TRIHEPTA SYRUP

Mechanism of action

Cyanocobalamin serves as a cofactor for methionine synthase and L-methylmalonyl-CoA mutase enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase is involved in the degradation of propionate, crucial for fat and protein metabolism. The lack of vitamin B12 results in the accumulation of methylmalonyl CoA, contributing to neurological manifestations. Additionally, it is vital for the synthesis of methionine from homocysteine, and its deficiency can lead to functional folate deficiency, which impacts red blood cell formation.

Pharmacodynamics

Cyanocobalamin corrects vitamin B12 deficiency and alleviates symptoms and laboratory abnormalities associated with pernicious anemia, such as megaloblastic indices, gastrointestinal lesions, and neurological damage. It is essential for growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. The drug significantly impacts fat and carbohydrate metabolism, as well as protein synthesis. Rapidly dividing cells, such as those in the bone marrow, have a high demand for vitamin B12. Parenteral administration of cyanocobalamin can quickly reverse the anemia and gastrointestinal symptoms of vitamin B12 deficiency, while also preventing the progression of related neurological damage.

Pharmacokinetics

Cyanocobalamin is absorbed in the intestine, primarily in the ileum, via specific transport mechanisms that may be impaired in individuals with intrinsic factor deficiency (as seen in pernicious anemia). Once absorbed, it is widely distributed in body tissues, with significant concentrations found in the liver, kidneys, and heart. The vitamin is stored in the liver, where it can be released into circulation as needed. Cyanocobalamin undergoes conversion to its active forms, methylcobalamin and adenosylcobalamin, which are utilized in various metabolic processes. The elimination half-life is variable, but it is generally excreted via urine as metabolites

Adverse effects

• Abdominal distension
• Decreased appetite
• Flatulence
• Nausea

Interactions

• Folic acid may interact with cyanocobalamin, especially in cases of megaloblastic anemia caused by folate deficiency.

Precautions

• Should not be given alone for pernicious anemia.
• Use caution in patients with Leber's disease, as it may worsen optic atrophy.

Pregnancy

Cyanocobalamin is essential during pregnancy as it helps prevent neural tube defects. It is advised that females of childbearing potential take 5 mg of folic acid daily before conception and throughout pregnancy.

Breast-feeding

Cyanocobalamin is generally considered safe during breastfeeding, but it is advised to monitor the infant for any adverse effects.

Storage

Store in a cool, dry place, away from direct sunlight. Protect from moisture.

Formulations

• Tablet: 1000 micrograms
• Tablet: 500 micrograms
• Tablet: 100 micrograms
• Oral solution: 50 micrograms per ml
• Solution for injection: 1000 micrograms per ml

Indications

• Vitamin B6 deficiency
• Isoniazid-induced neuropathy (prophylaxis and treatment)
• Idiopathic sideroblastic anaemia
• Prevention of penicillamine-induced neuropathy in Wilson's disease
• Metabolic diseases such as cystathioninuria and homocystinuria
• Premenstrual syndrome

Mechanism of action

Pyridoxine hydrochloride is converted in the body to pyridoxal phosphate, which is the active form of vitamin B6. It serves as a cofactor for more than 100 enzymatic reactions, particularly those involved in the metabolism of amino acids, the synthesis of neurotransmitters (such as serotonin, dopamine, and gamma-aminobutyric acid), and the production of hemoglobin. Its role in neurotransmitter synthesis makes it crucial for normal brain function and mood regulation.

Pharmacodynamics

Pyridoxine hydrochloride exerts its effects by facilitating the conversion of amino acids into neurotransmitters and is involved in the synthesis of heme. It impacts the metabolism of tryptophan to serotonin and is essential for the production of norepinephrine and gamma-aminobutyric acid, which are vital for proper neurological function. Deficiency of vitamin B6 can lead to neurological symptoms, including peripheral neuropathy and cognitive disturbances.

Pharmacokinetics

Pyridoxine hydrochloride is readily absorbed from the gastrointestinal tract. It is primarily metabolized in the liver, where it is converted to its active form, pyridoxal phosphate. The elimination half-life of pyridoxine is approximately 15-20 days, and it is excreted primarily through the urine. Renal impairment may affect the metabolism and excretion of pyridoxine, necessitating dose adjustments.

