Phar 722 Pharmacy Practice III

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Phar 722Pharmacy Practice III

• Trace Elements-
• Magnesium
• Spring 2006

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Magnesium Learning Objectives

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

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Magnesiums Biochemical Roles-1

• Catalytic Role
• Structural Role
• Regulatory Role

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Magnesiums Biochemical Roles-2

• Catalytic Role
• Over 300 specific magnesium metalloenzymes depend
  on magnesium for catalytic activity including
• Anaerobic energy generation
• Aerobic energy generation
• Synthesis of DNA and RNA
• Synthesis of carbohydrates and lipids
• Synthesis of glutathione

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Magnesiums Biochemical Roles-3

• Structural Role
• Forms a chelate with di- and tri-phosphates
  stabilizing their structures and shape for
  subsequent reactions.
• Component of bone, cell membranes and chromosomes.

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Magnesiums Biochemical Roles-4

• Regulatory Role
• Necessary for sodium, potassium-ATPase activity.
• Regulates potassium transport.
• Active transport of potassium and calcium across
  cell membranes.
• Conduction of nerve impulses
• Muscle contraction
• Cardiac rhythm
• Cell signaling
• Phosporylation of proteins
• Formation of cAMP (cyclic AMP)

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Magnesium Distribution

• Magnesium body content is approximately 25 gm
  (1,000 mmole).
• 50-60 is in bone.
• 33 of this magnesium is exchangeable and may
  serve as a reservoir to maintain magnesium
  homeostasis.
• Approximately 27 is in muscle
• 6-7 in other cells
• 1 found outside of cells
• (Other 5-6 not accounted for)
• Magnesium transport into and out of cells
  requires a carrier-mediated transport system.
• Efflux from the cell is coupled to sodium
  transport and requires energy.
• Influx into the cell appears linked to sodium and
  bicarbonate transport systems.

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Uptake and Excretion

• There is active transport across the intestinal
  mucosa.
• Interaction with other nutrients
• Zinc in supplement form can interfere with
  absorption of magnesium
• Large amounts of fiber can interfere with
  magnesium uptake
• Clinical significance is ambiguous.
• Protein may improve magnesium absorption.
• Low magnesium uptake parallels low protein
  intake.
• Subjects may be malnourished in other dietary
  components.
• The kidneys control magnesium excretion.

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Magnesium Deficiency-1

• Deficiency in healthy individuals is rare because
  magnesium is abundant in both plants and animal
  tissues.
• Deficiencies usually are disease or life-style
  related.
• Chronic inflammation of the intestinal tract.
• Renal disorders
• Loss of regulation of excretion at the kidney
• Chronic alcoholism
• A common cause of magnesium deficiency
• Gastrointestinal problems
• Poor dietary intake
• Increased urinary loss of magnesium
• Age
• May parallel decreased absorption of nutrients
  sometimes seen with aging.

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Magnesium Deficiency-2

• Symptoms
• Most are the result of experimentally induced
  deficiencies.
• Decreased parathyroid secretion
• Hypocalcemia
• Hypokalemia
• Sodium retention
• Tremor, muscle spasms, tetany
• There is a magnesium tolerance test based on
  magnesium excretion following parenteral
  administration of a loading dose of magnesium.

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Magnesiums Possible Role in Treatment of
Disease-1

• Hypertension
• May be beneficial
• Other nutrients found with magnesium.
• Intervention with magnesium supplements has been
  mixed.
• Preecclampsia-eclampsia (toxemia of pregnancy).
• IV magnesium sulfate has been the treatment of
  choice for preventing eclamptic seizure late in
  pregnancy or during labor.
• Myocardial infarction (MI)
• Use of IV magnesium sulfate in acute MI is
  controversial.
• Diabetes mellitus
• No definitive studies that magnesium supplements
  improve glucose tolerance.

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Magnesiums Possible Role in Treatment of
Disease-2

• Migraine headaches
• Mixed results from magnesium supplements
• Asthma
• No known value from oral supplements.
• Adverse reactions from magnesium supplements.
• Diarrhea
• Magnesium salts are used in laxatives.
• Milk of Magnesia
• Magnesium citrate

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Dosages Forms

• Magnesium oxide
• Magnesium gluconate
• Magnesium chloride
• Magnesium citrate
• Magnesium aspartate
• Magnesium hydroxide

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Drug Interactions

• Magnesium supplements interfere with the
  absorption of
• Digoxin
• Nitrofurantoin
• Certain anti-malarial drugs
• Bisphosponates
• Chlorpromazine
• Tetracyclines
• Penicillamine
• Separating the drug and supplement by about two
  hours can minimize the interaction.

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Dietary Reference Intakes-1

• AI
• Infants (0-12 months) 30-45 mg/day
• EAR
• Children (1-3 years) 65 mg/day
• Children (4-8 years) 110 mg/day
• Children (9-13 years) 200 mg/day
• Boys (14-18 years) 340 mg/day
• Girls (14-18 years) 300 mg/day
• Men (19-30 years) 330 mg/day
• Women (19-30 years) 255 mg/day
• Men (31-70 years) 350 mg/day
• Women (31-70 years) 265 mg/day
• Pregnancy (14-18 years) 335 mg/day
• Pregnancy (19-30 years) 290 mg/day
• Pregnancy (31-50 years) 300 mg/day
• Lactation (14-18 years) 300 mg/day
• Lactation (19-30 years) 255 mg/day
• Lactation (31-50 years) 265 mg/day

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Dietary Reference Intakes-2

• RDA
• Children (1-3 years) 80 mg/day
• Children (4-8 years) 130 mg/day
• Children (9-13 years) 240 mg/day
• Boys (14-18 years) 410 mg/day
• Girls (14-18 years) 360 mg/day
• Men (19-30 years) 400 mg/day
• Women (19-30 years) 310 mg/day
• Adults (31 years) 320 mg/day
• Pregnancy (14-18 years) 400 mg/day
• Pregnancy (19-30 years) 350 mg/day
• Pregnancy (31 years) 360 mg/day
• Lactation (14-18 years) 360 mg/day
• Lactation (19-30 years) 310 mg/day
• Lactation (31 years) 320 mg/day

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Dietary Reference Intakes-3

• UL
• Infants (0-12 months) Not established
• Children (1-3 years) 65 mg/day
• Children (4-8 years) 110 mg/day
• Children (9-13 years) 350 mg/day
• Adolescents (14-18 years) 350 mg/day
• Adults (19 years) 350 mg/day
• These are the levels prior to the appearance of
  laxative activity.

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Dietary Sources

• Wide variety of plants and animal tissues.
• Magnesium replaces iron in the heme ring of
  chlorophyll.