By

Mahmoud E. Abou El-Magd

DRUG-DRUG INTER-ACTION OF

PULMONARY CONCERN

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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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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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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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Mechanisms

Mechanisms

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TYPES OF PHARMACOKINETIC INTERACTION.

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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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TYPES OF PHARMACOKINETIC INTERACTION.

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CYP450 ISOENZYMES

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• 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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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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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

PHARMACODYNEMIC INTERACTION

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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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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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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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ExamplesExamples

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MISCELLANEOUS ANTIBACTERIAL ANTIBIOTICS

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ANTIMYCOBACTERIAL AGENTS

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ANTICOAGULANTS/THROMBOLYTIC AGENTS

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ANTICONVULSANTS

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ANTINEOPLASTIC AGENTS

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BRONCHODILATORS

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CORTICOSTEROIDS

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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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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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DRUG INDUCED NUTRITIONAL EFICIENCIES

DRUG AFFECTED NUTRIENTS POSSIBLE MECHANISM EFFECT

ANTIEPILECTIC DRUGS (phenytion , phenobarbitone, primidone, valproic acid)

FolateVitamin DVitamin EZinc

SeleniumVitamin K

Decreased absorptionEnzyme induction Excess utilization ?Chelation

Peroxide damage?

Megaloblastic anemiaOsteomalacia Haemolysis Anorexia , celebellar dysfunctionHepatotoxicityHemorrhage

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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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

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POSSIBLE MECHANISM

EFFECT

ISONIAZED (INH) Pyridoxine Complex formation Peripheral neuropathy, Convulsions, psychatric manifestation

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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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INFLUENCE OF SMOKING ON DRUG INTERACTIONS ?!!

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INFLUENCE OF ALCOHOL ON DRUG INTERACTION ?!!

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