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Counseling Your Patients On Drug Induced Nutritional Depletion and Vitamin SupplementationSponsored by Ortho Molecular Products, Inc.

Jeff Robins, RPh, FAAFRM

Jeff Robins, RPh, FAAFRM is the owner of Summit Functional Consulting. The conflict of interest was resolved by peer review of the slide content.

Disclosure

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• Apply course information to pharmacy patient database to identify patients with potential issues.

• Discuss prescription/OTC drug induced nutritional depletion with patients and recommend supplements.

• Create a plan to allow time, space, and manpower to counsel patients on their potential nutrient deficiencies.

• Counsel patients seeking wellness supplements on usage and interactions.

Learning Objectives

Courtesy of Linus Pauling Institute Oregon State University

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Courtesy of Linus Pauling Institute Oregon State University

• Patient presents with symptoms and is started on a medication.

• Medication helps with original symptoms• DIND starts to have effect on patients body-

insidious• Over weeks, months or years patient develops

another set of symptoms or out right disease state due to DIND.

• Patient returns to physician with new symptoms, and is started on another drug.

• Entire process may start all over again.

Etiology of A Drug-Induced Nutritional Deficiency

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• Inhibition of nutrient absorption.• Inhibition of nutrient synthesis.• Alterations in transport of nutrients across

membranes.• Increase or decrease in metabolism of

nutrients.• Increase or decrease in excretion of nutrients.• Alteration in the body’s ability to store nutrients.

How Drug-Induced Nutritional Deficiencies Develop

• Antacids• Antibiotics• Anticonvulsants• Antidiabetics• Antifungals• Anti-inflammatory drugs• Antivirals• Bronchodilators

Drug Classes that May Cause DIND

• Decongestants• Cardiovascular drugs• Cholesterol-Lowering drugs• Electrolyte Replacements• Female Hormones• Oral contraceptives• Laxatives• Psychotherapeutic drugs• Ulcer medications

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Cardiovascular Drugs

Medication Class and Name Example

Statins atorvastatin (Lipitor), Fluvastatin (Lescol), lovastatin (Mevacor, Altocor), pravastatin (Pravachol), rosuvastatin(Crestor), simvastatin (Zocor)

Nutrient Depleted

Co Enzyme Q10

Symptoms of Depletion

Congestive heart failure, high blood pressure, angina, mitral valve prolapse, cardiac, arrhythmias, lack of energy, muscle pain and weakness. Generalized weakening of the immune system.



ACE Inhibitors captopril (Capoten), enalapril (Vasotec), lisinopril (Prinivil, Zestril), quinapril (Accupril), ramipril(Altace)

Nutrient Depleted

Zinc


Acne, impaired sense of smell and taste, delayed wound healing, decreased immunity, frequent infections, depression, night blindness, problems with hair, skin and nails, component of insulin, needed for thyroid conversion of T4‐>T3.

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Cardiovascular DrugsMedication Class and Name Example

Beta Blockers atenolol (Tenormin), metoprolol (Lopressor, Toprol XL), nadolol (Corgard), carvedilol (Coreg)

Nutrient Depleted

Co Enzyme Q10


Congestive heart failure, high blood pressure, angina, mitral valve prolapse, cardiac arrhythmias ,lack of energy, muscle pain and weakness. Generalized weakening of the immune system.



Calcium Channel Blockers amlodipine (Norvasc), felodipine (Plendil), nifedipine (Procardia, Adalat), nimodipine(Nimotop), nisoldipine (Sular)

Nutrient Depleted

Vitamin D


Bone Loss, osteopenia, osteoporosis, muscle weakness, gradual loss of hearing, Leaky gut syndrome‐> allergies, and autoimmune problems.

