Vitamins

VITAMINS
© Sujana Shakya, M. Pharm., Department of Pharmacy, NMCAL

1 ⁻ Sujana Shakya
⁻ M. Pharm.
⁻ Department of Pharmacy
⁻ NMCAL
 Non-energy yielding organic compounds, essential for
human metabolism
NMCAL
© Sujana Shakya, M. Pharm., Department of Pharmacy,
 Must be supplied in small proportions in diet
 Importance-
1. Prevention and treatment of deficiency diseases
 Deficiency can occur due to-
1. Inadequate intake
2. Malabsorption
3. Increased tissue needs
4. Increased excretion
5. Drug-vitamin interactions
 Myths- vitamins energise the body; vitamins are

harmless
2
•2 groups of vitamins-

Fat soluble vitamins Water soluble vitamins
Vitamin A, D E, K Vitamin B complex, Vitamin

C
Stored for prolonged periods Act as co-factors for specific

enzyme metabolism; excess
is excreted
Regular ingestion of large Little chance of toxicity

amounts- cumulative toxicity 3
VITAMIN A
NMCAL
 Source- occurs in several forms-
1. Vitamin A1 (retinol)- marine fish, (cod, shark) liver
oil, egg yolk, milk products, butter, fish, liver
2. Vitamin A2 (dihydroretinol)- fresh water fishes
3. Carotenoids- carrots, green plants (turnip, spinach)
4. B-carotene- splits into 2 molecules of retinol
4
ABSORPTION AND FATE OF VITAMIN A
NMCAL
5
CM- chylomicrons, RBP-retinol binding protein, TTR-transthyretin

ABSORPTION AND FATE OF VITAMIN A
NMCAL
Retinoic acid has vit A activity in epithelial tissues and promotes growth, but6is
inactive in eye and reproductive organs. All-trans retinoic acid (Tretinoin) is
used topically, while 13-cis retinoic acid (Isotretinoin) is given orally for acne
RAR-Retinoic acid receptor, RXD-retinoid X receptors
PHYSIOLOGICAL ROLE AND ACTIONS
1. VISUAL CYCLE
NMCAL
Rhodopsin
(rods)
opsin light Visual nerve impulse
iodopsin
(cones) opsin
11 cis All trans

retinal retinal
11-cis All trans

retinol retinol
Rhodopsin- dim light; synthesized by rods

Iodopsin- bright light, color vision; synthesized by cones 7
Vitamin A deficiency- rods affected more than cones; irreversible structural
changes with permanent night blindness in long term deprivation
NMCAL
8
9
NMCAL
2 Epithelial •Differentiation and maintains
tissue structural integrity of epithelia all
over the body
•Promotes mucus secretion, inhibits
keratinization and improves
resistance to infection
•Retards development of
malignancies of epithelial
structures
3 Reproduction Spermatogenesis and foetal development
3 Immunity •Proper Ab response

•Normal lymphocyte proliferation and
10
killer cell function
DEFICIENCY SYMPTOMS

 Since, Vitamin A is stored in liver, deficiency
symptoms appear only after long term deprivation
 Manifestations-
1. Xerosis, keratomalacia, corneal opacities, night
blindness, may progress to total blindness
2. Dry and rough skin, hyperkeratinisation, atrophy of
sweat glands
3. Keratinization of bronchopulmonary epithelium,
increased susceptibility to infection
4. Unhealthy GI mucosa, diarrhoea
5. Urinary stone formation due to
shedding of ureteric epithelial lining
6. Sterility 11
THERAPEUTIC USES

1. Treatment of vitamin A deficiency- 50,000-100,000
IU i.m or orally for 1-3 days
2. Prophylaxis of vitamin A deficiency during infancy,
pregnancy, lactation, hepatobiliary diseases,
steatorrhoea: 3000–5000 IU/day
3. Skin diseases like acne, psoriasis
Hypervitaminosis A-
 Toxicity of Vitamin A due to regular ingestion of
excess of retinol leading to nausea, vomiting,
itching, dermatitis, exfoliation, hair loss, joint pains,
bleeding, irritability, chronic liver disease
 Daily intake should not exceed 20,000 IU
 Treatment- stop further ingestion 12
VITAMIN E
NMCAL
 Source- α-tocopherol- most abundant and potent
 D-isomer is more potent than L-isomer
 Richest source- wheat germ oil
 Others- spinach, egg yolk, cereals, nuts
 Daily requirement- 10 mg
13
NMCAL
1. Antioxidant-
 Prevent free radical oxidation damage
Deficiency symptoms-
 Recurrent abortion
 Haemolytic anaemia
 Degenerative changes in skeletal muscle, heart
Toxicity-
 Even large doses for long periods- no significant
toxicity
 Abdominal cramps, loose motions, lethargy
14
THERAPEUTIC USES
NMCAL
1. G-6-PD deficiency
 Prolonged treatment with 100 mg/day increases
survival time of erythrocytes
2. Acanthocytosis-
 100mg/week i.m normalizes oxidative fragility of

