Detaile information of different vitamins, their deficiency, different mechanisms and terms.

1. VITAMINS
• Vitamins are non energy producing organic
compounds, essential for normal human
metabolism that must be supplied in small
quantities in the diet. Vitamin deficiencies occur
due to inadequate intake, malabsorption,
increased tissue needs, increased excretion,
certain genetic abnormalities and drug vitamin
interactions. The importance of vitamins as drugs
is primarily in the prevention and treatment of
deficiency diseases.

2. • CLASSIFICATION of VITAMINS
• Vitamins are traditionally divided into two groups:
• Fat soluble (A, D, E, K): These (except vit K) are stored
in the body for prolonged periods and are liable to cause
cumulative toxicity.
• Water soluble (B complex, C): These are meagerly
stored; excess is excreted with little chance of toxicity.
They act as cofactors for specific enzymes of
intermediary metabolism.

3. Physiological role and actions of VITAMIN A
Visual cycle:
Retinal generated by reversible oxidation of retinol (vit A1) is a component
of the light sensitive pigment Rhodopsin which is synthesized by rods
during dark adaptation. This pigment gets bleached and split into its
components by dim light and in the process generates a nerve impulse
through a G-protein called Transducin.
A similar pigment (Iodopsin) is synthesized in the cones-responsible for
vision in bright light, colour vision and primary dark adaptation.
In vit A deficiency rods are affected more than cones; irreversible
structural changes with permanent night blindness occur if the deprivation
is long-term.

4. Epithelial tissue: Vit A promotes
differentiation and maintains
structural integrity of epithelia all over
the body. It also promotes mucus
secretion, inhibits keratinization and
improves resistance to infection.
Reproduction: Retinol is needed for
maintenance of spermatogenesis and
fetal development.
Immunity: Increased susceptibility to
infection occurs in vit A deficiency.

5. Vitamin A: Synthesis: treatment of b-ionone (I) with ethyl chloroacetate in presence of sodium
methoxide results in glycidic ester (II); saponification of II followed by decarboxylation and
transposition of the double bond leads to the so-called b-C14-aldehyde (III); by condensing III
with Grignard reagent (IV) the so-called b-C20-acetylindiol (V) is obtained; partial catalytic
hydrogenation of V affords the corresponding ethylene derivative (VI) which is acetylated and
dehydrated giving-after double-bond rearrangement-retinol acetate (VII).

6. DEFICIENCY SYMPTOMS of Vit. A:
• Xerophthalmia,
• Keratomalacia (softening of cornea)
• Corneal opacities
• Night blindness
• Dry and rough skin
• Hyperkeratosis
Uses:
in vitamin A deficiency, such as night blindness, xerophthalmia (in early stages),
some skin disorders (acne, inflammation of the gums, psoriasis).
Dosage:
by intramuscular route, in severe deficiency, 50,000 to 100,000 IU daily for 3
days, followed by 50,000 IU daily for 2 weeks. By oral route, in severe
deficiency, 100,000 IU daily for 3 days, followed by 50,000 IU daily for 2 weeks.

7. Vitamin D
Several vitamins D are found in nature, but only vitamin D2 (ergocalciferol) and
vitamin D3 (cholecalciferol/Calcitriol) have equal antirachitic activity in humans.
Both are steroid derivatives and are obtained by ultraviolet irradiation: the first, of
ergosterol; the second, of 7-dehydrocholesterol.
Calcitriol enhances absorption of calcium and phosphate from intestine. Calcitriol
enhances resorption of calcium and phosphate from bone. Caicitriol also
enhances tubular reabsorption of calcium and phosphate in the kidney.

8. Deficiency of Vit. D:
• Rickets in growing children
• Infantile tetany
• Osteomalacia
Plasma calcium and phosphate tend to fall due to inadequate intestinal
absorption. As a consequence, PTH is secreted → calcium is mobilized from
bone in order to restore plasma Ca2+. The bone fails to mineralize normally in the
newly laid area, becomes soft → rickets in children and osteomalacia in adults.

