Drug Interactions

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Drug Interactions

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Slide1:

Prof. R. K. Dixit Pharmacology and Therapeutics K.G.M.U. Lucknow dixitkumarrakesh@gmail.com Drug Interactions….. It’s Clinical relevance

Objectives:

Objectives To Recall and revise What is drug interaction Epidemiology of drug interaction Risky patient, Risky drugs, And Risky doctors Types of drug interactions Pharmaceutical, Pharmacokinetic, Pharmacodynamic Drug and Food (Nutraceuticals) interactions Drug and other therapy (Herbal) interactions Drug interactions. Are they always harmful???? Ways to reduce the drug interactions Ways to access the information of drug interactions Summary Not to teach but

Cavett:

Cavett Only salient points regarding DDI, DFI, DOTI, DHI etc Not cover each and every possible interaction, Impossible and Irrelevant to remember every possible interaction Must know Clinically significant interactions Causes for breakthrough of disease Causes Failure of therapy or prophylaxis Utilized for the rational therapeutics Life threatening

Slide4:

Era of DRUG EXPLOSION . Chances of DDI are high. Countless interactions can influence Good medical practices demands Polypharmacy and Polymedicine Loewe (1953) – First to study DDI scientifically.

What is drug interaction:

What is drug interaction Drug interactions follow when two or more drugs are given simultaneously or subsequently When a drug is administered a response is obtained, if additional drugs given and response is altered a drug interaction is said to have occurred. Bennet and Lorence “A measurable modification (in magnitude or duration or both) of the action of one drug by prior or concomitant or subsequent administration of another substance.” Drug-Drug (Rx, OTC, Herbal, Others) Drug-Food, Drug-Alcohol Drug-Lab, Drug-Disease Wright 2008. Drug Interactions. In: Melmon and Morrelli’s Clinical Pharmacology 2008

Slide6:

Alteration in (PPP-P-P) P harmacological action (Duration or magnitude or both)or P hysiochemical or P harmacokinetic properties Of a drug by administration of another drug (drugs) The administration may be Previously Concurrently Subsequently The interaction may be Well established Suspected Unsuspected The net effect may be Decreased Increased New effect is produced

:

The interactions (DDI, DFI OR DOTI) may be Clinically non-significant (common occurrence, Ignored) Clinically Significant Mild (May Know, No need of drug adjustment) Moderate (Should Know, Needs dose adjustment) Severe , life threatening (Must know, Contraindications) Utility in therapeutics (Must know, Indications) The interaction may be Desirable (Utilized in therapeutics) Undesirable (Needs avoidance)

Categories of seriousness of DDIs/ADRs:

Categories of seriousness of DDIs/ADRs Category A- Clinically Nonsignificant (atrial ectopics) Category B- Mild (amnesia, nausea, fatigue) Category C- Risk of failure of therapy of non serious conditions (Iron supplementation, analgesics) Category D- Risk of failure of therapy for serious non lethal diseases (Parkinsonism, Convulsions etc.) Category E- Risk of failure of life saving drugs , or prolonged QT interval, Pulmonary embolism, Rhabdomyolysis, Category F- Torsades de pointes, Ventricular tachycardia, Teratogenic , Bone marrow depression, Serotonin syndrome, Multi-organ failure, Death

Categories for Quality of Evidences regarding DDIs/ADRs:

Categories for Quality of Evidences regarding DDIs/ADRs Category 0- Pharmacodynamic Animal and Invitro studies with a limited predictive value for human in vivo situation (DATA ON FILE) Category 1- Incomplete , published case reports (no re-or-de-challenge, presence of other explaining factors for the DDIs/ADRs Category 2- Well documented , published case reports, retrospective analysis of case series Category 3- Controlled published interactions studies in patients or healthy volunteers with surrogate end points Category 4- Controlled Published interaction studies in patients or healthy volunteers with clinically relevant end points Note- Posters and abstracts from scientific meetings- 0 or 1 (Depending on relevant information) If the information of abstract is not published in peer reviewed journal within 3 years it goes to category 0

Slide10:

PK changes ≠ Pd changes ≠ Clinically Significant Statistically significant ≠ Clinically Significant Possible interactions ≠ Actual interactions (Clinical Skills and Experiences) Non significant in adult may be significant in special group Clinically observation by one clinician Vs other clinician Innumerable DDI but only few are of significance