erythrocytes
3. Large doses (400-600 mg/day)- have been reported
to afford symptomatic improvement in nocturnal
muscle cramps, fibrocystic breast cancer
15
VITAMIN D
NMCAL
Vitamin D3 Synthesized in the skin
Cholecalciferol under influence of UV
rays
Vitamin D2 Present in food (yeasts,
Calciferol fungi, bread, milk)
Vitamin D1 Present in food
16
NMCAL
17
ACTIVATION OF VITAMIN D
NMCAL
18
ACTIVATION OF VITAMIN D
NMCAL
19
 Vitamin D2 and D3- equally active
 Calcitriol (1,25 dihydroxy vitamin D, active form)-
NMCAL
more important physiologically
 1 alpha hydroxylation in kidney-
 rate limiting step
 Activated by Ca/Vitamin D deficiency
 Parathormone, estrogens, prolactin
o Calcitriol- negative feedback
o Vitamin D is hence a hormone since-
1. It is synthesized in the skin and not required in

diet
2. Transported by blood, activated and act on specific
receptors in target tissue
20
3. Feedback regulation occurs
NMCAL
21
NMCAL
22
PHYSIOLOGICAL ACTIONS
NMCAL
 Calcitriol-
1. Enhances absorption of calcium and phosphorous
from intestine and increases serum calcium level
2. Resorption of calcium and phosphorous from bone
3. Enhances tubular reabsorption of calcium and

phosphorous in kidney
HYPERVITAMINOSIS D-
 Due to chronic ingestion of large doses (eq. to 50000
I.U/day), manifestations are elevated plasma calcium
 Leads to hypercalcaemia, weakness, fatigue, nausea,
diarrhoea, polyuria, renal stones, hypertension
 Treatment- withholding vitamin, low calcium in diet,
23
plenty fluids
VITAMIN D DEFICIENCY
NMCAL
Inadequate intestinal
absorption
Ca and P level falls
Ca is metabolised from bone to

restore plasma Ca
Bone fails to mineralise

normally
Bone becomes soft :rickets in 24

children, osteomalacia in adults
USES OF VITAMIN D
Prophylaxis- in case of vitamin D deficiency-prevents
NMCAL
1.
rickets in children and osteomalacia in adults
2. Postmenopausal osteoporosis-
 Vitamin D3+ calcium= elderly males and osteoporotic
females
Vitamin D resistant Vitamin D Renal rickets
rickets dependent rickets
Hereditary disease in Deficiency of renal Hydroxylating does not

which Vitamin D hydroxylating occur due to chronic
metabolism is normal, mechanism renal disease
calcium and
phosphorous
metabolism deranged
25
Administration of P Administration of Administration of
with high dose of calcitriol or alfacalcidol calcitriol or alfacalcidol
PREPARATIONS
NMCAL
1. Calcitriol- 0.25-1 ug orally daily or on alternate days
2. Alfacalcidol- a prodrug that is hydroxylated rapidly
to calcitriol in the liver.
 Does not require hydroxylation at position 1 which
takes place in kidney
 So effective in renal bone disease, Vitamin D
dependent rickets, vitamin D resistant rickets
 1-2ug/day
 Children 0.5ug/day
3. Calciferol (vitamin D2) and cholecalciferol (vitamin

D3)- oily solution either filled in gelatin capsules or
for i.m
26
VITAMIN K
NMCAL
 Sources : green leafy vegetables, cabbage, spinach,
liver, cheese
 Daily requirement: 3-10microgram/day
 Deficiency of Vit K : it occurs due to liver disease,

obstructive jaundice.
 Symptoms  bleeding tendency haematuria
Uses:
 Prophylaxis and treatment of bleeding due to
deficiency of clotting factors as follows:
 Dietary deficiency of Vit K
 Obstructive jaundice, liver disease
27
WATER SOLUBLE VITAMINS
VITAMIN B COMPLEX GROUP
NMCAL
1.Thiamine (vitamin B1)-
 Source- outer layers of cereals, pulses, nuts, green
vegetables, yeast, egg, meat
Physiological role-
• Thiamine
• Thiamine pyrophosphate
• Co-factor for carbohydrate metabolism

