Watersoluble Vitamins

| Home | | Pharmacology |

Chapter: Essential pharmacology : Vitamins

These are meagerly stored: excess is excreted with little chance of toxicity. They act as cofactors for specific enzymes of intermediary metabolism.


WATERSOLUBLE VITAMINS

 

THE VITAMIN B COMPLEX GROUP

 

Thiamine (Aneurine, vit B1)

 

Chemistry And Source

 

A colourless, crystalline compound containing a pyrimidine and a thiazole ring. It is present in the outer layers of cereals (rice polishing), pulses, nuts, green vegetables, yeasts, egg and meat.

 

Absorption And Fate

 

Physiological amounts are absorbed by active transport. When large doses are given orally, some passive diffusion also occurs. Limited amounts are stored in tissues. About 1 mg/day is degraded in the body, excess is rapidly excreted in urine.

 

Physiological Role

 

After conversion in the body to Thiamine pyrophosphate, it acts as a coenzyme in carbohydrate metabolism: decarboxylation of ketoacids and hexose monophosphate shunt. Requirement is dependent upon carbohydrate intake—about 0.3 mg/ 1000 K cal. It also appears to play some role in neuromuscular transmission.

 

Pyrithiamine and oxythiamine are synthetic thiamine antagonists. Tea also contains a thiamine antagonist.

 

Deficiency Symptoms

 

The syndrome of thiamine deficiency beriberi is seen in dry and wet forms:


Dry beriberi: Neurological symptoms are prominent—polyneuritis with numbness, tingling, hyperesthesia, muscular weakness and atrophy resulting in ‘wrist drop’, ‘foot drop’, paralysis of whole limb, mental changes, sluggishness, poor memory, loss of appetite and constipation.

 

Wet beriberi: Cardiovascular system is primarily affected—palpitation, breathlessness, high output cardiac failure and ECG changes. Protein deficiency is commonly associated and adds to the generalised anasarka due to CHF.

 

Therapeutic Uses

 

Prophylactically (2–10 mg daily) in infants, pregnant women, chronic diarrhoeas, patients on parenteral alimentation. Glucose infusion unmasks marginal thiamine deficiency.

 

Beriberi—100 mg/day i.m. or i.v. till symptoms regress—then maintenance doses orally.

 

Acute alcoholic intoxication: thiamine 100 mg is added to each vac of glucose solution infused. Most neurological symptoms in chronic alcoholics are due to thiamine deficiency—peripheral neuritis, Wernick’s encephalopathy, Korsakoff’s psychosis: give 100 mg/day parenterally.

 

In neurological and cardiovascular disorders, hyperemesis gravidarum, chronic anorexia and obstinate constipation—thiamine has been used even without definite proof of its deficiency— symptoms improve dramatically if thiamine deficiency has been causative.

 

Adverse Effects

 

Thiamine is nontoxic. Sensitivity reactions sometimes occur on parenteral injection.

 

 

Riboflavin (vit B2)

 

Chemistry And Source

 

A yellow flavone compound found in milk, egg, liver, green leafy vegetables, grains.

 

Absorption And Fate

 

Well absorbed by active transport and phosphorylated in the intestine. Riboflavin phosphate (Flavin mononucleotide: FMN) is formed in other tissues as well. Body does not significantly store riboflavin; larger doses are excreted unchanged in urine. Thiamine and riboflavin are both synthesized by colonic bacteria but this does not become available to the host.

 


 

Actions And Physiological Role

 

Flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) are coenzymes for flavoproteins involved in many oxidationreduction reactions. Thiamine and riboflavin are devoid of pharmacological actions.

 

Deficiency Symptoms

 

Riboflavin deficiency generally occurs in association with other deficiencies. Characteristic lesions are angular stomatitis; sore and raw tongue, lips, throat, ulcers in mouth; vascularization of cornea. Dry scaly skin, loss of hair; anaemia and neuropathy develop later.