Terminologies:

Terminologies Polymedicine - Several practitioners for same patient/ Use of multiple medicines related to increasing number of medical problems Number of consultants α DDI Polypharmacy - Several medications given to same patient concurrently Use of four or more  medications)/ Inappropriate use of multiple medications Homergic - Drugs producing same overt effect ( eg . Bronchodilitation ) Homodynamic - Drugs producing given effect by means of same mechanism of action Heterodynamic - Drugs producing same given effect by different mechanism of action The common effect of homergic drugs can be the result of Homodynamic or Heterodynamic action

Epidemiological Data regarding DDI:

Epidemiological Data regarding DDI Exact incidence not known Ranges between 0.5% to 50% depends on settings Increases Exponentially as of drugs increases- Smith et al. Increase in mortality and hospital stay Represent 3–5 % of in-hospital ADRs Around 13% of ADRs in elderly Leape LL et al. JAMA 2011;474(1):35–43 Raschetti R et al. Eur J Clin Pharmacol 2015 ;254(12):959–963

Factors enhancing the chances of DDI:

Factors enhancing the chances of DDI Patient factors (Risky Patients) Age (Pediatrics and Geriatric age groups) Sex (Female especially pregnant) Genetics Nutritional status (Malnutrition) Diseases (Patients with multiple diseases) Physiological functions of organs (Liver, Kidney etc.) Patients with Alzheimer's, dementia, unconscious, bedridden Critically ill patients Immunocompromised Lack of Faith on treatment Unstable Personality/Psychiatric patients Food habit (Cheese, fruits, cigarette, wine, coffee etc.) Patients with multiple physicians involvement Hypochondriac, Roaming Drug abusers

Factors enhancing the chances of DDI:

Drug factors (Risky Drugs) Affecting vital process of body (Anticoagulants, Antidiabetic, Antihypertensive, Hormones etc.) Narrow therapeutic index (Digoxin, Lithium, Warfarin, Theophylline, Antidiabetics, Antiarrythemics, Anticonvulsants, Aminoglycosides, Antiretroviral drugs, Anticancer drugs etc.) Therapeutic window phenomenon ( Clonidine , Lithium, TCAs etc.) Steep Dose Response Curve ( Verapamil , Levodopa , etc.) With saturable kinetics/Zero order kinetics Exhibiting toxic effects recognizable easily Drugs used for long term to get required benefit (Cyclosporine, Corticosteroids, Antiepileptic, Antiarrhythmics) With property of Induction or Inhibition of enzymes Breakthrough ( eg . OCPs, Corticosteroids, Antiepileptics etc.) Factors enhancing the chances of DDI

Factors enhancing the chances of DDI:

Physician factors (Risky Physicians) Number Skill and training Setting (OPD Vs IPD, Less severe Vs Severe patients, Elective Vs Emergency setting) Handling the risky patients, risky drugs (Anesthetists, Oncologists, ICU, NICU, etc.) Attitude (Over treatment) Overenthusiastic physician/Crazy/Young/Interns/Inova Be not the first by whom new drugs are tried Nor yet the last to lay the old aside Factors enhancing the chances of DDI

Factors enhancing the chances of DDI:

Other factors Patient habits (Smoking, Alcohol, etc..) Hidden personals (Non medical personals, Neighbours,) Hidden therapists (Ayurveda, Unani, Homeopathy etc.) Hidden formulations (OTCs, Nutraceuticals, Tonics etc.) Hidden chemical exposures (Environmental factors like exposures to insecticides, pesticides, pollutants etc.) Factors enhancing the chances of DDI Beware of

Slide18:

Types of drug–drug interactions • Behavioural – When one drug alters the patient’s behavior to modify compliance with another drug.(eg. A depressed patient taking antidepressant may become more compliant with medication) • Pharmaceutical– When formulation of one drug is altered by another before it is administered. (eg. Precipitation of sodium thiopentone and vecuronium within an intravenous giving set.) • Pharmacokinetic– When one drug changes the systemic concentration of another drug, altering ‘how much’ and for ‘how long’ it is present at the site • Pharmacodynamic– When interacting drugs have either additive or opposing effects

