DRUG INTERACTIONS

DRUG INTERACTIONS

 DEFINITION

Drug interaction is defined as the pharmacological activity of  one drug is altered by the concominant use of another drug or by the presence of some other substance.

The Drug whose Activity is effected by such an Interaction is called as a “Object drug.”

 The agent which precipitates such an interaction is refered to as the “Precipitant”.

1.Drug-drug interactions.

2.Drug-food interactions.

3.Chemical-drug interactions.

4.Drug-laboratory test interactions.

5.Drug-disease interactions.

The Net effect of a Drug Interaction is:

Generally quantitative i.e.increased or decreased effect.

Seldom qualitative i.e.rapid or slower effect.

Precipitation of newer or increased adverse effect.

Drug interactions are thus-

Mostly undesirable

Rarely desirable(beneficial): for eg.,enhancement of activity of penicillins when administered with probenecid.

Factors contributing to drug interactions:

1.Multiple drug therapy.

2.Multiple prescribers.

3.Multiple pharmacological effects of drug.

4.Multiple diseases/predisposing illness.

5.Poor patient compliance.

6.Advancing age of patient.

7.Drug-related factors.

Mechanisms of drug interactions:

     

The three mechanisms by which an interaction can develop are-

1.Pharmaceutical interactions.

2.pharmacokinetic interactions.

3.Pharmacodynamic interactions.

   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 .

Example:-

Ampicillin ,chlorpromazine &barbituates interact with dextran in solutions and are broken down or from chemical compounds.

Pharmacokinetic Interactions:

“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.

These are classified as:
1.Absorption interactions
2.Distribution interactions
3.Metabolism interactions
4.Excretion interactions.

Absorption  interactions

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Are those where the absorption of the object drug is altered. The net effect of such an interaction is:

 Faster or slower drug absorption.

 More, or, less complete drug absorption.

Major mechanisms of absorption interactions are:

1.Complexation and adsorption.

2.Alteration in GI pH.

3.Alteration in gut motility.

4.Inhibition of GI enzymes.

5.Alteration of GI micro flora.

6.Malabsorption syndrome.

Distribution interactions

Are those where the distribution pattern of the object  drug is altered :

The major mechanism for distribution interaction is alteration in protein-drug binding.

METABOLISM INTERACTIONS:

Are those where the metabolism of the object drug is altered.

Mechanisms of metabolism interactions include:

1.Enzyme induction: 

Increased rate of metabolism.

2.Enzyme inhibition:

Decreased rate of metabolism. It is the most significant  interaction in comparison to  other  interactions and can be fatal.

EXCRETION INTERACTIONS

Are these where the excretion pattern of the object drug is altered. Major mechanisms of excretion interactions are-

Alteration in renal blood flow

Alteration of urine PH

Competition for active secretions

Forced diuresis

Pharmacodynamic interactions:

Are those in which the activity of the object drug at its site of action is altered by the precipitant. Such interactions may be direct or indirect.

1.These are of two types1.direct pharmacodynamic                   interactions.                                                                          2.Indirect  pharmacodynamic interactions.

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.

Antagonism:

The interacting drugs have opposing actions 

Example: Acetylcholine and noradrenaline have opposing effects on heart rate.

Addition or summation:

The interacting drugs have similar actions and the resultant effect is the some of individual drug responses

Example:CNS depressants like sedatives and hypnotics,…etc

Synergism or potentiation:

It is an enhancement  of action of one drug by another 

Example: Alcohol enhances the analgesics activity of aspirin.

Indirect pharmacodynamic interaction:

In which both the object and the precipitant drugs have unrelated effects.but the latter in Some way alerts the effects but latter in some way alerts the effectsof the former.

Example: salicylatesdecrease the ability of the platelets to aggregate thus impairing the Homeostasis if warfarin indused bleeding occurs.

CONSEQUENCES OF DRUG INTERACTIONS:

The consequences of drug interactions may be:

Major: Life threatening.

Moderate: Deteriotion of patients status.

Minor: Little effect.

REDUSING THE RISK OF DRUG  INTERACTIONS:

1.Identify the patients risk factors.

2.Take  through drug history.

3.Be knowledge about the actions of the drugs being used.

4.Consider therapeutic alternatives.

5Avoid complex therapeutic regiments when possible.

6.Educate the patient.

7.Monitor therapy.

INFLUENCE OF SMOKING ON DRUG INTERACTIONS:

Smoking increases the activity of drug metabolizing enzymes in the liver, With the result that certain therapeutic agents.

Example: Diazepam, propoxyphene, theophylline, olanzapine.

Are metabolized more rapidly,and their effect is decreased.

INFLUENCE OF ALCOHOL ON DRUG INTERACTION:

Chronic use of alcohol beverages may increases the rate of metabolism of drugs such as warfarin and phenytoin, probably by increasing the activity of hepatic enzymes.

Acute use of alcohol by non alcoholic individuals may cause an inhibition of hepatic enzymes.

Use of alcoholic beverages with sedatives and other depressants drugs could result in an excessive depressant response.

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.

The type of food may be important with regard to the absorption of concurrently administered Drugs.

Example: Dietary items such as milk and other dairy products that contain calcium may decrease .

The absorption of tetracycline and  flouroquinolone derivatives.

Diet also may influence urinary  pH  values.