Contra-indications

• Hyperkalaemia
• Severe liver damage

Adverse effects

• Peripheral neuritis
• Hepatitis
• Hypoglycaemia
• Urine discolouration

Interactions

• Potassium aminobenzoate
• Isoniazid

Precautions

• Caution in renal impairment (increased risk of hyperkalaemia)
• Interrupt treatment during periods of low food intake (such as fasting, anorexia, and nausea) to reduce risk of hypoglycaemia
• Monitor liver function tests monthly during high-dose therapy

Pregnancy

Manufacturer advises avoiding use in pregnancy due to potential risk of birth defects; however, no adverse effects have been reported at normal dietary levels.

Breast-feeding

Theoretical risk of toxicity in infants if mothers take large doses.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Pyridoxine hydrochloride 10 mg tablets
• Pyridoxine hydrochloride 20 mg tablets
• Pyridoxine hydrochloride 50 mg tablets
• Pyridoxine hydrochloride oral solution 20 mg per 1 ml

Indications

• Papulopustular rosacea
• Inflammatory acne vulgaris

Dosage

Children: Refer to the BNF for Children for specific dosing recommendations.

Adults: For papulopustular rosacea, apply daily for up to 4 months. The treatment course may be repeated; discontinue if no improvement is observed after 3 months. For inflammatory acne vulgaris, apply twice daily, reduced to once daily or alternate days if irritation occurs.

Mechanism of action

Nicotinamide exhibits anti-inflammatory effects by inhibiting the release of pro-inflammatory cytokines and enhancing the barrier function of the skin. It is also involved in the NAD salvage pathway, which is essential for maintaining cellular energy levels and promoting cell repair mechanisms. Additionally, nicotinamide contributes to the synthesis of coenzymes involved in metabolic processes, including the conversion of niacin into NAD+.

Pharmacodynamics

Nicotinamide is known for its ability to improve skin hydration and reduce transepidermal water loss. It has been shown to decrease the appearance of acne lesions and rosacea by modulating inflammatory responses and accelerating cell turnover. Its antioxidant properties also help to protect the skin from oxidative stress and UV damage.

Pharmacokinetics

When applied topically, nicotinamide is absorbed through the skin layers, with minimal systemic absorption. Its peak plasma concentrations are generally low, and the drug has a half-life that varies depending on the route of administration. The metabolism of nicotinamide occurs primarily in the liver, where it is converted into its active forms, including NAD+. The elimination route is via the kidneys, with metabolites excreted in urine.

Contra-indications

• Pregnancy
• Severe acne involving large areas
• Severe skin reactions

Adverse effects

• Sunburn
• Skin reactions (common or very common)
• Cheilitis
• Eyelid oedema
• Flushing
• Dry skin
• Eye irritation
• Photosensitivity reactions
• Transient skin pigmentation changes

Interactions

• Clindamycin
• Topical retinoids
• Abrasive cleaners
• Comedogenic cosmetics

Precautions

• Avoid exposure to UV light, including sunlight and sunlamps
• Wash hands immediately after use
• Avoid contact with eyes and mucous membranes
• Use moisturizers to reduce the risk of skin irritation
• Discontinue treatment if severe irritation occurs

Pregnancy

Avoid use during pregnancy due to potential risks, as limited information is available regarding toxicity.

Breast-feeding

Amount of drug in milk after topical application is probably too small to be harmful; ensure infant does not come in contact with treated areas.

Storage

Store at room temperature away from moisture and light.

Formulations

• Cream
• Gel

Indications

• Vitamin B1 deficiency
• Wernicke-Korsakoff syndrome
• Beriberi
• Isoniazid-induced neuropathy (prophylaxis and treatment)
• Severe depletion or malabsorption of vitamins B and C

Dosage

Adults: For vitamin deficiency: 25–100 mg daily. For severe deficiency: 200–300 mg daily in divided doses. For

Mechanism of action

Thiamine functions primarily as a precursor for several phosphorylated active forms, which act as coenzymes in metabolic pathways. It reduces intracellular protein glycation by redirecting glycolytic flux and supports the synthesis of nucleic acids necessary for cell survival and proliferation. Additionally, thiamine has been shown to inhibit glucose-induced proliferation of endothelial cells, thus possibly playing a role in the modulation of vascular health.