Types of DDI:

Types of DDI In Vitro Pharmaceutical interactions Mixing During Oral and Parenteral preparations Drugs in infusion fluid Drug in same syringe Topical preparations Drug container interactions Infusion material interactions Photochemical interactions Thermochemical interactions Others

Pharmaceutical interactions:

Pharmaceutical interactions Aminophyllin – in infusion containing ascorbic acid Phenytoin – 5% dextrose Amphotericin – in Normal saline Thiopental- with Succinylcholine , Pancuronium Hydrocortisone – with Penicillin, Heparin Gentamicin with Carbencillin Protamine zinc insulin with plain insulin Ceftriaxone in calcium containing fluid No drug into Parenteral Nutrition Solutions, Albumin, Blood, Plasma Some incompatibility reactions can be recognized (color change, formation of precipitant or gas), but Most often cannot be noticed at the macro level which leads problems in practice.

Drug Container Interactions:

Drug Container Interactions Absorption to matrix or to surface (Nitroglycerine, Amiodarone, Insulin) Leaching- component of plastic to medicine (Paclitaxel) Permeation - through container wall Nitroglycerin Adsorption of insulin to glass and PVC surfaces Nitroglycerine adsorbs to and penetrates the wall of plastic container of infusion set. PVC reduces NTG concentration by 15%. It remains possible that changes in hemodynamic status could occur in patients on NTG if change in container type (from PVC to glass or vice versa) is made during the course of therapy

Slide23:

In Vivo Pharmacokinetic interactions (DADME) D issolution A bsorption D istribution, Plasma protein binding, Free drug M etabolism, Enzyme inhibition, Enzyme induction E xcretion, Biliary, Renal and others Pharmacodynamic Interactions At organ level At receptor level

Pharmacokinetic Basis of Interactions:

Pharmacokinetic Basis of Interactions Absorption Depends on Formulation- Enteric coating may get removed pH- Antacids, H2 Blockers, PPI, Lipid solubility Chelation Blood flow Motility and gastric emptying Bacterial flora of gut Gastrointestinal mucosal lining

Alteration in gastric pH:

Alteration in gastric pH Increased pH Increased absorption Glibenclamide Glipizide Tobutamide Decreased absoption Ketoconazole Nalidixic acid Nitrofurantoin Warfarin Phenylbutazone Cefuroxime Decreased pH Increased absorption Amitryptiline Aspirin Decreased absorption Ephedrine Quinine

Drugs :

Drugs Weak Acids Acetylsalicylic acid Furosemide Ibuprofen Levodopa Acetazolamide Ampicillin Chlorpropamide Ethacrynic Acid Phenobarbital Warfarin Theophyllin Phenytoin Paracetamol Weak Bases Reserpine Amphetamine Procaine Ephedrine Atropine Diazepam Hydralazine Pindolol Propranolol Salbutamol Terbutaline Amiloride Chlorpheniramine

Slide27:

Chelation Iron, Alumunium, Magnesium, Calcium, Reduce absorption of Quinolones Tetracyclines Thyroxin Digoxine Levodopa Mucosal damage by Neomycine Colchicin Mefenamic acid Antineoplastic drugs

Slide28:

Motility Reduced by Anticholinergic drugs TCA Phenothiazines Antihistaminics Antiparkinsons Opioids Motility increased by Metoclopramide Prokinetics

Slide30:

Transporter based interactions Transporter proteins govern Uptake into the enterocytes and Secretion in renal tubules Induction or inhibition of transporter proteins like OAT, OCT, OCTN, PEPT, CNT, ENT, MATE, ABC, MDR, OST, etc. P-glycoprotein (P- gp , Permeability Glycoprotein) Expressed on the apical aspect of the enterocyte , endothelial cells of BBB and hepatocytes . Works as a ‘ Detoxification Pump’ ejecting drugs and reducing oral bioavailability of some drugs. Organic anion transporters (OAT), Organic cation transporters (OCT), Organic cation/carnitine transporters (OCTN), Peptide transporters (PEPT), Concentrative nucleoside transporters (CNT), Equilibrative nucleoside transporter (ENT), Multidrug and toxin extrusion transporters (MATE), ATP-binding cassette transporter (ABC), Multidrug resistance proteins (MDR), Organic solute transporters (OST)

