ENV Tablets 

COMPOSITION: Each tablet contains Doxylamine succinate 10 mg , Pyridoxine Hcl 10 mg, Folic acid 2.5 mg.

PRESENTATION: In 1 x 10 tables Alu – Alu pack.

Mechanism of Action

 

Doxylamine competes with histamine for H1-receptor sites on effector cells; blocks chemoreceptor trigger zone, diminishes vestibular stimulation, and depresses labyrinthine function through its central anticholinergic activity. Pyridoxine is a vitamin which may have modest antiemetic effects.

Pharmacodynamics/Kinetics

Absorption: Well absorbed Distribution: Vd: 2.5 L/kg Half-life elimination: 10-12 hours Excretion: Urine (primarily as metabolites)

Dosage

 

Oral: Adults: Two delayed release tablets (a total of doxylamine 20 mg and pyridoxine 20 mg) at bedtime; in severe cases or in cases with nausea/vomiting during the day, dosage may be increased by 1 tablet in the morning and/or afternoon

Dosage adjustment in renal impairment: No dosage adjustment required

Administration. Main dose should be taken at bedtime to provide relief in the early morning hours.

Contraindications:

Hypersensitivity to doxylamine, pyridoxine, or any component of the formulation

Warnings/Precautions:

May cause drowsiness; patient should avoid tasks requiring alertness             (eg, driving, operating machinery) until effects are known. Sedative effects of CNS depressants or ethanol are potentiated. Use with caution in patients with angle-closure glaucoma, pyloroduodenal obstruction (including stenotic peptic ulcer), urinary tract obstruction (including bladder neck obstruction and symptomatic prostatic hyperplasia), hyperthyroidism, increased intraocular pressure, and cardiovascular disease (including hypertension and tachycardia).

Adverse Reactions :

 

Cardiovascular: Palpitations, tachycardia

Central nervous system: Dizziness, disorientation, drowsiness, headache, paradoxical CNS stimulation, vertigo

Gastrointestinal: Anorexia, dry mucous membranes, diarrhea, constipation, epigastric pain, xerostomia

Genitourinary: Dysuria, urinary retention

Ocular: Blurred vision, diplopia

Drug Interactions

 

Anticholinergic agents: Central and/or peripheral anticholinergic syndrome can occur when administered with narcotic analgesics, phenothiazines and other antipsychotics (especially with high anticholinergic activity), tricyclic antidepressants, quinidine and some other antiarrhythmics, and antihistamines.

Cholinergic agents: Drugs with high anticholinergic activity may antagonize the therapeutic effect of cholinergic agents; includes donepezil, rivastigmine, and tacrine.

CNS depressants: Sedative effects may be additive with CNS depressants; includes ethanol, benzodiazepines, barbiturates, narcotic analgesics, and other sedative agents; monitor for increased effect.

DOTSON-MD Tablets

Dotson-MD Alu-AluTabs

Ondansetron 4 mg.  Mouth Dissolve

Ondansetron (INN) (pronounced /ɒnˈdænsɛtrɒn/) or Zofran is a serotonin 5-HT₃ receptor antagonist used mainly as an antiemetic to treat nausea and vomiting following chemotherapy. Its effects are thought to be on both peripheral and central nerves. Ondansetron reduces the activity of the vagus nerve, which activates the vomiting center in the medulla oblongata, and also blocks serotonin receptors in the chemoreceptor trigger zone. It has little effect on vomiting caused by motion sickness, and does not have any effect on dopamine receptors or muscarinic receptors.

Clinical uses

 

The 5-HT₃ receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting (CINV). Many times they are given intravenously about 30 minutes before beginning therapy. Ondansetron is also effective in controlling post-operative (PONV) and post-radiation nausea and vomiting, and is a possible therapy for nausea and vomiting due to acute or chronic medical illness or acute gastroenteritis.