 

Therapeutic Uses

 

To prevent and treat ariboflavinosis (2–20 mg/day oral or parenteral), generally along with other B complex members.

 

There is no proof of benefit in any other condition.

 

Niacin (vit B3)

 

Chemistry And Source

 

Niacin refers to Nicotinic acid as well as Nicotinamide—pyridine compounds, initially termed pellagra preventing factor. Sources are liver, fish, meat, cereal husk, nuts and pulses.

 

The amino acid tryptophan (mainly from animal protein) can be regarded as a provitamin, as it is partially converted in the body to nicotinic acid (60 mg tryptophan = 1 mg nicotinic acid). Maize eaters have suffered from pellagra because corn flour is poor in tryptophan and it is believed to contain a niacin antagonist. Thus, daily requirement of niacin is affected by the amount of tryptophan in diet.

 

Absorption And Fate

 

Niacin is completely absorbed from gastrointestinal tract. Physiological amounts are metabolized in the body, while large doses are excreted unchanged in urine. Modest amounts are stored in liver.

 

Physiological Role And Actions

 

Nicotinic acid is readily converted to its amide which is a component of the coenzyme Nicotinamide-adeninedinucleotide (NAD) and its phosphate (NADP) involved in oxidation-reduction reactions. These pyridine nucleotides act as hydrogen acceptors in the electron transport chain in tissue respiration, glycolysis and fat synthesis. Flavoproteins regenerate them by oxidizing NADH and NADPH.

 

Nicotinic acid (but not nicotinamide) in large doses is a vasodilator, particularly of cutaneous vessels. It also lowers plasma lipids (see Ch. No. 45).

 

Deficiency Symptoms

 

Niacin deficiency produces ‘Pellagra’, cardinal manifestations of which are:

 

Dermatitis—sunburn like dermal rash on hands, legs and face which later turn black, crack and peal.

 

Diarrhoea—with enteritis, stomatitis, glossitis, salivation, nausea and vomiting.

 

Dementia—with hallucinations preceded by headache, insomnia, poor memory, motor and sensory disturbances.

 

Anaemia and hypoproteinaemia are common in pellagra. Chronic alcoholics are particularly at risk of developing pellagra, because in addition to dietary deficiency, niacin absorption is impaired in them. Other B vitamin deficiencies are often associated.

 

Therapeutic Uses

 

Prophylactically (20–50 mg/day oral) in people at risk of developing pellagra.

 

Treatment of pellagra—200 to 500 mg/day in divided doses orally or parenterally. Striking improvement occurs in 1–2 days, but skin lesions take weeks to months. Nicotinamide is preferred, especially for injection, because it does not cause flushing and other side effects seen with nicotinic acid.

 

Hartnup’s disease: in which tryptophan transport is impaired, and in carcinoid tumours which use up tryptophan for manufacturing 5HT, need niacin supplementation.

Nicotinic acid (not nicotinamide) has been used in peripheral vascular disease and as hypolipidaemic (Ch. No. 45).

 

Adverse Effects

 

Nicotinic acid, in pharmacological doses, has many side effects and toxicities.   Nicotinamide is innocuous.

 

Pyridoxine (vit B6)

 

Chemistry And Source

 

Pyridoxine, Pyriodoxal and Pyridoxamine are related naturally occurring pyridine compounds that have vit B6 activity. Dietary sources are—liver, meat, egg, soybean, vegetables and whole grain.

 

Absorption And Fate

 

All three forms of the vitamin are well absorbed from the intestine. They are oxidized in the body and excreted as pyridoxic acid. Little is stored.

 

Physiological Role And Actions

 

Pyridoxine and pyridoxamine are readily oxidized to pyridoxal, which is then phosphorylated to pyridoxal phosphate—the coenzyme form. Pyridoxal dependent enzymes include transaminases and decarboxylases involved in synthesis of nonessential amino acids, tryptophan and sulfur containing amino acid metabolism, formation of 5HT, dopamine, histamine, GABA and aminolevulinic acid (first step in the synthesis of haeme). High protein diet increases pyridoxine requirement.