Transporters Inducers and Inhibitors:

Transporters Inducers and Inhibitors Inducers Carbamazepine Dexamethasone Doxorubicin Nefazodone Prazosin Rifampicin St. John’s wort Tipranavir Trazodone Vinblastin Inhibitors Amiodarone Atorvastatin , Simvastatin Clarithromycin , Erythromycin Grapefruit juice Itraconazole Ketoconazole Verapamil , Amlodipine , Diltiazem Progesterone Carvedilol Cyclosporine Colchicin Dipyridamol Mefloquine Quinidine Ranolazine Tacrolimus Tamoxifen

How Do Pharmacokinetics alters?:

How Do Pharmacokinetics alters? Changes in the absorption, distribution, metabolism and excretion (ADME) of a drug Toxic Effective Ineffective 0 6 12 18 24 TIME Concentration

Slide33:

Drug distribution interactions Displacement of each others binding to plasma proteins. Competitive binding for the same site Increasing the amount of free drug in plasma and tissues. Eg. Warfarin with phenylbutazone In hypoalbuminemia more free or active drug available. Drugs likely to lead to clinically significant interactions are Those 90% or more protein bound, Bound to tissues or having a small volume of distribution, Displacing drugs include NSAID’s, Sulfonamides.

Proportionality of drug metabolizing enzymes:

Proportionality of drug metabolizing enzymes ADH , alcohol dehydrogenase; ALDH, aldehyde dehydrogenase; CYP, cytochrome P450; DPD , dihydropyrimidine dehydrogenase; NQO1, NADPH:quinone oxidoreductase, COMT, catechol O -methyltransferase; GST, glutathione S -transferase; HMT, histamine methyltransferase; NAT, N -acetyltransferase; STs , sulfotransferases; TPMT, thiopurine methyltransferase; UGTs , uridine 5'-triphosphate glucuronosyltransferases.

Slide36:

The Cytochrome P450 (CYP) system Super Family of haemoproteins with enzymatic activity Found in endoplasmic reticulum and mitochondria of Hepatic (and Intestinal, CNS) cells Responsible for the oxidative metabolism of Xenobiotics and endogenous compounds. Involved in numerous interactions (DDI, DFI, DHI). The term ‘ Cytochrome P450’ was coined because of Its spectral properties. In Cytochrome P450, Cytochrome stands for a hemoprotein, P for pigment and 450 reflects the absorption peak at 450 nm .

Slide37:

Nelson proposed nomenclature system. Basis of classification- Amino acid sequence homologies In Man 18 families governed by 57 genes. 40% or more similarity- Family (by Arabic number) . 60% or more similarity – Subfamily (by a Capital letter) and after this The individual genes are numbered . ‘ CYP’ for human, ‘Cyp’ for animals (mouse).

Slide39:

Most important enzymes are CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4. CYP2E1 Enzymes can either be Stimulated (enzyme induction) or Inhibited (enzyme inhibition). Factors affecting CYP expression include genetic polymorphisms, environmental exposures, xenobiotics CYP2D6 has the largest phenotypical variability

Percent Distribution of CYP 450 distribution and role in metabolism:

Percent Distribution of CYP 450 distribution and role in metabolism

Slide43:

