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					      Drug interactions
Definition;
 It is the modification of the effect of one drug
    (the object drug ) by the prior concomitant
  administration of another (precipitant drug).
Why Study Pharmacokinetics (PK)
and Pharmacodynamics (PD)?

 Individualize patient drug therapy
 Monitor medications with a narrow therapeutic index
 Decrease the risk of adverse effects while maximizing
  pharmacologic response of medications
 Evaluate PK/PD as a diagnostic tool for underlying
  disease states
Outcomes of drug interactions
1) Loss of therapeutic effect
2) Toxicity
3) Unexpected increase in pharmacological activity
4) Beneficial effects e.g additive & potentiation
   (intended) or antagonism (unintended).
5) Chemical or physical interaction
       e.g I.V incompatibility in fluid or syringes mixture
Outcomes of Drug Interactions
 Harmful
    increased toxicity
    decreased efficacy
 No clinical significance
 Beneficial
    increased activity
   eg penicillins/cephalosporins with probenecid
    When prescribing medicines a
 doctor’s aim should be to achieve
an appropriate concentration
of an appropriate drug
at an appropriate receptor
for an appropriate length of time
           Drug Interactions



Outside Body                   Pharmacokinetic
Pharmaceutical

                 Pharmacodynamic
Why worry……Who cares……………

Most of the time it’s not a problem even if there are drug interactions (High
Therapeutic Index)

BUT BUT BUT

Combination of particular drugs is dangerous

Commonly occurs in drugs with a Low Therapeutic Index

                  Anticoagulants
                  Antidysrhythmics
                  Anticonvulsants
                  Immunosuppressants
                  Mood Stabilizers
Drug Interactions
 Possible methods of classification
   Beneficial or Harmful
   By Pharmacological group
   By individual drug
   By mechanism of interaction
Mechanisms of Drug Interaction
 Pharmacokinetic
    Reduced rate and/or completeness of absorption
    Altered bioavailabilty
    Reduced plasma protein binding
    Altered tissue distribution
    Altered hepatic metabolism
    Altered renal excretion
    Haemodynamic interactions

 Pharmacodynamic
    Potentiation/antagonism at target receptor
    Potentiation at non-target receptor
    Alteration of fluid/electrolyte environment
    Interference with transport mechanisms
Pharmacokinetic Interactions
 Outcome is a direct effect of change in drug level
 Chance of interaction occurring difficult to predict
 Nature of interaction can be predicted
Pharmacodynamics
 Study of the biochemical and physiologic
 processes underlying drug action
   Mechanism of drug action
     Drug-receptor interaction

   Efficacy
   Safety profile
 “What the drug does to the body”
    Cellular level
    General
Pharmacodynamic Interactions

 Decreased effectiveness
 Increased effectiveness/toxicity
 Predictable within a class of drugs
Risk factors:
1) High risk drugs; these are the drugs that show a narrow
   therapeutic index e.g., corticosteroids, rifampin,
   oral contraceptives, quinidine, lidocaine

2) High risk patients; these are the groups of patients
   that should be treated with caution due to a specific
   heath condition e.g., pregnant women, malignant cases,
  diabetic patients, patients with liver or kidney disorders
  asthmatic patients and cardiac disorders.
Older Persons at Risk
 Multiple chronic disease states
 Multiple prescribers
 Multiple medications (interactions/ADRs)
 Lack of education
 Poor adherence with complex drug regimens
 Age related physiological changes
 Declining cognition/sensorium
 Non-prescription medications
Onset of drug interaction
 It may be seconds up to weeks for example in case of
enzyme induction, it needs weeks for protein synthesis,
while enzyme inhibition occurs rapidly.
 The onset of action of a drug may be affected by the
half lives of the drugs e.g., cimitidine inhibits
metabolism of theophylline.
   Cimitidine has a long half life, while, theophylline
has a short one.
  When cimitidine is administered to a patient regimen
for Theophylline, interaction takes place in one day.
Pharmacodynamic Interactions:
 Similar Clinical Responses
     Different brands of same drug
     Beta-blockers/verapamil/amiodarone/digoxin
     ACEIs/ARBs/K+/K-sparing diuretics
     CNS depressants/CNS depressants/Alcohol
     Anticholinergics/anticholinergics
     Nitrates with silendafil (Viagra)
     Additive Antihypotensive/Antihypertensive effects
     Methotrexate + co-trimoxazole
     “Serotonin syndrome”
Pharmacodynamic Interactions:
 Opposing Clinical Responses
     NSAIDs X Antihypertensives
     Diuretics X Hypoglycaemics
     β –blockers X β-agonists
     CNS depressants X
      Sympathomimetics/Caffeine
     Warfarin X Vitamin K
     Lithium X NSAIDs
Pharmacodynamic Interactions:
   Alterations of Electrolyte Levels
     ACEIs, ARBs X K-sparing diuretics, K supplements


     Diuretics X Digoxin
     NSAIDS /Sodium intake X Lithium (ex)
     NSAIDS X Antihypertensive agents
Prevention of drug interaction
1) Monitoring therapy and making adjustments

2) Monitoring blood level of some drugs with narrow
   therapeutic index e.g., digoxin, anticancer agents…etc

3) Monitoring some parameters that may help to characterize the
   early events of interaction or toxicity e.g., with warffarin
   administration, it is recommended to monitor the prothrombin
   time to detect any change in the drug activity.

4) Increase the interest of case report studies to report different
   possibilities of drug interaction
Things to Remember
 Interactions are easily forgotten when prescribing
 Interactions are difficult to remember
 Pharmacodynamic interactions can often be predicted
  across drug classes
 Pharmacokinetic interactions can not be predicted –
  experiments needed
 Many interactions probably remain undescribed – so look
  out for them
 The chances of interaction are 60 times higher in a patient
  taking 5 drugs than in one taking 2.

				
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posted:8/31/2012
language:English
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