Role of Zinc in Health & Disease Zinc as a Therapeutic Agent

Dr. T.R.RAMANUJAM. M.D.,

Professor & Head, Dept of Pharmacology,
Sri Ramachandra Medical College & Research Institute,   
Porur ,   
Chennai - 600 116 
SOUTH INDIA. 

• PROLOGUE
• PHARMACOLOGY OF ZINC
• PHARMACOKINETICS OF ZINC
• DOSING INFORMATION
• PRECAUTIONS FOR DIETARY OR SUPPLEMENTAL ZN THERAPY
• RECOMMENDED INCREASE IN DIETARY INTAKE OR SUPPLEMENTATION IS NEEDED IN
• ZINC SUPPLEMENTS (SYSTEMIC)
• PATIENTS ON ZINC REQUIRE MONITORING OF THE FOLLOWING PARAMETERS
• SIDE/ADVERSE EFFECTS OF ZINC
• References on Zn def & uses
• Other therapeutic uses of Zn

PROLOGUE

Zinc is a divalent cation exhibiting important role in health & disease as evidenced by the role of Zn in the functional capacity more than 200 metallic enzymes including Carbonic anhydrase, Carboxypeptidases, Alcohol dehydrogenases, Alkaline phophatases, and RNA Polymerases etc., It is also required to maintain the structure of nucleic acid protein, cell membrane and also exerts vital role in various physiological functions viz., Cell growth, division, maturation and reproduction, Dark adaptation, night vision, Wound healing, host immunity, Taste acuity, Maintenance of pregnancy ,fetal growth etc., etc., Hence the importance of Zn in pre3gnancy,pediatrics, dermatology and their supplementation if total parenteral nutrition (TPN) need not be overemphasized . Therefore knowledge of the current status of Zn therapeutics as well as its adverse effects becomes mandatory for rationalized application of this divalent cation.

PHARMACOLOGY OF ZINC:

Zn is an essential element of nutrition and traces are present is wide range of foods. Zn salts( usually Zn sulfate) are used as supplements to correct Zn deficiency and have been used to treat large number of conditions because of an associated reduction in the concentration of Zn in the body. Zn sulfate is used orally at doses of 220 mg thrice daily in the treatment of acrodermatitis enteropathica and in Wilson's disease ( other Zn salts like Zn gluconate, Zn acetate are also used).

Zn carbonate, Zn oxide, and Zinc chloride are used in Dermatological disease as astringents.

Zn hydroxybenzene sulphonate is used as a deoodrant and antiperspirant.

Zn sulfate is being used topically in ophthalmology as eye drops.

Pharmacokinetics of Zinc:

The molecular weight of elemental Zn is 65.37 and Zn sulfate is 287.5 and the crude Zn sulfate is also known as white Vitriol or' white Copperas. Each gram of Zn sulfate represents 3.5 milli mole of Zn. Zn sulfate is approximately equivalent to 50mg of elemental Zn and its solubility is 1 in 0.6 ml of water and insoluble in alcohol. The UISP injection has pH 2-4 & stored in non-metallic containers. 

Zn and its salts are poorly absorbed from GIT ( in duodenum and ileum) and only small portion of dietary Zn is absorbed and is widely distributed throughout the body and excreted mainly in the feces and only traces are found in the urine since kidney has little role in regulating body Zn content. Endogenous Zn be reabsorbed in ileum and colon creating enterohepatic circulation of Zn.

After absorption Zn is bound ibn the intestines to protein metallo thionein. Zn is primarily stored in RBCs, WBCs, muscle, bone,Skin, Kidneys, Liver, Pancreas,retina, prostate etc., The extent of binding is - -0% to plasma albumin, 30-40 % to alpha 2 macroglobulins or transferrin and 1% to amino acids like histidine and cysteine.Peak plasma concentration occurs in approximately 2 hours and elimination is primarily fecal constituting 90% and small amounts in urine and sweat.

DOSING INFORMATION:

Zn supplements is usually administered 1 hour before or 2 hours after food. In the presence of gastric irritation Zn has to be given with food.

Sources of Zn- Red lean meats, marine foods like herrings and oysters, Peas, Beans, Whole grain. But large amounts of whole grain reduces the absorption of Zn from dietary sources.

Recommended Dietary intake:

Parenteral administration of Zn is indicated only when oral Zn is not acceptable (Nausea, Vomiting, pre & post operative conditions) or malabsorption syndromes, or following gastric resection etc.,

PRECAUTIONS FOR DIETARY OR SUPPLEMENTAL ZN THERAPY:

Zinc is administered 2 hrs before taking fiber diet, whole grain cereals and P containing foods like milk or poultry etc.,.
Patients should avoid taking Zn supplements within 2 hrs of iron, copper or phosphate supplements. Because of infrequency of Zn deficiency alone, combination of several vitamins and minerals are often used irrationally.

Zinc deficiency state or deficiency leads to:

· Growth retardation
· Hypogonadism in males
· Anorexia (changes in taste & olfactory acuity)
· Reduced mental function, dermatitis
· Impaired wound healing
· Diarrhea
· Abnormal Vitamin A metabolism with impaired vision.

RECOMMENDED INCREASE IN DIETARY INTAKE OR SUPPLEMENTATION IS NEEDED IN 

· Alcoholism, burns
· Cirrhosis liver
· Diabetes mellitus
· Eating disorders like anorexia nervosa / bulimia
· Gastrectomy
· Genetic dis: Acrodermatitis enteropathica
Down's syndrome
Sickle cell disease
Thalassemia
· In haemodialysis
· Premature infants
· Chronic infection with reduced immunity
· Intestinal disease like;
Coeliac disease
Crhon's diarrhea
Sprue & ulcerative colitits
· Intestinal parasitism
· Malabsorption syndrome:
Pancreatic def
Cystic fibrosis
· Renal diseases- nephrotic syndrome & uremia
· Short bowel syndrome
· Dermatological disorders;
Exfoliative dermatitis, Psoriasis
· Prolonged stress and trauma.

Zn deficiency can occur with some unusual diets like reducing diets, in patients with total parenteral nutrition and in malnutrition diets (imbalanced diets)

Zinc prophylaxis of zinc deficiency Dietary intake rather than supplement is advised whereas for treatment of zinc deficiency, Zn supplementations are preferred.

Zionc supplementations are indicated in the prevention and treatment of zinc deficiency.