1. Phar 722 Pharmacy Practice III Trace Elements- Magnesium Spring 2006

2. 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.

3. Magnesium’s Biochemical Roles-1 Catalytic Role Structural Role Regulatory Role

4. Magnesium’s 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

5. Magnesium’s 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.

6. Magnesium’s 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)

7. 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.

8. 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.

9. 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.

10. 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.

11. Magnesium’s 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.

12. Magnesium’s 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

13. Dosages Forms Magnesium oxide Magnesium gluconate Magnesium chloride Magnesium citrate Magnesium aspartate Magnesium hydroxide

14. 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.

15. 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

16. 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

17. 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.

18. Dietary Sources Wide variety of plants and animal tissues. –Magnesium replaces iron in the heme ring of chlorophyll.