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Cardiac Glycosides digoxin (Lanoxin, Digitek)

Nutrient Depleted

Magnesium, Potassium


Magnesium is used in over 300 enzymatic processes in the body, muscle cramps, weakness, insomnia, loss of appetite, GI disorders, kidney stones, osteoporosis, nervousness, restlessness, depression, anxiety, confusion, fatigue, HBPPotassium‐Irregular heart beat, edema, muscle weakness, fatigue, dizziness, confusion



Potassium Supplements potassium chloride (Klor‐Con)

Nutrient Depleted

Vitamin B12


Fatigue, Peripheral neuropathy, tongue and mouth irregularities, macrocytic anemia, depression, confusion, memory loss, easy bruising, dermatitis, loss of appetite

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Diuretic DrugsMedication Class and Name ExampleLoop Diuretics bumetanide (Bumex), furosemide (Lasix)Thiazide Diuretics chlorthalidone indapamide(Lozol), hydrochlorothiazide methyclothiazidePotassium Sparing Diuretics Amiloride hydrochloride, spironolactone (Aldactone), triamterene (Dyrenium)

Nutrient Depleted

B1, B6, Vitamin C, Calcium, Magnesium, Zinc, Potassium Magnesium, B1, B6, Phosphorous, Potassium, Zinc, Coenzyme Q10

Calcium, Magnesium

Symptoms of DepletionPhosphorous is essential for building soft tissue (phospholipids), creating cellular energy (ATP), coenzyme for enzymatic processes, acts as buffer, needed for cellular and protein synthesisVit B1‐ depression, memory loss, muscle weakness, confusion, fatigue, nerve inflammation, rapid pulse rate

Antidiabetic Drugs


Biguanidesmetformin (Glucophage)

Nutrient Depleted

Folic Acid, Vit B12


Folic‐Megaloblastic anemia, birth defects, cervical dysplasia, elevated homocysteine, headache, fatigue, hair loss, increased infections.B12‐Fatigue, Peripheral neuropathy, tongue and mouth irregularities, macrocytic anemia, depression, confusion, memory loss, easy bruising, dermatitis, loss of appetite

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Antidiabetic DrugsMedication Class and Name Example

Sulfonylureas glyburide (Diabeta, Glynase, Micronase),glipizide (GlipiZIDE XL, Glucotrol), glimepiride (Amaryl)

Nutrient

Healthy Intestinal Bacteria, Coenzyme Q10


Healthy bacteria‐ Gas, bloating, constipation, diarrhea, chronic yeast infections, bad breath, decrease immune response, depression, anxiety.CoQ10‐Congestive heart failure, high blood pressure, angina, mitral valve prolapse, cardiac, arrhythmias, lack of energy, muscle pain and weakness. Generalized weakening of the immune system.

Antacids/ Antiulcerative DrugsMedication Class and Name Example

H2 Inhibitors famotidine (Pepcid), cimetidine (Tagamet), ranitidine (Zantac) Proton‐pump inhibitors omeprazole (Prilosec, Zegerid), lansoprazole (Prevacid), esomeprazole (Nexium), rabeprazole(Aciphex) Antacids Amphojel, Basaljel, Aluminum Hydroxide plus Magnesium, (Gaviscon‐2, Gelusil, Maalox, Mylanta)

Nutrient

Folic Acid, B12, Vitamin D, Calcium, Iron, Zinc

Beta‐Carotene, B12, Folic Acid, Calcium, Zinc, Iron

Folic Acid, Vitamin D, Zinc, Calcium, Magnesium, Chromium, Iron


Iron‐ Anemia, thyroid disorder, weakness, fatigue, hair loss, brittle nails, frequent infections.

Beta‐carotene‐Weaker immune system, increase risk of cancer, night blindness, Xerophthalmia, dry rough skin.

Calcium‐ muscle cramps, heart palpitations, HBP, brittle and soft bones, insomnia, leg and back pain.

