this topic related drug interactions

1. KINETICS OF DRUG INTERACTIONS
Presented by
S.L.S(M. Pharm)
15AB1SO308
Under the esteemed guidance of
Prof.Dr.G.KISHORE BABU.,
M.Pharm ., Ph.D.
HOD, Department Of Pharmaceutics
VIGNAN PHARMACY COLLEGE
(Approved by AICTE, PCI & Affiliated to JNTU KAKINADA)
VADLAMUDI, GUNTUR DIST, ANDHRA PRADESH, INDIA,PIN:522 213
2015
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2. • Definition.
• Types of interactions.
• Factors contributing to drug interactions.
• Conclusion.
• Reference.
CONTENTS
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3. Drug interaction can be defined as the modifications of the effects of one drug by the
prior or concomitant administration of another drug.
Drug that precipitates the interaction - Precipitant drug
Drug whose action is affected - Object drug
DEFINITION
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4. Drugs likely involved in interactions
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 Drugs highly bound to plasma
proteins
 Used for long term
 Enzyme inducers or inhibitors
 Two drugs simultaneously given for
same disease
Precipitating drugs
• Narrow therapeutic index
• Zero order kinetics
Object Drugs

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6. DI
Drug -Food
Drug-Herbal
Drug-DrugDrug-Disease
Drug-Alcohol
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7. Drug -Food
Interactions
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8. Drugs effect food By
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Food intake
Alteration
in gut flora
Nutrient
absorption
Nutrient
metabolism
Nutrient
excretion

9. How food can effect drugs
Increase
absorption
Decrease
absorption
Irritation
of
digestive
tract
No effect
• Rifampicin- without food
• Rifabutin- with food
• Rifapentin- no effect of food
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10. Milk Fruit juice
Tea/coffee Alcohol
Swallowing of
the medicine
• Erythromycin
• Ketoconazole
• celiprolol
 Tetrcayclines
 Bisacodyl
 Iron supplements
 Mercaptopurin
• Wine-tyramine
reaction
• iron absorbtion
• theophylline
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11. 10-12-2015 Vignan pharmacy college 11
DRUG – ALCOHOL
INTERACTIONS

12. In the absence of alcohol
After moderate alcohol
consumption
In chronic heavy drinkers
who are sober
In chronic heavy drinkers
who are intoxicated
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13. Class Names Interaction Effect
1. Analgesics Aspirin
Acetaminophen
 Increase gastric
emptying
 Toxic metabolite of
acetaminophen
Faster alcohol
absorbtion
Liver damage
2. Anticonvulsant Phenytoin Induces phenytoin
breakdown
Decrease effect
3. Antihistamines Chlorpheniramine Increase CNS effect sedation
4. Antidiabetics Chlorpropamide
Glyburide
Metformin
Increase risk of
hypoglycemia
Unconsciousness
Disulfiram like reaction
Lactic acidosis
5. BZDs Diazepam Increase effect Sedation
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Table:1

14. Drug Drug Interactions
DI
Outside the
body
Syringe Iv fluids
Inside the
body
Pharmacoki
netic
Pharmacody
namic
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15. Also called as incompatibility. It is a physicochemical interaction that occurs
when drugs are mixed in i.v . Infusions causing precipitation or inactivation of active
principles .
Example:-
Ampicillin , chlorpromazine & barbituates interact with dextran in solutions
and are broken down or form chemical compounds.
Pharmaceutical interactions
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16. Interactions outside the body
• Mixing of the drugs in the same syringe
1. Thiopentone and succinylcholine.
2. Carbenicillin inactivate aminoglycosides.
3. Hydrocortisone inactivates penicillins.
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Fig:1

17. • Giving drug in i.v infusion
1. Quinopristin and Dalfopristin.
2. Ampicillin, sodium salts of phenytoin, heparin.
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Fig:2

18. Unstable
Infuse within 2-
4hrs
Stable for
6-8 hrs
Stable for
12 hrs
Photosensitive
drugs
Not infused
after 6 hrs
Ampicillin Benzyl penicillin Fluoxacillin Amphoterecin Cephaloridine
Erythromycin Diazepam Tetracycline Dacarbazine colistin
Stability of drugs in Saline or Dextrose solution
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Table:2

19. Prevention of Pharmaceutical Interactions
1. Give iv drugs by bolus.
2. Do not add infusion solutions.
3. Avoid mixing of drugs in the same infusion.
4. Mix the drug thoroughly in the infusion.
5. Use 2 separate infusion sites if drugs administered simultaneously .
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Fig:3

20. “These interactions are those in which ADME properties of the object drug is
altered by the precipitant and hence such interactions are also called as ADME
interactions”.
•The resultant effect is altered plasma concentration of the object drug.
PHARMACOKINETIC INTERACTIONS
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21. Interactions inside the body
Absorbtion Distribution
Excretion Metabolism
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22. .
Drug interactions can effect the rate and the extent of systemic
drug absorption (Bioavailability)from the absorption site, resulting in
increased or decreased drug bioavailability.
• Faster or slower drug absorption.
• More, or, less complete drug absorption.
Absorption interactions
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Fig:4

