Drug – Nutrient Interactions:

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vA Drug - Nutrient interaction occurs when a drug causes Malabsorption, Depletion or Retention of a nutrient.

vDrug - Nutrient interaction results in to either deficiency or toxicity of nutrients.

vThe absorption of vitamins and minerals is lowered by the use of laxatives.

vBile Acid Sequestrants such as Cholestyramine and Colestipol reduce the absorption of fat-soluble vitamins A, D, E, and K due to removal of bile acids.

vOral Contraceptives can lower the levels of vitamin B6 and folate in the body.

vDiuretics can (Furosemide, Hydrochlorothiazide ) increase the excretion of minerals through urine.

vThe levels of micronutrients like Vitamins and Minerals are affected by certain medications.

DRUG – VITAMINS Interactions

vThe drugs like Oral contraceptives, Isoniazid, Hydralazine and Penicillamine reduce the level of Vitamin B6 (Pyridoxine).

vThe absorption of Vitamin B12 may be affected by the drugs such as Colchicine, Cimetidine, Famotidine and Nizatidine.

vThe drugs like Methotrexate and Barbiturates may cause malabsorption of Folate.

vThe level of Vitamin C could be reduced by Salicylates and Tetracyclines.

vThe Retinoids (Isotretinoin and Acitretin) interact with Vitamin A (Supplement) and increase the risk of toxicity (Nausea, Vomiting, Dizziness, Blurred vision, Poor muscle coordination).

vThe absorption of vitamin A might be decreased by Neomycin.

vBile Acid Sequestrants such as Cholestyramine and Colestipol reduce the absorption of fat-soluble vitamins A, D, E, and K due to removal of bile acids.

vDicumarol inhibits hypoprothrombin activity of Vitamin K.

DRUG – MINERALS Interactions

vThe serum sodium levels could be decreased by drugs such as Diuretics (Thiazides and loop), ACEIs, Li, TCAs, SSRIs, MAOIs, Opioids, Sulfonylureas, Clofibrate, Antineoplastic agents (Cisplatin), Vasopressin and Oxytocin.

vThe drugs like NSAIDs, Estrogens, Corticosteroids and Antacids with NaHCO3 may increase the risk of sodium retention.

vThe risk of hypokalemia may be increased by the drugs like Diuretics (Thiazides and loop), Amphotericin B, Bronchodilators (Terbutaline, Albuterol), Aminoglycosides (Gentamycin, Tobramycin), Corticosteroids, Digoxin, Laxatives, Li, Ethanol and Aspirin.

vThe drugs such as Potassium- sparing diuretics (Triamterene, Amiloride, Spiranolactone), Beta blockers (Atenolol, Betaxolol, Labetalol), ACEIs, ARBs and NSAIDs may increase the risk of hyperkalemia.

vHypocalcemia might be induced by drugs such as Loop diuretics, Triamterene, Aminoglycosides, Corticosteroids, Indomethacin, Thyroid hormones and Aluminium containing antacids due to increased calcium elimination.

vMalabsorption of calcium could be induced by drugs like Bile acid sequestrants (Cholestyramine, Colestipol), Corticosteroids (Prednisone), Antibiotics (Minocycline, Erythromycin, Neomycin) and Sulfonamides.

vThe drugs such as NSAIDs, Estrogens, Corticosteroids and Antacids with NaHCO3 may increase the risk of Hypercalcemia by inducing calcium retention.

vThe elimination of phosphorous and the risk of hypophosphatemia might be increased by drugs such as Antacids, Albuterol, Indomethacin, Cisplatin and Sucralfate.

vThe risk of hypomagnesemia may be elevated by the administration of drugs like Diuretics (Loop and thiazides), Albuterol, Amphotericin B, Cyclosporine, INH, Corticosteroids, Digoxin, Oral contraceptives and Ethanol.

vColchicine and overuse of laxatives may produce malabsorption of Magnesium.

vThe risk of hypermagnesemia may be increased by the drugs such as Laxatives (Epsom salts, Aluminium magnesia), Potassium sparing diuretics and Estrogens.

vThe serum levels of Iron might be decreased by drugs like Aspirin, NSAIDs, Deferoxamine and Stanozolol.

vThe drugs such as MgOH containing antacids, Cholestyramine, H2 blockers, Tetracyclines, neomycin, Penicillamine and Zinc may induce malabsorption of Iron.

vOral contraceptives may induce the retention of Iron.

v The serum levels of copper might be decreased by the administration of Penicillamine, Zidovudine, Allopurinol or Valproic acid.

