DRUG-DRUG INTERACTION OF PULMONARY
CONCERN
By

Mahmoud E. Abou El-Magd
INTRODUCTION
• An interaction occurs when the effects of one drug are changed
by another drug, food, drink or exposure to ...
RISK FACTORS
• Genetic make up .
• Multiple prescribers .

• Multiple pharmacies .
• Specific population like e.g, females...
OUTCOMES OF DRUG INTERACTIONS
1) Loss of therapeutic effect .

2) Toxicity .
3) Beneficial effects e.g additive & potentia...
DRUG - DRUG INTERACTIONS

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Mechanisms

DRUG - DRUG INTERACTIONS

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TYPES OF PHARMACOKINETIC INTERACTION.

DRUG - DRUG INTERACTIONS

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ALTERED GIT ABSORPTION.
•Altered pH
•Altered bacterial flora
• formation of drug chelates or complexes
• drug induced muco...
TYPES OF PHARMACOKINETIC INTERACTION.

DRUG - DRUG INTERACTIONS

9
CYP450 ISOENZYMES
• Present in lipid layer of the endoplasmic reticulum of
hepatocytes .
• Major enzymes involved in metab...
CYTOCHROME P450 (CYP450)
• Inducer
• Speeds up metabolism
• Decreases substrate level (lack of efficacy is concern)
• Grad...
DRUG - DRUG INTERACTIONS

12
DRUG - DRUG INTERACTIONS

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PHARMACODYNEMIC INTERACTION
It means alteration of the dug action without change in its
serum concentration by pharmacokin...
DIRECT PHARMACODYNAMIC INTERACTIONS:
In which drugs having similar or opposing pharmacological effects are
used concurrent...
INDIRECT PHARMACODYNAMIC INTERACTION:
In which both the object and the precipitant drugs have unrelated
effects.but the la...
PHARMACEUTICAL INTERACTIONS
Also called as incompatibility.it is a physicochemical interaction that

occous when drugs are...
Examples

DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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MISCELLANEOUS ANTIBACTERIAL
ANTIBIOTICS

DRUG - DRUG INTERACTIONS

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ANTIMYCOBACTERIAL AGENTS

DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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ANTICOAGULANTS/THROMBOLYTIC
AGENTS

DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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ANTICONVULSANTS

DRUG - DRUG INTERACTIONS

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ANTINEOPLASTIC AGENTS

DRUG - DRUG INTERACTIONS

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BRONCHODILATORS

DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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CORTICOSTEROIDS

DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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FOOD-DRUG INTERACTIONS…
• -Advise patients to take medication with a full glass of
water.
• -Do not take vitamin pills at ...
INFLUENCE OF FOOD ON DRUG INTERACTION:
 Food effects the rate and extent of absorption of drugs from the
GI tract.
Exampl...
DRUG INDUCED NUTRITIONAL EFICIENCIES
DRUG
ANTIEPILECTIC DRUGS
(phenytion ,
phenobarbitone, primidone,
valproic acid)

AFFE...
DRUG

AFFECTED
NUTRIENTS

POSSIBLE
MECHANISM

EFFECT

CORTICOSTEROIDS

Calcium

Decreased Ca, vitamin D
metabolism

Bone d...
DRUG

AFFECTED
NUTRIENTS

POSSIBLE
MECHANISM

EFFECT

PARA – AMINO
SALICYCLIC (PAS)

Vitamin B12

decreased absorption

Me...
DRUG - DRUG INTERACTIONS

50
INFLUENCE OF SMOKING ON DRUG
INTERACTIONS ?!!

DRUG - DRUG INTERACTIONS

51
INFLUENCE OF ALCOHOL ON DRUG
INTERACTION ?!!

DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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DRUG - DRUG INTERACTIONS

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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.
  • Drug - Drug Interaction of pulmonary concern

