r r e e t t p p a CChh 10.1 1.4 Pharmacodynamics Vitamins and Trace (Mode of Action of Drugs) Elements Vitamins are exogenous chemical substance required by the body in very small amount for the various metabolic functions of the body and categorized as essential nutrients They not yield energy but enable the body to use other nutrients and are primarily used in the prevention and treatment of certain deficiency diseases Vitamins are vital for normal metabolism in body They vary in their chemical structure and are supplied in very small quantity in diet, because they are not synthesized in body or their rate of production is not sufficient for maintenance of health Vitamin deficiency leads to development of deficiency symptoms Different vitamin preparations are available for treatment and prophylaxis Most of the vitamins are nontoxic but on chronic administration can cause toxicity especially vitamin A and D Vitamins are classified into two main groups: I Fat soluble vitamins, includes vitamin A, D, E and K II Water soluble vitamins, includes Bcomplex group and vitamin C The fat soluble vitamins are stored in the body and excessive administration of fat soluble vitamins can cause toxicity, while water soluble vitamins are rapidly excreted in the urine and cause very less toxicity The different market preparation available for vitamins are given in table 10.1.1 and the deficiency diseases which occur with deficient supply of various vitamins are listed in table 10.1.2 Table 10.1.1: Classification of various preparations of vitamins Vitamin A (ROVIGON) Vitamin D (CALCIROL) Vitamin E (EVION) Alfacalcidol (ALCIDOL) Vitamin B complex group Vitamin B1 (Thiamine; BENALGIS) Vitamin B2 (Riboflavin; LIPABOL) Vitamin B (Calcium pantothenate; SIGMA PANTOTHENATE) Vitamin B6 (Pyridoxine; PYRICONTIN) Vitamin B 12 (Cyanocobalamin/Mecobalamin; METHYCOBAL) Folic acid (FOLVITE) Vitamin C (Ascorbic acid; CELIN) Multivitamins preparations B1 + B6 + B12 (NEUROBION) B complex (B , B , B , B , B , B 12 + folic acid; BECOSULE) Section 10/ Vitamins and Trace Elements 384 Table 10.1.2: Diseases due to deficient supply of vitamins Vitamins Vitamin A Vitamin D Vitamin E Vitamin K Vitamin B1 (Thiamine) Vitamin B2 (Riboflavin) Vitamin B3 (Niacin or Nicotinic acid) Vitamin B5 (Pantothenic acid) Vitamin B6 (Pyridoxine) 10 Vitamin B12 (Cyanocobalamin) 11 Vitamin C (Ascorbic acid) 12 Folic acid Deficiency Night blindness (inability to see in dim light), conjunctival xerosis (dry and non-wettable conjunctiva), corneal xerosis (dry and non-wettable cornea and become opaque), keratomalacia (cornea becomes soft and burst open and vision is lost), Bitot’s spots, growth retardation, dry and rough skin, sterility due to faulty spermatogenesis Rickets (reduced calcification of growing bones) Axonal degeneration, ophthalmoplegia (however, vitamin E deficiency does not occur clinically) Decreased prothrombin content of blood and blood clotting time is prolonged Beriberi (characterized by nerve involvement – peripheral neuritis), Wernicke’s encephalopathy (characterized by ophthalmoplegia, polyneuritis and mental disorientation) Angular stomatitis (occurs in malnourished children) Pellagra (characterized by diarrhoea, dermatitis and dementia) Clinical deficiency is not known (has role in biosynthesis of corticosteroids) Peripheral neuritis, mental confusion, impairs the optimal utilization of pyridoxine [INH (anti TB drug) is a recognised antagonist] Megaloblastic anaemia (pernicious anaemia), demyelinating neurological lesions in the spinal cord & infertility Scurvy Megaloblastic anaemia and gastrointestinal disturbances such as diarrhoea, distension and flatulence Severe folate deficiency causes infertility or even sterility FAT SOLUBLE VITAMINS VITAMIN A Vitamin A is widely distributed in plant and animal foods In plants, the main source of vitamin A is green leafy vegetables e.g spinach and amaranth The darker the green leaves, the higher the carotene present Vitamin A is also present in green & yellow vegetables and fruits e.g pumpkin, papaya and mango, and in roots e.g carrots (richest source among plant source) The most important carotenoid is betacarotene which has the highest vitamin A percentage Carotenes are converted to vitamin A in the small intestine In animal foods, vitamin A is present in liver, eggs, butter, cheese, milk, fish and meat Fish liver oil are the