 

Pyridoxine has been shown to interact with steroid hormone receptors, but its clinical implication is not clear. Prolonged intake of large doses of pyridoxine can give rise to dependence, and mega doses (0.2–2.0 g/day) have been linked with sensory neuropathy. Otherwise, pyridoxine is free from pharmacological actions and side effects. However, suppression of lactation has been noted in nonsuckling postpartal women given high doses of pyridoxine: may be due to increased dopamine action on pituitary lactotropes.

 

 

Drug Interactions

 

Isoniazid reacts with pyridoxal to form a hydrazone, and thus inhibits generation of pyridoxal phosphate. Isoniazid also combines with pyridoxal phosphate to interfere with its coenzyme function. Due to formation of hydrazones, the renal excretion of pyridoxine compounds is increased. Thus, isoniazid therapy produces a pyridoxine deficiency state.

 

Hydralazine, cycloserine and penicillamine also interfere with pyridoxine utilization and action.

 

Oral  contraceptives  reduce  pyridoxal  phosphate  levels  in  some women.

Pyridoxine, by promoting formation of dopamine from levodopa in peripheral tissues, reduces its availability in the brain, abolishing the therapeutic effect in parkinsonism, but not when a peripheral decarboxylase inhibitor is combined with it. 4-deoxypyridoxine is a vit B6 antagonist.

 

Deficiency Symptoms

 

Deficiency of vit B6 usually occurs in association with that of other B vitamins. Symptoms ascribed to pyridoxine deficiency are—seborrheic dermatitis, glossitis, growth retardation, mental confusion, lowered seizure threshold or convulsions (due to fall in brain GABA levels), peripheral neuritis and anaemia.

 

Therapeutic Uses

 

Prophylactically (2–5 mg daily) in alcoholics, infants and patients with deficiency of other B vitamins.

 

To prevent and treat (10–50 mg/day) isoniazid, hydralazine and cycloserine induced neurological disturbances. Acute isoniazid poisoning has been successfully treated with massive doses (in grams) of pyridoxine.

 

To treat mental symptoms in women on oral contraceptives (50 mg daily).


Pyridoxine responsive anaemia (due to defective haeme synthesis) and homocystinuria are rare genetic disorders that are benefited by large doses of pyridoxine (50–200 mg/day).

 

Convulsions in infants and children.

 

Pantothenic Acid

 

Pantothenic acid is an organic acid, widely distributed in food sources, especially liver, mutton, egg yolk and vegetables. It is quickly absorbed and excreted unchanged in urine with little storage.

 

It is a component of coenzyme-A which functions in carbohydrate, fat, steroid and porphyrin metabolism by catalysing acetate transfer reactions. Clinical deficiency of pantothenic acid is not known. Experimental deficiency in man causes insomnia, intermittent diarrhoea, flatulence, vomiting, leg cramps and paresthesias. Calcium/ sodium pantothenate is included in B complex and multivitamin preparations. Intravenous calcium pantothenate has been tried in paralytic ileus.

 

Biotin

 

Biotin is a sulfur containing organic acid found in egg yolk, liver, nuts and many other Ch. No.s of food. Some of the biotin synthesized by intestinal bacteria is also absorbed. It is well absorbed from intestine and excreted mainly unchanged in urine. Not much is stored in the body. Avidin, a heat labile protein in egg white, binds and prevents the absorption of biotin. Some other biotin antagonists are also known. Biotin is a coenzyme for several carboxylases involved in carbohydrate and fat metabolism. Deficiency symptoms include seborrheic dermatitis, alopecia, anorexia, glossitis and muscular pain. Spontaneous deficiency of biotin has been noted only in subjects consuming only raw egg white and in patients on total parenteral nutrition. Except for these unusual instances and rare genetic abnormalities of biotin dependent enzymes, there are no clearly defined therapeutic uses of biotin. It is present in some multivitamin preparations.