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Osteoporosis DrugMedication Class and Name Example

Bisphosphonates alendronate (Fosamax), risedronate (Actonel), ibandronate (Boniva), etidronate (Didronel), zoledronic Acid (Reclast)

Nutrient

Calcium, Magnesium


Calcium‐muscle cramps, heart palpitations, HBP, brittle and soft bones, insomnia, leg and back pain. Magnesium is used in over 300 enzymatic processes in the body, muscle cramps, weakness, insomnia, loss of appetite, GI disorders, kidney stones, osteoporosis, nervousness, restlessness, depression, anxiety, confusion, fatigue, HBP

Antibiotic DrugsMedication Class and Name Example

Antibiotics Levaquin, Avelox, Ciprofloxacin, Noroxin, Trovan, Amoxicillin, Amoxil, Trimox, Penicillin, Erythromycin, Azithromycin, Biaxin, Zithromax

Nutrient

Biotin, B1, B2, B3, B6, B12, Zinc, Calcium, Magnesium, Potassium, Vitamin K, Healthy Intestinal Bacteria


Biotin ‐Hair loss, B1‐depression, irritability, confusion, muscle weakness, nerve inflammation, numbness, memory loss, B2‐ dry itchy skin, cheilosis, reddening tearing burning of eyes,B6‐Depression, insomnia, PMS, Elevated homocysteine, lethargy

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Hormone DrugsMedication Class and Name Example

Conjugated Estrogens Premarin, Prempro, Estrace

Bio‐Identical Hormones Estradiol, Estriol, Estrone

Oral Contraceptives

Nutrient

B6, B12, Vitamin D, Calcium, Magnesium, Zinc, Folic Acid


Depression, low energy, low libido, osteopenia, osteoporosis, insomnia, more illnesses, low blood count, heart palpitations, weight gain

Narcotic/Analgesic DrugsMedication Class and Name Example

NSAIDS aspirin, celecoxib (Celebrex), diclofenac (Voltaren), ibuprofen (Motrin), ketorolac (Toradol), naproxen (Aleve, Naprosyn) Opiates hydrocodone (Vicodin), morphine (MS Contin, Kadian), oxycodone (Oxycontin, Percocet)

Nutrient

Folic Acid, Vitamin C, Iron, Potassium


Vitamin C‐Capillary fragility, muscle weakness, tender swollen joints, easy bruising, gums that bleed easily

Folic‐Megaloblastic anemia, birth defects, cervical dysplasia, elevated homocysteine, headache, fatigue, hair loss, increased infections. Potassium‐Irregular heart beat, edema, muscle weakness, fatigue, dizziness, confusion

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Order in product

Make space and time to talk to your patients

How to Get Started with your Patients?

Use product lines that are exclusive to professional practices.

Use products that have a track record of safety.

Use products that are proven to be efficacious.

What Kind of Products to Order?

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Which Products to Order?

Multivitamin‐ Capsule form take twice daily, activated forms of vitamins

CoEnzyme Q 10‐ Bioavailable form.

B‐complex‐ Acitvated form of B vitamins

Probiotics‐Minimum of 10 billion cultures per capsule. Saccharomyces boulardii

Vitamin D3 5000U‐ proven potency

Multi‐mineral supplement‐Bioavailable thru chelating mineral to an amino acid

Pharmacists should be behind the counter only to:

Check prescriptions

Talk to patients on the phone

Talk to other healthcare providers

Create the Time to Talk to Your Patients

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Drug –induced nutritional depletions are real.

Body functions start to break down without vitamins

Replacing nutrient depletions is easy and inexpensive.

Set your pharmacy apart from your competition by meeting your patient’s needs.

Remember

1. Centers for Disease Control and Statistics. Health United States 2006. www.cdc.gov/nchs/data/hus/hus06.pdf#093.

2. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. JAMA 2002;288:2998‐3007.

3. Clayton JA, Rodgers S, Blakey J. Thiazide diuretic prescription and electrolyte abnormalities in primary care. Br J Clin Pharmacol 2006 Jan;61:87‐95.

4. Pak CY. Correction of thiazide‐induced hypomagnesemia by potassium‐magnesium citrate from review of prior trials. Clin Nephrol 2000;54:271‐275.