Pharmacodynamics

Thiamine exhibits antioxidant properties and contributes to erythropoiesis, cognitive function, and mood regulation. It has protective effects against oxidative stress, particularly in neuronal tissues, where deficiency can lead to neuronal death due to increased free radical production. Thiamine also modulates glucose metabolism, influencing smooth muscle cell proliferation and potentially impacting the progression of atherosclerosis.

Pharmacokinetics

Thiamine is rapidly absorbed from the gastrointestinal tract, primarily in the jejunum, and is distributed throughout the body, with higher concentrations found in the liver, heart, and brain. It is excreted in urine, and its half-life is relatively short. The vitamin is converted into active forms within tissues, including thiamine diphosphate (TDP), which is the coenzyme form involved in carbohydrate metabolism. The body does not store significant amounts of thiamine, making regular dietary intake essential.

Adverse effects

• Allergic reactions
• Anaphylaxis (rare)
• Gastrointestinal disturbances

Precautions

• Facilities for treating anaphylaxis should be available when parenteral thiamine is administered
• Use with caution in patients with a history of hypersensitivity to thiamine

Pregnancy

Thiamine crosses the placenta but no adverse effects have been reported. Information regarding high doses is limited.

Breast-feeding

Severely thiamine-deficient mothers should avoid breast-feeding as thiamine is present in breast milk.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Thiamine hydrochloride 20 mg/ml oral solution
• Thiamine hydrochloride 50 mg tablets
• Thiamine hydrochloride 100 mg modified-release tablets
• Thiamine hydrochloride oral suspension

Indications

• Allergic conditions
• Hay fever
• Urticaria
• Pruritus
• Appetite stimulation

Dosage

Children: For children aged 6 months to 5 years, the dose is 5-15 mg daily in divided doses, adjusted according to weight, with a maximum of 2 mg/kg per day. For children aged 6-17 years weighing up to 40 kg, the initial dose is 15-25 mg daily in divided doses, adjusted as necessary to a maximum of 2 mg/kg per day. For those weighing 40 kg and above, the initial dose is 15-25 mg daily in divided doses, increased if necessary to 50-100 mg daily.

Adults: Initially, 25 mg daily, taken at night; may be increased if necessary to 25 mg 3-4 times a day. Maximum dose is 32 mg per day.

Mechanism of action

Cyproheptadine acts as a competitive antagonist at histamine H1 receptors, thereby inhibiting the action of histamine, which is responsible for allergic symptoms. Additionally, it may also block serotonin receptors, contributing to its appetite-stimulating effects.

Pharmacodynamics

The drug exhibits sedative effects by crossing the blood-brain barrier, leading to central nervous system depression. It can also produce anticholinergic effects, such as dry mouth and urinary retention, due to its action on muscarinic receptors. The sedative properties can impair the performance of skilled tasks and may be potentiated by alcohol consumption.

Pharmacokinetics

Cyproheptadine is well-absorbed from the gastrointestinal tract and undergoes hepatic metabolism. Its elimination half-life is approximately 8-12 hours, and it is excreted primarily in urine. The onset of action is typically within 1-2 hours, with effects lasting for several hours.

Contra-indications

• Acute porphyrias
• Prolonged QT-interval
• Risk factors for QT prolongation

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Nausea
• Constipation
• Headache
• Palpitations
• Tachycardia
• Fatigue
• Irritability
• Paradoxical excitability
• Tremor

Interactions

• Antihistamines
• Sedating agents
• Alcohol

Precautions

• Use with caution in the elderly
• Patients with epilepsy
• Prostatic hypertrophy
• Pyloroduodenal obstruction
• Susceptibility to angle-closure glaucoma
• Urinary retention

Pregnancy

Most manufacturers of antihistamines advise avoiding their use during pregnancy; however, there is no evidence of teratogenicity. Use in the latter part of the third trimester may cause adverse effects in neonates.

Breast-feeding

Most antihistamines are present in breast milk in varying amounts; although not known to be harmful, most manufacturers advise avoiding their use in mothers who are breastfeeding.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Oral suspension
• Tablets (4 mg)

Indications

• Allergic rhinitis
• Allergic conjunctivitis
• Urticaria
• Angioedema
• Anaphylaxis (as adjunct therapy)
• Appetite stimulation in certain conditions

Dosage

Children: Refer to BNF for Children for appropriate pediatric dosing, as it varies by age and condition. Generally, doses may start at 0.25 mg/kg for younger children, but specific guidelines should be

Adults: The usual adult dose for allergic conditions is 4 mg three times daily, which may be increased to a maximum of 12 mg per day as needed. For appetite stimulation, the starting dose is often 4 mg taken once or twice daily.