Enzymes Inducers Inhibitors Substrates CYP 1A2 Montelukast , Phenytoin , Smoking, Phenobarbital Cimetidine , Ciprofloxacin, Fluvoxamine , Grapefruit juice Theophylline , Caffeine, Melatonin, Raelteon , Tacrine , Tinzanidine , Imipramine CYP 2C9 and CYP 2C19 Rifapicin , Phenytoin , Barbiturates Fluconazole , Fluvoxamine , Fluoxetine , Ritonavir , Omeprazole Diclofenac , Warfarin , Phenytoin , Diazepam, Clobazam , Lansoprazole , Repaglinide , Bupropion , Efavirenz , Paclitaxel , Warfarin , CYP 3A4 Carbamazepine , Phenytoin , Phenobarital , Rifampicin , St. John’s wort , Bosentan , Efavirenz , Nafcillin , Modafinil , Prednisone, Cimetidine , Erythromyycin , Clarithromycin , Itraconazole , Ketoconazole , Nefazodone , Fluvoxamine , Fluoxetine , Ritonavir , Nelfinavir , Indinavir , (HIV Protease Inhibitors), Grape fruit juice, Amiodarone , Terfenadine , Benzodiazipines , Cyclosporine, Tacrolimus , Diltiazem , Verapamil , Dihydropyridines , HMG- CoA reductases , Sildenafil , Buspirone , Trazodone , Amiodarone , Quinidine , Ergotamine, Ethiny estradiol , Haloperidol, Terfenadine , Carbamazepine , Budesonide , Midazolam , Quitapine , Astemizole , Fentanyl , Pimozide , Quinidine , CYP 2D6 Phenobarbitone , Dexamethazone , Rifampicin Haloperidol, Paroxetine , Fluoxetine , Bupropion , Quinidine , Amiodarone , Cimetidine , Thioridazine Betablockers , Codeine and derivativez , Amiodarone , Antihistaminics , SSRIs, Thioridazine , Pimozide , Detromethorphan ,

Slide44:

Liver Induction Drug A induces the body to produce more of an enzyme to metabolized Drug B This reduces the amount of Drug B and may lead to loss of Drug B’s effectiveness Inhibition Drug A inhibits the production of enzymes to metabolize Drug B This increases the amount of Drug B in the body and could lead to an overdose or toxic effects

Slide46:

Excretion interactions Only the free fraction can be removed through the kidney. Protein bound form not available for renal excretion The excretion of drugs from the kidney has the same properties as that of any other organic solute: Passive filtration, and Active secretion. Active Secretion is subject to conditions relating to the saturability of the transported molecule and competition between substrates. (Key Sites) Filtration depends on a number of factors including the pH of the urine (Key in managing poisoning)

Pharmacotherapeutics is based on the wise utilization of agonists, antagonist (and their best possible interactions):

Pharmacotherapeutics is based on the wise utilization of agonists, antagonist (and their best possible interactions)

Herbal Drugs as Inhibitors or Inducers (Fruits, Vegetables):

Herbal Drugs as Inhibitors or Inducers (Fruits, Vegetables) Grape fruit Juice, Grapes, Mango, Apple, Orange, Papaya Inhibitor of CYP 3A4, P- gp and OATP Black pepper, Spinach, Tomato, Broccoli, Carrot Inhibitor of CYP 3A4, P- gp Garlic Inhibitor of CYP 3A4 Gingko Inhibitor of CYP 3A4, Inducer of CYP 2C19 Valerian Inhibition of CYP 2C19, CYP 2D6 Echinacea Inhibitor of CYP 3A4 Ginseng Inhibitor of hepatic CYP 3A4 Kava Kava Pregnane X receptor activator ( PXR a lso known as the steroid and xenobiotic sensing nuclear receptor ( SXR ) or nuclear receptor subfamily) St. John’s Wort Inducer of CYP 3A4 and P- gp , Pregnanne X receptor

Slide54:

Ginkgo biloba ( Balkuvari ) Used for improving cognitive function in Alzheimer’s and dementia. Active compounds- Flavonoids and Terpenoids Induction of CYP 2C9, Nonselective MAO inhibition Risk of Bleeding associated (inhibition of platlet activating factor) Flaxseed ( Alsi ) Stool softening and hypocholesterol , Can bind with drugs, cardiac glycosides Feverfew Used for prophylaxis of migraine headaches., Inhibits platelet activity Ginger ( Adrak ) Potent inhibitor of thromboxane synthetase . Kava Kava Taken to Relieve anxiety, and nervousness, Acts as dopamine antagonist, modulates GABA, calcium channels, Sodium channels, MAO-B inhibitor Decrease response to anti- Parkinsonian meds Potentiates alcohol, tranquilizers, antidepressants, antiplatlet action

Slide55:

St. John’s Wort Mechanism is like SSRIs Not used withnSSRIs and MAO inhibitors. ( Pharmacodynamic interaction) It acts in the cytochrome P-450 3A4 of the liver. Short term inhibition Long term Induction (most important clinically) Reduce concentration of drugs to sub-therapeutic level Hyperforin is active constituent Induces P-glycoprotein, MDR-1 and other drug transporters and Potentiates photosensitivity. Ephedra (ma- huang ) For weight loss, energy boosters, Asthma, Bronchitis Active compounds- Ephedrine, Pseudoephedrine, Norephedrine , Mechanism- Mixed action at α 1 β 1 β 2 Caution along with MAO inhibitors, Sympathomimetics , Halothane