5. Khedun SM, Naicker T, Maharaj B. Zinc, hydrochlorothiazide and sexual dysfunction. Cent Afr J Med 1995;41:312‐315.

6. Zenuk C, Healey J, Donnelly J, et al. Thiamine deficiency in congestive heart failure patients receiving long term furosemide therapy. Can J Clin Pharmacol 2003;10:184‐188.

7. Kishi T, Watanabe T, Folkers K. Bioenergetics in clinical medicine XV: Inhibition of coenzyme Q10‐enzymes by clinically used adrenergic blockers of beta‐receptors. Res Commun ChemPathol Pharmacol 1977;17:157‐164,

References

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8. Stoschitzky K, Sakotnik A, Lercher P et al Influence of Beta‐blockers on Melatonin Release. Eur J Clin Pharmacol. Apr1999;55(2):111‐15.

9. Langsjoen PH, Langsjoen AM. The clinical use of HMG CoA‐reductase inhibitors and the associated depletion of coenzyme Q10: A review of animal and human publications. Biofactors 2003;18(1‐4):101‐111.

10 Crane FL. Biochemical functions of coenzyme Q10. J Am Coll Nutr2001;20:591‐598.

11. Folkers K, Langsjoen P, Willis R, et al. Lovastatin decreases coenzyme Q levels in humans. Proc Natl Acad Sci U S A 1990;87:8931‐8934.

12. Valuck RJ, Ruscin JM. A case‐control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J Clin Epidemiol 2004;57:422‐428.

References

13. Russell RM, Golner BB, Krasinski SD. Effect of antacid and H2 receptor antagonists on the intestinal absorption of folic acid. J Lab Clin Med 1988;112:458‐463.14. Sturniolo GC, Montino MC, Rossetto L, et al. Inhibition of gastric acid secretion reduces zinc absorption in man. J Am Coll Nutr 1991;10:372‐375.15. Yang, YX, Lewis JD, Epstein S, Metz DC. Long‐term proton pump inhibitor therapy and risk of hip fracture. JAMA 296 (24): 2947‐5316. Zhao‐Wei Ting R, C Chun Szeto, M Ho‐Ming Chan, et al. “Risk factors of vitamin B12 deficiency in patients receiving metformin.” Archives of Internal Medicine Oct 9, 2006: 1975‐1979.17. Wulffele MG, Kooy A, Lehert P, et al. Effects of short‐term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: A randomized, placebo‐controlled trial. J Intern Med 2003;254:455‐463.18. Bottiglieri T. “Folate, vitamin B12 and neuropsychiatric disorders.” Nutrition Review Dec 1996; 54(12): 382‐390.

References

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References19. Bottiglieri T, M Laundy, R Crellin, et al. “Homocysteine, folate, methylation, and monoamine metabolism in depression.” Journal of Neurology, Neurosurgery & Psychiatry Mar 2001; 70(3): 419.

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22. Modi S, Collins J, Relma D, “ Antibiotics and the Gut Microbita”; The Journal of Clinical Investigation Oct 2014; Volume 124 issue 10

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26. Rose D, Strong R, Adams P, Harding P ”Experimental Vitamin B6 Deficiency and the Effect of Oestrogen Containing Oral Contraceptives on Trptophan and Vitamin B6 Requirements Clinical Science; April 1972, 42(4) 465‐477

27. Butterworth C,Hatch K, et al, “Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives”, The American Journal for Clinical Nutrition; april 1982

28.Lindenbaum J, Whitehead N, Reyner F, “Oral contraceptive hormones, folate metabolism, and the cervical epithelium”; The American Journal of Clinical Nutrition; Oct 1975

29. Brown G, Greenwood J,” Drug and nutrition‐induced hypophosphatemia: mechanisms and relevance in the critically ill”; Annals of Pharmacotherapy; May 1994 volume 28 (5) 626‐632

30.Deichmann R, Lavie C, Andrews S,” Coenzyme Q 10 and statin‐induced mitochondrial dysfunction” The Ochsner Journal; Spring 2010 10(1) 16‐21