Mechanism of action

Cyproheptadine exerts its effects by competing with free histamine and serotonin for binding at their respective receptors. Its action as an H1 blocker is complemented by its antagonism of serotonin at 5-HT2A receptors, particularly influencing the appetite center in the hypothalamus. This dual action accounts for its appetite-stimulating properties and mitigates several pharmacodynamic effects of serotonin.

Pharmacodynamics

Cyproheptadine antagonizes several effects of serotonin and histamine, including bronchoconstriction and vasodepression. Its efficacy in combatting histamine-mediated effects has been established, although the details regarding its role in preventing anaphylactic shock remain unclear, likely linked to its anti-serotonergic activity. The drug's sedative properties arise from its central nervous system effects.

Pharmacokinetics

Cyproheptadine is well-absorbed after oral administration. It is metabolized in the liver, with a variable half-life and is primarily excreted in urine. The onset of action typically occurs within one to two hours, and the duration of action can last up to 12 hours. The pharmacokinetic profile may be influenced by individual metabolic variations.

Adverse effects

• Drowsiness
• Dizziness
• Dry mouth
• Constipation
• Blurred vision
• Increased appetite

Interactions

• cyproheptadine+metyrapone: Severe (decreases effects)
• cyproheptadine+fenfluramine: Unknown (decreases efficacy)

Precautions

• Caution in patients with glaucoma
• Caution in patients with prostate hypertrophy
• Use with caution in elderly patients due to increased sensitivity

Pregnancy

Cyproheptadine should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus. Limited data are available on its safety.

Breast-feeding

Cyproheptadine is excreted in breast milk. Caution is advised when administered to breastfeeding mothers.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Formulations

• Tablets
• Syrup

Indications

• Herpes simplex virus infections
• Lysine deficiency

Dosage

Children: Refer to the BNF for Children for specific dosage recommendations.

Adults: Refer to the BNF for specific dosage recommendations.

Mechanism of action

Lysine inhibits the viral replication of the herpes simplex virus by altering the amino acid ratio in the tissue culture media. A higher concentration of L-lysine compared to L-arginine has been shown to reduce viral growth and cytopathogenicity. Additionally, lysine facilitates calcium absorption from the small intestine and is involved in protein synthesis through its role in the tRNA charging process, linking amino acids to their corresponding tRNA for translation.

Pharmacodynamics

Lysine ensures adequate calcium absorption and is involved in the formation of collagen, essential for bone, cartilage, and connective tissues. It aids in the production of various biological molecules, including antibodies, hormones, and enzymes. Deficiency in lysine can manifest as tiredness, inability to concentrate, irritability, and other health issues.

Pharmacokinetics

Lysine is absorbed in the small intestine and is transported in the bloodstream to various tissues, where it participates in protein synthesis and other metabolic processes. The metabolism of lysine involves its degradation and utilization in various biosynthetic pathways.

Adverse effects

• Gastrointestinal upset
• Diarrhea
• Nausea
• Abdominal pain

Precautions

• Use with caution in individuals with kidney disease
• Consult a healthcare professional before use if pregnant or breastfeeding

Pregnancy

Safety in pregnancy has not been established. Consult a healthcare professional before use.

Breast-feeding

Lysine is generally considered safe in breastfeeding, but consult a healthcare professional before use.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Oral tablet
• Oral capsule
• Powder for oral solution

Indications

• Vitamin B6 deficiency
• Peripheral neuropathy associated with isoniazid therapy
• Supplementation in specific dietary deficiencies

Dosage

Children: Refer to the BNF for Children for specific paediatric dosing guidance.

Adults: Refer to the BNF for specific dosing details, typically 10-50 mg daily for deficiency.

Mechanism of action

Pyridoxine, mainly in its active form pyridoxal 5'-phosphate, is involved in numerous biochemical reactions, including amino acid metabolism, glycogen breakdown, nucleic acid synthesis, and the production of key neurotransmitters. It aids in the synthesis of hemoglobin and sphingolipids, and its deficiency can impair several physiological processes, including immune response and vascular health.

