PHAR 300 Lecture Notes - Lecture 8: Methotrexate, Clopidogrel, Imipramine
7 Jun 2018
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PHAR300
Drug interactions
Common issue
-in the hospital, patients often receive more than 20 drugs
-with each additional drug, the possibility for interaction will increase
-combination of prescription and over the counter drugs can happen
-relationship between number of drugs and side effects is linear (the more drugs we take at the
same time the greater risk we have to have side effects)
-some people have multiple disorders at the same time
-e.g. recent paper showed co-morbodity of people with various diseases => people with
chronic diseases often have more than one
-smoking is common in most of these diseases
-poor lifestyle -> people end up with multiple diseases at the same time => multiple
medications at the same time => more drug interactions
Drug interactions
-sometimes beneficial
-most of the time we end up with difficulties, which can usually be avoided ahead of time
-interactions even with herbal remedies (as long as there is biological action)
-information for consumers is widely available
-we also have to be careful with prescription medication and «!recreational!» drugs
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-many interactions with alcohol
-we can also have drug interactions with food, plants (because they have chemicals)
-anutrient chemicals found in food : 625 in coffee!! -> roasted coffee is a mixture of over
1000 bioactive compounds (slightly different number depending on how the coffee is made)
-anutrient chemicals also found in beef, wine, tomato, banana, orange juice, cheddar cheese
Drug-drug interactions
-why do we still observe these types of interactions ?
-the physician may not be aware of them
-computer screening may not have worked
-pharmacist may not be aware of what other drugs people are taking
-patient risk factors can vary depending on the lifestyle
-drug administration
-patient education -> whether or not we pay attention to what we have been told
-whether or not people are monitored
-outcome of drug interactions is highly variable
-patient factors : genetics, diseases, diet/nutrition, environment, smoking, alcohol
-drug administration : dose, duration, dosing times, sequence (drug A before drug B or the
other way around), route, dosage form
Classification of drug interactions
-consequence : beneficial or adverse
-site : external (pretty rare) or internal
-mechanism : pharmacodynamic, pharmacokinetic, physiologic (action of one drug is opposite to
the action of the other drug)
Results of drug interactions
-additive
-synergistic : unexpected larger outcomes
-potentiation : one drug has an effect, the other one not ; when put together we have a larger
outcome
-antagonism : same as potentiation except that the result is half the expected outcome
Pharmacokinetic mechanisms
-possibility for interaction of a second drug at any point from absorption to excretion
-alter plasma level of the drug
-ideally, we want complete separation between efficacy and toxicity curves BUT with
pharmacokinetic interactions, we may end up moving the efficacy curve closer to the toxicity
curve
-absorption : oral -> stomach -> small intestine
-when it reaches the stomach, we have gastric pH, if
empty stomach we have hydrochloric acid so the pH
is about 1.- ; we can alter it to treat gastritis
-e.g. if we take tetracycline with antacid or with milk,
we get binding of the drug to calcium in the milk =>
the complex is not absorbed
-e.g. calcium carbonate inhibits Thyroxine absorption
: 49 year-old woman on thyroxine 150mcg/day
developed symptoms of hyperthyroidism and
increased TSH -> patient was taking Tums TID and
one Tums was taken with thyroxine -> she was
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Document Summary
In the hospital, patients often receive more than 20 drugs. With each additional drug, the possibility for interaction will increase. Combination of prescription and over the counter drugs can happen. Relationship between number of drugs and side effects is linear (the more drugs we take at the same time the greater risk we have to have side effects) Some people have multiple disorders at the same time. E. g. recent paper showed co-morbodity of people with various diseases => people with chronic diseases often have more than one. Smoking is common in most of these diseases. Poor lifestyle -> people end up with multiple diseases at the same time => multiple medications at the same time => more drug interactions. Most of the time we end up with dif culties, which can usually be avoided ahead of time. Interactions even with herbal remedies (as long as there is biological action)
