This is a presentation regarding to Interaction between Prescription Drugs and nutraceuticals. Here you can able to find about information regarding to this topic and its health effects and precautions. E-mail: Siddheshwarshinde@hotmail.com Mr. Siddheshwar Bhagwanrao Shinde College of Food Technology VNMKV Parbhani

1. COLLEGE OF FOOD TECHNOLOGY,
VNMKV PARBHANI
INTERACTION OF PRESCRIPTION DRUGS AND
NEUTRACEUTICALS
Submitted by Course guide
Mr. Siddheshwar B. Shinde
Reg. No: 2020T14M
M. Tech First year
College of food technology
VNMKV Parbhani 431402
Dr. K.S. Gadhe
HOD Dept. of Food Chemistry
& Nutrition
College of food technology
VNMKV Parbhani 431402

2. • What is prescription drugs
• Introduction
• Drugs Metabolism
• CYP3A4
• P-gp
• Role of CYP3A4 & P-gp
• Inhibition of Drug Metabolism
• Types of Drug Nutrient Interactions
• Herb-drug Interaction
• Neutraceutical drugs Interaction

3. What is Prescription Drugs
• Pharmaceutical drug that are legally require a medicinal prescription to be
dispensed
• RX mark "Rx only" / "prescription only" is (approximately) "for
provision and use only at a licensed physician's direction and under medical
supervision"
What is Neutraceuticals
• Any substance that is a food or part of a food and provides
medical or health benefits, including the prevention and
treatment of disease
• Ex. Basil leaves, Aloevera, Turmeric, Amla, Drumstick etc.

4. Global nutraceutical market
• Predication of growth of nutraceutical market is about $671.30 Billion by 2024
• Most of the developing countries likely to use nutraceuticals in disease
treatments.
• Various private companies and in competition to create nutraceutical medicines to
treat the disease.
• Raising demand of Herbal nutraceutical in Asian region.

5. • Interactions between Neutraceuticals /Food supplements and drugs present
complex and challenging problems.
• Some serious consequences
like treatment failure
• Two side story of interaction
 Success of drug treatment
 Adverse side effects
Drug Interaction is defined as the
pharmacological activity of one drug is
altered by simultaneous use of another drug
or by the presence of some other substances
like nutraceuticals

6. Factors Contributing to drug Interactions
1) Multiple drug therapy
2) Multiple Prescribers
3) Multiple Pharmacological effect of drugs
4) Multiple Disease/predisposing illness
5) Poor patient compliance
6) Advancing age of patient
7) Drug related factors

7. DRUG METABOLISM
• The ability to halt drug action is an important aspect of drug therapy in humans
• The amount of drug that reaches the target tissue in an active form depends not
only on its physicochemical characteristics but also on the extent of metabolism
occurring mainly in the gastrointestinal tract (GIT), liver, and lung.
• Metabolism and excretion by these organs before a drug can reach the systemic
arterial circulation is referred to as Presystemic drug elimination.
• Extensive Presystemic (first-pass) metabolism or Presystemic clearance.
• It is of considerable clinical, pharmacological, and toxicological importance and
can limit the usefulness of certain drugs.
• Thus, many drugs are normally given by injection because when given orally,
most are destroyed by Presystemic metabolism.
• The drug-metabolizing enzyme systems are primarily located in the liver and
small intestine microsome enzymes, but they are also present to a lesser extent
in other organs (e.g, lungs, adrenals).
• The activity of the hepatic enzymes is in general higher than that of drug
metabolizing enzymes located elsewhere in the body

8. Continue…
• Metabolism of drugs by the liver, as well as clearance, depends on the relative
affinity of plasma and hepatic proteins to bind it, the concentration gradient
between blood and liver, and the activity of drug metabolizing enzymes.
• Drugs are metabolized by phase I (catalyzed by CYP450 enzymes) and phase II
(catalyzed by conjugation enzymes such as glutathione-S-transferase GST and
UDP enzymes
• When drugs enter the gut they are exposed to a number of systems with the
potential to chemically modify or to chelate the drug molecules not found within
the tissues of the host.
• These include extremes of pH, unabsorbed nutrients and xenobiotics, digestive
enzymes, and intestinal microflora.
• Interactions between drugs and other nutrient in the gut lumen can result in the
formation of a chemical complex that is absorbed poorly.
• Chemical interactions of this type have been described between tetracycline
antibiotics and divalent or trivalent metal ions such as calcium, magnesium, and
iron.
• Reduction of iron absorption from food occurs in the presence of antacid drugs.
• The Maillard reaction is an example of chemical interaction between dextrose
and amino acids in parenteral nutrition.

