Pharm 100 - Lesson E.1

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Pharm 100 - Lesson E.1
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Lesson E.1
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  1. vitamin Definition
    A vitamin is a substance essential for the maintenance of normal metabolic functions, but is not made in the body and therefore must be provided from an outside source.
  2. Discovery of Vitamins
    Vitamins were discovered by studying several deficiency diseases. Thus, a study of scurvy led tothe discovery of vitamin C, while a study of rickets led to the discovery of vitamin D. A study of Beriberi, a form of polyneuritis seen in east Asia from consumption of polished rice lacking a vitamin rich husk, led to the discovery of vitamin B1 (thiamin). Pernicious anemia was found to be caused by a deficiency of vitamin B12, while Pellagra was shown to be caused by a deficiency of vitamin B3(niacin)
  3. Classification
    The vitamins are classified into water soluble (vitamin C and eleven vitamins in the B group) and fat soluble (vitamins A, D, E and K).
  4. Are vitamins drugs?
    When a healthy person obtains vitamins from a healthy diet, we do not consider the vitamins inthe food as drugs. However, when vitamins are consumed in the chemically pure form as a tablet,they are considered to be drugs.
  5. DRIs
    • Dietary recommended intakes.
    • Note that DRIs are intended to keep people healthy people healthy and are not intended to treatdisease or the malnourished individual.
  6. EAR-
    Estimated average requirement. The value is determined to meet the requirements for 50% ofthe people in any one category based on age, gender and ethnicity.
  7. RDA
    Recommended daily allowance. Daily intake sufficient to meet the needs of 97% to 98% ofhealthy people in a group. (Age, gender ).
  8. AI
    Adequate intake. Recommended daily intake based on observed or scientific data for specificgroups of individuals (age, gender etc).
  9. UL
    Upper limit. The highest recommended daily intake that is not likely to pose an adverse healthrisk to all individual
  10. 1. Inadequate intake:
    • (a) Individuals who consume an inadequate diet for reasons of poverty and/or geography. A goodexample are the aboriginal people living in the Canadian north.
    • (b) Individuals consuming a diet consisting of one major food. An example are black groups inSouth Africa living on a corn diet.
    • (c) Individuals consuming an eccentric diet due to a psychiatric disturbance.
    • (d) Individuals who have particular ideas leading to an idiosyncratic diet.
    • (e) Individuals who, for religious reasons, consume an inadequate diet.
    • (f) Alcohol-dependent individuals who have an inadequate food intake since they obtain a largenumber of calories from alcohol.
    • (g) Individuals on restrictive diets.
    • (h) Individuals on restricted diets for disease management.
  11. 2. Disturbances in absorption:
    • (a) Prolonged diarrhea
    • (b) Liver disease.
    • (c) An individual taking antibiotics that alter intestinal bacteria. Vitamin K and biotin (one of thevitamin B group) are derived from intestinal bacteria3.
  12. 3. Increased requirements:
    • (a) During growth.
    • (b) During periods of hard physical work, e.g. working deep underground in a gold mine under hotand humid conditions.
    • (c) Pregnancy, lactation (breast feeding), menstruation.(d) Stress.
    • In illness:
    • (a) Hyperthyroidism (overactive thyroid).
    • (b) Fever.
    • (c) Tissue wasting.
  13. Consequences of excessive intake of vitamins:
    • (a) Nutritional approach: This is the rational approach where one selects a diet aimed at supplying the RDA for each vitamin or a multivitamin preparation which supplies the RDA of each vitamin.
    • (b) Megavitamin approach: This approach is based on the delusion that “if a small dose is good, a larger dose must be better.” However, according to the principles of pharmacology, increasingthe dose of a therapeutic compound leads to a maximum effect and a further increase leads to theproduction of toxic effects. Millions of individuals ingest vitamins in excess of the RDA. Theexcess of some water-soluble vitamins is rapidly excreted in the urine, and for this reason, NorthAmericans have been said to excrete the most expensive urine in the world. It was assumed that water-soluble vitamins were readily excreted and therefore were safe irrespective of magnitudeof dose. However, more recent studies have shown that overdosing of vitamin B6 (pyridoxine)can cause nerve injury. It is clear that taking high doses of the fat-soluble vitamins A, D and E can result in accumulation in body fat and can cause severe toxic effects.
