Drug Interactions Lecture

Question 1

What are the interesting facts taught in todays lecture?

Answer 1

• 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)

Question 2

What were the conclusions of the hospital study?

Answer 2

• 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

Question 3

What is a drug interaction?

Answer 3

An interaction between a drug and another substance that alters the pharmacological effect of the drug (can either be a pharmacodynamic or pharmacokinetic effect)

Question 4

What result can occur from the interactions?

Answer 4

Beneficial, Adverse or Neutral.

Question 5

What is a beneficial interaction?

Answer 5

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)

Question 6

What is an adverse interaction?

Answer 6

Adverse: reduced therapeutic effect (treatment failure) or increased side effects (toxicity)

Question 7

What is a neutral reaction?

Answer 7

No clinically significant change

Question 8

What are the types of drug interactions?

Answer 8

Drug - drug
Drug - nutrient
Drug - condition

Question 9

What is a drug - drug interaction?

Answer 9

an interaction with another drug (prescription or over the counter)

Question 10

What is a drug - nutrient interaction?

Answer 10

interaction with a food, beverage or supplement (ex: tyramine and MAOIS)

Question 11

What is a drug - condition interaction?

Answer 11

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)

Question 12

What are the two mechanisms that cause drug interactions?

Answer 12

Pharmacodynamics and Pharmacokinetics

Question 13

What is pharmacodynamics in this respect?

Answer 13

(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”

Question 14

What is pharmacokinetics in this respect?

Answer 14

(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”

Question 15

What are the two possible pharmacodynamic reactions?

Answer 15

Synergism and Antagonism

Question 16

Explain Synergism

Answer 16

Potentiated or enhanced effect of a drug. In a synergistic relationship, both drugs have the same final effect, hence enhancing the effect.

Question 17

What did the figure say about synergistic relationships and bacteria?

Answer 17

In combo with A and B, it increases the effect of drug A and decreases bacteria count to almost zero

Question 18

Explain Antagonism

Answer 18

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.

Question 19

What did the figure say about antagonistic relationships and bacteria?

Answer 19

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

Question 20

Example using NSAIDS and antihypertensives

Answer 20

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.

Question 21

Where do the PD drug interactions occur?

Answer 21

Receptors (sensitivity is decreased), Signalling Second Messenger Pathways, and effectors (physiological response)

Question 22

Where do the pharmacokinetic drug interactions?

Answer 22

in the ADME process

Question 23

What are the drug interactions in the Absorption stage?

Answer 23

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)

Question 24

Why do interactions involving absorption generally have effects when the drug is administered orally?

Answer 24

Drugs that are administered orally have more barriers to face than IV.

Question 25

What are the drug interactions in the Distribution stage?

Answer 25

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%).

Question 26

What are the drug interactions in the Metabolism stage? (most commonly seen drug interaction)

Answer 26

Altered metabolism by inhibition or induction of CYP 450 enzymes.

Question 27

What does inhibition do?

Answer 27

Reduced activity of enzymes, causes toxicity.

Question 28

What does induction do?

Answer 28

increase activity of enzymes, and causes a sub-therapeutic effect

Question 29

Does induction or inhibition happen faster?

Answer 29

Inhibition happens rapidly and is often reversibly, whereas induction occurs gradually and sometimes takes days or weeks.

Question 30

What are the drug interactions in the Excretion stage?

Answer 30

• 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,

Question 31

Who is at highest risk for drug interactions?

Answer 31

• 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

Question 32

What are the high risk drug/substances?

Answer 32

• Drugs with a narrow therapeutic index

- Known enzyme inhibitors or inducers

Question 33

Management of drug interactions?

Answer 33

• 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

Question 34

How to reduce the risk of drug interactions?

Answer 34

• 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