richest source of retinol It is vital for the functioning of retina Vitamin A is essential for differentiation and growth of epithelial tissue It enhances function of immune system and protect against development of certain malignancies Different forms of vitamin A mediate different functions Vitamins and Trace Elements Retinoids: They influence a wide variety of biological activities including cellular proliferation, cellular differentiation, immune function, inflammation e.g tretinoin, isotretinoin, etretinate Isotretinoin is a retinoid, recently approved for use in capsule form (10-20 mg) It decreases the amount of sebum that sebaceous glands produce Isotretinoin exhibits antiproliferative and antiandrogenic effects on the sebaceous glands It also interacts with the formation of androgens in sebaceous glands It is indicated in the treatment of severe nodular acne, acne conglobata and recalcitrant acne It is available in International market under the brand name ‘ACCUTANE’ by Roche pharmaceuticals Deficiency symptoms: Bitot’s spots, xerosis, night blindness, keratomalacia, diarrhoea, follicular hyperkeratosis, papular eruptions, drying of epidermis, urinary calculi, degeneration of testis, impaired spermatogenesis, sterility, abortion, impairment of smell and taste It is indicated in night blindness, vitamin A deficiency (in infants, in pregnancy, lactation, malabsorption syndrome), for prophylaxis of vitamin A deficiency, acne, ichthyosis, psoriasis, xerophthalmia, Bitot’s spots (especially children) 385 VITAMIN D The term vitamin D is used for a range of compounds which possess the property of preventing or curing rickets They include ergocalciferol (calciferol, vitamin D2), cholecalciferol (vitamin D3), dihydrotachysterol, alfacalcidol (1α-hydroxycholecalciferol) and calcitriol (1,25-dihydroxycholecalciferol) It plays an important role in calcium metabolism It regulates calcium homeostasis and maintains normal levels of plasma calcium and phosphate Deficiency symptoms: Rickets occurs in patients who are having deficiency of vitamin D The bones are unusually soft and due to stress and strain of weight bearing produce characteristic deformities It is indicated in prophylaxis and treatment of rickets, postmenopausal osteoporosis, Fanconi syndrome and hypoparathyroidism Adverse effects include headache, weakness, nausea, vomiting, dry mouth, muscle pain, constipation, somnolence, ectopic calcification, hypertension, nephrocalcinosis and weight loss ALFACALCIDOL Dosage: Severe deficiency with xerophthalmia: 50,000 IU per day for three days followed by 50,000 IU per day for two weeks It regulates calcium metabolism by increasing calcium and phosphate absorption from the intestinal tract and also mobilises minerals from the bone Severe deficiency: 100,000 IU per day for three days followed by 50,000 IU per day for two weeks After oral administration it is absorbed in the small intestine and undergoes rapid metabolism to 1,25 (OH)2 D3 in liver and further distribution to bone and intestine is nearly similar to its physiological distribution Children: 5,000 to 10,000 IU per day for two weeks Section 10/ Vitamins and Trace Elements 386 Adverse effects include hypercalcaemia and hyperphosphataemia It is indicated in osteoporosis, hypoparathyroidism, hyperparathyroidism (with bone disease), renal osteodystrophy, nutritional and malabsorptive rickets, hypophosphataemic vitamin D resistant rickets and osteomalacia Dosage: Adults: Initially mcg daily adjusted according to response Elderly: Initially 0.5 mcg daily adjusted according to response Children: Over 20 kg: Initially mcg daily adjusted according to response Under 20 kg: 0.05 mcg/kg body wt daily VITAMIN E It is an presumably coenzyme Q peroxidation fatty acids antioxidant vitamin It prevents oxidation of and inhibits generation of products from unsaturated Vitamin E is a family of eight compounds, four tocopherols and four tocotrienols Tocotrienols appear to affect a key enzyme in the liver (HMG CoA reductase), which plays a key role in the synthesis of cholesterol As such tocotrienols help maintain good cardiovascular health Vitamin E is an antioxidant and prevents the oxidation of LDL (the bad cholesterol) Vitamin E functions as anticoagulant, which means it delays the clotting of the blood It can help prevent thrombosis, the formation of blood clots in the arteries Deficiency symptoms: In vitamin E deficiency in experimental animals the manifestations are seen in several systems including cardiovascular, reproductive and haematopoietic The clinical manifestations are axonal degeneration, gait disturbances, ophthalmoplegia, hyporeflexia and necrotizing myopathy Adverse effects include nausea, fatigue, headache, blurred vision, diarrhoea It is indicated in premature infants exposed to high concentration of oxygen, correction of established vitamin E deficiency, in patients at risk of developing vitamin E deficiency, nocturnal muscle cramps, intermittent claudication, fibrocystic breast disease, coronary artery disease and as an antioxidant Dosage: Adults: – Nocturnal muscle cramps: 400 mg daily for to 12 weeks – Intermittent claudication: 400 mg daily for 12 to 18 weeks – Fibrocystic breast disease: 600 mg daily for to months Children: 200 mg daily WATER SOLUBLE VITAMINS VITAMIN B GROUP Vitamin B1 (Thiamine) Vitamin B1 is the first member of the B complex Thiamine pyrophosphate is a coenzyme and the active form of vitamin B1 It functions as coenzyme in decarboxylation of αketo acid and in hexose monophosphate shunt Deficiency symptoms: In severe vitamin B1 deficiency beriberi develops Vitamins and Trace Elements It is indicated in wet beriberi, dry beriberi, Wernicke’s encephalopathy, prophylaxis of thiamine deficiency, hyperemesis gravidarum, Korsakoff’s syndrome, chronic alcoholics, multiple neuritis, toxic and confusional states, delirium tremens and anorexia nervosa Dosage: Mild chronic deficiency: 10-25 mg daily; severe deficiency, 200-300 mg daily VITAMIN B2 (RIBOFLAVIN) It carries its physiological function in its active forms, flavin mononucleotide (FMN) and flavin adenine dinucleotide These coenzymes are involved in various biochemical reactions Deficiency symptoms: It is characterized by glossitis, dermatitis of trunk and extremities, angular stomatitis, cheilosis, anaemia, neuropathy, cataract formation and vascularization of cornea It is indicated in arteriosclerosis, as adjunct in treatment of hypertension, diabetes and obesity VITAMIN B3 (NIACIN) Niacin was initially called pellagra preventing factor 387 features of this condition are diarrhoea, dermatitis and dementia Nausea, vomiting, stomatitis, dizziness, depression, insomnia, headache develops In severe deficiency hallucinations and dementia occurs Adverse effects include flushing, activation of peptic ulcer, vomiting, diarrhoea, pruritus, skin rash and transient headache It is indicated in pellagra, for prophylaxis, Hartnup disease, hyperlipoproteinaemia VITAMIN B5 (CALCIUM PANTOTHENATE) Pantothenic acid is traditionally considered to be vitamin B substance It is widely distributed in meat, legume and whole grain cereals, egg, milk, vegetables and fruit It is a component of coenzyme A which is essential in the metabolism of carbohydrate, fat and protein Deficiency symptoms: Deficiency of panthothenic acid is unlikely in man because of its widespread distribution in food, though it has been administered by mouth as a nutritional supplement as the calcium salt and usually in conjunction with other vitamins of the B group It is converted to coenzymes, nicotinamide adenine dinucleotide (NAD) or nicotinamide adenine dinucleotide phosphate (NADP) These coenzymes are bound to hydrogenases, function as oxidants by accepting hydrogen and electrons from substrates and become reduced It is involved as a coenzyme (pyridoxal phosphate) in metabolism of tryptophan, in several metabolic transformations of amino acids including transamination, decarboxylation and racemization Deficiency symptoms: In niacin deficiency, pellagra develops The main Deficiency symptoms: Peripheral neuritis, seizures, stomatitis, anaemia, Dosage: 50 to 100 mg per day VITAMIN B6 (PYRIDOXINE) ... Nocturnal muscle cramps: 400 mg daily for to 12 weeks – Intermittent claudication: 400 mg daily for 12 to 18 weeks – Fibrocystic breast disease: 600 mg daily for to months Children: 200 mg daily... e.g tretinoin, isotretinoin, etretinate Isotretinoin is a retinoid, recently approved for use in capsule form (10-20 mg) It decreases the amount of sebum that sebaceous glands produce Isotretinoin... malabsorption syndrome), for prophylaxis of vitamin A deficiency, acne, ichthyosis, psoriasis, xerophthalmia, Bitot’s spots (especially children) 385 VITAMIN D The term vitamin D is used for a range of