9. Vitamin E
Vitamin E is comprised of a group of naturally occurring a-, b-, -, and d-
tocopherols, which are distributed widely in nature. A number of tocopherols, of
which α tocopherol is the most abundant and potent, have vit E activity.
Clinically used vitamin E is predominantly a-tocopherol, especially the (+)-isomer,
and the racemic mixture.
Physiological role and actions
Vit E acts as antioxidant, protecting unsaturated lipids in cell membranes,
coenzyme Q etc. from free radical oxidation damage and curbing generation of
toxic peroxidation products.
Deficiency symptoms
Experimental vit E deficiency in animals produces recurrent abortion, degenerative
changes in spinal cord, skeletal muscles and heart, and macrocytic & hemolytic
anemia.

10. Lipid peroxidation refers to the oxidative degradation of lipids. It is the process
whereby free radicals "steal" electrons from the lipids in cell membranes, resulting in cell
damage. This process proceeds by a free radical chain reaction mechanism. It most often
affects polyunsaturated fatty acids, because they contain multiple double bonds in
between which lie methylene -CH2- groups that possess especially reactive hydrogens.

11. Mechanism of Vitamin E to protects lipids from peroxidation. In the process, Vitamin E
can be oxidized to tocopheryl quinone or into tocopheroxyl free radical. It is reduced in
both cases by ascorbate (Vitamin C), which is oxidized in the process into either
dehydroascorbate or ascorbate free radical.
Vitamin E is a major antioxidant found in the lipid phase of membranes and, like other
chemically related molecules, acts as a powerful terminator of lipid peroxidation. During
the reaction between vitamin E and a lipid radical, the vitamin E radical is formed, from
which vitamin E can be regenerated in a reaction involving GSH and ascorbate.

12. Lipid peroxidation refers to the oxidative degradation of lipids. It is the process
whereby free radicals "steal" electrons from the lipids in cell membranes, resulting in cell
damage. This process proceeds by a free radical chain reaction mechanism. It most often
affects polyunsaturated fatty acids, because they contain multiple double bonds in
between which lie methylene -CH2- groups that possess especially reactive hydrogens.

13. Mechanism of Vitamin E to protects lipids from peroxidation. In the process, Vitamin E
can be oxidized to tocopheryl quinone or into tocopheroxyl free radical. It is reduced in
both cases by ascorbate (Vitamin C), which is oxidized in the process into either
dehydroascorbate or ascorbate free radical.
Vitamin E is a major antioxidant found in the lipid phase of membranes and, like other
chemically related molecules, acts as a powerful terminator of lipid peroxidation. During
the reaction between vitamin E and a lipid radical, the vitamin E radical is formed, from
which vitamin E can be regenerated in a reaction involving GSH and ascorbate.

14. 4. VITAMIN K
• It is a fat-soluble dietary principle required for the
synthesis of clotting factors.
• Physiological role and actions
• Vit K acts as a cofactor at a late stage in the
synthesis by liver of coagulation proteins
prothrombin, factors VII, IX and X. The vit K
dependent change (γ carboxylation of glutamate
residues of these zymogen proteins) confers on
them the capacity to bind Ca2+ and to get bound
to phospholipid surfaces → properties essential
for participation in the coagulation cascade.

16. DEFICIENCY SYMPTOMS
• Deficiency of vit K occurs due to liver disease,
obstructive jaundice, malabsorption, long-term
antimicrobial therapy which alters intestinal flora.
However, deficient diet is rarely responsible. The
most important manifestation is bleeding
tendency due to lowering of the levels of
prothrombin and other clotting factors in blood.
Hematuria is usually first to occur; other common
sites of bleeding are GIT, nose and under the
skin.

17. Vitamins
Fat-Soluble Vitamins
Vitamins A, D, E, K
Water-Soluble Vitamins
Ascorbic acid,
biotin,
folic acid,
niacin,
niacinamide,
pantothenic acid,
pyridoxine,
riboflavin,
thiamine, and
vitamin B12.
Deficiency
Vit. A:
hyperkeratosis, xerophthalmia, keratomalacia, and night blindness;
Vit. D:
rickets in growing children, infantile tetany, and osteomalacia;
Vit. E:
 macrocytic, and hemolytic anemia in infants;
Vit. K:
hypoprothrombinemia.

