Pharmacology: Drug-Drug Interactions

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Questions and Answers

What are the two main groups of drug transporter proteins?

P-glycoprotein and solute carrier superfamily

ATP-binding cassette family and solute carrier superfamily (correct)

P-glycoprotein and OATP

ATP-binding cassette family and P-glycoprotein

How does the inhibition of P-glycoprotein in enterocytes affect drug availability?

Does not affect drug absorption

Decreases oral bioavailability

Increases oral bioavailability (correct)

Reduces systemic absorption

What major adverse effects were identified with the drug cisapride?

Severe allergic reactions

Liver toxicity

Venticular arrhythmias (correct)

Kidney damage

What is one of the key mechanisms through which drug interactions can occur?

Drug transporter proteins Signup and view all the answers

Which factor can lead to the discontinuation of a drug like cisapride in the United States?

Major adverse events Signup and view all the answers

What does the inhibition of P-glycoprotein in the liver or kidney typically result in?

Reduced drug elimination Signup and view all the answers

How can potentially clinically relevant drug-drug interactions be identified?

Retrospective cohort studies Signup and view all the answers

What affects the amount of drug entering hepatocytes during metabolism?

OATP1B1 activity Signup and view all the answers

What is polypharmacy typically defined as?

The routine administration of five or more medications. Signup and view all the answers

Which step in the deprescribing process involves assessing each medication for potential drug-related harm?

Weighing benefits against harms for each medication. Signup and view all the answers

What are clinical pharmacists encouraged to monitor after discontinuing medications?

Improvements in patient outcomes or any adverse effects. Signup and view all the answers

Which patient characteristic is a risk factor for polypharmacy?

Manifesting advanced or end-stage disease. Signup and view all the answers

What is one of the negative consequences of polypharmacy?

Increased health care use. Signup and view all the answers

What should clinical pharmacists consider in patients with new symptoms potentially indicative of an adverse drug reaction?

The possibility of deprescribing some medications. Signup and view all the answers

When targeting medications for deprescribing, which should be prioritized?

Medications with the highest burden and lowest benefit. Signup and view all the answers

Which statement best describes the role of clinical pharmacists in relation to polypharmacy?

They can help prevent drug interactions through deprescribing. Signup and view all the answers

What is a significant risk factor for drug interactions in older adults?

Receiving several medications for chronic conditions Signup and view all the answers

What steps should be taken to prevent potential drug interactions?

Use deprescribing resources like the Beers Criteria Signup and view all the answers

What is defined as polypharmacy?

Routine use of five or more medications Signup and view all the answers

What should you do after obtaining a complete medication list from the patient?

Determine an indication for each product Signup and view all the answers

Which of the following increases a patient's drug interaction risk?

Experiencing multiple chronic diseases Signup and view all the answers

What should be monitored when discontinuing a medication?

Potential adverse effects and improved outcomes Signup and view all the answers

Which of the following is NOT a suggested method for managing drug interaction risk?

Engaging in regular physical activity Signup and view all the answers

What is an appropriate action if a patient cannot recall their natural product use?

Query further to obtain additional details Signup and view all the answers

What is an example of altered absorption due to changes in GI pH?

Decreased bioavailability of posaconazole with PPIs Signup and view all the answers

What mechanism describes the interaction when one drug binds to another and reduces its absorption?

Adsorption and chelation Signup and view all the answers

What is the outcome of induction of drug transporter proteins?

Decreased absorption of digoxin Signup and view all the answers

In which type of drug interaction does competition for serum protein binding sites occur?

Protein binding Signup and view all the answers

What effect does carbamazepine have on simvastatin metabolism?

Induces CYP3A4 enzyme activity Signup and view all the answers

An example of enzyme inhibition affecting drug metabolism is:

Increased warfarin concentrations with amiodarone Signup and view all the answers

How does metoclopramide affect cyclosporine absorption?

It enhances gut motility Signup and view all the answers

What is a consequence of increased first-pass metabolism?

Decreased absorption of ritonavir Signup and view all the answers

Which mechanism is involved in the increased exposure of drugs in the CNS due to drug interactions?

