Drug Interactions Lecture Flashcards
What are the interesting facts taught in todays lecture?
- ⅔ patients who visit a doctor leave with at least one prescription for medication
- Around 12% of the Canadian population takes 4 or more prescription medications
- The use of multiple medications is known as polypharmacy
- Polypharmacy increases the risk of drug interactions
- It is very difficult to assess the overall clinical importance of many drug interactions (some interactions that are non-clinically related are not reported)
What were the conclusions of the hospital study?
- The rate of drug interactions in patients taking 6-10 drugs was 7%. Those taking 16-20 drugs have an increased rate of 40%
- Seniors taking >5 drugs are at risk of drug interactions at twice the amount based on the figure
What is a drug interaction?
An interaction between a drug and another substance that alters the pharmacological effect of the drug (can either be a pharmacodynamic or pharmacokinetic effect)
What result can occur from the interactions?
Beneficial, Adverse or Neutral.
What is a beneficial interaction?
Beneficial: enhanced therapeutic effect (for example: during an overdose, increasing elimination of that drug with another drug or substance can help save a life. Ex: taking two drugs together to get a specific beneficial effect)
What is an adverse interaction?
Adverse: reduced therapeutic effect (treatment failure) or increased side effects (toxicity)
What is a neutral reaction?
No clinically significant change
What are the types of drug interactions?
Drug - drug
Drug - nutrient
Drug - condition
What is a drug - drug interaction?
an interaction with another drug (prescription or over the counter)
What is a drug - nutrient interaction?
interaction with a food, beverage or supplement (ex: tyramine and MAOIS)
What is a drug - condition interaction?
interaction with a co-existing medical condition (ex: kidney or liver disease. These are key because they are the two main sites for metabolism/excretion and can alter the effect of the drug)
What are the two mechanisms that cause drug interactions?
Pharmacodynamics and Pharmacokinetics
What is pharmacodynamics in this respect?
(altered effect) - a drug/nutrient/condition that alters the pharmacological mechanism and or the final effect of another drug “what the drug does to the body”
What is pharmacokinetics in this respect?
(altered concentration) - a drug/nutrient/condition that alters the absorption, distribution, metabolism and/or excretion of another drug. It alters the plasma drug concentration.
“what the body does to the drug”
What are the two possible pharmacodynamic reactions?
Synergism and Antagonism
Explain Synergism
Potentiated or enhanced effect of a drug. In a synergistic relationship, both drugs have the same final effect, hence enhancing the effect.
What did the figure say about synergistic relationships and bacteria?
In combo with A and B, it increases the effect of drug A and decreases bacteria count to almost zero
Explain Antagonism
it causes a counteracting or opposing effect, and involves competition for the same receptor. The response of at least one drug is decreased.
In an antagonistic relationship, the drugs have different MOA and essentially change the psychological response.
What did the figure say about antagonistic relationships and bacteria?
When drug A and B are combined, the effectiveness of drug A is decreased and is less effective, hence there is more bacteria present and causes a treatment failure
Example using NSAIDS and antihypertensives
NSAIDS should not be used with antihypertensives as it counteracts the effect of antihypertensive by increasing blood pressure. This is because NSAIDS block COX enzymes. In the body within the inner lining of the blood vessel endothelial cells, it produces COX which allows the conversion of acid into prostacyclin; a powerful vasodilator. This drug works to increase the diameter of the blood well to decrease BP. If NSAID inhibits COX, then the blood vessels stay constrained and hence cause an increased BP.
Where do the PD drug interactions occur?
Receptors (sensitivity is decreased), Signalling Second Messenger Pathways, and effectors (physiological response)
Where do the pharmacokinetic drug interactions?
in the ADME process
What are the drug interactions in the Absorption stage?
Overall, faster or slower drug absorption or incomplete absorption.
Altered GI motility - (this reduces the rate of absorption of the drug that may need to be dissolved in the stomach)
Altered pH at the site of absorption - For example a drug like a proton pump inhibitor can inhibit the production of hydrogen ions, hence increasing the pH. This can effect ionization of some drugs which, reduce their ability to absorb.
Chelation of compounds- Chelation is when organic molecules form bonds with ionic molecules. This forms an insoluble compound that is unable to pass through the bloodstream. (do not take pills with milk or positive ion containing products)
Why do interactions involving absorption generally have effects when the drug is administered orally?
Drugs that are administered orally have more barriers to face than IV.
What are the drug interactions in the Distribution stage?
This causes an overall change in the plasma protein binding. A drug that may be protein bound may get displaced by another drug, hence increasing the amount of “free” drug in the system. This as a result, could cause toxicity.
- in general it is not usually clinically significant and effects drugs that are highly protein bound (>90%).
What are the drug interactions in the Metabolism stage? (most commonly seen drug interaction)
Altered metabolism by inhibition or induction of CYP 450 enzymes.
What does inhibition do?
Reduced activity of enzymes, causes toxicity.
What does induction do?
increase activity of enzymes, and causes a sub-therapeutic effect
Does induction or inhibition happen faster?
Inhibition happens rapidly and is often reversibly, whereas induction occurs gradually and sometimes takes days or weeks.
What are the drug interactions in the Excretion stage?
- Altered renal tubular function
- Altered renal flow: reduced blood flow to the glomerus where drug is filtered, hence reducing the amount of drug excreted.
- Altered urinary pH: increase in pH can cause a drug to stay ionized,
Who is at highest risk for drug interactions?
- Old individuals or very young individuals
- Very sick individuals or those with diseases/disorders
- Use of multiple medications (higher percentage risk based on the study)
- Those who have renal/ liver impairment
What are the high risk drug/substances?
- Drugs with a narrow therapeutic index
- Known enzyme inhibitors or inducers
Management of drug interactions?
- Severity may require immediate discontinuation of the medication
- Dose-related events may be managed by changing the dose
- Switching to another drug, dose spacing between medications, or sometimes food restrictions
How to reduce the risk of drug interactions?
- Take drugs as instructed
- Learn about drug interactions associated with
- Keep a list of all drugs taken and discuss with doctor or pharmacist
- Report symptoms
- Consult doctor before taking new drugs or dietary supplements
