Zinc Sulfate Injection

General Information

After iron, zinc it the second most abundant trace element in the human body. It is a divalent cation and the 30th element as well as the first element in group 12 of the periodic table. It is an essential micronutrient that plays a key role in the catalysis of over 100 enzymes such as alkaline phosphatase, lactic dehydrogenase, and RNA and DNA polymerase. It assists in the synthesis of RNA and DNA, cell proliferation and differentiation, and the stabilization of cell membranes and cell structures. Zinc exerts its gene regulatory and expressive effects through the formation of zinc finger proteins (ZnF).

The Role of Zinc in the Human Body

Zinc also plays a role in the regulation of the immune system. Being an essential element, it is not synthesized by the human body but must be ingested through food or mineral supplements. Some of the common food sources of zinc include beef, poultry, seafood, and grains, among others. In adults, normal serum zinc levels are between 70 and 250 ug/dl. After oral ingestion, zinc absorption occurs mainly in the ileum and duodenum and its binds to plasma proteins such as albumin in the blood. Following its metabolism, it is excreted mainly in the stool; some metabolites are also excreted in the urine and sweat, but to a significantly lower extent.

Administration Methods of Zinc

Zinc is usually clinically administered in the form of zinc sulfate as a supplement. The most common routes of administration of zinc sulfate are oral and parenteral. Exogenous zinc administration is typically indicated in the management of zinc deficiency.

Symptoms of Zinc Deficiency

With zinc playing a significant role in many of the body’s key processes, zinc deficiency can result in a variety of illnesses and medical disorders. Some of the clinical manifestations include, but are not limited to, the following:

• Hair and weight loss.
• Delayed wound healing and skin lesions such as oral lichen planus, pemphigus vulgaris, bullous pemphigoid, and epidermodysplasia verruciformis, among others.
• Decreased taste sensation and loss of appetite.
• Altered cognitive and motor performance in neonates and infants.
• Increased susceptibility to infections due to decreased functionality in monocytes, neutrophils, granulocytes, and phagocytosis.
• Exacerbation of hypertension as well as other cardiovascular diseases.
• Delayed puberty and growth retardation in adolescents.
• Osteoporosis as well as other abnormalities in bone mineralization and development.
• Decreased folate absorption which may result in macrocytic megaloblastic anemia.
• Mental lethargy and mood disorders.

Mechanisms of Action

With zinc playing a prominent role in many major processes within the human body, its mechanism of action varies depending on the organ system as well as the relevant process involved.

Immune System and Anti-Inflammation

In the immune system, zinc functions as a second messenger for immune cells; intracellular zinc participates in signaling events in immunity. It is involved in the development of monocytes and macrophages and regulates macrophagic functions such as phagocytosis and the production of proinflammatory cytokines. Zinc also inhibits phosphodiesterase, resulting in increased levels of guanosine-3′ 5′- cyclic monophosphate which leads to the suppression of Tumor Necrosis Factor alpha (TNF-a), interleukin-1 beta (IL-1B), as well as other inflammatory cytokines. Additionally, zinc increases the expression of peroxisome proliferator-activated receptor- alpha; this results in the downregulation of inflammatory cytokines and adhesion molecules. Due to these and several other actions in the immune system, zinc is considered to be a key anti-inflammatory agent in the human body.

Zincs Effect on Skin

In the skin, zinc exerts its effects through several means in the development and maintenance of the skin cells. Zinc is most concentrated in the stratum spinosum layer of the skin compared to the other three layers namely basal layer, stratum granulosum, and stratum corneum. Studies have shown that zinc facilitates the proliferation as well as the survival of keratinocytes in the stratum spinosum; it also suppressed the activation of interferon-gamma and tumor necrosis factor-alpha by these keratinocytes. Additionally, zinc plays an active role in the development of Langerhans cells, a type of antigen-presenting cells, within the skin. Furthermore, the expression of melanocytes in the human skin is facilitated by zinc through mechanisms that are not yet fully understood.