  14. Vitamin C (Ascorbic Acid)
    The RDA for vitamin C is 60 mg in non-smokers and 100 mg for smokers. M. Levine et al.(Proceeds of the National Academy of Science, U.S.A., 93: 3704, 1996) have shown that 200 mg/dayof vitamin C, from eating fruits and vegetables, maintains maximum body pools of the vitamin.
  15. Mechanism of action and results of deficiency:
    Cells are held together in organs by a framework of collagen and intercellular ground substance. Collagen and intercellular ground substance require vitamin C for their formation. If adequate vitamin C is not provided, then cells will not be held together adequately. Thus, a defect in the framework holding cells together in blood vessels leads to bleeding. A similar defect in the framework holdingcells together in the gums leads to spongy gums and a loosening of teeth. These conditions areassociated with severe vitamin C deficiency, namely scurvy.
  16. history of scurvy
    It had been suspected for many years that scurvy was caused by an inadequate diet. JacquesCartier was able to cure scurvy in his ship’s crew by administering an extract of spruce leaves. He acquired this information from the Indians in Canada. Scurvy presented a major problem to sailors onships undertaking long voyages in the sixteenth to eighteenth centuries, without a supply of fresh fruitand vegetables. In 1745, a physician in the British Navy demonstrated that administration of citrus fruits provided a cure for scurvy. This led to theBritish Navy providing a daily ration of lime juice to their sailors and to the designation “Limies” to British sailors. In 1652, the Dutch built a fort andformed a small colony in Cape Town, South Africa, the purpose of which was to grow fresh vegetables andreplenish the ships sailing on the long voyages from Holland to their colonies in the Dutch East Indies. Thus, vitamin C played a role in white settlement inSouth Africa and thesubsequent political problems between settlers and the native population which has only recently been resolved.
  17. Therapeutic uses of vitamin c:
    • (a) Prevention and treatment of scurvy.
    • (b) Prevention and treatment of the common cold? The therapeutic use of vitamin C for this purpose is highly controversial.
  18. Studies of the use of vitamin C for prevention and treatment of the common cold:
    Clinical trials on the use of vitamin C in the therapy of the common cold began as early as 1942. However, prior to 1970, a review of the studies indicated that the therapeutic effects claimed were toosmall to merit attention, and moreover that there were defects in the clinical trials that had been carriedout. In 1970, Linus Pauling, a scientist of great stature who had won two Nobel Prizes for Chemistryand Peace, presented arguments in favour of vitamin C use for therapy and prevention of the commoncold. He claimed that, if previous clinical trials were properly analysed, substantial benefit wasindicated. Moreover, in his view, the doses of vitamin C used in previous studies were much too lowand he advocated using high doses of vitamin C, greatly in excess of the RDA of 60 mg. For example,a dose of 4,000 mg/day was not considered excessive. Because of his stature as a scientist, additional clinical studies were undertaken. In a Canadian study conducted in 1972, volunteers were given 1,000mg of vitamin C daily in a double-blind study. The common cold was not prevented, nor was theduration of the common cold shortened. However, there was a reduction in the total number of dayslost from work as the colds were apparently milder.
  19. Adverse effects: of vitamin c
    • When vitamin C is taken in doses well above the RDA, that is in megadosage (greater than 1,000mg/day), diarrhea may result as well as formation of kidney stones from enhanced excretion of oxalate. In addition, high dosage of vitamin C on a continuing basis can result in induction of pathways of vitamin C metabolism, so that when individuals on high dosage of vitamin C suddenly cease taking vitamin C, rebound scurvy may occur.