 

VITAMIN C (ASCORBIC ACID)

 

Chemistry And Source

 

Ascorbic acid is a 6 carbon organic acid with structural similarity to glucose. It is a potent reducing agent and l-form is biologically active. Citrus fruits (lemons, oranges) and black currants are the richest sources; others are tomato, potato, green chillies, cabbage and other vegetables. Human milk is richer in vit C (25–50 mg/L) than cow’s milk.

 

Absorption And Fate

 

It is nearly completely absorbed from g.i.t. and widely distributed extra and intracellularly. Plasma concentration and total body store of vit C is related to daily intake. The usual 60 mg/day intake results in about 0.8 mg/dl in plasma and 1.5 g in the body as a whole. Increasing proportions are excreted in urine with higher intakes. Body is not able to store more than 2.5 g. It is partly oxidized to active (dehydroascorbic acid) and inactive (oxalic acid) metabolites.

 

Physiological Role And Actions

 

Vit C plays a role in many oxidative and other metabolic reactions, e.g. hydroxylation of proline and lysine residues of proto-collagen—essential for formation and stabilization of collagen triple helix; hydroxylation of carnitine, conversion of folic acid to folinic acid, biosynthesis of adrenal steroids, catecholamines, oxytocin and vasopressin and metabolism of cyclic nucleotides and prostaglandins. It directly stimulates collagen synthesis and is very important for maintenance of intercellular connective tissue. A number of illdefined actions have been ascribed to ascorbic acid in mega doses, but none is proven.

 

Deficiency Symptoms

 

Severe vit C deficiency Scurvy, once prevalent among sailors is now seen only in malnourished infants, children, elderly, alcoholics and drug addicts. Symptoms stem primarily from connective tissue defect: increased capillary fragility—swollen and bleeding gums, petechial and subperiosteal haemorrhages, deformed teeth, brittle bones, impaired wound healing, anaemia and growth retardation.

 

Therapeutic Uses

 

Prevention of ascorbic acid deficiency in individuals at risk (see above) and in infants: 50–mg/ day. Vit C or orange juice can be routinely included in infant diet.

 

Treatment of scurvy—0.5–1.5 g/day.

 

Postoperatively (500 mg daily): though vit C does not enhance normal healing, suboptimal healing can be guarded against. It has also been found to accelerate healing of bedsores and chronic leg ulcers. Requirement of ascorbic acid is increased in postinjury periods.

 

Anaemia: Ascorbic acid enhances iron absorption and is frequently combined with ferrous salts (maintains them in reduced state). Anaemia of scurvy is corrected by ascorbic acid, but it has no adjuvant value in other anaemias.

 

To acidify urine (1 g TDS–QID) in urinary tract infections (see Ch. No. 54).

 

Large doses (2–6 g/day) of ascorbic acid have been tried for a variety of purposes (common cold to cancer) with inconsistent results. No definite beneficial effect has been noted in asthma, cataract, cancer, atherosclerosis, psychological symptoms, infertility, etc. However, severity of common cold symptoms may be somewhat reduced, but not the duration of illness or its incidence. Improved working capacity at submaximal workloads has been found in athletes but endurance is not increased.

 

Adverse Effects

 

Ascorbic acid is well tolerated in usual doses. Mega doses given for long periods can cause ‘rebound scurvy’ on stoppage— probably due to enhancement of its own metabolism or tissue acclimatization. The risk of urinary oxalate stones may be increased. High doses may also be cytotoxic when added to iron preparations.

 

Contact Us, Privacy Policy, Terms and Compliant, DMCA Policy and Compliant

TH 2019 - 2024 pharmacy180.com; Developed by Therithal info.