28
of Pharmacy, NMCAL
© Sujana Shakya, M. Pharm., Department
 Thiamine deficiency should always be considered in unexplained
lactic acidosis. Focal damage due to lactic acidosis is its effect on 29
vulnerable brain structures (mamillary bodies and postmedial
thalamus). There is focal lactate production in the brain. Apoptotic
cell death due to N-methy is responsbile for neurologic symptoms in
DEFICIENCY SYMPTOMS-
NMCAL
Dry beriberi Wet beriberi
Neurological symptoms- Cardiovascular effects-

Numbness Palpitations
Tingling Breathlessness
Muscular weakness ECG changes
Atrophy resulting in “wrist Cardiac failure
drop”, “foot drop”
Paralysis of whole limbs
Mental changes
Sluggishness
Poor memory, loss of appetite
Ocular abnormality
constipation
30
THERAPEUTIC USES
1. Prophylactically (2-10 mg daily) in infants, pregnant
women, chronic diarrhoea, patients on parenteral
NMCAL
nutrition (In critically-ill patients, the metabolism of
glucose is promoted by aggravation of inflammation
probably caused by promotion of metabolism, and this
increases the demand for vitamin B1 resulting in
lowering the blood concentration of vitamin B1. The
body requires a minimum of 0.33mg thiamine for every
1000 kcal consumed)
2. Beriberi- 100mg/day i.m or i.v till symptoms regress
3. Acute alcoholic intoxication- thiamine 100 mg added to
glucose solution infused. Most neurological symptoms in
chronic alcoholics are due to thiamine deficiency
(Ethanol reduces the rate of intestinal absorption of
thiamine and inhibits the thiamine transport through
active process) 31
4. Neurological and cardiovascular disorders

RIBOFLAVIN (VITAMIN B2)
NMCAL
 Source- milk, egg, liver, green leafy vegetables,
grains
Physiological Role-
Well absorbed by active transport and phosphorylated
in the intestine. Riboflavin phosphate (Flavin
mononucleotide: FMN) is formed in different tissues.
 FAD (Flavin adenine dinucleotide) and FMN (Flavin
adenine mononucleotide) are co-enzymes of
flavoprotein involved in oxidation reduction reactions
Deficiency symptoms-
 Stomatitis, sore and raw tongue, lips, throats, ulcers
in mouth, vascularization of cornea, dry scaly skin,
loss of hair, anaemia, neuropathy
Uses- 32
 Generally used along with other B complex members

VITAMIN B3
Chemistry and source-
NMCAL
 “Nicotinic acid” and “nicotinamide”
 Liver, fish, meat, cereal, nuts, pulses
Tryptophan
Nicotinic acid
amino acid
Previtamin 1 mg
60 mg
 Maize- contains “niacin” antagonist and poor source

of tryptophan so can cause “pellagra” (sunburn like
dermal rashes on hands, legs, face which crack and
33
peel)
VITAMIN B3
NMCAL
PHYSIOLOGICAL ROLE AND ACTIONS-
Oxidation-
Nicotinic Coenzyme
Nicotinamide reduction
acid for NADP reactions
1. It acts as hydrogen acceptor in tissue respiration,

glycolysis.
2. Lowers plasma lipid level-
 TG and VLDL rapidly decrease, cholesterol modest fall
 Increase in HDL level
3. In large doses, act as vasodilators 34
VITAMIN B3
DEFICIENCY-
NMCAL
1. Pellagra- dermatitis (sunburn like
dermal rashes on hands, legs, face
which crack and peel). Risk of
developing pellagra is more in
chronic alcoholics due to impaired
absorption of niacin
2. GI- diarrhoea, stomatitis, glossitis,
nausea, vomiting
THERAPEUTIC USES-
1. Prophylactic use for pellagra- (20-
50mg/day oral)
2. Treatment of pellagra- (200-500
mg/day) in divided doses orally or
parenterally
3. Hypolipidaemics 35
VITAMIN B6
Pyridoxine, pyridoxal, pyridoxamine
NMCAL
 Source- liver, meat, egg, soyabean, vegetables, whole
grain
Physiological Role and actions-
Pyridoxine and pyridoxamine
Oxidised to pyridoxal
Phosphorylated to 36
pyridoxal phosphate(co-
enzyme form)
PHYSIOLOGICAL ROLE AND ACTIONS-