9. CYP3A4
• Cytochrome P450 3A4 is an important enzyme in the body, mainly found in the
liver and in the intestine.
• CYP is a large multigene family of heme-containing enzymes located in the
endoplasmic reticulum (ER) of cells throughout the body.
• CYP3A isoforms constitute 70% of CYP enzymes in enterocytes.
• It oxidizes small foreign organic molecules (xenobiotics), such as toxins or
drugs, so that they can be removed from the body.
• Approximately half of all drugs used in humans are handled by CYP3A4 .
• Because of the lack of absolute specificity of the CYP enzymes, the metabolism
of a drug may change with an increase in drug concentration or an inhibition of
the CYP enzyme.
• Competition for the active site on a CYP enzyme by two or more drugs can
result in decreased inactivation of one of the drugs and an increase of its activity
and a prolongation of its effects.
• CYP3A4 is closely associated with P-glycoprotein (P-gp).

10. P-glycoprotein (P- gp) Role
• P-gp like CYP is active in the liver and small intestine.
• P-gp is a 170- to 180-kDa transmembrane protein that acts as a multidrug
resistance factor in tumor cells.
• P-gp was discovered during a course of investigations of drug resistance in the
treatment of cancer
• That actively secretes absorbed drugs back into the gut lumen
• P-gp is also functionally expressed in the enterocytes that border the epithelium
of the intestinal tract,
• Where it plays a role together with intestinal metabolism and is an important part
of the biochemical barrier function of the intestinal mucosa.
• Responsible for limiting the bioavailability of several drugs after oral intake by
pumping them out into the intestinal lumen.
• Not all 3A4-metabolized drugs are P-gp substrates.

11. Role of CYP3A4 & P-gp
• The induction of P-gp activity is frequently the result of exposure to the same
drugs that induce CYP3A4.
• Moreover, the inhibition of CYP3A4 by drugs or other xenobiotics is often
accompanied by inhibition of P-gp which can slow drug absorption.
• The organic anion transporting polypeptide (OATP) system is an intestinal
system that plays a role in absorption of specific drugs and may be involved in
drug interactions with grapefruit juice.
• P-gp can affect the oral bioavailability, biliary or renal clearance, and brain
uptake of drug.
• The substrate range for these proteins is diverse and includes drugs, nutrients,
amino acids, sugars, and peptides.
• Once taken up by the enterocytes, a lipophilic drug may be metabolized by
CYP3A4 or be pumped back into the lumen by the P-gp.
• Hence, the oral delivery of many drugs is limited by the actions of CYP3A4 or
P-gp.
• Metabolism by CYP3A4 will also occur in the liver before the drug finally
enters the systemic circulation.

12. Inhibition of Drug Metabolism
• Variously termed K-cat inhibitors, suicide enzyme inactivators, enzyme-activated
irreversible inhibitors, and suicide enzyme inhibitors
• Represent a relatively new approach to specific irreversible inactivation of
enzymes.
• Simply stated, this approach requires the inhibitor to contain a latent reactive
grouping and to be accepted as a substrate by the target enzyme, following which
the normal catalytic activity of the enzyme results in its own irreversible
inactivation or “suicide.”
• A number of food– drug reactions are based on the inhibition of metabolism of
certain drugs by food;
• the result of such interactions is an increase in the duration and intensity of
pharmacological activity.
• Two points of view are seen regarding the clinical value of enzyme inhibitors:
(i) As potential food/drugs.
(ii) As causing side effects or food–drug interactions.

13. TYPES OF DRUG–NUTRIENTS INTERACTIONS
• Several types of drug–nutrient interactions are categorized based on their nature
and mechanisms.
• They may arise either from alterations of the absorption, distribution,
biotransformation, or excretion of one drug by another nutrient or from a
combination of their actions or effects.
1. Drug–nutrients interaction in vitro (within glass)
• These are ex vivo bio-inactivation that refer to interactions between the drug and
the nutritional element or formulation through biochemical or physical reactions,
such as hydrolysis, oxidation, neutralization, precipitation, or complexation.
• They usually occur in the delivery device
• There are several recommendations to minimize these drug–nutrient
interactions.
• For instance, drugs should not be mixed directly with feeding enteral or
parenteral formulas. Tubes should be flushed with water before and after drug
administration