    • Thus, while it is important to consume a diet containing the RDA of vitamin C, the conclusion regarding megadosage of vitamin C is:
    • Any preventive benefit that might be derived from such use of ascorbic acid (vitamin C) seems small when weighed against the expense and risks of megadosage treatment”.
  20. Vitamin B
    The B group of vitamins, traditionally consisting of eleven members, are grouped in a singleclass because they were originally isolated from the same sources, namely liver and yeast. Some ofthe B vitamins and their RDA’s are listed below.
  21. Folate:
    It has been shown to be important to supplement the diet of women of childbearing age with 400ug of folic acid per day. The reason for the supplement is the demonstration that such a supplementcan markedly decrease the incidence of neural tube defects (such as spina bifida) in their offspring.
  22. Vitamin B6
    Some studies indicate a relationship between a high intake of vitamin B6, decreased serum concentrations of homocysteine and a lower risk of heart disease
  23. Vitamin B12
    Since 10-30% of Americans over 60 years of age have difficulty absorbing vitamin B12, theyshould take vitamin B12 as a supplement, or take B12-fortified foods. As individuals age absorption ofthis vitamin decreases.
  24. Vitamin A
    • RDA = 1,000 micrograms retinol
    • = 1,000 retinol equivalents
    • 1 retinol equivalent = 1 :g retinol = 6 :g $-carotene
  25. Effects of deficiency of vitamin A:
    • (a) Growth and development will be retarded.
    • (b) Vitamin A is a constituent of a complex molecule, called rhodopsin, in rods of the eye, and isrequired for night vision. Deficiency of vitamin A leads to night blindness and to drying of the surface of the eye, a condition called xerophthalmia (dry eye). When deficiency is severe, visual impairment and blindness may result.
    • (c) Deficiency of vitamin A leads to changes in cells lining the bronchioles in the lung and enhances the opportunity for respiratory infection.
    • (d) Deficiency of vitamin A leads to a dry, thick and horny skin
  26. Effects of excessive intake: of vitamin A
    Toxicity results from excessive intake, and the degree of toxicity depends upon age, dose and duration of administration. Toxic symptoms include a dry itchy skin, vomiting, headache, a feeling ofpressure in the head, and an enlarged liver and spleen
  27. Therapeutic uses: of vitamin A
    • (a) Treatment of vitamin A deficiency. Vitamin A deficiency is a serious nutritional deficiency disease. It is particularly common in South East Asia, Africa, Central and South America, andthe Middle East, resulting in irreversible blindness in approximately one-quarter million children per year. Obviously extreme poverty is a major reason.
    • (b) Administration in periods of increased requirement such as infancy, pregnancy and lactation.
    • (c) Used in the treatment of acne and some other skin diseases.
  28. Vitamin D
    • RDDA = 10 :g of cholecalciferol = 400 I.U. vitamin D
    • Prior to the discovery of vitamin D, a high percentage of urban children, especially those livingin temperate zones, developed rickets. Some scientists suggested that rickets was caused by lack of a dietary factor, while others argued that it was caused by a lack of sunshine. Both suggestions wereshown to be correct. The reason for the correctness of both ideas was the following: Vitamin D ispresent in foods such as meat and fish and may be formed in the body by the action of sunlight on provitamin D which is present in the skin. Vitamin D undergoes conversion in the liver to 25-hydroxyvitamin D, which in turn is converted in the kidney to the active form of the vitamin, namely 1,25-dihydroxyvitamin D.
    • In several countries, milk is fortified with vitamin D. Since some elderly people are exposed tolittle sunlight and do not drink milk, they require supplements of vitamin D.
  29. vitamin d diagram
  30. Actions of vitamin D:
    • (a) Increases the absorption of calcium and phosphate from the intestine. The calcium and phosphate is utilized for formation of new bone.
    • (b) The blood calcium level must be maintained within prescribed limits for optimal health and vitamin D is involved in regulation of the blood calcium level.
    • (c) Vitamin D is involved in removal of calcium from older bone.
  31. Results of vitamin D deficiency:
    • (a) Decreased absorption of calcium and phosphate from intestine.
