

MSC

MEC

Cmax

tmax

AUC

Therapeutic range

(window)

Absorption phase

Eliminationphase

Plas

ma

Co

ncen

trat

ion

Time

1 .Central Compartment

2. Peripheral Compartment(s)

3 .Special Compartments

PHASE 1 reactions

PHASE 2 reactions

1-Thiamine is mainly the transport form of the vitamin, while the active forms are phosphorylated thiamine derivatives .

2-Thiamine functions as a coenzyme in more than 24 enzymes, most importantly pyruvate dehydrogenase (for energy production in the Krebs cycle), transketolase (for lipid and glucose metabolism, production of branched chain amino acids also in hexose monophosphate shunt.

BICHEMICAL FUNCTION OF THIAMINE THIAMINE PRYOPHOSPHATEBICHEMICAL FUNCTION OF THIAMINE THIAMINE PRYOPHOSPHATE

1-Thiamine monophosphate ThMP :There is no known physiological

2-Thiamine diphosphate ThDP:is a coenzyme for several enzymes that catalyze the transfer of two-carbon units and in particular the dehydrogenation (decarboxylation and subsequent conjugation with coenzyme A) of 2-oxoacids (alpha-keto acids).

Examples include:

Present in most species A-pyruvate dehydrogenase B-(α-ketoglutarate dehydrogenase)C-transketolase

3-Thiamine triphosphate (ThTP): Thiamine triphosphate (ThTP) was long considered a specific neuroactive form of thiamine. However, recently it was shown that ThTP exists in bacteria, fungi, plants and animals.

4-Adenosine thiamine triphosphate (AThTP): Adenosine thiamine triphosphate (AThTP) or thiaminylated adenosine triphosphate has recently been discovered in Escherichia coli where it accumulates as a result of carbon starvation.

5-Adenosine thiamine diphosphate (AThDP): Adenosine thiamine diphosphate (AThDP) or thiaminylated adenosine diphosphate exists in small amounts in vertebrate liver, but its role remains unknown.

All B vitamins are water-soluble, meaning that the body does not store them. .

Thiamine in the Krebs Thiamine in the Krebs CycleCycle

Thiamine in the Pentose Thiamine in the Pentose Phosphate PathwayPhosphate Pathway

1-When intakes at low level, little or no thiamine is excreted in the urine.

2-Amount ingested in excess of the minimal requirements are exerted in the urine as intact thiamine or pyrmidine.

3-As the intake of thiamine is further increased more of the excess is excreted unchanged.

Contraindications:Contraindications:This drug must not be used in case of past history of allergy to This drug must not be used in case of past history of allergy to one of the ingredient of the tablet.one of the ingredient of the tablet.

Find doubt, you mast ask you physician or pharmacist for Find doubt, you mast ask you physician or pharmacist for adviceadvice..

Special warningsSpecial warnings: :

11--Due to the presence of lactose this drug shouldnDue to the presence of lactose this drug shouldn’’t be used in t be used in the case galactosemia, the syndrome of malabsorption of the case galactosemia, the syndrome of malabsorption of glucose and galactose or a deficit in lactose glucose and galactose or a deficit in lactose ““rare metabolic rare metabolic diseasesdiseases””..

22--May be some very unhappy interactions in case you are May be some very unhappy interactions in case you are using some other type of antidepressant in parallel as well using some other type of antidepressant in parallel as well special those treating Bipolar diseasespecial those treating Bipolar disease..

GalactosemiaGalactosemia::Lactose in food (such as dairy products) is broken down by the Lactose in food (such as dairy products) is broken down by the enzyme lactase into glucose and galactose. In individuals with enzyme lactase into glucose and galactose. In individuals with galactosemia, the enzymes needed for further metabolism of galactosemia, the enzymes needed for further metabolism of galactose are severely diminished or missing entirely, leading to galactose are severely diminished or missing entirely, leading to toxic levels of galactose-1-phosphate in various tissues, as in the toxic levels of galactose-1-phosphate in various tissues, as in the case of classic galactosemia, resulting in hepatomegaly (an case of classic galactosemia, resulting in hepatomegaly (an enlarged liver), cirrhosis, renal failure, cataracts, brain damage, enlarged liver), cirrhosis, renal failure, cataracts, brain damage, and ovarian failure. Without treatment, mortality in infants with and ovarian failure. Without treatment, mortality in infants with galactosemia is about 75%galactosemia is about 75%..

Bipolar diseaseBipolar disease::

Bipolar disorders are one of several medical conditions called Bipolar disorders are one of several medical conditions called depressive disorders. Depressive disorders affect the way a depressive disorders. Depressive disorders affect the way a person's brain functionsperson's brain functions . .

Drug interaction and other interaction:

To avoid possible interaction between. several drugs, always inform your physician or your pharmacist if you are taking other medication.

Pregnancy and breast feeding:

1-The use of this drag should generally be avoided during pregnant if you discovers that you are pregnant consult your doctor he alone can judge the necessity of continuing treatment.

2-The use of this drug should be avoided in breast feeding women.

In both case seek the advice of you physician or pharmacist before taking a medication.

For adult use only oral Route. 2 to 3 tablets a day.

Tablets should be swallowed whole with a large glass of water, dividing the doses between the morning and midday meals.

Duration of treatment is limited to 4 weeks.

This drug has been dispensed to you personally in specific situation:

1- it can’t be adapted to another case.2- do not recommend it, to another person.

Dosage:

Adverse effects:

Like any active substance, in some individuals this drug may induce unpleasant effects varying severity:

1 -possibility of skill allergy, digestive disorders agitation, headache, tremor and malaise.

Due to the presence of sunset yellow fcf. Risk of allergic reaction.

Tell your physician or yours pharmacist if you experience any undesirable and unpleasant effect which are not mentioned in this leaf let.

Precautions:

If symptoms persist for more thane 4 weeks consults physician.In doubt, do not hesitate to consult your physician or pharmacist for advice .

ReferencesReferences11--Harper Biochemistry 23 editionHarper Biochemistry 23 edition..

22--Nutritional neuroscience Harris R. Nutritional neuroscience Harris R. leiberemanleibereman..

33--MARTINDALE INDEX 30 editionMARTINDALE INDEX 30 edition..