Phar 722 Pharmacy Practice III

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Phar 722Pharmacy Practice III

• Trace Elements-
• Zinc
• Spring 2006

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Zinc Learning Objectives

• Know the uptake, distribution and excretion of
  zinc.
• Know the bioavailability of dietary zinc.
• Know the biodistribution of zinc.
• Know the biochemical functions of zinc.
• Know the causes and symptoms of zinc deficiency.
• Know the symptoms of zinc toxicity.
• Know the current efficacy of zinc supplements in
  certain diseases discussed in class.
• List the common side effects of oral zinc
  therapy.
• Know the RDAs for adults and ULs for children and
  adults.

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Zincs Three Biochemical Roles-1

• Catalytic Role
• Structural Role
• Regulatory Role

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Zincs Three Biochemical Roles-2

• Catalytic Role
• Over 100 specific zinc metalloenzymes depend on
  zinc for catalytic activity including
• Alcohol dehydrogenase
• Ribonucleic acid polymerases
• Carbonic anhydrase
• Alkaline phosphatase
• Carboxypeptidase
• Glutamic dehydrogenase
• Lactic dehydrogenase
• Mechanism
• Zinc is a Lewis acid accepting electrons
  (different from oxidation-reduction reactions)

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Zincs Three Biochemical Roles-3

• Structural Role
• Coordinates with electron rich amino acid side
  chains of proteins stabilizing tertiary and
  quaternary structure.
• Copper-zinc superoxide dismutase
• Copper is the cofactor in the oxidation-reduction
  reaction and zinc stabilizes tertiary structure.
• Intracelluar binding of tyr kinase to T-cell
  receptors.
• Coordination with cys and his residues produces
  zinc finger-like structure.
• Zinc fingers are important regulators of DNA
  binding transcription factors.

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Zincs Three Biochemical Roles-4

• Regulatory Role
• This function is poorly understood. Examples
  include
• Regulator of gene expression possibly by changes
  in binding to transcription factors.
• Zinc transporter proteins
• Metallothionein gene producing a metalloprotein
  that regulates zinc trafficking.
• Apoptosis
• Protein kinase C activity
• Cell signaling

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Uptake, Utilization Excretion-1

• Dietary zinc is bound in metalloproteins (see
  previous slides).
• The digestive process frees it
• It then becomes bound to endogenous proteins
  found in the intestinal lumen.
• There is active transport in the jejunum.
• Zinc transport speeds up in states of zinc
  depletion.
• The human body contains about 2 gm zinc.
• Over 85 of these 2 gm is in skeletal muscle and
  bone.
• 0.1 of total zinc (10 15 µmol/L) in plasma.

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Uptake, Utilization Excretion-2

• Zinc apparently uses the same transport systems
  as other divalent cations.
• Iron supplements might lower the percent of zinc
  absorbed.
• Zinc supplements might lower the percent of
  copper absorbed.
• Zinc elimination is by secretion into the
  intestine followed by excretion in the feces.

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Zinc Deficiency

• Symptoms do not correlate with zincs biochemical
  roles.
• Depressed growth
• Delayed sexual maturation
• Immune dysfunction
• Diarrhea
• Altered cognition
• Defects in carbohydrate utilization
• Causes
• Intestinal disease
• Sprue, Crohns Disease, short bowel syndrome
• Eating grains high in phytic acid (inositol
  hexaphosphate)
• May be an important consideration for strict
  vegetarians who concentrate on grains.
• NOTE There is no agreed-upon clinical test for
  zinc
• status.

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Zincs Possible Role in Treatment of Disease-1

• Common Cold
• The results of zinc lozenges are mixed.
• There is risk of overdosing if these lozenges are
  used for prolonged periods (6-8 weeks).
• Zinc is an astringent and may irritate the mound
  and GI tract.
• Age-related macular degeneration.
• Three is no evidence that zinc either causes or
  reduces the risk of this disease.
• There are ongoing trials of anti-oxidant vitamins
  and selenium.
• Diabetes mellitus
• Zinc does affect glucose metabolism.
• Patients with diabetes taking zinc supplements
  should carefully monitor their blood-glucose
  levels.

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Age-Related Macular Degeneration
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Zincs Possible Role in Treatment of Disease-2

• Wound healing
• This claim has been made for nearly 40 years.
• There have been recommendations that zinc
  supplements hastens healing of bed sores and
  other forms of skin ulcerations.
• Immune system
• Zinc is required for a proper immune response.
• There is some evidence that HIV/AIDS patients may
  benefit from zinc supplements.
• For these studies, it is important to check on
  the nutritional status of HIV/AIDS patients.
• Otherwise, the results are mixed that zinc
  facilitates the immune response.

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Zinc Toxicities

• Zinc is a potent astringent.
• Acute Symptoms
• Many of the symptoms probably caused by zincs
  astringent properties.
• Epigastric pain
• Nausea
• Vomiting
• Abdominal cramps
• Diarrhea
• Chronic Symptoms
• Zinc competes with other metals at the transport
  sites.
• Suppression of immune response
• Decrease in HDL
• Decrease in copper levels

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Dosages Forms

• Zinc acetate
• Zinc gluconate
• Zinc picolinate
• No evidence that the zinc in this salt is more
  bioavailable.
• Zinc sulfate
• Zinc oxide

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Dietary Reference Intakes-1

• AI
• Infants (0-6 months) 2.0 mg/day
• EAR
• Infants (7-12 months) 2.5 mg/day
• Children (1-3 years) 2.5 mg/day
• Children (4-8 years) 4 mg/day
• Children (9-13 years) 7 mg/day
• Boys (14-18 years) 8.5 mg/day
• Girls (14-18 years) 7.3 mg/day
• Men (19-70 years) 9.4 mg/day
• Women (19-70 years) 6.8 mg/day
• Pregnancy (14-18 years) 10.0 mg/day
• Pregnancy (19-50 years) 9.5 mg/day
• Lactation (14-18 years) 10.9 mg/day
• Lactation (19-50 years) 10.4 mg/day

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Dietary Reference Intakes-2

• RDA
• Infants (7-12 months) 3 mg/day
• Children (1-3 years) 3 mg/day
• Children (4-8 years) 5 mg/day
• Children (9-13 years) 8 mg/day
• Boys (14-18 years) 11 mg/day
• Girls (14-18 years) 9 mg/day
• Men (19-70 years) 11 mg/day
• Women (19-10 years) 8 mg/day
• Pregnancy (14-18 years) 12 mg/day
• Pregnancy (19-50 years) 11 mg/day
• Lactation (14-18 years) 13 mg/day
• Lactation (19-50 years) 12 mg/day

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Dietary Reference Intakes-3

• UL
• Infants (0-6 months) 4 mg/day
• Infants (7-12 months) 5 mg/day
• Children (1-3 years) 7 mg/day
• Children (4-8 years) 12 mg/day
• Children (9-13 years) 23mg/day
• Boys (14-18 years) 34 mg/day
• Girls (14-18 years) 34 mg/day
• Men (19-70 years) 40 mg/day
• Women (19-70 years) 40 mg/day
• Pregnancy (14-18 years) 34 mg/day
• Pregnancy (19-50 years) 40 mg/day
• Lactation (14-18 years) 34 mg/day
• Lactation (19-50 years) 40 mg/day

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Dietary Sources

• Shellfish
• Beef and other red meats
• Nuts and legumes
• The zinc in leavened whole grain breads is more
  bioavailable.
• Yeast consumes some of the phytic acid.