Drug interactions

AKASH,PRINCE,SANKET1111038

DRUG INTERACTIONS

OUTLINE

DRUG INTERACTIONS - INTRODUCTION

DRUG – DRUG INTERACTIONS

FOOD – DRUG INTERACTIONS

DO WE REALLY NEED TO STUDY DRUG INTERACTIONS?

Meta analysis of 39 prospective clinical trials has proved : Adverse Drug Reactions are 4th most frequent cause of death1

Analysis of USA National Drug Register has proved : The cause of 2/3 of ADRs are drug interactions2

1Lazarou et al: JAMA 19982Phillips et al: JAMA 2001

DEFINITION

A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own.

Effects of drug interaction Drug interaction can result in

Increased effect – Additive or Synergistic effectIncreased therapeutic effect

goodIncreased toxic or adverse

effect bad Decreased effect – Antagonistic

effectDecreased therapeutic effect

badDecreased toxic effect

good Drug interactions usually happen

unexpectedly and result in adverse drug reactions

Drug interactions for good therapeutic effects are usually used intentionally and their results are already known by physicians

EXAMPLES Synergistic drug-drug interaction : xanax is a drug

which belongs to benzodiazepine class of drugs ,if it is taken along with an antidepressant like Prothiadine , the drowsiness effect of both drugs is enhanced and multiplied.

antagonistic drug-drug interaction : Ibuprofen enhances salt retention by the body and the diuretic like furosemide gets the body rid of the salt.

DIFFERENT KINDS OF DRUG INTERACTION

PHARMACOKINETIC (PK)

Drug interactions:

PHARMACODYNAMIC (PD)

Interaction drug - drug Interaction drug - alcohol Interaction drug - foods (and soft drinks) Interaction drug – food supplements

All these kinds are divided into:

Drug interactions: clinically relevant not clinically relevant

PHARMACOKINETIC INTERACTION Most drug interactions involve an

alteration in the pharmacokinetics of the drug.

Probably no ‘overlap’ in the therapeutic effects of the two drugs.

Difficult to predict 1. Absorption

2. Distribution

3. Metabolism

4. Excretion

Drug absorptio

n

Drug excretion

Drug metabolism

(biotransformation)

CYP3A4, CYP2D6, CYP2C9…

Drug displacemen

t (protein-binding)

Transport of the drug inside the

body

Drug Absorption Drug interactions can either delay the

onset of drug action or increase or decrease the amount of drug absorbed.

Rate of drug absorption is a concern when a fast onset of absorption is necessary.

An example of this would be analgesics. A rapid response is often desired when the patient is in pain.

This is important because it can ultimately affect drug levels.

Distribution

When the drug leaves the systemic circulation and moves to various parts of the body

Drugs in the bloodstream are often bound to plasma proteins; only unbound drugs can leave the blood and affect target organs

Low serum albumin can increase availability of drugs and potentiate their effects

Metabolism (biotransformation)

Primarily in the liver; cytochrome P-450 enzyme system facilitates drug metabolism; metabolism generally changes fat soluble compounds to water soluble compounds that can be excreted

Foods or dietary supplements that increase or inhibit these enzyme systems can change the rate or extent of drug metabolism

Excretion

• Drug interactions that involve excretion can affect the amount of drug that is either secreted or reabsorbed.

• Some strong acids/bases are actively secreted/reabsorbed by renal tubules.

• Digoxin excretion may be reduced by verapamil and quinidine.Some drugs sensitive to changes in urinary pH or sodium balance.

Pharmacodynamic mechanisms Two drugs acting upon the same (or

similar) mechanism in the same ‘direction’ (i.e. two agonists). E.g. Two beta-blockers additive E.g. Morphine plus diazepam additive E.g. Pen-G plus gentamicin synergistic

Two drugs acting upon the same (or similar) mechanism in opposite ‘directions’ (i.e. agonist plus antagonist). E.g. Beta-blocker plus salbutamol antagonistic E.g. Frusemide plus NSAID indirectly

antagonistic

Probability of drug interaction

0%

10%

20%

30%

40%

50%

60%

2 5 10 15 20

number of drugs used

risk

of dru

g inte

ract

ion

Probability of drug interaction rises with the number of drugs patient uses

More drug = More interactions

THANKS A LOT!