18. Ascorbic acid:
scurvy, which consists in degeneration of collagen and intercellular ground
substance, resulting in disturbances of bone growth, hemorrhages of the gums
and other parts of the body, loosening of the teeth, capillary fragility with
consequent cutaneous hemorrhages, and other abnormalities.
Thiamine:
Beriberi, which manifests itself in two main forms:
dry beriberi, whose principal symptom is polyneuropathy; and
acute wet beriberi, whose predominant symptoms are edema and serous
effusions.
Riboflavin:
loss of hair (alopecia),
lesions of the skin, eyes, lips, mouth, and genitalia.

19. Pyridoxine:
seborrheic and desquamative dermatitis of the eyes and mouth,
glossitis and stomatitis,
intertrigo of breasts and inguinal region of women, and many other clinical
changes.
Niacin:
pellagra, whose manifestations are symmetrically distributed erythematous
lesions on exposed surfaces of the body,
red swelling of the tongue and oral mucous membranes, and
central-nervous-system and gastrointestinal disturbances
Pantothenic:
several discomforts, such as malaise, fatigue, headache, nausea, sleep
disturbances, and abdominal cramps.
Biotin:
mild dermatitis, glossitis, lethargy, nausea, abdominal pains, anorexia,
mental depression, and other symptoms of small severity.

20. Vitamin A: Synthesis: treatment of b-ionone (I) with ethyl chloroacetate in presence of sodium
methoxide results in glycidic ester (II); saponification of II followed by decarboxylation and
transposition of the double bond leads to the so-called b-C14-aldehyde (III); by condensing III with
Grignard reagent (IV) the so-called b-C20-acetylindiol (V) is obtained; partial catalytic hydrogenation
of V affords the corresponding ethylene derivative (VI) which is acetylated and dehydrated giving-
after double-bond rearrangement-retinol acetate (VII).

21. Uses:
in vitamin A deficiency, such as night blindness, xerophthalmia (in early stages),
some skin disorders (acne, inflammation of the gums, psoriasis).
Dosage:
by intramuscular route, in severe deficiency, 50,000 to 100,000 IU daily for 3
days, followed by 50,000 IU daily for 2 weeks. By oral route, in severe
deficiency, 100,000 IU daily for 3 days, followed by 50,000 IU daily for 2 weeks.

22. Vitamin D
Several vitamins D are found in nature, but only
vitamin D2 (ergocalciferol) and vitamin D3
(cholecalciferol) have equal antirachitic activity in
humans. Both are steroid derivatives and are
obtained by ultraviolet irradiation: the first, of
ergosterol; the second, of 7-dehydrocholesterol.
A third type of vitamin D is dihydrotachysterol (DHT
Intensol, Hytakerol), but its antirachitic potency is
only 0.25% of that of calciferol; its main use is in all
forms of parathyroid tetany.

23. Vitamin E
Vitamin E is comprised of a group of naturally occurring a-, b-, -, and d-
tocopherols, which are distributed widely in nature. The best dietary sources
are legumes (soybean), cereal products (rice, corn), vegetable oils, eggs,
butter.
Clinically used vitamin E is predominantly a-tocopherol, especially the (+)-
isomer, and the racemic mixture.

26. Vitamin C (Ascorbic Acids)
Synthesis: catalytic hydrogenation of D-glucose (I) affords D-sorbitol (II),
which by oxidation with Acetobacter suboxydans, gives L-sorbose (III);
treatment of III with acetone, in the presence of concentrated sulfuric acid and
a catalyst, results in diacetone sorbose (IV); oxidation of IV with potassium
permanganate in strongly alkaline medium leads to diacetone sorburonic acid
(V); by heating V with concentrated hydrochloric acid 2-keto-L-gulonic acid
(VI) is formed; treatment of VI with a solution of gaseous hydrochloric acid in
ethanol-chloroform solution leads to ascorbic acid (VII).