Central Nervous System

In the central nervous system, zinc is essential in the formation and development of the growth factors, hormones, enzymes, and proteins during neurodevelopment; mild zinc deficiency during pregnancy has been shown to result in learning and memory abnormalities. Zinc helps in the development of the neural tube, the first brain structure that develops during pregnancy, the neural crest, and the process of stem cell proliferation during neurogenesis. Furthermore, free zinc is found in synaptic vesicles where it acts to modulate a variety of postsynaptic receptors; in the synaptic cleft it reduces the inhibitory actions of GABA receptors. Free zinc also exerts inhibitory actions on the release of glutamate, an excitatory neurotransmitter.

Pharmacokinetics

Zinc can be administered orally or parenterally as an intravenous solution. For intravenous administration, zinc should be diluted in sterile water. After oral ingestion, about 20 to 23% of zinc is absorbed from the duodenum and ileum. The amount of zinc absorbed within the gastrointestinal system is dependent on its bioavailability. The bioavailability of zinc, which is the fraction of total zinc intake that can be absorbed and used by the body, is dependent on three factors:

• The availability of soluble zinc from the ingested food
• The total zinc content of the ingested food
• The zinc status of the individual

Other ingested foods can have an impact on the amount of zinc absorbed from the intestines. Phytates, which are negatively charged substances and found in food sources such as cereals and legumes, bind with zinc which is a positively charged cation. By strongly binding with zinc, phytates prevent the absorption of zinc from the intestine. Additionally, some studies have shown that high doses of inorganic iron in the diet can also reduce the bioavailability of zinc in the diet. In contrast, proteins have a positive effect on oral zinc bioavailability. Eating foods such as beef, eggs, and cheese enhances the absorption of zinc from the intestines.

After intestinal absorption, zinc is bound to the protein metallothionein. It is also bound to plasma proteins such as albumin and alpha-2-macroglobulin. It is then transported throughout the body and stored in a variety of locations such as red blood cells, white blood cells, muscles, bones, skin, kidneys, liver, pancreas, and prostate. Following its metabolism, zinc is excreted primarily in stool and, to a much lesser extent, in urine and sweat.

Contraindications/Precautions

While exogenous zinc supplements are generally well tolerated, there are some situations or circumstances that may warrant some degree of caution before it is administered. These include:

• Renal impairment: Care should be exercised when administering zinc to individuals with renal compromise. As zinc is excreted in the urine, renal disease may impair its excretion in the urine and increase the likelihood of developing zinc toxicity.
• Hypersensitivity reactions: Individuals may be hypersensitive to additional substances in the zinc supplement. Individuals with demonstrated hypersensitivity to any of the additional substances should not receive exogenous zinc supplements.
• Drug interactions: Zinc is known to interact with a variety of other medications which may impair their efficacy. Extreme care should be exercised when administering zinc to individuals taking other medications at the same time. Some medications that have the potential to interact with exogenously administered zinc are quinolones, tetracyclines, and penicillamine; zinc inhibits the absorption of these medications from the intestine. Also, thiazide diuretics, when given concurrently with zinc, increases the renal excretion of zinc and may also deplete zinc levels in the tissue. It may be necessary to monitor serum zinc levels when administered in conjunction with other medications.

Pregnancy/Breastfeeding

Exogenous zinc sulfate has been assigned to the pregnancy category C by the Food and Drug Administration. Though there is the possibility of fetal harm, the likelihood of this occurring is very remote. Zinc can be used in pregnancy since the dangers of zinc deficiency is substantially greater than any risks that may occur from its administration. Zinc crosses the placenta to the fetus where it plays a role in fetal neurodevelopment, as previously stated. Additionally, zinc also crosses from nursing mothers to infants through breast milk during lactation.

Adverse Reactions/Side Effects

Apart from the likelihood of developing hypersensitivity reactions to exogenous zinc, the common adverse effect to watch out for is zinc toxicity. This may occur through an increased ingestion of zinc or a reduced excretion. Toxic levels of zinc in the human body is typically associated with a marked decrease in serum copper levels. Some of the clinical features that may arise as a result of zinc toxicity are hematemesis, hematuria, acute tubular necrosis, sideroblastic anemia, granulocytopenia, diarrhea, and myelodysplastic syndrome, among others. If zinc toxicity occurs, the exogenous administration of zinc should be discontinued immediately, and measures should be initiated to bring the zinc levels back down within normal ranges.