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 deat...
DEFINITION
A

drug interaction
is a situation in
which a substance
affects the activity
of a drug, i.e. the
effects are
i...
Effects of drug interaction


Drug interaction can result in
 Increased

effect – Additive or
Synergistic effect
 Incre...
EXAMPLES


Synergistic drug-drug interaction : xanax is a drug which
belongs to benzodiazepine class of drugs ,if it is t...
DIFFERENT KINDS OF DRUG
INTERACTION
PHARMACOKINETIC (PK)
Drug interactions:
PHARMACODYNAMIC (PD)


Interaction drug - dru...
PHARMACOKINETIC INTERACTION





Most drug interactions involve an
alteration in the pharmacokinetics of the
drug.
Prob...
Drug
absorption

Transport of

the drug inside
the body

Drug
displacement
(protein-binding)

Drug metabolism
(biotransfor...
Drug Absorption
 Drug

interactions can either delay the onset
of drug action or increase or decrease the
amount of drug ...
Distribution


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



Drugs in the bloo...
Metabolism
(biotransformation)


Primarily in the liver; cytochrome P-450 enzyme
system facilitates drug metabolism; meta...
Excretion
• Drug interactions that involve
excretion can affect the amount
of drug that is either secreted or
reabsorbed.
...
Pharmacodynamic
mechanisms


Two drugs acting upon the same (or similar)
mechanism in the same ‘direction’ (i.e. two
agon...
Probability of drug interaction

risk of drug interaction

60%
50%
40%
30%
20%
10%
0%
2

5

10

15

20

number of drugs us...
More drug = More interactions
Drug interactions
Drug interactions
Drug interactions
Drug interactions
Drug interactions
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Drug interactions

  1. 1. OUTLINE  DRUG INTERACTIONS - INTRODUCTION  DRUG – DRUG INTERACTIONS  FOOD – DRUG INTERACTIONS
  2. 2. DO WE REALLY NEED TO STUDY DRUG INTERACTIONS?
  3. 3.  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 2Phillips et al: JAMA 1998 et al: JAMA 2001
  4. 4. 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
  5. 5. Effects of drug interaction  Drug interaction can result in  Increased effect – Additive or Synergistic effect  Increased therapeutic effect  Increased toxic or adverse effect good bad  Decreased effect effect – Antagonistic  Decreased therapeutic effect  Decreased toxic effect bad good
  6. 6. 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.
  7. 7. 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
  8. 8. 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
  9. 9. Drug absorption Transport of the drug inside the body Drug displacement (protein-binding) Drug metabolism (biotransformation) CYP3A4, CYP2D6, CYP2C9… Drug excretion
  10. 10. 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.
  11. 11. 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
  12. 12. 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
  13. 13. 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.
  14. 14. 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
  15. 15. Probability of drug interaction risk of drug interaction 60% 50% 40% 30% 20% 10% 0% 2 5 10 15 20 number of drugs used Probability of drug interaction rises with the number of drugs patient uses
  16. 16. More drug = More interactions
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