Pharmacodynamics

Pyridoxine is utilized for the prevention and treatment of vitamin B6 deficiency, particularly in individuals undergoing treatment with isoniazid, which can deplete vitamin B6 levels. It may also have beneficial effects on blood pressure and lipid profiles, as studies have shown it can lower both systolic and diastolic blood pressure, inhibit platelet aggregation, and improve cholesterol levels. Additionally, it plays a role in enhancing immune function and protecting endothelial cells from injury.

Pharmacokinetics

Pyridoxine is rapidly absorbed from the gastrointestinal tract. It is transported to tissues where it is phosphorylated to its active form, pyridoxal 5'-phosphate. The vitamin is primarily excreted in urine as pyridoxine and its metabolites. Its half-life varies depending on the individual’s nutritional status and other factors. Adequate dietary intake is essential for maintaining optimal levels in the body.

Pregnancy

Pyridoxine is generally considered safe during pregnancy. However, high doses should be avoided unless specifically prescribed.

Breast-feeding

Pyridoxine is excreted in breast milk, but at normal dietary levels it is considered safe for breastfeeding mothers.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Tablets
• Oral solution
• Injectable form

Indications

• Thiamine deficiency
• Wernicke's encephalopathy
• Beriberi
• Alcoholism-related complications
• Certain metabolic disorders

Dosage

Children: Refer to BNF for Children for appropriate dosing information.

Adults: Refer to established clinical guidelines or BNF for specific dosing recommendations.

Mechanism of action

Thiamine is a coenzyme for several important enzymatic reactions, including the pyruvate dehydrogenase complex and alpha-ketoglutarate dehydrogenase. It is essential for converting carbohydrates into energy, facilitating the metabolism of glucose, and maintaining normal nerve function.

Pharmacodynamics

Thiamine deficiency leads to impaired carbohydrate metabolism, which can result in neurological and cardiovascular dysfunction. Supplementation with thiamine helps restore normal metabolic function and can alleviate symptoms associated with deficiency, such as Wernicke's encephalopathy and Beriberi. It also plays a role in the synthesis of neurotransmitters and in maintaining myelin integrity.

Pharmacokinetics

Thiamine is readily absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-2 hours after oral administration. It is distributed throughout the body, primarily in the liver, kidneys, and heart. Thiamine is metabolized in the liver to its active form, thiamine pyrophosphate. It has a biological half-life of about 9-18 days and is excreted primarily in the urine. Excess thiamine is excreted, making toxicity rare.

Adverse effects

• Allergic reactions
• Hypersensitivity reactions
• Gastrointestinal disturbances

Interactions

• May interact with certain diuretics, leading to altered thiamine levels

Precautions

• Use with caution in patients with renal impairment
• Monitor patients with a history of thiamine deficiency

Pregnancy

Thiamine is considered safe during pregnancy, as it is an essential nutrient.

Breast-feeding

Thiamine is excreted in breast milk, but supplementation is generally considered safe for breastfeeding mothers.

Storage

Store in a cool, dry place away from direct sunlight.

Formulations

• Thiamine hydrochloride injection
• Thiamine hydrochloride oral tablets
• Thiamine hydrochloride oral solution

Mechanism of action

Vitamin B12 serves as a cofactor for _methionine synthase_ and _L-methylmalonyl-CoA mutase_ enzymes. Methionine synthase is essential for the synthesis of purines and pyrimidines that form DNA. L-methylmalonyl-CoA mutase converts L-methylmalonyl-CoA to _succinyl-CoA_ in the degradation of propionate, an important reaction required for both fat and protein metabolism. It is a lack of vitamin B12 cofactor in the above reaction and the resulting accumulation of methylmalonyl CoA that is believed to be responsible for the neurological manifestations of B12 deficiency. Succinyl-CoA is also necessary for the synthesis of hemoglobin. In tissues, vitamin B12 is required for the synthesis of _methionine_ from homocysteine. Methionine is required for the formation of S-adenosylmethionine, a methyl donor for nearly 100 substrates, comprised of DNA, RNA, hormones, proteins, as well as lipids. Without vitamin B12, tetrahydrofolate cannot be regenerated from 5-methyltetrahydrofolate, and this can lead to functional folate deficiency,. This reaction is dependent on methylcobalamin (vitamin B12) as a co-factor and is also dependent on folate, in which the methyl group of methyltetrahydrofolate is transferred to homocysteine to form _methionine_ and _tetrahydrofolate_. Vitamin B12 incorporates into circulating folic acid into growing red blood cells; retaining the folate in these cells. A deficiency of vitamin B12 and the interruption of this reaction leads to the development of megaloblastic anemia.

