2. INTRODUCTION
• An interaction occurs when the effects of one drug are changed
by another drug, food, drink or exposure to an environmental
chemical.
• A drug interaction occurs when two or more drugs interact in
such a way that the effectiveness or toxicity of one or more of
the drugs is altered.
• Interactions can be harmful, either by increasing the toxicity of a
drug or by reducing its efficacy. However, some drug
interactions can also be beneficial .
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3. RISK FACTORS
• Genetic make up .
• Multiple prescribers .
• Multiple pharmacies .
• Specific population like e.g, females , elderly, obese, criticaly ill
patient , trasplant recipient .
• Specific illness E.g. Hepatic disease, Renal dysfunction .
• Narrow therapeutic index drugs as warfarin , digoxin ,
theophyllin .
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4. OUTCOMES OF DRUG INTERACTIONS
1) Loss of therapeutic effect .
2) Toxicity .
3) Beneficial effects e.g additive & potentiation (intended) or
antagonism (unintended).
4) Chemical or physical interaction e.g I.V incompatibility in
fluid or syringes mixture .
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8. ALTERED GIT ABSORPTION.
•Altered pH
•Altered bacterial flora
• formation of drug chelates or complexes
• drug induced mucosal damage
• altered GIT motility.
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10. CYP450 ISOENZYMES
• Present in lipid layer of the endoplasmic reticulum of
hepatocytes .
• Major enzymes involved in metabolism and bioactivation .
• About 75% of reactions .
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11. CYTOCHROME P450 (CYP450)
• Inducer
• Speeds up metabolism
• Decreases substrate level (lack of efficacy is concern)
• Gradual onset/offset
• Inhibitor
• Slows metabolism
• Increases substrate level (toxicity is concern)
• Quick onset/offset
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14. PHARMACODYNEMIC INTERACTION
It means alteration of the dug action without change in its
serum concentration by pharmacokinetic factors.
These are of two types
1.direct pharmacodynamic interactions.
2.Indirect pharmacodynamic interactions
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15. DIRECT PHARMACODYNAMIC INTERACTIONS:
In which drugs having similar or opposing pharmacological effects are
used concurrently.
The three consequences of direct interactions are
1.Antagonism.
2.Addition or summation.
3.Synergism or potentiation.
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16. INDIRECT PHARMACODYNAMIC INTERACTION:
In which both the object and the precipitant drugs have unrelated
effects.but the latter in Some way alerts the effects of the former.
Example: salicylatesdecrease the ability of the platelets to aggregate
thus impairing the Homeostasis if warfarin indused bleeding occurs.
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17. PHARMACEUTICAL INTERACTIONS
Also called as incompatibility.it is a physicochemical interaction that
occous when drugs are mixed in i.v . Infusions causing precipitation
or inactivation of active principles .
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45. FOOD-DRUG INTERACTIONS…
• -Advise patients to take medication with a full glass of
water.
• -Do not take vitamin pills at the same time you take
medication (i.e, take medication 1 hour after taking
vitamins).
• -Not mix medication into hot drinks, because the heat
from the drink may destroy the effectiveness of the
drug.
• -Never take medication with alcoholic drinks.
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46. INFLUENCE OF FOOD ON DRUG INTERACTION:
Food effects the rate and extent of absorption of drugs from the
GI tract.
Example: Many anti biotics should be given atleast 1hr before or 2hr
after meals to achieve Optimal absorption.
Diet also may influence urinary pH values.
Lime juice is most acidic
Milk products alter pH
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47. DRUG INDUCED NUTRITIONAL EFICIENCIES
DRUG
ANTIEPILECTIC DRUGS
(phenytion ,
phenobarbitone, primidone,
valproic acid)
AFFECTED NUTRIENTS
POSSIBLE MECHANISM
EFFECT
Folate
Vitamin D
Vitamin E
Zinc
Decreased absorption
Enzyme induction
Excess utilization ?
Chelation
Selenium
Vitamin K
Peroxide damage
?
Megaloblastic anemia
Osteomalacia
Haemolysis
Anorexia , celebellar
dysfunction
Hepatotoxicity
Hemorrhage
ANTIFOLATE DRUGS
(e.g. methotrexate,
pyrimethamine,
trimethamine, trimethoprim)
Folate
Dihydrofolate reductase
inhibition
Megaloblastic anemia,
cytopenia
CEPHALOSPORINS
(Cefamendole,
cefoperazone, latamoxef)
Vitamin K
Decreased prothrombin
synthesis
Bleeding episodes
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48. DRUG
AFFECTED
NUTRIENTS
POSSIBLE
MECHANISM
EFFECT
CORTICOSTEROIDS
Calcium
Decreased Ca, vitamin D
metabolism
Bone disorders
COUMARIN
ANTICOGULANTS
Vitamin K
?
