Lecture 31: Drug Interactions Flashcards
Where are drug interactions usually listed?
In product monographs
What does information about the product monograph do?
Informs physicians about contraindicated conditions or potential drug interactions
What kind of drugs are most susceptible to issues with drug interactions?
Drugs with a narrow therapeutic window
What is a consequence of small change in a therapeutic window?
Small changes in our responsiveness can lead to toxic outcomes
What are the types of Pharmacodynamic Interactions?
- Antagonistic Interactions
- Synergism or Additive interactions
- Indirect interactions
How does Antagonistic Interaction work?
Drug A may act as an antagonist at a receptor for Drug B reducing the effectiveness of drug B
what is an example of Antagonistic Interaction?
Vitamine K rich foods and Warfarin
What is Warfarin?
An anticoagulant in patients with blood clots
How does Warfarin work?
It inhibits Vitamin K epoxide reductase which recycles oxidized vitamin K to reduced vitamin K which is used in clotting factors
What is Clotting closely monitored using?
The Prothrombin time
What is Prothrombin Time?
A measure of time required for blood to clot under a set of standard lab conditions
How is PT usually reported?
As INR
What does a high INR mean?
The sample required a long time to form a clot like in the case of an individual taking warfarin
How do foods rich in Vitamin K affect Warfarin?
They weaken the effectiveness of warfarin because they compete for occupancy of K epoxide reductase
What is Synergism or Additive interactions?
When multiple agonists/modulators act on the same receptor leading to excessive activation
What does Synergism refer to?
Effects that are greater than the individual effects of two drugs
What does Additive refer to?
Effects that are roughly the sum of the individual effects of two drugs
What is an example of Synergism or additive interactions?
Drugs like benzos, alcohol, barbiturates acting on GABAA receptors
What kind of channel is the GABAA channel?
A chloride channel
What are examples of Benzos?
- Xanax
* Valium
How do Benzos affect GABAa?
They are positive allosteric modulators of GABAa
What are Barbiturates to GABAA receptors?
They are positive allosteric modulators or agonists of GABAA
What is Alcohol to GABAA receptors?
They are PAM of GABAa
What are Zolpidem to GABAA receptors?
Positive allosteric modulators of GABAA
What kind of interactions are Benzos, Barbiturates, Alcohol and Zolpidem at the same time?
Synergism or additive interactions
What are Indirect reactions?
The effects of multiple drugs influence the same signalling pathways but not the same receptor
What is an example of Indirect interactions?
Serotonin Syndrome
What does Serotonin syndrome arise from?
Combinations of drugs that lead to overabundance of 5-HT/serotonin in the CNS and overstimulation of 5-HT receptors
What is Serotonin Syndrome characterized by?
High body temperature, agitation, sweating, dilated pupils, muscle twitching, elevated BP
What are the 6 key drugs involved in Serotonin Syndrome?
- Monoamine oxidase inhibitors
- Tricyclic antidepressants, SSRIs and SNRIs
- Opioids
- St. John’s wort
- Recreational drugs (MDMA, methamphetamine)
- Precursors of Serotonin
How are MAOs involved in serotonin syndrome?
They prevent the breakdown of 5-HT. serotonin by MAO-A and lead to increased cellular levels of 5-HT
How are Tricyclic antidepressants, SSRIs, and SNRIs involved in serotonin syndrome?
The prevent the reuptake of 5-HT from the synaptic cleft prolonging the lifetime of 5-HT in the synapse
How are various opioids involved in serotonin syndrome?
Their metabolites may have direct serotonergic effects or interfere with serotonin reuptake
How is St. John’s wort involved in serotonin syndrome?
It acts as a serotonin reuptake inhibitor
How are recreational drugs involved in involved in serotonin syndrome?
MDMA and Meth promote serotonin release by causing uptake pumps to act in reverse
How Precursors of Serotonin involved in serotonin syndrome?
5-HTP and L-tryptophan are used as antidepressants
What do Pharmacokinetic interactions do?
They alter drug availability
What are the mechanisms that affect absorption and distribution (pharmacokinetic interactions)?
- 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
How can drugs./food affect CYP enzymes?
- 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
What is the most common enzyme for the biotransformation of drugs?
CYP3A4
How does CYP3A4 affect warfarin?
It breaks down warfarin
How does an increase in CYP3A4 affect warfarin?
People taking something that increase CYP3A4 will be resistant to warfarin because it breaks down warfarin
What can inhibit CYP3A4?
Grapefruit juice