    1. 1. DRUG-DRUG INTERACTION OF PULMONARY CONCERN By Mahmoud E. Abou El-Magd
    2. 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 . DRUG - DRUG INTERACTIONS 2
    3. 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 . DRUG - DRUG INTERACTIONS 3
    4. 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 . DRUG - DRUG INTERACTIONS 4
    5. 5. DRUG - DRUG INTERACTIONS 5
    6. 6. Mechanisms DRUG - DRUG INTERACTIONS 6
    7. 7. TYPES OF PHARMACOKINETIC INTERACTION. DRUG - DRUG INTERACTIONS 7
    8. 8. ALTERED GIT ABSORPTION. •Altered pH •Altered bacterial flora • formation of drug chelates or complexes • drug induced mucosal damage • altered GIT motility. DRUG - DRUG INTERACTIONS 8
    9. 9. TYPES OF PHARMACOKINETIC INTERACTION. DRUG - DRUG INTERACTIONS 9
    10. 10. CYP450 ISOENZYMES • Present in lipid layer of the endoplasmic reticulum of hepatocytes . • Major enzymes involved in metabolism and bioactivation . • About 75% of reactions . DRUG - DRUG INTERACTIONS 10
    11. 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 DRUG - DRUG INTERACTIONS 11
    12. 12. DRUG - DRUG INTERACTIONS 12
    13. 13. DRUG - DRUG INTERACTIONS 13
    14. 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 DRUG - DRUG INTERACTIONS 14
    15. 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. DRUG - DRUG INTERACTIONS 15
    16. 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. DRUG - DRUG INTERACTIONS 16
    17. 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 . DRUG - DRUG INTERACTIONS 17
    18. 18. Examples DRUG - DRUG INTERACTIONS 18
    19. 19. DRUG - DRUG INTERACTIONS 19
    20. 20. DRUG - DRUG INTERACTIONS 20
    21. 21. DRUG - DRUG INTERACTIONS 21
    22. 22. DRUG - DRUG INTERACTIONS 22
    23. 23. DRUG - DRUG INTERACTIONS 23
    24. 24. DRUG - DRUG INTERACTIONS 24
    25. 25. DRUG - DRUG INTERACTIONS 25
    26. 26. MISCELLANEOUS ANTIBACTERIAL ANTIBIOTICS DRUG - DRUG INTERACTIONS 26
    27. 27. ANTIMYCOBACTERIAL AGENTS DRUG - DRUG INTERACTIONS 27
    28. 28. DRUG - DRUG INTERACTIONS 28
    29. 29. ANTICOAGULANTS/THROMBOLYTIC AGENTS DRUG - DRUG INTERACTIONS 29
    30. 30. DRUG - DRUG INTERACTIONS 30
    31. 31. DRUG - DRUG INTERACTIONS 31
    32. 32. DRUG - DRUG INTERACTIONS 32
    33. 33. ANTICONVULSANTS DRUG - DRUG INTERACTIONS 33
    34. 34. ANTINEOPLASTIC AGENTS DRUG - DRUG INTERACTIONS 34
    35. 35. BRONCHODILATORS DRUG - DRUG INTERACTIONS 35
    36. 36. DRUG - DRUG INTERACTIONS 36
    37. 37. DRUG - DRUG INTERACTIONS 37
    38. 38. CORTICOSTEROIDS DRUG - DRUG INTERACTIONS 38
    39. 39. DRUG - DRUG INTERACTIONS 39
    40. 40. DRUG - DRUG INTERACTIONS 40
    41. 41. DRUG - DRUG INTERACTIONS 41
    42. 42. DRUG - DRUG INTERACTIONS 42
    43. 43. DRUG - DRUG INTERACTIONS 43
    44. 44. DRUG - DRUG INTERACTIONS 44
    45. 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. DRUG - DRUG INTERACTIONS 45
    46. 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 DRUG - DRUG INTERACTIONS 46
    47. 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 DRUG - DRUG INTERACTIONS 47
    48. 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 DRUG - DRUG INTERACTIONS 48
    49. 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 DRUG - DRUG INTERACTIONS 49
    50. 50. DRUG - DRUG INTERACTIONS 50
    51. 51. INFLUENCE OF SMOKING ON DRUG INTERACTIONS ?!! DRUG - DRUG INTERACTIONS 51
    52. 52. INFLUENCE OF ALCOHOL ON DRUG INTERACTION ?!! DRUG - DRUG INTERACTIONS 52
    53. 53. DRUG - DRUG INTERACTIONS 53
    54. 54. DRUG - DRUG INTERACTIONS 54
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