Vitamins

·          B & C are H₂O soluble; excreted rapidly in kidney; overdoses are rare

·          A,D,E, & K are fat soluble; stored; hypervitaminosis syndromes result

·         usually multiple deficiencies of Vit B exist (not single) so supplementation is in multiple combos

Thiamine (Vit B-1) – precursor for TPP which is required for decarboxylation of a-keto acids and is a co-

       factor for transketolase.

·          most common vitamin deficiency

·          Deficiency = Beri-Beri

·          The demand for TPP is related to the glucose state

Ø  IV glucose results in increased glucose metabolism that increases the need for thiamine

Ø  Hypermetabolic states also increase the need. (pregnancy, hyperthyroidism)

·          deficiency common in Alcoholics, pregnant women, the elderly, and “polished” rice diets

·          dry beri-beri

Ø  Peripheral neuropathy in pregnancy and alcoholics

Ø  Wernicke’s encephalopathy

Ø  Korsakoff’s psychosis

·          wet beri-beri

Ø  heart failure due to high output CHF

·          No toxicity from administration because it is not stored

 

Vitamin B-12 (Cyanocobalamin) – cofactor in formation of methionine and SAM from homocysteine

·          deficiency causes megaloblastic anemia and neurologic disease

Ø  deficiency results in

1)       trapping of folic acid in inactive form (CH₃-THF)

2)       abnormal nucleotide pools and disordered DNA synthesis

·          causes of Vit B-12 deficiency (remember pathway of absorption)

1)       Pernicious anemia – autoimmune syndrome that results in loss of parietal cell function and thus decreased intrinsic factor secretion

2)       Post-gastrectomy syndrome

3)       Ileal insufficiency – can be due to surgery or small bowel disease

·          Megaloblastic anemia due to impaired red cell maturation and shortened red cell survival

·          Neuritis and Encephalopathy due to interference with normal myelin metabolism which leads to IRREVERSIBLE impairment of spinal cord and cortical function

·          Therapy

Ø  Remember that B-12 deficiency is often due to malabsorption and thus it has to be via injection

Ø  No toxicity exists

Folic Acid – precursor of several folate derivatives that serve as co-factors for the enzymes involved in 4-carbon metabolism

·          very common in alcoholics

·          deficiency

1)       leads to megaloblastic anemia – like Vit B-12

2)       spina bifida and anencephaly

3)       leads to abnormalities in amino acid and purine synthesis

·          absorbed in the proximal intestine; enterohepatic recirculation of folate derivatives in important

·          Causes of deficiency

1)       small bowel disease (sprue) or surgery

2)       agents that interfere with enterohepatic circulation (alcohol)

·          DOES NOT cause the irreversible spinal cord and cortical injury characteristic of B-12 deficiency

·         Therapy – watch out for overlying B-12 deficiency; alcoholics; before pregnancy

 Pyridoxine (Vitamin B-6) – converted to pyridoxal phosphate, a cofactor in amino acid metabolism

·          Deficiency

1)       complication of INH therapy

2)       can be seen in severe malnutrition

3)       causes dermatitis, neuritis, and maybe carpal tunnel syndrome

·          Therapy

Ø  prophylaxis for those on INH therapy

Ø  CONTRA: Parkinson’s patients on L-DOPA therapy because it stimulates the activity of dopa decarboxylase in peripheral tissues

Niacin (B-3) – (Nicotinic Acid) precursor for NAD and NADP

·          Deficiency – Pellagra

1)       3 D’s of pellagra – Dermatitis, Dementia, and Diarrhea

2)       severely malnourished and alcoholics

3)       rare

·          Therapy

Ø  Uncomplicated

·          Syllabus listed it as B-5 that’s incorrect.  B-5 is pantothenic acid. Niacin is B-3

Riboflavin (B-2) – precursor for FMN and FAD which are cofactors for several respiratory enzymes