Pharmacodynamics

**General effects** Cyanocobalamin corrects vitamin B12 deficiency and improves the symptoms and laboratory abnormalities associated with pernicious anemia (megaloblastic indices, gastrointestinal lesions, and neurologic damage). This drug aids in growth, cell reproduction, hematopoiesis, nucleoprotein, and myelin synthesis. It also plays an important role in fat metabolism, carbohydrate metabolism, as well as protein synthesis. Cells that undergo rapid division (for example, epithelial cells, bone marrow, and myeloid cells) have a high demand for vitamin B12. **Parenteral cyanocobalamin effects** The parenteral administration of vitamin B12 rapidly and completely reverses the megaloblastic anemia and gastrointestinal symptoms of vitamin B12 deficiency. Rapid parenteral administration of vitamin B12 in deficiency related neurological damage prevents the progression of this condition. **Nasal spray effects** In 24 vitamin B12 deficient patients who were already stabilized on intramuscular (IM) vitamin B12 therapy, single daily doses of intranasal cyanocobalamin for 8 weeks lead to serum vitamin B12 concentrations that were within the target therapeutic range (>200 ng/L).

Mechanism of action

It is thought that the mechanism of action of thiamine on endothelial cells is related to a reduction in intracellular protein glycation by redirecting the glycolytic flux. Thiamine is mainly the transport form of the vitamin, while the active forms are phosphorylated thiamine derivatives. Natural derivatives of thiamine phosphate, such as thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), also sometimes called thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), and thiamine triphosphate (AThTP), that act as coenzymes in addition to their each unique biological functions. Metabolic control analysis predicts that stimulators of transketolase enzyme synthesis such as thiamin (vitamin B-1) support a high rate of nucleic acid ribose synthesis necessary for tumor cell survival, chemotherapy resistance, and proliferation. Metabolic control analysis also predicts that transketolase inhibitor drugs will have the opposite effect on tumor cells. This may have important implications in the nutrition and future treatment of patients with cancer.

Pharmacodynamics

Thiamine is a vitamin with antioxidant, erythropoietic, cognition-and mood-modulatory, antiatherosclerotic, putative ergogenic, and detoxification activities. Thiamine has been found to protect against lead-induced lipid peroxidation in rat liver and kidney. Thiamine deficiency results in selective neuronal death in animal models. The neuronal death is associated with increased free radical production, suggesting that oxidative stress may play an important early role in brain damage associated with thiamine deficiency. Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation. Inhibition of endothelial cell proliferation may also promote atherosclerosis. Endothelial cells in culture have been found to have a decreased proliferative rate and delayed migration in response to hyperglycemic conditions. Thiamine has been shown to inhibit this effect of glucose on endothelial cells.

Mechanism of action

Cyproheptadine appears to exert its antihistamine and antiserotonin effects by competing with free histamine and serotonin for binding at their respective receptors. Antagonism of serotonin on the appetite center of the hypothalamus may account for cyproheptadine's ability to stimulate the appetite. CYPROHEPTADINE...IS A SEROTONIN & HISTAMINE ANTAGONIST... ... It is an effective H1 blocker. Cyproheptadine also has prominent 5-H blocking activity on smooth muscle by virtue of its binding to 5-HT2A receptors. ... It has weak anticholinergic activity and possess mild central depressant properties.

Pharmacodynamics

Cyproheptadine has been observed to antagonize several pharmacodynamic effects of serotonin in laboratory animals, including bronchoconstriction and vasodepression, and has demonstrated similar efficacy in antagonizing histamine-mediated effects. The reason for its efficacy in preventing anaphylactic shock has not been elucidated, but appears to be related to its anti-serotonergic effects.

