713 311 PRINCIPLES OF VETERINARY PHARMACOLOGY

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Pharmacodynamics Drug Interaction
Topic 11

• 713 311 PRINCIPLES OF VETERINARY PHARMACOLOGY
• Dr. Korawuth Punareewattana

Faculty of Veterinary Medicine, Khon Kaen
University
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Topics on Drug Interactions

• Definition
• Effects of drug interaction
• Types of drug interaction
• Pharmaceutical interaction
• Pharmacodynamic interaction
• Pharmacokinetic interaction

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Definition

• Drug interaction can be defined as the
  modifications of the effects of one drug by the
  prior or concomitant of another drug
  (poly-pharmacy)
• 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.

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Effects of drug interaction

• Drug interaction can result in
• Increased effect Additive or Synergistic effect
• Increased therapeutic effect good
• Increased toxic or adverse effect bad
• Decreased effect Antagonistic effect
• Decreased therapeutic effect bad
• Decreased 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

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Drug-Drug interaction may alter drug effect by

• Additive effect 1 1 2
• Synergistic effect 1 1 gt 2
• Potentiation effect 1 0 2
• Antagonism 1 - 1 0 or 0.5

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Effect of Drug interaction

• Therapeutic drug interaction could be used in 2
  objectives
• To produce synergistic therapeutic effects
• Examples are found by several antibiotic
  combinations
• Penicillin-Sreptomycin
• Penicillin-Probenecid
• Sulfa-trimethoprim
• To detoxify or lower toxic effects
• Examples are those antidotes of certain toxic
  agents
• Xylazine-Yohimbine

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Types of drug interaction

• There are at least 3 types of drug interaction
• Pharmaceutical interaction minor
• Pharmacodynamic (PD) interaction major
• Pharmacokinetic (PK) interaction major

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Pharmaceutical interaction

• Interactions that occur prior to systemic
  administration
• At manufacturing process
• At clinical process by mixing 2 or more drugs in
  the same container
• Drug incompatibility having drug interaction
• Drug compatability no interaction
• Chemical or Physical interactions
• Usually result in pharmacological loss

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Pharmacodynamic interaction

• Definition interaction that one drug may cause
  changes in another drug action, effect or
  response without PK alteration
• Pharmacodynamic interaction could result in
  either
• Additive effect
• Synergistic effect
• Antagonistic effect
• Pharmacodynamic interaction can happen at these
  levels
• Level of drug action
• Level of drug effect
• Level of drug response
• At this level, it could be called Physiological
  interaction

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Pharmacokinetic interaction

• Pharmacokinetic (PK) interactions sometimes are
  also referred to as dispositional interactions.
• These interactions are characterized by the
  alteration of the PK or disposition (ADME) of one
  drug by another.
• Change in absorption
• Change in distribution
• Change in Metabolism
• Change in Excretion
• Important PK interactions are those associated
  with
• Altered drug metabolism
• Drug transporters
• Protein binding

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PK interaction associated with altered drug
metabolism

• Altered phase I metabolism
• CYP induction
• CYP inhibition
• Altered phase II metabolism
• Induction of phase II enzyme
• UDP-glucuronyl transferases (UGTs)
• Inhibition of phase II enzyme
• Competitive use of conjugate molecules

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PK interaction associated with drug transporters

• Transporters Playing Key Roles in Drug Absorption
  and Excretion
• Important drug transporters
• P-glycoproteins (PgP)
• very important for excretion processes
• Other transporters
• Interaction usually result in
• Inhibit function of transporters
• And inhibit drug excretion
• And finally cause AUC of a drug to increase or
  more drug in the body

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Examples of Clinically Significant Drug
interactions Associated with Inhibition of
Transporters Other Than PgP
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PK interaction associated with Protein binding

• The major plasma proteins to which most drugs
  bind are albumin and a1-acid glycoprotein the
  former typically binds acidic, anionic drugs
  whereas the latter typically favors basic drugs
• Competitive protein binding by another drug will
  result in increase concentration of free drug,
  and that will yield more drug response