14. 2. Drug–nutrients interactions in the GIT
• Gastro intestinal Tract interactions affect absorption.
• They cause either an increase or decrease of oral bioavailability.
• The precipitant agents may modify the function of enzymes or transport
mechanisms that are responsible for biotransformation.
• Complexation, binding, and/or other deactivating processes occur in the GIT and
reduce absorption.
• Meal intake stimulates gastric and intestinal secretions, which usually improve
the dissolution of drugs and facilitate absorption.
• Meals with higher fat content stimulate the release of bile salts, which increase
the intestinal uptake of highly lipophilic drugs or of substances that require bile
salts for optimal absorption.
• In addition, high fat content of the food also stimulates the release of
cholecystokinin, which slows gastrointestinal motility and increases the contact
time between the drug and the intestine and possibly also absorption
• One example is oral contraceptives. These drugs have initiated serious anemia
in apparently normal women due to a significant suppression of their intestinal
absorption of dietary polyglutamic folate.

15. Continue…
• One of the simplest of these is deficiency in the fat-soluble vitamins A and D
caused by chronic consumption of liquid paraffin as a laxative.
• Liquid paraffin is poorly absorbed in the gut; by local action it takes up fat-
soluble vitamins, thus preventing their absorption
• More serious example of this type of reaction is related to the interference of
vitamin K with anticoagulant therapy.
• Oral dosage with some antibiotics (e.g., chloramphenicol, tetracyclines, or
neomycin) reduces the intestinal population of microorganisms and thereby
reduces the microbial synthesis of vitamin K.

16. NUTRIENT–DRUG INTERACTIONS
• The Food and Drug Administration (FDA) standardized meal used in product
labeling of drug–food interactions is a high-fat, high-caloric diet that provides
only a small amount of dietary vitamins and minerals
• Food increases the absorption of theophylline, which can result in side effects
of nausea, vomiting, headache, and irritability.
• As a result, many drugs are labeled may be taken with or without food while
they may be also labeled do not take with antacids (Acidity Tab)
• Chelation and adsorption interactions, which cause decreased drug absorption,
will certainly occur between fortified foods and drugs.
• fortified foods contain a quantity of polyvalent ions that approaches or exceeds
that contained in antacid formulations, which may changes in gastric pH,
changes in urinary pH, and otherwise unspecified decreases in absorption are
also possible.

17. HERB–DRUG INTERACTIONS
• Prescription drugs and herbal medicines Co-administration for safety and
convenience .
Magnify
Oppose
Mimic
• Concurrent use of herbs cause effect on drugs.
• Just like Drug-Drug interaction.
- Inhibition or induction of CYP enzymes

18. Some possible
Neutraceutical Herbs &
Drugs interaction

19. • Hypotensive property
• Hypocholesterolemic effect
• Act as anti-inflammatory agent
• Anti-bacterial as well as antifungal property
• Garlic taken with anticoagulant may increase
the risk of Bleeding
Anticoagulant
(Warfarin)
• Garlic intensify the effect of these drugs,
causing an excessive decrease in blood sugar
levels (Hypoglycemia)
Hypoglycemic drugs
(Insulin & Glipizide)
• It decreases blood levels of protease
inhibitors, making them less effective.
Protease Inhibitor
(Indinavir or Saquinavir)

20. • It is used to treat stomach problems
• As Carnitive Agent including,
• Ginger along with diabetes medications It
might decrease blood sugar extensively.
Anti-Diabetic drug
(Insulin, Metformin,
Glucophase)
• Garlic taken with anticoagulant may increase
the risk of Bleeding
Anticoagulant
(Warfarin)
• Ginger along with these medications causes
extra high drop in blood pressure and causes
irregular heart beat
High B.P. Medications
(calcium channel blockers-
Nifedipine, Verapamil)
 Motion sickness
 Upset stomach
 Diarrhea
 Nausea
 Loss of appetite
Uses

21. Green Tea
• Improve mental alertness and
thinking
• Bone loss (osteoporosis)
• Solid tumer cancer
Green tea is also used to treat-
 Corhn’s disesse
 Perkinson’s disesse
 Cardio vascular diseses
 Diabetes
 Low blood pressure
 Chronic fatigue syndrome
 Dental cavities
 Kidney stone
 Skin
Stimulant drug:
(Amphetamines,
Ephedrine)
• Increased heart rate
and blood pressure
Anti-coagulant
(Warfarin)
• Makes Warfarin to
be less effective
Bortezomib (velcade)
For cancer treatment
• Decreases the effect
of Bortezomib