vMalabsorption of Copper might be induced by drugs such as Zinc salts, H2 blockers, ACEIs and Ciprofloxacin.

vOral contraceptives may increase the risk of retention of copper.

vThe serum levels of Zinc might be decreased by drugs like Diuretics (Thiazides and loop), ACEIs, Penicillamine, Zidovudine, Tetracycline, Corticosteroids, Aspirin, Ethanol and Oral contraceptives.

vCholestyramine may induce the malabsorption of Zinc.

vThe drugs like Estrogens, Medroxyprogesterone and Methyltestosterone may increase the risk of retention of Zinc.

vGrowing children, Pregnant women, Older adults, Persons on a poor diet, Persons with serious health problems, , Persons taking two or more medications at the same time, Persons using prescription and over-the counter medications together, Persons not following medication directions, Persons taking medications for a long periods of time and Persons who drink alcohol or smoke excessively are all at more risk of developing Drug-Nutrient interactions.

Food – Drug Interactions:

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•        A Food - Drug interaction occurs when a food interferes with the effects of a drug in the body.

•        The content of certain foods interact with some drugs and produce alterations in the Pharmacokinetic (Absorption, Distribution, Metabolism and Elimination) and Pharmacodynamic (Physiologic actions) effects of the drugs.

•        Tyramine rich foods (Aged Cheese) may induce Life-threatening hypertensive reaction by interacting with Non-selective MAOIs (tranylcypromine, phenelzine etc.) or MAO-B Inhibitor (Higher dose of Selegeline). Patients taking any of the non-selective MAOIs should not eat foods containing substantial amounts of tyramine.

•        Dairy Products (Milk) reduce the absorption and therapeutic efficacy of Fluoroquinolones (Ciprofloxacin, Norfloxacin), Tetracyclines and Bisphosphonates (Alendronate, Risedronate, and Ibandronate).

•        Vitamin K Rich Foods (Kale, Collards, Spinach, Turnip greens, Mustard greens, Beet greens, Dandelion greens, Brussels sprouts and Broccoli) may interact with Warfarin and increase the risk of clot formation. Suddenly increasing or decreasing intake of Vitamin K rich foods can alter the effectiveness of the warfarin. So eat greens in consistent amounts. 

•        Potassium Rich Foods may interact with ACEIs (Lisinopril, etc), ARBs (Losartan, etc), Direct Renin Inhibitors (Aliskiren) or Potassium sparing Diuretics (Spiranolactone, etc) and increase the risk of Hyperkalemia.

•        Fiber Rich Foods may interact with Digoxin, Amoxicillin, Levothyroxine or TCAs (Doxepin and Desipramine) and delay their absorption. Avoid ingesting high-fiber foods concomitantly.  

•        Protein Rich Foods may increase the bioavailability of Propranolol.

•        High Fat Meals may elevate the plasma levels of Griseofulvin. Patients should be instructed to take griseofulvin after a high-fat content meal.

•        Fruit juices like Grapefruit juice (GFJ), Apple juice or Orange juice may reduce the therapeutic efficacy of Fexofenadine.

•         Grapefruit juice (GFJ) may interact with CYP3A4 substrates such as Simvastatin, Amiodarone, Erythromycin, Apixaban, etc. and increase the risk of their toxic effects.

•        Seville orange juice may interact with CYP3A4 substrates like Colchicine, etc. and increase the risk of toxic effects.

•        Orange juice may interact with drugs like Fexofenadine, Atenolol or Fluoroquinolones and reduce their therapeutic efficacy.

•        Apple juice may reduce the therapeutic efficacy of Fexofenadine or Atenolol.

•        Licorice may decrease the effectiveness of Antihypertensives such as Amlodipine, Aliskiren, Valsartan, Captopril, Carvedilol, etc. The people with high blood pressure, heart failure, pulmonary hypertension or kidney disease should avoid or limit the consumption of licorice.

•        Fish (Omega-3 fatty acids) may increase the risk of Bleeding by interacting with drugs like Anticoagulant / Antiplatelet drugs (Aspirin, Clopidogrel, Ticlopidine, Dipyridamole, Alteplase, Dalteparin, Enoxaparin, Heparin, warfarin and others). It is recommended to consult the physician when the patients experience any unusual bleeding or bruising, swelling, vomiting, blood in your urine or stools, headache, dizziness, or weakness during treatment with these medications.

•        Pharmacist or physician should determine the clinical relevance of the interactions of drugs with certain foods or beverages and advise patients appropriately.

Drug Interactions of OTC Decongestants:

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ª  Pseudoephedrine is an oral OTC decongestant available commonly.