27. Figure: Industrial synthesis of ascorbic acid

28. Uses:
prevention and treatment of scurvy,
facilitation of healing and recovery from extensive burns or severe trauma (in this
case doses 300 to 500% higher than the RDA (recommended dietary allowances)
are administered),
treatment of some types of anemia (which is common in the patients with
scurvy), and
maintenance of an acid urine when this is necessary.
Dosage:
Prophylactic: by oral or intramuscular routes, 45 to 60 mg daily; during
pregnancy and lactation, an additional 20 to 40 mg.
Therapeutic: by oral, intramuscular, or intravenous routes: 100 mg three times
daily for several weeks, for treatment of scurvy; 200 to 500 mg daily, for severe
burns.

30. Vitamin B1 (Thiamine)
Synthesis: condensation of 2-methyl-4-amino-5-chloromethylpyrimidine
hydrochloride (I) with 4-methyl-5-(P-hydroxyethyl)thiazole (II) results directly in
thiamine hydrochloride(III).
Uses: in thiamine deficiency; examples: beriberi, neuritis associated with pregnancy
and neuritis of pellagra, Wernicke's encephalopathy, chronic alcoholism.
Dosage: by oral, intramuscular, or intravenous routes: for deficiency, 5 to 10 mg
three times daily.

32. Vitamin B2 (Riboflavin)
Synthesis: reaction between 4,5-dimethyl-N-(1'-ribityl)aniline tetraacetate (I) and
p-nitro-phenyldiazonium chloride (II) leads to the azoderivative (III), which by
reacting with barbituric acid (IV), results in riboflavin (V).

33. Uses:
In riboflavin deficiency, characterized by a well-defined syndrome, with the
following features: cheilosis, angular stomatitis, glossitis, seborrheic folicular
keratosis of the nasolabial folds, nose and forehead, dermatitis of the anogenital
region, and "burning feet."
Certain ocular symptoms, such as pruritus, photophobia, burning,
blepharospasm, and visual impairment.
Dosage:
oral, for deficiency: 5 to 25 mg daily, preferably in a preparation containing the
other B-complex vitamins.

35. Vitamin B6 (Pyridoxine)
It is a mixture of pyridoxine, pyridoxal, and pyridoxamine, which are interconverted in the body.
Synthesis: by heating ethyl N-formylalaninate (I) with phosphorus pentoxide, 4-methyl 5-
ethoxyoxazole (lI) is formed; reaction between II and 2,5-dihydrofurane (III) and using a
mineral acid and hydroquinone as catalysts yields, after adduct decomposition, the internal
ether (IV), which by hydrolysis and salification; gives pyridoxine hydrochloride (V).

36. Uses:
in pyridoxine deficiency, such as convulsions in infants, hypochromic anemia,
some types of megaloblastic anemia, homocystinuria, or xanthinuric aciduria.
It is used as prophylactic against peripheral neuritis in patients treated with
isoniazid, cycloserine, hydralazine, penicillamine, and other pyridoxine
antagonists.
It improves symptoms refractory to thiamine, riboflavin, and niacin.
Dosage:
oral (preferred), intramuscular, intravenous: in pyridoxine dependency syn-
dromes, 10 to 250 mg daily; for drug-induced peripheral neuritis, 50 to 200 mg
daily: for prophylaxis in patients taking pyridoxine antagonists, 25 to 50 mg daily;
for deficiency. 5 to 25 mg daily for 3 weeks, followed by 1.5 to 2.5 mg daily in a
multivitamin preparation for maintenance; in pregnancy and lactation, same dose
as for deficiency.

38. Niacinamide (Nicotinamide)
Synthesis: esterification of nicotinic acid (I) affords ethyl nicotinate (II); amidation of
II with ammonia in ethanol results in niacinamide (III).
Uses: prevention and treatment of pellagra, which is characterized by loss of
appetite, diarrheia, weakness, lethargy, skin disorders, and mental and
neurological changes.
Dosage: oral (preferred), for pellagra, initially, 300 to 500 mg daily in divided
doses; for maintenance, preparation containing RDA amounts of niacinamide,
thiamine, riboflavin, and pyridoxine. Intravenous, initially, 25 to 100 mg every 2 or
3 hours, given very slowly.