23. Surface
area
Motility
Alter GI
PH
Chelation &
Complexation
Alter
Intestinal
flora
Alter drug
transporter
s
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Fig:5

24. Drug-induced mucosal damage.
Antineoplastic agents: e.g., cyclophosphamide
vincristine
procarbazine
Inhibit absorption
of several drugs
eg., digoxin
Surface area
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25. Al 3+ , Mg 2+ + Prednisolone  Insoluble Complexes
Ca2+ + TC  Formation of chelating compounds
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Chelation and Complexation
Fig:6
Fig:7
Fig:8

26.  Antacid (aluminum or magnesium hydroxide) Decrease absorption of
ciprofloxacin by 85%
due to chelation
 Cholestyramine + Digoxin and Warfarin
(Resin)
BA of Digoxin and Warfarin
 Sodium polystyrene + cations Renal clearence of
bicorbonate resulting in
systemic acidosis
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27.  The non-ionized form of a drug is more lipid
soluble and more readily absorbed from GIT than the
ionized form does.
Alteration in pH
PH Absorption of
weak acids
PH Absorption of weak bases
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Fig:9

28. antiacids Decrease the tablet
dissolution
of Ketoconazole (acidic)
H2 antagonists
Therefore, these drugs must be separated by at least 2h
in the time of administration of both .
Increases absorption of weak
bases like
Anti coagulents, warfarin,
phenyl butazone
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29. Forming an absorbtive layer
 Cholestyramine inhibits absorbtion of Digoxin,warfarin
 Sucralfate interferes with absorbtion of Phenytoin
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Fig:10

30. Altered Gut flora
 Bacterial flora has a marked role in metabolization
of some drugs.
 Long term antibiotics may kill normal flora and
affect drug absorption.
Ex : erythromycin and digoxin
40% or more of the administered digoxin dose is
metabolised by the intestinal flora. Coadministration of
antibiotics leads to increase in digoxin levels.
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Fig:11

31. Metoclopramide
(antiemitic)
Increase absorption of cyclosporine due
to the increase of stomach empting time
Increase the toxicity
of cyclosporine
Altered gastric emptying
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Fig:12

32.  Atropine/opiods  reduce absorption of drugs
 Purgatives  decrease absorbtion of digoxin
 Psyllium + Fibre + fluid 
Increase in gi motility & decrease the time
available for coadministered drugs to be
absorbed
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33. Alteration of drug transporters
Oral drug inhibitor transporter
Digoxin quinidine P gp
Paclitaxel Cyclosporin P gp
Effect on Transporters
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Table:3
Fig:13

34. TCA
Antipsychotics
Corticosteroids
Sulfonylureas
Methylphenidate
Fenfluramine
Dexfenfluramine
Sibutramine
Orlistat
appetite
appetite
Alteration in appetite
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35. Beneficial absorbtion interactions
Metoclopramide
Increases gastric emptying
Increases absorbtion of
analgesic in treatment of
acute attack of migraine
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36. There is an important factor :
Vd
Protein binding interactions :
- unbound molecules remain free and pharmacological active.
- bound molecules are pharmacological inactive.
Some drugs may compete others for binding to protein depending on affinity
and concentration.
Distribution Interactions
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37. 10-12-2015 37Vignan pharmacy college
Displacement from
tissue binding site
Displacement from
protein binding site
Impaired renal excretion
Quinidine given to a patient on digoxin
1. Displacement from tissue binding sites

38. 2. Displacement from plasma protein binding
Can be clinically important if 2 criteria are fulfilled
 Drug should be highly protein bound (>90%)
 Low apparent volume of distribution
Precipitant drugs involved
1. Salicylates
2. Phenylbutazone
3. Sulfonamides
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39.  Warfarin (99% bound) and Phenytoin (90% bound)
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Fig:14 Fig:15

40. Metabolism (biotransformation) Interactions
• Most drugs are chemically altered within Liver to less
toxic and less lipid-soluble metabolites.
• Hepatic metabolism has two pathways :
– Phase 1 (modification)
– Phase 11 (conjugation)
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Fig:16

41. Pathways of drug metabolism
CYP450
Pathways of drug metabolism
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42. • CYP450 most important isoenzymes responsible
for liver metabolism.
– CYP 3A4
– CYP 2D6
– CYP 2C8
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Fig:17

43. Metabolism
Enzyme Induction
S No. Precipitant drug Object drug
1. Alcohol Warfarin, Phenytoin
2. Barbiturates Chlorpromazine, Phenytoin
3. Phenytoin Tolbutamide
4. Rifampicin Warfarin, Tolbutamide
5. St. John’s Wort Carbamazepine, SSRIs, Warfarin
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Table:4