ª  Oxymetazoline and Xylometazoline are topical OTC decongestants and are available as nasal drops or nasal sprays.

ª  Concomitant use of Pseudoephedrine and
MAO Inhibitors such as Selegiline, Rasagiline, Clorgyline, Pargyline, Toloxatone, Iproniazid, Moclobemide, Nialamide, Procarbazine, Phenelzine , Isocarboxazid, Tranylcypromine, Furazolidone is contraindicated, due to elevated risk of hypertensive crisis characterized by hypertension, hyperpyrexia and headache.

ª  It is contraindicated to use Pseudoephedrine and Linezolid concomitantly, due to increased blood pressure.

ª  Co-administration of Pseudoephedrine and Dihydroergotamine is contraindicated, due to extreme elevation of blood pressure.

ª  The blood pressure control of Guanethidine and Methyldopa is lost due to concomitant use of Pseudoephedrine.

ª  Bitter orange contains synephrine which can interact with Pseudoephedrine and increase the risk of hypertensive crisis.

ª  Topical decongestants (Oxymetazoline or Xylometazoline) increase the risk of hypertensive crisis by interacting with MAO Inhibitors.

ª  Pseudoephedrine should be avoided during pregnancy, if possible.

ª  People with heart disease, high blood pressure, diabetes, hyperthyroidism and enlarged prostate should consult a doctor or pharmacist before they take decongestants because side effects can be dangerous.

ª  Physicians should be aware of potential drug interactions with OTC medicines when prescribing new medications.

ª  Pharmacists can be instrumental in assisting patients with using OTC medications safely and effectively.

ª  Pharmacists should warn consumers of the risks of misusing OTC pain relievers.

Drug Interactions of OTC Antihistamines (Part 2):

Drug Interactions of Second Generation Antihistamines:

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·      Second generation OTC Antihistamines include Loratadine, Cetirizine and Fexofenadine.

·      Amiodarone may elevate the risk of “Torsades de pointes” by blocking CYP3A4 induced metabolism of Loratadine.

·      P-glycoprotein (P-gp) inhibitors such as Tocofersolan, Nilotinib, Lomitapide and Simeprevir block the P-glycoprotein-mediated efflux transport of Fexofenadine and increase the plasma levels of Fexofenadine.

·      Amiodarone also increase the plasma levels of Fexofenadine by blocking CYP enzymes induced metabolism and P-glycoprotein efflux transport of Fexofenadine.

·      Fruit Juices like Grapefruit juice, Orange juice and Apple juice decrease the effectiveness of fexofenadine by inhibiting organic anion transporting polypeptide (OATP).

·       Patients should thoroughly read the labels of all over-the-counter and prescription medicines.

·      Patients should talk to their doctor or pharmacist before taking any new prescription or over the counter medication.

·      Physicians should be aware of potential drug interactions with OTC medicines when prescribing new medications.

·      Pharmacists can be instrumental in assisting patients with using OTC medications safely and effectively.

·      Pharmacists should warn consumers of the risks of misusing OTC pain relievers.

Drug Interactions of OTC Antihistamines (Part 1):

Drug Interactions of First Generation Antihistamines:

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§  First-Generation OTC Antihistamines include Brompheniramine, Chlorpheniramine, Dimenhydrinate, Diphenhydramine, and Doxylamine.

§  The risk of serotonin syndrome (hypertension, hyperthermia, myoclonus, mental status changes) is elevated by the concomitant administration of Brompheniramine or Chlorpheniramine with Antidepressants (SSRIs, SNRIs, TCAs, Trazodone, Vortioxetine, Amoxapine) or serotonergic drugs (Lorcaserin, Almotriptan, Hydroxytryptophan, Fentanyl and Tramadol).

§  Excessive anticholinergic activity (severe dry mouth, constipation, decreased urination, excessive sedation, blurred vision) may resulted due to combination of Chlorpheniramine or Diphenhydramine and drugs having anticholinergic activity (Belldonna, Clomipramine, Amitriptyline, Triflupromazine, amoxapine and Linezolid).

§  Coadministration of Diphenhydramine and Opioids (Hydromorphone, Oxycodone, Hydrocodone, Fentanyl, Tapentadol), Other CNS depressants (Zolpidem, Loxapine, Meclizine, Carbinoxamine) or Ethanol increase the risk of CNS depression.

§  The American Congress of Obstetricians and Gynecologists (ACOG) and the American College of Allergy, Asthma and Immunology (ACAAI) recommend Chlorpheniramine as the antihistamine of choice during pregnancy.