·          Deficiency

1)       dermatitis, neuritis

2)       no clinically distinctive features

·          Therapy

Ø  uncomplicated

Other B- Vitamins – Biotin, Pantothenic Acid, Choline, Carnitine

Vitamin C (Ascorbic Acid) – also a cofactor; protein hydroxylation reactions

·          used for:

1)       collagen synthesis

2)       GI iron absorption

3)       Anti-oxidant

·          Deficiency – Scurvy

1)       malnourished elderly and infants fed ascorbate deficient diet

2)       results in

a.        weakening of extracellular matrices

b.        hyperkeratosis of the skin

c.        petechia

d.        loosening of the teeth, gingivitis

e.        imparied wound healing

·          Treatment

Ø  for replacement, and anti-oxidant capabilities

Ø  no toxicity (remember that it is H₂O soluble), rapidly excreted by the kidney

·          Side effects from treatment with Vitamin C

1)       can give false + results in urine tests for glucose

2)       can suppress hematest for occult blood in stool

3)       if given in megadoses – diarrhea, renal damage 2^o to oxalate stones

 

Vitamin K  (Phytonadione) – cofactor for enzymes that carboxylate the amino acid side chains of blood clotting factors

·          Deficiency causes abnormal bleeding due to hypothrombinemia and has an increased PT time.

·          Sources of Deficiency

1)       prolonged antibiotic therapy

2)       malabsorption syndromes – esp those due to biliary insufficiency

3)       intestinal disease (sprue, regional enteritis, bowel resections

·          transient Vit K deficiency in the newborn is common

·          Therapy

Ø  phytonadione i.m. for standard deficiency

Ø  prophylactic therapy to normal newborns

 

Vitamin E (a-tocopherol) and the other anti-oxidants (Vit C and A)

·          thought to have its therapeutic effect via its ability to consume free radicals and reactive O₂ species

·          prevention of atherosclerosis

·          Vit E (a-tocopherol), Vitamin C (ascorbic acid) and b-carotene (Vit A precursor) serve as anti-oxidants by blocking free radical chain reactions and scavenging reactive oxygen and peroxide by-products

·          Vit E is lipid soluble and is transported in serum lipoproteins (makes it physically close to cholesterol)

Ø  Treatment with Vit E: exclusively in the treatment of patients w/ atherosclerosis

·          Vit A: may be protective against tobacco smoke and thus lung cancer.

·          Vit C: unclear

 

Vitamin D (Cholecalciferol) – more later

·          remember 1,25- (OH)₂-D₃ is active form

·          bind to nuclear hormone receptors

·         used pharmacologically to treat disorders of calcium and bone metabolism

Vitamin A (Retinoids) – In the eye, retinol is converted to retinaldehyde which is a cofactor in the conversion of opsin to rhodopsin.  Other tissues the retinol is converted to retinoic acid and binds to nuclear receptors and aids in the control of transcription of genes that regulate cellular growth and differentiation.

·          Retinol is derived from dietary b-carotene and retinyl esters

·          Effects on:

1)       vision

Ø  deficiency will lead to defective rhodopsin function and “night blindness”

2)       Cell Growth and Differentiation

Ø  physiological role in controlling proper growth and differentiation of tissues during embryogenesis

Ø  also, important in regulating the growth and differentiation of epithelial surfaces

·          Deficiency

1)       night blindness and xerophthalmia

2)       loss of barrier function of the respiratory and GI mucosa

3)       increased susceptibility to death from common infections

4)       takes years for adults to develop because the liver stores so much of it

5)       not too uncommon in the neonate esp. in foreign countries

·          Treatment

Ø  In US used for treatment of skin diseases and cancer

1)       Derm – Psoriasis , Acne, Keratinization disorders, Photo-aging

2)       Cancer – Leukemias (APL), leukoplakia

·          Hypervitaminosis A

Ø  occurs because the Vit A is stored in tissues and excessive ingestion can easily cause distinct toxicity

Ø  Teratogen – do not take if pregnant or likely to become pregnant

Ø  Skin and mucus membrane toxicity

Ø  Cerebral Edema – headache and increased ICP

Ø  Bone toxicity – bone spurs and fusion of the vertebral bodies