    • (b) Decrease in blood calcium level.
    • (c) Calcium removed from bone in attempt to maintain blood calcium level. As a result, defective bone growth occurs in infants and children leading to bow leggedness – a condition referred to as rickets. Rickets also occurs in adults.
  32. Effects of excessive intake: of vitamin D
    • The RDA of vitamin D is 400 I.U. When 50,000 units or more are consumed daily(megadosage), continuously, toxicity may result.
    • (a) Calcium levels are elevated in the blood and calcium is deposited in several tissues, including the kidney, heart, lungs, blood vessels and skin. The fetus also suffers from the high blood calcium levels.
    • (b) Paradoxically, excess removal of calcium from bone occurs.
    • (c) Individuals suffer fatigue, nausea, vomiting and diarrhea, as well as impaired kidney function.
  33. Vitamin D and osteoporosis.
    The osteoporosis society of Canada recommends that all women over the age of 55 take 1000 IU of vitamin D and 1500mg of elemental calcium in order to reduce the incidence or slow the onset of osteoporosis. Men over the age of 55 are recommended to take 1200mg of elemental calcium.
  34. Vitamin D and cancer
    A recent study has suggested that vitamin D may have protective effects against breast cancer in premenopausal women and this has lead the Canadian Cancer Society to recommend that all women take 1000IU vitamin D daily. A 2008 study has concluded that the protective effect of Vitamin D does not include prostrate cancer.
  35. Vitamin E
    The RDA for vitamin E is 10 mg. In 1962, a report appeared of a long-term controlled study of vitamin E depletion in humans. Individuals on a vitamin E-deficient diet took months to produce a significant decrease in blood vitamin E levels. More over, no clinical signs of vitamin E depletion were observed and it was concluded at that time that vitamin E was present in adequate amounts in the normal adult diet.
  36. Actions on reproductive system Vitamin E
    Vitamin E has been shown to be essential for normal reproduction in several mammalian species. Thus, in vitamin E-deficient female rats, pregnancy is terminated in approximately ten days with fetal death, and irreversible sterility occurs in the vitamin E-deficient male rat. With this background,vitamin E has been studied as a possible treatment for habitual abortion and for male and female sterility in humans without any evidence of benefits.
  37. Actions on the muscular system: Vitamin E
    Vitamin E deficiency was found to lead to muscular dystrophy (degeneration) in several animal species. However, in humans with muscular dystrophy, there was no evidence for vitamin E deficiency and vitamin E administration did not produce any beneficial effects in humans suffering from muscular dystrophy
  38. Treatment of anemia: Vitamin E
    Vitamin E deficiency is associated with anemia in several animal species. Vitamin E has been found to be useful in the treatment of premature babies with an uncommon type of hemolytic anemia.
  39. Actions on the cardiovascular system: vitamin E
    Vitamin E deficiency leads to heart muscle degeneration in several animal species. For this reason, vitamin E has been tested for efficacy in several types of human heart disease. However,controlled clinical trials initially showed no difference in efficacy between vitamin E and place botherapy. There have been reports which indicate a lower incidence of coronary artery disease in women and men taking vitamin E supplements for two years. However, there have been other recent studies that do not show a beneficial effect of high dietary intake of vitamin E on cardiovasculardisease. The dose of vitamin E taken appears to be an important determinant of the response. It may provide benefit a certain doses but as the dose increases the benefit disappears and may actually beharmful. The questions of usefulness of vitamin E in cardiovascular disease therefore awaits to be resolved.
  40. Summary: of vitamin E
    • (a) Effective in premature babies with an uncommon type of hemolytic anemia.
    • (b) Some studies indicate a beneficial effect of high dietary intake of vitamin E in cardiovasculardisease. Other studies do not confirm beneficial effects. Questions of usefulness remains to be resolved.
    • (c) Ineffective in muscular dystrophy, habitual abortion and sterility.
    • (d) Claims of effectiveness in minor skin ailments and in schizophrenia have not been substantiated

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