Slide56:

Garlic ( Allium sativum ) Inhibits CYP2E1, Produced hypoglycemia, and anticoagulant effects Licorice ( Glcyrrhiza glabra )-may produce pseudoaldosteronism (Potassium depletion, sodium retention, edema, hypertension and weight gain). Also has estrogenic effects Herbs containing coumarin or it’s derviatives - Angelica root, Anise, Licorice, Red clover, Rue, Ginseng Echinacea- used as immunomodulator but hepatotoxic , Inhibits CYP 1A2 Bitter melon, Nopal or Prickly pear cactus, Gymnema , Fenugreek, Ginseng Cinnamon, Glucomannan , Guar gum, produce hypoglycemic actions . Ginseng- May reduce opioid’s effects., May prolong QT interval, and hypoglycemia, warfarin’s anticlotting effect

Complementary and Alternative Medicine:

Complementary and Alternative Medicine >40% of patients take alternative medicines < 40% of patients inform (A belief that “natural,” must be safe.Fear of how Doctor would respond to self-medication) Most commonly – Echinacea , Feverfew , Garlic , Ginseng , Ginkgo , Kava , St . John’s wort , Saw palmetto, Valerian Ephedra Pharmacotherapy 2010;20:877-91

Herbal and Supplement Products That Interact with Warfarin :

Herbal and Supplement Products That Interact with Warfarin Increased INR Ginkgo Biloba Dong Quai ( Angelica sinesis ) Danshen ( Salvia miltiorrhiza ) Vitamin E Decreased INR St. John’s Wort Coenzyme Q10 American ginseng Altered Platelets Garlic [ Allium sativum ] Feverfew Ginseng Turmeric Meadowsweet Willow bark Contain Coumarins* Horse chestnut Red clover Lancet 2000;355:13438 J Clin Pharm Ther 2002;27:391-401

Slide59:

* Foods and Products High in Vitamin K Alfalfa tablets Broccoli Brussels sprouts Cabbage Cauliflower ( raw ) Green leafy vegetables ( spinach, collard greens ) Green tea Liver Soybean Vegetable oils ( canola, soybean ) Watercress

Food-Drug Interaction   :

Food-Drug Interaction   M ay decrease absorption: Calcium containing foods High fiber foods M ay increase absorption: S quinavir , Griseofulvin – Choose alternative drug ? – Increase dose if taken with food? – Take before or after meal?

Slide61:

Grapefruit juice (Chakotara the Notorius ) Affects metabolism of several drugs. Inhibition of CYP3A4 in the intestinal wall Large amounts also inhibit CYP450 in the liver Other mechanisms – Inhibition of intestinal P-glycoprotein and Organic anion transporting peptide (OATP). Important for drugs with high first pass metabolism. Constituents implicated Flavonoids, Naringin, Naringenin, Furanocoumarins, Bergapten and Dihydroxybergamottin.

Important Drugs Showing DFI with Grape Fruit Juice:

Important Drugs Showing DFI with Grape Fruit Juice Amiodarone Antidepressants- Sertaline, Buspirone, Clomipramine Antiretroviral agents- Saquinavir, Indinavir Benzodiazepines- Midazolam, Diazepam, Triazolam Budesonide, Methylprednisolone Caffeine Calcium Channel Blockers (Amlodipine, Verapamil, Diltiazem) Carbamazepine Cisapride Cyclosporine Dextromethorphan Erythromycin Estradiol HMG-CoA reductase inhibiotors (Atorvastatin, Lovastatin, Simvastatin) Methadone Sildenafil Sirolimus, Tacrolimus Theophylline Warfarin South American Medicine J. 2009; 102(3):308-9

Environmental Factors:

Environmental Factors Microsomal Enzyme Inducers Tobacco Smoke Pollutants such as hydrocarbons Pesticides Polychlorinated biphenyls used in industry,

Drugs increasing Dangerous Arrhythmia:

Drugs increasing Dangerous Arrhythmia Disopyramide,Procainamide, Quinidine, Bipridil, Amiodarone, Erythromycin, Clarithyromycin, Halofantrine, Pentamidine, Sparfloxacin, Chlorpromazine, Haloperidol, Thioridazine Methadone Gupta A et all Am Heart J 2007;153:891-899.