31.Rao R, Pandurange P, et al Digoxin toxicity with normal digoxin and serum levels: beware of magnesium, the hidden malefactor”; Journal of Emergency Medicine Aug 2013 45(2) 31‐34

References

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32. Andress D, et al “Antiepileptic drug‐induced bone loss in young male patients who have seizures”; JAMA May 2002 volume 59(5)

33.Monteleone P, Maj M, et al “Depressed nocturnal plasma melatonin levels in drug‐free paranoid schizophrenics”; Schizophrenia Research; April 1992, volume 7(1) 77‐84

34. Barringer T, Kirk J, et al “Effect of a multivitamin and mineral supplement infection and quality of life”; Annals of Internal Medicine; March 2003, Vol 138(5)

35. Farhat G, Yamout B, et al “ Effect of ntiepilectic drugs on bone density in ambulatory patients” ;Neurology ; May 2002 vol 58 (9) 1348‐1353.

36. Brewer G, Dressman J, et al “Effect of intagastric pH on theabsoption of oral zinc acetate and zinc oxide in young healthy volunteers” ;Journal of Parenteral and Enteral Nutrition; Sept 1995 vol 19 (5) 393‐397.

37. Marcuard S, Albernaz L, et al “Omeprazole therapy causes malabsorption of cyanocobalamin” Annal of Internal Medicine 1994 vol 12093) 211‐215.

References

38. Djeridane Y, Touitou Y, “Chronis diazepam administration differentially affect melatonin synthesis in rat pineal and harderian glands” Psychopharmacology 2001 vol154 403‐407.

39. Howden C, “Vitamin B12 levels during prolonged treatment with proton pump inhibitors” Journal of Clinical Gastroenterology; Jan 2000 vol30 (1) 29‐33.

40. Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: update regarding thiazolidinediones: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care2008;31:173–175.

41. Bailey CJ, Wilcock C, Scarpello JH. Metformin and the intestine. Diabetologia2008;51:1552–1553.

42. Tomkin GH. Malabsorption of vitamin B12 in diabetic patients treated with phenformin: a comparison with metformin. Br Med J 1973;3:673–675.

43. Ting RZ, Szeto CC, Chan MH, et al. Risk factors of vitamin B(12) deficiency in patients receiving metformin. Arch Intern Med 2006;166:1975–1979

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44. Caspary WF, Zavada I, Reimold W, et al. Alteration of bile acid metabolism and vitamin‐B12‐absorption in diabetics on biguanides. Diabetologia 1977;13:187–193.

45. Schäfer G. Some new aspects on the interaction of hypoglycemia‐producing biguanides with biological membranes. Biochem Pharmacol 1976;25:2014–2024.

46. Bauman WA, Shaw S, Jayatilleke E, et al. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care 2000;23:1227–1231.

47. Eriksson JG, Forsen TJ, Mortensen SA, Rohde M. The effect of coenzyme Q10 administration on metabolic control in patients with type 2 diabetes mellitus. Biofactors. 1999;9(2‐4):315‐318.

48. Folkers K, Morita M, McRee J Jr. The activities of coenzyme Q10 and vitamin B6 for immune responses. Biochem Biophys Res Commun. 1993; 28(19391):88‐92.

49. Kishi T, Kishi H, Watanabe T, Folkers K. Bioenergetics in clinical medicine. XI. Studies on coenzyme Q and diabetes mellitus. J Med. 1976;7(3‐4):307‐321.

50. Artuch R, Colome C, Vilaseca MA, et al. [Ubiquinone: metabolism and functions. Ubiquinone deficiency and its implications in mitochondrial encephalopathies. Treatment with ubiquinone]. Rev Neurol. 1999;29(1):59‐63.

References

51. Pelton R, Lavalle J; The Nutritional Cost of Drugs;Morton Publishing 2004

52. Pelton R, Lavalle J, Hawkins E, Krinsky D; Drug‐Induced Nutrient Depletion Handbook; Lexi comp inc 2001

References

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Thank You!

Jeff Robins RPh, FAAFRMSummit Functional Consulting

[email protected]#309-453-4660

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