Although it is highly effective, its high cost had limited its use to controlling PONV and CINV- although it is now available in cheaper generic forms. It is also used off-label to treat hyperemesis gravidarum in pregnant women, but there is no conclusive data available on its safety in pregnancy, especially during the first trimester. It is also often used to treat cyclic vomiting syndrome; although there have been no formal trials to confirm efficacy, case reports suggest it can be helpful in some cases. The drug is administered 1–3 times daily, depending on the severity of nausea and/or vomiting. The normal oral dose for adults and children over the age of 12, is 8 mg initially, followed by a second dose of 8 mg, eight hours later. The drug is then administered once every 12 hours, usually not for more than 2-3 days. Following oral administration, it takes about 1.5–2 hours to reach maximum plasma concentrations. This drug is removed from the body by the liver and kidneys.

The clinical effect of ondansetron (and other drugs from the same group) can be potentiated by combining it with dexamethasone

Adverse effects

 

Ondansetron is a well-tolerated drug with few side effects. Headache, constipation, and dizziness are the most commonly reported side effects associated with its use. There have been no significant drug interactions reported with this drug's use. It is broken down by the hepatic cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system

Biological roles of folate

 

DNA and cell division

Folate is necessary for the production and maintenance of new cells.^[1] This is especially important during periods of rapid cell division and growth such as infancy and pregnancy. Folate is needed to synthesize DNA bases (most notably thymine, but also purine bases) needed for DNA replication. Thus folate deficiency hinders DNA synthesis and cell division, affecting most notably bone marrow and cancer, both of which participate in rapid cell division. RNA transcription, and subsequent protein synthesis, are less effected by folate deficiency as the mRNA can be recycled and used again (as opposed to DNA synthesis where a new genomic copy must be created). Since folate deficiency limits cell division, erythropoiesis, production of red blood cells (RBCs) is hindered and leads to megaloblastic anemia which is characterized by large immature RBCs. This pathology results from persistently thwarted attempts at normal DNA replication, DNA repair, and cell division and produces abnormally large cells (megaloblasts) with abundant cytoplasm capable of RNA and protein synthesis but with clumping and fragmentation of nuclear chromatin. Some of these large cells, although immature, are released early from the marrow in an attempt to compensate for the anemia caused by lack of RBCs. ^[2] Both adults and children need folate to make normal RBCs and prevent anemia.^[3] Deficiency of folate in pregnant women has been implicated in neural tube defects and so many cereals sold in developed countries are enriched with folate to avoid such complications.

Biochemistry of DNA base and amino acid production

In the form of a series of tetrahydrofolate (THF) compounds, folate derivatives are substrates in a number of single-carbon-transfer reactions, and also are involved in the synthesis of dTMP (2'-deoxythymidine-5'-phosphate) from dUMP (2'-deoxyuridine-5'-phosphate). It is a substrate for an important reaction that involves vitamin B12 and it is necessary for the synthesis of DNA, required for all dividing cells.

The pathway leading to the formation of tetrahydrofolate (FH₄) begins when folate (F) is reduced to dihydrofolate (DHF) (FH₂), which is then reduced to THF. Dihydrofolate reductase catalyses the last step.^[4] Vitamin B₃ in the form of NADPH is a necessary cofactor for both steps of the synthesis.

Methylene-THF (CH₂FH₄) is formed from THF by the addition of methylene groups from one of three carbon donors: formaldehyde, serine, or glycine. Methyl tetrahydrofolate (CH₃-THF) can be made from methylene-THF by reduction of the methylene group with NADPH. If is important to note that Vitamin B₁₂ is the only acceptor of methyl-THF. There is also only one acceptor for methyl-B₁₂ which is homocysteine in a reaction catalyzed by homocysteine methyltransferase. This is important because a defect in homocysteine methyltransferase or a defeciency of B₁₂ can lead to a methyl-trap of THF and a subsequent deficiency. Thus, a deficiency in B₁₂ can generate a large pool of methyl-THF that is unable to undergo reactions and will mimic folate deficiency. Another form of THF, formyl-THF or folinic acid) results from oxidation of methylene-THF or is formed from formate donating formyl group to THF. Finally, histidine can donate a single carbon to THF to form methenyl-THF.