We can cause Serotonin Syndrome:

We can cause Serotonin Syndrome L-tryptophan Amphetamine, Sibutramine Alcohol Dopamine agonists, Selegiline SSRIs, SNRIs, TCAs, Mirtazapine, trazodone St. John’s Wort MAO inhibitors, Lithium Linezolide, furazolidone Codeine, Tramadol, Fentanyl, pentazocine, dextromethorphan Triptans, Ergot alkaloids Ondansetron, Granisetron Cocaine, LSD, Ecstasy Sun-Edelstein. Expert Opin Drug Safe 2008;7:587-596

Food Rich in Tyramine:

Food Rich in Tyramine Avocados, Ale Banana Beans Canned figs, Caviar Cheese (especially aged) Chicken liver Chocolate Coffee and Cola beverages Meat (Fermented like Salami, Sausage, Pepperoni) Raspberries Soy sauce, Sour cream, Tofu Wines (especially red) Yeast preparations, Yogurt M ay, R.J. (1993). Adverse drug reactions. In J.T. DiPiro et al (Eds.), P harmacotherapy: A P athopysiologic approach (2 nd ed., p. 71). Norwalk , CT, Appleton & Lange

Information regarding DDI:

Information regarding DDI Hansten and Horn’s Clinically Important Drug Interactions, Applied Therapeutics, Koda-Kimble et al (2011) Handbook of Applied Therapeutics, 8 th ed, Mozayani A & Raymon LP (2009) Handbook of Drug Interactions- Rodrigues AD (2006) Drug-Drug Interactions, Taylor & Francis, New York British National Formulary (BNF) Martindale - The Complete Drug Reference National Medicines Information Centre (NMIC) Textbook of Clinical Pharmacology Clinical Pharmacokinetics

Computer help for DDI:

Computer help for DDI www.drug-interactions.com http://medicine.iupui.edu/clinphar/DDIs www.dcri.duke.edu/research/fields/certs. https://en.wikipedia.org/wiki/Drug_interaction www.sph.unc.edu/healthoutcomes/certs/index.htm www.naturalstandard.com www.naturaldatabase.com www.micromedex.com . WWW.medscape.com www.arizonacert.org WWW.medicines.ie www.penncert.org www.uab.edu WWW.imb.ie

Role of Pharmacists is immense in reducing DDI but in India:

Role of Pharmacists is immense in reducing DDI but in India

Slide71:

“Show me a drug with no interaction and I’ll show you a drug with no actions” Sir Derrick Dunlop Chairman, Committee on Safety of Drugs, UK Founder of the Yellow Card System Must know the Clinically Relevant Interactions to maximize the therapeutic effects and minimize the adverse effects - Rosenheim 1965, Martin 1971, M. L .

Slide73:

DDI, DFI, DHI, DOTI,……….IIIIIIIII

At the End:

At the End • List all medications including OTCs, Herbals, • Minimize the number of drugs if possible Tell how and when to take medications • Don’t ignore any adverse effects during or after medication. Whenever a patients course deteriorates, look out for a possible adverse drug interaction. IF the deterioration is due to drug therapy, it probably is reversible. • Prescription refilled from the qualified Pharmacist • Instruct not to stir medication into food, milk or drink • Always read the drug inserts Vigilant with low therapeutic index drugs and to high risk patients Risk of a potential interaction is always there. Know them to Prevent them

H.E.R.B.A.L. (Take Home Message) :

H.E.R.B.A.L. (Take Home Message) H ear the Patient E ducate the patient E ducate yourself to be in limits (U sing few and knowing them well, ………If in doubt, don’t.. ‘’) R ecord, Respect, Risks, Responsibility, Reevaluate B eware of hidden factors A gree to discuss with seniors and peers A pply clinical pharmacology principles L earn about important interactions L isten Lecture on Drug interactions it’s clinical relevance at SRMS Bareilly

Slide76:

DDI, DFI, DHI, DOTI,……….IIIIIIIII

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