 Pyridoxal dependent enzymes like transminases and
decarboxylases involved in the synthesis of non-
essential amino acids like-
1. Tryptophan and sulfur containing amino acids like
methionine
2. Formation of 5-HT, dopamine, histamine , GABA,
animolevulinic acid (first step in synthesis of
haeme)
Deficiency-
 Dermatitis, glossitis, mental confusion (fall in brain
GABA levels), peripheral neuritis, anaemia
37
THERAPEUTIC USES
NMCAL
1. Prophylactically (2-5 mg daily) in alcoholics,
infants and patients with deficiency of B vitamins
2. Isoniazid, hydralazine induced neurological
disturbance (10-50 mg/day)
3. Mental symptoms in women in OCP (50 mg daily)
4. Pyridoxine responsive anaemia (due to defective
haeme synthesis)
5. Convulsions in infants and children
38
DRUG INTERACTIONS
NMCAL
Isoniazid interact with pyridoxal
Coverts to hydrazone
Inhibition of synthesis of pyridoxal

phosphate
Increased excretion of pyridoxine
Pyridoxine deficiency state 39

DRUG INTERACTIONS
NMCAL
Interacting drugs Result
1 Hydralazine, Decrease the utilization of
cycloserine, pyridoxal phosphate
penicillamine
2 Oral contraceptives Decrease pyridoxal phosphate
level in some women
40
VITAMIN C
NMCAL
 Source- citrus fruits (lemons, oranges), tomatoes,
potatoes, green chillies, cabbage, broccoli, strawberries,
pineapple
PHYSIOLOGICAL ROLES AND ACTIONS-
1. Hydroxylation of proline and lysine residues of
procollagen and formation and stabilisation of collagen
triple helix
2. Maintainence of intercellular connective tissue
3. Conversion of folic acid to folinic acid
4. Biosynthesis of oxytocin, vasopression, metabolism of
prostaglandins
 Deficiency- Scurvy (increased capillary fragility,
swollen and bleeding gums, deformed teeth, brittle
41
bones, impaired wound healing, anaemia, growth
retardation)
VITAMIN C
NMCAL
USES-
1. Prevention of vitamin C deficiency (50-100 mg/day)
2. Scurvy (0.5-1.5 g/day)
3. Postoperative (500 mg daily)- accelerates healing of

leg ulcers, bed sores
4. Anaemia: Ascorbic acid enhances iron absorption
and is frequently combined with ferrous salts
(maintains them in reduced state).
42

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VITAMINS

© Sujana Shakya, M. Pharm., Department of Pharmacy, NMCAL

1. Prevention and treatment of deficiency diseases

 Deficiency can occur due to-

3. Increased tissue needs

 Myths- vitamins energise the body; vitamins are

© Sujana Shakya, M. Pharm., Department of Pharmacy, NMCAL

Vitamin A, D E, K Vitamin B complex, Vitamin

Stored for prolonged periods Act as co-factors for specific

Regular ingestion of large Little chance of toxicity

CM- chylomicrons, RBP-retinol binding protein, TTR-transthyretin

11 cis All trans

11-cis All trans

Rhodopsin- dim light; synthesized by rods

3 Reproduction Spermatogenesis and foetal development

3 Immunity •Proper Ab response

© Sujana Shakya, M. Pharm., Department of Pharmacy, NMCAL

© Sujana Shakya, M. Pharm., Department of Pharmacy, NMCAL

 Richest source- wheat germ oil

 Others- spinach, egg yolk, cereals, nuts

 Degenerative changes in skeletal muscle, heart

 100mg/week i.m normalizes oxidative fragility of

 rate limiting step

 Activated by Ca/Vitamin D deficiency

 Parathormone, estrogens, prolactin

o Calcitriol- negative feedback

o Vitamin D is hence a hormone since-

1. It is synthesized in the skin and not required in

3. Enhances tubular reabsorption of calcium and

Ca and P level falls

Ca is metabolised from bone to

Bone fails to mineralise

Bone becomes soft :rickets in 24

Hereditary disease in Deficiency of renal Hydroxylating does not

3. Calciferol (vitamin D2) and cholecalciferol (vitamin

 Deficiency of Vit K : it occurs due to liver disease,

 Obstructive jaundice, liver disease

• Co-factor for carbohydrate metabolism

Neurological symptoms- Cardiovascular effects-

4. Neurological and cardiovascular disorders

 Generally used along with other B complex members

 Liver, fish, meat, cereal, nuts, pulses

 Maize- contains “niacin” antagonist and poor source

1. It acts as hydrogen acceptor in tissue respiration,

Pyridoxine and pyridoxamine

© Sujana Shakya, M. Pharm., Department of Pharmacy, NMCAL

Inhibition of synthesis of pyridoxal

Pyridoxine deficiency state 39

2. Scurvy (0.5-1.5 g/day)

3. Postoperative (500 mg daily)- accelerates healing of

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