Hemorrhage
DIURETICS
Zn , Ca, K, Mg
Urinary loss depression
Weakness , electrolyte
imbalance
DRUG
AFFECTED
NUTRIENTS
POSSIBLE
MECHANISM
EFFECT
ISONIAZED (INH)
Pyridoxine
Complex formation
Peripheral neuropathy,
Convulsions, psychatric
manifestation
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49. DRUG
AFFECTED
NUTRIENTS
POSSIBLE
MECHANISM
EFFECT
PARA – AMINO
SALICYCLIC (PAS)
Vitamin B12
decreased absorption
Megaloblastic anaemia
POTASSIUM CHLORIDE
Vitamin B12
decreased ileal Ph
Decreased absorption
RIFAMPCIN
Vitamin D
Enzyme induction
Osteomalacia
SALICYLATES
Vitamin C, Folate
Increased excretion,
decreased uptake
Anemia ,infection
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for example, an additive effect is seen when diuretics and beta-blockers are combined to treat hypertension
Antacids and binding agents such as cholestyramine may impair absorption of other drugs from the gastrointestinal tract by forming complexes with them.For example, antacids reduce the absorption of quinolones such as ciprofloxacin. Otherdrugs, such as metoclopramide or opiates, may affect gut transit time. This generally influences the rate, rather than the extent, of drug absorption. Most absorption interactions are not clinically significant and can be managed by separating the administration of the drugsDrug displacement interactions occur when two drugs compete for the same protein binding site and one or both is displaced. This results in an increase in the concentration of free (active) drug, but is usually compensated for by an increase in excretion.These interactions usually involve highly protein bound drugs such as phenytoin, warfarin and tolbutamide. However, the effects of displacement interactions are usually minor and transient.Many drugs are metabolised in the liver, mainly by the cytochrome P450 enzyme system. Induction of enzymes by one drug can increase the rate of metabolism of another, resulting in a reduced effect. Conversely, enzyme inhibitors may result in accumulation and increased toxicity of other drugsFinally, drugs that alter renal excretion can affect plasma levels of other drugs. For example, methotrexate and non-steroidalanti-inflammatory drugs compete for renal excretion. Concomitant use of these agents may result inraised methotrexate levels and an increased risk of toxicity, although this combination may be used successfully under specialist supervision. The importance of this type of interaction depends on the extentto which a drug and/or its metabolites are renally excreted.The mechanism of an interaction can also have an effect on its time course.Enzyme inducers stimulate the production of new metabolising enzymes and it often takes between one and three weeks before their effects are at a maximum. In contrast, enzyme inhibitors usually have an effect on hepatic metabolism within 24 hours.
Antacids and binding agents such as cholestyramine may impair absorption of other drugs from the gastrointestinal tract by forming complexes with them.For example, antacids reduce the absorption of quinolones such as ciprofloxacin. Otherdrugs, such as metoclopramide or opiates, may affect gut transit time. This generally influences the rate, rather than the extent, of drug absorption. Most absorption interactions are not clinically significant and can be managed by separating the administration of the drugsDrug displacement interactions occur when two drugs compete for the same protein binding site and one or both is displaced. This results in an increase in the concentration of free (active) drug, but is usually compensated for by an increase in excretion.These interactions usually involve highly protein bound drugs such as phenytoin, warfarin and tolbutamide. However, the effects of displacement interactions are usually minor and transient.Many drugs are metabolised in the liver, mainly by the cytochrome P450 enzyme system. Induction of enzymes by one drug can increase the rate of metabolism of another, resulting in a reduced effect. Conversely, enzyme inhibitors may result in accumulation and increased toxicity of other drugsFinally, drugs that alter renal excretion can affect plasma levels of other drugs. For example, methotrexate and non-steroidalanti-inflammatory drugs compete for renal excretion. Concomitant use of these agents may result inraised methotrexate levels and an increased risk of toxicity, although this combination may be used successfully under specialist supervision. The importance of this type of interaction depends on the extentto which a drug and/or its metabolites are renally excreted.The mechanism of an interaction can also have an effect on its time course.Enzyme inducers stimulate the production of new metabolising enzymes and it often takes between one and three weeks before their effects are at a maximum. In contrast, enzyme inhibitors usually have an effect on hepatic metabolism within 24 hours.