22. • Traditional Chinese medicine (TCM), particularly for the treatment of
asthma, indigestion, cough.
• Medicinal uses : Alzheimer’s disease (AD), dementia, memory loss,
cardiovascular disease, premenstrual syndrome.
• Active ingredient unidentified
• Concurrent use of ginkgo with antiplatelet, anticoagulant, or antithrombotic
agents increases the risk of bleeding.
• Reduces the effectiveness of Nicardipine (to treat high blood pressure) by
interacting with the CYP450 system.
Clinical Studies
Flavonoids (kaempferol, quercetin, iso rhamnetin)
Terpenoids (ginkgolides, bilobalide)

23. Licorice (Glycyrrhiza glabra)
• Root is used as a sweetening and flavoring agent.
• Active component glycyrrhizic acid
• Herbal remedy for gastritis and upper respiratory tract infections
• Increases fertility in women with hormonal disorder i.e. Polycystic ovary
syndrome
• Against Prostate cancer & Skin disorder Eczema
BENIFITS
Digoxin
• Licorice increases
urine formation
• Concurrent with
Digoxin then
Potassium level
decreases
• Digoxin toxicity
Antiarrhythmics
• Risk of abnormal
heart rhythm
• Antiarrhymic
therapy less
effective
Monoamines
• Intensify effect of
these drugs,
increase risk of side
effects
• Headache, Tremors,
manic episode.

24. • Intensify effect of Diuretics Increased
rapid loss of Potassium
Diuretic or water pills
( Thalitone, Diuril )
• Licorice increases salt and water retention
and increases blood pressure, making
these drugs less effective
Anti-Hypertensive

25. • Native to south pacific origin.
• To calm anxiety, stress, restlessness, insomnia.
• Reduces anxiety & hot flashes in women with menopause.
SEDATIVE
(Barbiturates &
Benzo diazepines)
Kava intensify or
prolong the effect
of sedatives
Kava interact with drugs, including drugs used for Parkinson's disease &
Alcohol or acetaminophen (Tylenol), which may injure the liver.

26. Grapefruit Juice
• One or more flavonoids found in grapefruit juice inhibit CYP enzymes.
• Results in reduced metabolism of drugs that are cleared by the same
system.
• drug bioavailability can markedly augment by as much as 200%.
• Patients should avoid drinking grapefruit juice for 2 h before and 4 h after
taking drugs in this category.
 Furano-co-umarins4 irreversibly inhibit CYP3A4
in the small intestine.
 Which results in a significant reduction in drug
presystemic metabolism
 Increased plasma concentration results…..
 Ex. excessive lowering of blood pressure with
calcium channel antagonists,

27. Black Pepper (Piper Nigrum)
• It contain Piperine as the chief active constituent
• It used as spices as well as carminative & to
treat the Asthma, Stomach upset, sinus infection.
• It inhibit cytochrome enzyme which increases
blood level.
• Hence should not taken along with
Carbamazepine, Midazolam, warfarin etc.
• It increase risk of bleeding when mixed with
anticoagulants or blood thinning drugs like
Heparin and warfarin.

28. • Human medicines can treat and cure many health problems; however, they
must be taken appropriately to ensure that they are safe and effective.
• Certain foods can interact with medications; food–drug interactions are
defined as alterations of pharmacokinetics or pharmacodynamics
• More attention has been given to dietary supplements such as vitamins,
minerals, and herbs.
• Herbal extracts or single, isolated compounds can be either inhibitors or
inducers of various CYP enzymes or transporters.
• Interactions between herbal products and prescribed drugs are a major
safety concern, especially with respect to drugs with a narrow therapeutic
index.
• Such an interaction may cause adverse effects, which may be life-
threatening.

29. REFERENCES
• FDA, 2007. Food-Effect Bioavailability and Bioequivalence Studies. Draft
Guide for Industry, Bethesda, MD.
• Hodgson E, Ryu D, Adams N, Levi P E. Biphasic responses in synergistic
interactions. Toxicology 1995; 105: 211–216
• Raffa R, Cowan A, Tallarida R. Analgesic and glucosamine compositions.
PCT International Applications, 2002: 1–24
• Raffa R, Cowan A, Tallarida R. Analgesic and glucosamine compositions.
PCT International Applications, 2002: 1–24
• Croft J E. A synergistic composition comprising mussel protein extract and
glycosaminoglycan suitable for treatment of arthritis. British UK Patent
Application, 2000: 1–10.
• Cavazza C. Composition for the prevention and/or treatment of disorders due
to abnormal lipid metabolism, comprising propionyl L-carnitine and chitosan.
PCT International Application, 2001: 1–12.

30. Thank You
Nutraceuticals