Modulation of drug transporter proteins Signup and view all the answers

What happens when drug binding sites on serum proteins are competed for?

Increased risk of toxicity Signup and view all the answers

What type of information is primarily included in Specialty Drug Interaction Resources?

Overall warning statement and mechanism of interaction Signup and view all the answers

What severity level category describes an interaction with limited clinical effects?

Minor Signup and view all the answers

Which authors are known for the textbook 'Drug Interactions, Analysis and Management'?

Hansten and Horn Signup and view all the answers

What resource provides a focus on both professional and consumer data regarding drug interactions?

Drugs.com Signup and view all the answers

Which of the following interactions does Gold Standard monitor?

Interactions with caffeine and grapefruit juice Signup and view all the answers

What kind of data does Hansten and Horn's 2019 book include?

Individual monographs for the top 100 interactions Signup and view all the answers

What is the primary focus of the open access site mentioned for clinical pharmacists?

Drug interactions with warfarin Signup and view all the answers

Which resource is specifically noted for providing thorough reference data on drug interactions?

Hansten and Horn’s Drug Interactions Signup and view all the answers

Study Notes

Common DDI mechanisms

One drug can change the pH of the GI tract and alter the absorption of another drug - For example posaconazole suspensions absorption can be reduced when taken with PPIs.
Drug absorption can be reduced by adsorption, chelation, or complexing of one drug with another where the combination is poorly soluble. For example tetracycline absorption is reduced when taken with antacids
Changes in GI motility can affect the absorption of drugs. Increased motility from metoclopramide can enhance cyclosporine exposure
Drug transporter proteins in the gastrointestinal tract can lead to changes in the absorption of a drug. For example, rifampin, increases the activity of P-glycoprotein, decreasing the absorption of disoxin
Drug interactions can also occur when two drugs compete for the same protein binding sites. Valproic acid can displace warfarin from its binding sites, leading to increased warfarin exposure

Mechanism of drug interactions and distribution

Drug interactions can occur during distribution when a drug changes the uptake of another drug to a site of action. For example, ketoconazole can inhibit P-glycoprotein leading to an increase of ritonavir in the CNS.
Drug interactions can affect metabolism through changes to first-pass metabolism. For example, verapamil can increase dofetilide concentrations, which can lead to serious heart complications.
Drugs can induce the production of enzymes that metabolize other drugs. For example, carbamazepine can increase the activity of CYP3A4, decreasing the concentration of simvastatin.
Drugs can inhibit the activity of the enzymes that metabolize other drugs. For example, amiodarone can inhibit the activity of CYP2C9, CYP3A4, and CYP1A2, increasing the concentration of warfarin.

Drug transporter proteins

Drug transporter proteins affect the pharmacokinetics of drugs within the body through uptake and efflux actions.
Important examples of drug transporter proteins include the ATP-binding cassette family and the solute carrier superfamily

Polypharmacy

Polypharmacy is the routine administration of five or more medications.
Polypharmacy is growing and leads to:
- reduced quality of life
- increased risk of adverse events
- increased risk of mortality
- increased healthcare costs

Deprescribing

Deprescribing is the process of discontinuing medications.
It is considered to be a risk reduction and management strategy used in polypharmacy.

Drug interaction resources

Clinical pharmacists can use several resources to help identify and manage drug interactions. This includes:
- Hansten and Horn’s Drug Interactions
- Stockley’s Drug Interactions
- Drugs.com
- Gold Standard

Using resources and patient management

Clinical pharmacists need to consider several factors when using drug interaction resources:
- Type and extent of information in each resource
- Target audience of the resource
- Consumer focused vs. Healthcare professional focused
- Drug interaction details
- Clinical management, including appropriate monitoring.

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Description

This quiz explores common mechanisms of drug-drug interactions, focusing on how one drug can impact the absorption and efficacy of another. Key concepts include changes in pH, GI motility, transporter proteins, and protein binding sites. Test your knowledge on these crucial pharmacological principles.