Lecture 31: Drug Interactions

Question 1

Where are drug interactions usually listed?

Answer 1

In product monographs

Question 2

What does information about the product monograph do?

Answer 2

Informs physicians about contraindicated conditions or potential drug interactions

Question 3

What kind of drugs are most susceptible to issues with drug interactions?

Answer 3

Drugs with a narrow therapeutic window

Question 4

What is a consequence of small change in a therapeutic window?

Answer 4

Small changes in our responsiveness can lead to toxic outcomes

Question 5

What are the types of Pharmacodynamic Interactions?

Answer 5

• Antagonistic Interactions
• Synergism or Additive interactions
• Indirect interactions

Question 6

How does Antagonistic Interaction work?

Answer 6

Drug A may act as an antagonist at a receptor for Drug B reducing the effectiveness of drug B

Question 7

what is an example of Antagonistic Interaction?

Answer 7

Vitamine K rich foods and Warfarin

Question 8

What is Warfarin?

Answer 8

An anticoagulant in patients with blood clots

Question 9

How does Warfarin work?

Answer 9

It inhibits Vitamin K epoxide reductase which recycles oxidized vitamin K to reduced vitamin K which is used in clotting factors

Question 10

What is Clotting closely monitored using?

Answer 10

The Prothrombin time

Question 11

What is Prothrombin Time?

Answer 11

A measure of time required for blood to clot under a set of standard lab conditions

Question 12

How is PT usually reported?

Answer 12

As INR

Question 13

What does a high INR mean?

Answer 13

The sample required a long time to form a clot like in the case of an individual taking warfarin

Question 14

How do foods rich in Vitamin K affect Warfarin?

Answer 14

They weaken the effectiveness of warfarin because they compete for occupancy of K epoxide reductase

Question 15

What is Synergism or Additive interactions?

Answer 15

When multiple agonists/modulators act on the same receptor leading to excessive activation

Question 16

What does Synergism refer to?

Answer 16

Effects that are greater than the individual effects of two drugs

Question 17

What does Additive refer to?

Answer 17

Effects that are roughly the sum of the individual effects of two drugs

Question 18

What is an example of Synergism or additive interactions?

Answer 18

Drugs like benzos, alcohol, barbiturates acting on GABAA receptors

Question 19

What kind of channel is the GABAA channel?

Answer 19

A chloride channel

Question 20

What are examples of Benzos?

Answer 20

• Xanax

* Valium

Question 21

How do Benzos affect GABAa?

Answer 21

They are positive allosteric modulators of GABAa

Question 22

What are Barbiturates to GABAA receptors?

Answer 22

They are positive allosteric modulators or agonists of GABAA

Question 23

What is Alcohol to GABAA receptors?

Answer 23

They are PAM of GABAa

Question 24

What are Zolpidem to GABAA receptors?

Answer 24

Positive allosteric modulators of GABAA

Question 25

What kind of interactions are Benzos, Barbiturates, Alcohol and Zolpidem at the same time?

Answer 25

Synergism or additive interactions

Question 26

What are Indirect reactions?

Answer 26

The effects of multiple drugs influence the same signalling pathways but not the same receptor

Question 27

What is an example of Indirect interactions?

Answer 27

Serotonin Syndrome

Question 28

What does Serotonin syndrome arise from?

Answer 28

Combinations of drugs that lead to overabundance of 5-HT/serotonin in the CNS and overstimulation of 5-HT receptors

Question 29

What is Serotonin Syndrome characterized by?

Answer 29

High body temperature, agitation, sweating, dilated pupils, muscle twitching, elevated BP

Question 30

What are the 6 key drugs involved in Serotonin Syndrome?

Answer 30

* Monoamine oxidase inhibitors * Tricyclic antidepressants, SSRIs and SNRIs * Opioids * St. John's wort * Recreational drugs (MDMA, methamphetamine) * Precursors of Serotonin

Question 31

How are MAOs involved in serotonin syndrome?

Answer 31

They prevent the breakdown of 5-HT. serotonin by MAO-A and lead to increased cellular levels of 5-HT

Question 32

How are Tricyclic antidepressants, SSRIs, and SNRIs involved in serotonin syndrome?

Answer 32

The prevent the reuptake of 5-HT from the synaptic cleft prolonging the lifetime of 5-HT in the synapse

Question 33

How are various opioids involved in serotonin syndrome?

Answer 33

Their metabolites may have direct serotonergic effects or interfere with serotonin reuptake

Question 34

How is St. John's wort involved in serotonin syndrome?

Answer 34

It acts as a serotonin reuptake inhibitor

Question 35

How are recreational drugs involved in involved in serotonin syndrome?

Answer 35

MDMA and Meth promote serotonin release by causing uptake pumps to act in reverse

Question 36

How Precursors of Serotonin involved in serotonin syndrome?

Answer 36

5-HTP and L-tryptophan are used as antidepressants

Question 37

What do Pharmacokinetic interactions do?

Answer 37

They alter drug availability

Question 38

What are the mechanisms that affect absorption and distribution (pharmacokinetic interactions)?

Answer 38

* Drugs that alter gut motility, pH, can alter the absorption of a drug * Drugs that alter local blood flow can alter absorption of a drug

Question 39

How can drugs./food affect CYP enzymes?

Answer 39

* they can induce the expression of specific CYP enzymes that will reduce the lifetime and abundance of their substrates * They inhibit CYP enzyme activity which will prolong the lifetime and activity of their substrates

Question 40

What is the most common enzyme for the biotransformation of drugs?

Answer 40

CYP3A4

Question 41

How does CYP3A4 affect warfarin?

Answer 41

It breaks down warfarin

Question 42

How does an increase in CYP3A4 affect warfarin?

Answer 42

People taking something that increase CYP3A4 will be resistant to warfarin because it breaks down warfarin

Question 43

What can inhibit CYP3A4?

Answer 43

Grapefruit juice