Mechanism of action

Proteins of the herpes simplex virus are rich in L-arginine, and tissue culture studies indicate an enhancing effect on viral replication when the amino acid ratio of L-arginine to lysine is high in the tissue culture media. When the ratio of L-lysine to L-arginine is high, viral replication and the cytopathogenicity of herpes simplex virus have been found to be inhibited. L-lysine may facilitate the absorption of calcium from the small intestine. Amino acids are selected for protein synthesis by binding with transfer RNA (tRNA) in the cell cytoplasm. The information on the amino acid sequence of each individual protein is contained in the sequence of nucleotides in the messenger RNA (mRNA) molecules, which are synthesized in the nucleus from regions of DNA by the process of transcription. The mRNA molecules then interact with various tRNA molecules attached to specific amino acids in the cytoplasm to synthesize the specific protein by linking together individual amino acids; this process, known as translation, is regulated by amino acids (e.g., leucine), and hormones. Which specific proteins are expressed in any particular cell and the relative rates at which the different cellular proteins are synthesized, are determined by the relative abundances of the different mRNAs and the availability of specific tRNA-amino acid combinations, and hence by the rate of transcription and the stability of the messages. From a nutritional and metabolic point of view, it is important to recognize that protein synthesis is a continuing process that takes place in most cells of the body. In a steady state, when neither net growth nor protein loss is occurring, protein synthesis is balanced by an equal amount of protein degradation. The major consequence of inadequate protein intakes, or diets low or lacking in specific indispensable amino acids relative to other amino acids (often termed limiting amino acids), is a shift in this balance so that rates of synthesis of some body proteins decrease while protein degradation continues, thus providing an endogenous source of those amino acids most in need. /Amino acids/ The mechanism of intracellular protein degradation, by which protein is hydrolyzed to free amino acids, is more complex and is not as well characterized at the mechanistic level as that of synthesis. A wide variety of different enzymes that are capable of splitting peptide bonds are present in cells. However, the bulk of cellular proteolysis seems to be shared between two multienzyme systems: the lysosomal and proteasomal systems. The lysosome is a membrane-enclosed vesicle inside the cell that contains a variety of proteolytic enzymes and operates mostly at acid pH. Volumes of the cytoplasm are engulfed (autophagy) and are then subjected to the action of the protease enzymes at high concentration. This system is thought to be relatively unselective in most cases, although it can also degrade specific intracellular proteins. The system is highly regulated by hormones such as insulin and glucocorticoids, and by amino acids. The second system is the ATP-dependent ubiquitin-proteasome system, which is present in the cytoplasm. The first step is to join molecules of ubiquitin, a basic 76-amino acid peptide, to lysine residues in the target protein. Several enzymes are involved in this process, which selectively targets proteins for degradation by a second component, the proteasome. /Amino acids/

Pharmacodynamics

Insures the adequate absorption of calcium; helps form collagen ( which makes up bone cartilage & connective tissues); aids in the production of antibodies, hormones & enzymes. Recent studies have shown that Lysine may be effective against herpes by improving the balance of nutrients that reduce viral growth. A deficiency may result in tiredness, inability to concentrate, irritability, bloodshot eyes, retarded growth, hair loss, anemia & reproductive problems.

Mechanism of action

Vitamin B6 is the collective term for a group of three related compounds, pyridoxine (PN), pyridoxal (PL) and pyridoxamine (PM), and their phosphorylated derivatives, pyridoxine 5'-phosphate (PNP), pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP). Although all six of these compounds should technically be referred to as vitamin B6, the term vitamin B6 is commonly used interchangeably with just one of them, pyridoxine. Vitamin B6, principally in its biologically active coenzyme form pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).

Pharmacodynamics

Vitamin B6 (pyridoxine) is a water-soluble vitamin used in the prophylaxis and treatment of vitamin B6 deficiency and peripheral neuropathy in those receiving isoniazid (isonicotinic acid hydrazide, INH). Vitamin B6 has been found to lower systolic and diastolic blood pressure in a small group of subjects with essential hypertension. Hypertension is another risk factor for atherosclerosis and coronary heart disease. Another study showed pyridoxine hydrochloride to inhibit ADP- or epinephrine-induced platelet aggregation and to lower total cholesterol levels and increase HDL-cholesterol levels, again in a small group of subjects. Vitamin B6, in the form of pyridoxal 5'-phosphate, was found to protect vascular endothelial cells in culture from injury by activated platelets. Endothelial injury and dysfunction are critical initiating events in the pathogenesis of atherosclerosis. Human studies have demonstrated that vitamin B6 deficiency affects cellular and humoral responses of the immune system. Vitamin B6 deficiency results in altered lymphocyte differentiation and maturation, reduced delayed-type hypersensitivity (DTH) responses, impaired antibody production, decreased lymphocyte proliferation and decreased interleukin (IL)-2 production, among other immunologic activities.