2. DRUG INTERACTION
Multiple drug therapy
Drug monitoring and supervision
Contribution in providing safe drug therapy
Definition:
Situation in which the effect of one drug are altered by
prior or concurrent administration of another drug.
Factors responsible for DI :
1. Food and dietary products
2. Lab test results
3. Exposure to Chemicals
4. Alcohol
5. Smoking
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3. To study the interaction:
Interacting drugs can usually be used together with
closer drug monitoring of therapy.
Beneficial Interaction.
Second drug is used to modify effect of first e.g.
probenecid is given to increase the effect of penicillin
derivative.
Antiparkinson drug with antipsychotic agent.
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4. Reasons for DI:
Drug Potency
- influence physiological systems
- two drugs affect on same system in the body
Patient consult several Physicians
- pharmacist role
Use of prescription and Non prescription drug
e.g. Aspirin, antacids
Patient Non-compliance
Directions not followed
Drug abuse or misuse
Antichiatric Drugs taken by depressed patients
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5. Factors causing Drug Interaction:
Variables influence the activity of drug
- Dosage
- Route of administration
- Time of administration
- Sequence of administration
- Duration of therapy
Age (pediatric and geriatric patients)
Genetics (unexpected drug response)
Disease state
- Impaired renal function (excreted unchanged)
- Impaired hepatic function (metabolized slowly)
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6. Types of Drug Interactions:
Drug-Drug Interaction
-Primary attention on drug-drug interaction
- Controlled and investigated
i) Prescription Drugs
- not clinically significant
- Contraindicated
- DI is not only among Drugs having different therapeutics
action but also among drugs used for the same disease condition
- Enteric coated tablet of aspirin and ferrous sulphate (with
antacid tablet)
ii) Over the Counter Products (OTC)
- Self medication of drugs
- Pharmacist recommendations are imp
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7. Drug- Food Interaction
- Food modify absorption pattern
e.g. Riboflavin absorption , Penicillin & Tetra
- Type of food e.g Griseofulvin with fatty meal
- Dietary products e.g. Tetracycline derivative
- Alcoholic beverages
- Data collected from health team members and
coordinate with patient
Drug Alcohol Interaction
- Heavy drinking speed up metabolism (liver
enzyme)
e.g. warfarin, phenytoin, tolbutamide
- with depressant drugs synergistic effect.
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8. Drug smoke interaction
- Smoking increases drug metabolism in liver so
certain agent metabolized more rapidly and therapeutic
effect decreases
e.g. activity of Daizepam , Chlordiazepoxide less
in heavy smokers than light smokers
Drug- Laboratory test interaction
- Drug interfere with laboratory test results due to
their chemical nature
- wrong interpretation
Drug- Environmental
- patient contact with environmental contaminants
- Industrial fumes, solvent vapours, pesticides
DDT
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9. Pharmacokinetics Interaction
ADME pattern of one drug is altered in presence of
another drug.
Pharmacodynamics interaction
Altered action of drug due to concurrent
administration of another drug having similar or
apposing pharmacological action
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10. Pharmacokinetics Interaction
1. Alteration of GI Absorption
2. Alteration of Distribution
3. Alteration of Metabolism
4. Alteration of Excretion
Pharmacodynamics interaction
1. Drug having Opposing Pharmacological Effects
2. Drug having similar Pharmacological effect
3. Alteration of electrolyte levels
4. Alternation of receptor site interaction
5. Antibiotic Combination
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11. Pharmacokinetics Interaction
1. Alteration of GI Absorption
Change in the absorption of a drug by different mechanism
Absorption may be delayed (in case of rapid relief)
Slower absorption (hypnotic agents)
Penicillin G (degraded in stomach)
i) Alternation of pH:
-Lipid Soluble
-Ionized-nonionized form
e.g. Phenobarbital-Antacid
Pseudoephedrine-Antacid (aluminum hydroxide gel)
ii) Complexation and Adsorption
e.g. Tetracyclines- metals (form complex which is
poorly soluble)
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12. iii) Alternation of motility:
e.g. Cathartics (increases GI motility- increases the rate at
which drug passes through GI tract)
iv) Effect of Surfactants:
Surfactant interact with biological membrane and modify
membrane permeability- rate and extent of absorption.
v) Inhibition of GI enzymes:
e.g. Folic acid-Phenytoin
Polyglutamate to monoglutamate by intestinal enzyme
which is inhibited by phenytoin
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13. 2. Alteration of Distribution
i) Displacement from Protein binding site
- Drug that are capable of binding to protein site
- Noncompetitive Displacement
- Competitive Displacement
- Affinity of drug
e.g. warfarin-Phenylbutazone (affinity for albumin-hemorrhage)
3. Alternation of Metabolism
i) Stimulation of metabolism
- Enzyme induction
- Favor the conversation to more active form
e.g. Phenytoin-Phenobarbital (later on stimulate microsomal
enzyme activity- decrease in blood serum level of phenytoin )
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14. ii) Inhibition of metabolism
One drug inhibit metabolism of second by inhibiting
enzyme responsible
e.g. Alcohol- Disulfiram
Alcohol-Acetaldehyde by aldehyde dehydrogenase which
is inhibited by disulfiram
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15. 4. Alternation of Excretion
i) Alternation of Urinary pH
- alternation affect drugs that are excreted in
unchanged form or in the form of an active metabolite.
e.g. Methanamine-Acidifying agents
(Methanamine converted into active formaldehyde at low pH so
acidifying agents are given to low pH)
ii) Interference with urinary excretion
e.g. Penicillins-Probenecids
(Probenecid blocks tubular excretion of penicillin and
increases serum level)
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16. Pharmacodynamics Interactions
1. Drug having Opposing Pharmacological Effects
-Drugs that have apposite pharmacological effects
- Antagonism
e.g. CNS depressant - stimulants
2. Drug having similar Pharmacological Effects
e.g. Alcohol-sedative
3. Alternation of electrolyte level
-therapy with diuretics deplete the conc. Of electrolyte.
e.g. Digitalis Glycoside- Calcium
(increased level of calcium increases the sensitivity of DG to
heart)
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17. 4. Alternation of receptor site interaction
- Increases the effect of another drug by increasing its
affinity towards receptor site
e.g. Warfari-Dextrothyroxine
5. Antibiotic Combinations
- Antagonism effects are observed when bacteriostatic
(tetracyclines) drugs administered with bactericidal
(penicillin)
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