§  According to the World Health Organization, use of chlorpheniramine in nursing mothers should be avoided if possible.

§  Patients should thoroughly read the labels of all over-the-counter and prescription medicines.

§  Patients should talk to their doctor or pharmacist before taking any new prescription or over the counter medication.

§  Physicians should be aware of potential drug interactions with OTC medicines when prescribing new medications.

§  Pharmacists can be instrumental in assisting patients with using OTC medications safely and effectively.

§  Pharmacists should warn consumers of the risks of misusing OTC drugs.

Drug Interactions of OTC Analgesics (Part 5):

Drug Interactions of Naproxen:

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ü Naproxen is a Non-Steroidal Anti-inflammatory drug (NSAID) and is available as an OTC analgesic drug.

ü Naproxen is commonly used for the reduction of pain, fever, inflammation and stiffness caused by conditions including migraine, osteoarthritis, kidney stones, rheumatoid arthritis, psoriatic arthritis, gout, ankylosing spondylitis, menstrual cramps, tendinitis and bursitis.

ü Concomitant use of Ketorolac and Naproxen is contraindicated due to cumulative risks of inducing serious NSAID-related adverse events (peptic ulcers, gastrointestinal bleeding and/or perforation).

ü Bleeding risk is elevated by the coadministration of Naproxen with drugs such as Warfarin, Heparin, Low Molecular Weight Heparins (LMWHs) (Enoxaparin, Dalteparin, Tinzaparin, etc.), Coumarins and other anticoagulants (Acenocoumarol, Dicumarol, Phenprocoumon, Dabigatran, Anisindione, Phenindione), Direct thrombin inhibitors (Dabigatran, Desirudin, Lepirudin, Bivalirudin, Argatroban), Direct factor Xa inhibitors (Apixaban, Rivaroxaban), Antiplatelets (Clopidogrel, Aspirin, Prasugrel, Ticagrelor, Ticlopidine, Dipyridamole, Abciximab, Eptifibatide, Tirofiban), Danaparoid, Fondaparinux, Selective serotonin reuptake inhibitors (SSRIs) (Escitalopram, Fluvoxamine, Paroxetine, Vortioxetine,  Sertraline, Nefazodone, vilazodone), Selective serotonin and norepinephrine reuptake inhibitors (SNRIs) (Venlafaxine, Desvenlafaxine, Duloxetine, Milnacipran, Levomilnacipran, Sibutramine), Cilostazol, Protein C, Pentoxyfilline, Ginkgo, Meadowsweet, Erlotinib and Gossypol.

ü Plasma concentration of Naproxen is reduced by the administration of drugs such as Dabrafenib and Elvitegravir which induce the CYP2C9 mediated Naproxen metabolism.

ü The drugs like Mifepristone and Sulfamethoxazole elevated plasma levels of Naproxen by inhibiting CYP2C9 mediated Naproxen metabolism.

ü Use of Naproxen in patients taking ACE Inhibitors (Captopril, Enalapril, Imidapril, Temocapril, Delapril, Ramipril, Perindopril, Cilazapril), Angiotensin II receptor blockers (ARBs) (Losartan, Valsartan, Telmisartan), Beta adrenergic blockers, Calcium Channel Blockers, Thiazide Diuretics and Loop Diuretics may decrease the antihypertensive effects by decreasing renal prostaglandin production.

ü Naproxen can decrease the renal prostaglandin synthesis and increase the toxicity of Cyclosporine, Tacrolimus and Lithium.

ü The toxicity of Methotrexate, Pralatrexate and Premetrexed may be elevated by the concomitant use of Naproxen, due to decreased clearance.

ü Concomitant use of Naproxen and Fluoroquinolones (Ofloxacin, Levofloxacin, Norfloxacin) may elevate the risk of seizures.

ü Tobacco smoke contains Polycyclic aromatic hydrocarbons (PAHs) which can stimulate CYP1A2-mediated metabolism of Naproxen and reduce its plasma concentration.

ü Due to the risk of earlier closure of ductus arteriosus, Naproxen should be avoided after 30 weeks of gestation in Pregnant women.

ü Patients should thoroughly read the labels of all over-the-counter and prescription medicines.

ü Patients should talk to their doctor or pharmacist before taking any new prescription or over the counter medication.

ü Physicians should be aware of potential drug interactions with OTC medicines when prescribing new medications.

ü Pharmacists can be instrumental in assisting patients with using OTC medications safely and effectively.

ü Pharmacists should warn consumers of the risks of misusing OTC pain relievers.