44. Metabolism
Enzyme Inhibition
S No. Precipitant Drug Enzyme Object drug
1. Allopurinol Xanthine Oxidase Azathioprine
2. Carbidopa Dopa decarboxylase L-Dopa
3. Disulfiram Aldehyde dehydrogenase Alcohol
4. MAO Inhibitors Monomine Oxidase Amine containing
foods
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Table:5

45. S.no Precipitant drug Object drug Effect
1. Cimetidine Diazepam CNS effects
2. Macrolides Theophylline Cardiac toxicity
3. Metronidazole Alcohol Disulfiram like action
4. Chloramphenicol Tolbutamide Hypoglycemia
Enzyme Inhibition
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Table:6

46. Alteration in nutrient metabolism
Ex:
 Anticoagulant drug warfarin and vitamin K
 Statins inhibit HMG –CoA Reductase inhibitor – precursor for
cholesterol and coenzyme Q10
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47. Excretion Interactions
• Most drug are excreted in Urine or Bile.
• Some drugs are reabsorbed from renal tubules or
enterohepatic recirculation.
• Some drugs are excreted in acidic urine, so changing
urine PH will affect there serum level.
• These interaction is rare.
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Fig:18

48. Mechanisms :
• Altered urine PH
 Change in active tubular secretion.
Some drugs may compete for excretion.
E.g. probenecid and penicillin.
 Enterohepatic recirculation.
E.g. penicillins and oral contraceptives.
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49. Excretion
S. No. Precipitant Drug Object Drug Result
1. Probenecid Penicillin Penicillin Retention
2. Quinidine Digoxin Digoxin Toxicity
3. Salicylates Methotrextate Methotrexate toxicity
4. Salicylates Uricosuric Drugs Reduced Uricosuria
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Table:7

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Fig:19

51. Alteration in nutrient excretion
• D- penicillamine & EDTA binds metals Zn2+ and eliminates it via urine.
• Diuretics cause loss of ions such as Mg 2+ ,K+ ,Na+ , Ca 2+.
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52. Pharmacodynamic Interactions
A) Direct Pharmacodynamic Interactions
1. Antagonism at same site
● Opiates with Naloxone
● Warfarin with Vitamin K
 These interactions occur when the pharmacodynamic effect of the drug is alter by
another drug, chemical ,or food element, producing an antagonistic, synergistic , or
addtive effect
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Fig:20

53. 2. Synergism at same site
● Effects of depolarising skeletal muscle relaxants potentiated
by antibiotics like aminoglycosides, polymixin B
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54. Dihydropteroate diphosphate+ P-aminobenzoic acid(PABA)
Dihydropteroate synthetase sulfonamides
Dihydropteroic acid
Dihydrofolic acid
× trimethoprim
Tetrahydro folic acid
×
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Fig:21

55. 3. Summation of similar effects at different sites
● Effect of alcohol as a depressant potentiated by other
centrally acting drugs
● Effect of trimethoprim and sulfamethoxazole
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56. B) Indirect Pharmacodynamic Interactions
1. Cardiovascular system
 Loss of Antihypertensive action of ACEI with NSAIDS
 Bradycardia- beta blockers + verapamil
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2. Fluid and electrolyte imbalance
 Thiazide and loop diuretics - hypokalemia
3. CNS
 Sedation- BZD+ Alcohol

57. DRUG HERB
INTERACTION
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58. HERBS
Betel Nuts
Area Catechu
• Contains
arecoline
• Extrapyramida
l symptoms
Ginkgo Biloba
• Inhibits PAF
• spontaneous
Subarachnoid
hemorrhage
St. Johns Wort
Hypericum
perforatin
• Inducer of
CYP3A4
• May elevate
serotonin
Garlic
Allium sativum
• Increases INR
• Post operative
bleeding
Liquorice
Glycyrrhizin
• Inhibits
degradation
of cortisol
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59. • Polypharmacy people (elder)
• Hepatic disorders
• Renal disorders
• Genetic factors
Patients in high risk of drug interactions
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Fig:22
Fig:23 Fig:24
Fig:25

60. PHARMACIST’S ROLE IN DRUG INTERACTIONS
Advising
Monitoring
Reporting
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Fig:26
Fig:27

61.  Health care professionals and pharmacists have to play an important role in giving
advisory knowledge on monitoring concurrent use of herbal and conventional
medicines and to collect data for suspected drug interactions.
We need to bring into lime light about the drug
interactions
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62. REFERENCES
 LEON SHARGEL, ALANH.MUTNICK, PAULF.SOUNEY, LARRY
N.SWANSON, Comprehensive Pharmacy Review, Eight edition,
Pg.no: 271-276
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 ROGER WALKER & CATE WHITTLESEA, Clinical Pharmacy and
Therapeutics, 5th Edition, Pg.no: 52-59

63. 10-12-2015 Vignan pharmacy college 63
Online Drug Interaction
Checker
http://reference.medscape.com/drug-interactionchecker
,,,,,,,
https://online.epocrates.com/u/1300/MultiCheck?ICID
=search-DDI
,,,,,,
http://www.drugs.com/drug_interactions.html

64. THANKS
TO
ALL
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