In other words: F → DHF₂ → THF → CH_{2-THF Formyl-THF <--> Methynl-THF <--> Methylene-THF --> Methyl-THF}

Overview of drugs that interfere with folate reactions A number of drugs interfere with the biosynthesis of folic acid and THF. Among them are the dihydrofolate reductase inhibitors such as trimethoprim, pyrimethamine and methotrexate; the sulfonamides (competitive inhibitors of para-aminobenzoic acid in the reactions of dihydropteroate synthetase).

Recommended Daily Allowence (RDA)

1998 RDAs for Folate
Men	Women
(19+)	(19+)	Pregnancy	Breast feeding
400 µg	400 µg	600 µg	500 µg
1 µg of food folate = 0.6 µg folic acid from supplements and fortified foods

The National Health and Nutrition Examination Survey (NHANES III 1988-91) and the Continuing Survey of Food Intakes by Individuals (1994-96 CSFII) indicated that most adults did not consume adequate folate.^[5][6] However, the folic acid fortification program in the United States has increased folic acid content of commonly eaten foods such as cereals and grains, and as a result diets of most adults now provide recommended amounts of folate equivalents.^[7]

Human reproduction

Folic acid is very important for all women who may become pregnant. Adequate folate intake during the periconceptional period, the time just before and just after a woman becomes pregnant, helps protect against a number of congenital malformations including neural tube defects.^[8] Neural tube defects result in malformations of the spine (spina bifida), skull, and brain (anencephaly). The risk of neural tube defects is significantly reduced when supplemental folic acid is consumed in addition to a healthy diet prior to and during the first month following conception.^[9][10] Women who could become pregnant are advised to eat foods fortified with folic acid or take supplements in addition to eating folate-rich foods to reduce the risk of some serious birth defects. The most notable birth defects that occur from folate deficiency are neural tube defects. Taking 400 micrograms of synthetic folic acid daily from fortified foods and/or supplements has been suggested. The Recommended Dietary Allowance (RDA) for folate equivalents for pregnant women is 600-800 micrograms, twice the normal RDA of 400 micrograms for women who are not pregnant.^[11]

Recent research has shown that it is also very important for men who are planning on fathering children, reducing birth defect risks.^[12]

Folic acid supplements and masking of B₁₂ deficiency

There has been concern about the interaction between vitamin B₁₂ and folic acid.^[13]Folic acid supplements can correct the anemia associated with vitamin B₁₂ deficiency. Unfortunately, folic acid will not correct changes in the nervous system that result from vitamin B₁₂ deficiency. Permanent nerve damage could theoretically occur if vitamin B₁₂ deficiency is not treated. Therefore, intake of supplemental folic acid should not exceed 1000 micrograms (1000 mcg or 1 mg) per day to prevent folic acid from masking symptoms of vitamin B₁₂ deficiency. In fact, to date the evidence that such masking actually occurs is scarce, and there is no evidence that folic acid fortification in Canada or the US has increased the prevalence of vitamin B₁₂ deficiency or its consequences.

However one recent study has demonstrated that high folic or folate levels when combined with low B₁₂ levels are associated with significant cognitive impairment among the elderly.^[15] If the observed relationship for seniors between folic acid intake, B₁₂ levels, and cognitive impairment is replicated and confirmed, this is likely to re-open the debate on folic acid fortification in food, even though public health policies tend generally to support the developmental needs of infants and children over slight risks to other population groups.

In any case, it is important for older adults to be aware of the relationship between folic acid and vitamin B₁₂ because they are at greater risk of having a vitamin B₁₂ deficiency. If you are 50 years of age or older, ask your physician to check your B₁₂ status before you take a supplement that contains folic acid.