Basics of Drug Interactions

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Questions and Answers

A patient's TSH level is 83 mIU/L. What does this indicate?

  • The patient's thyroid gland is producing too little thyroid hormone. (correct)
  • The patient's thyroid gland is functioning normally.
  • The patient's thyroid gland is producing too much thyroid hormone.
  • The patient's TSH level is within the normal range.

Which of the following best describes the mechanism of drug interactions that affect absorption?

  • Induction of drug-metabolizing enzymes.
  • Direct inhibition of enzyme activity.
  • Alterations in solubility or chelation. (correct)
  • Competition for protein binding sites.

Drug interactions that involve protein binding primarily affect which aspect of drug action?

  • Distribution. (correct)
  • Metabolism.
  • Absorption.
  • Excretion.

What is the primary site of action for CYP450 enzymes?

<p>Liver and Intestines. (D)</p> Signup and view all the answers

What can happen when drugs compete for the same CYP450 enzyme subgroup?

<p>Increased metabolism of one drug and decreased metabolism of the other. (A)</p> Signup and view all the answers

What type of drug interaction is described in the text?

<p>Pharmacokinetic (B)</p> Signup and view all the answers

Which of the following pharmacokinetic parameters can be affected by drug interactions?

<p>All of the above (D)</p> Signup and view all the answers

What is the primary goal of managing pharmacokinetic interactions?

<p>To keep the plasma drug concentration of the affected drug relatively unchanged (D)</p> Signup and view all the answers

How can increased absorption interactions be influenced?

<p>All of the above (D)</p> Signup and view all the answers

Which of the following is NOT a characteristic of P-glycoprotein (P-gp)?

<p>P-gp inducers can increase the concentration of P-gp substrates. (A)</p> Signup and view all the answers

What is an example of a medication whose absorption is affected by antacids?

<p>Levothyroxine (A)</p> Signup and view all the answers

What is the primary role of Organic Anion Transporting Polypeptides (OAT-P) in drug metabolism?

<p>They mediate the uptake of medications and endogenous compounds by the liver. (A)</p> Signup and view all the answers

Which type of drug interaction primarily leads to increased drug bioavailability?

<p>Enzyme inhibition (D)</p> Signup and view all the answers

Why might spacing dose administration be a viable way of managing absorption interactions?

<p>To minimize the effect of the interacting drug on absorption (C)</p> Signup and view all the answers

What is the potential impact of long-term antibiotic use on drug absorption?

<p>Decreased absorption of other medications (A)</p> Signup and view all the answers

What is the primary consequence of enzyme induction in drug metabolism?

<p>Decreased drug levels in the body (D)</p> Signup and view all the answers

Which of the following statements is TRUE about the duration of drug interaction effects?

<p>Both enzyme inhibition and induction effects last until the drug is eliminated from the body. (D)</p> Signup and view all the answers

In the patient case presented, what drug interaction is potentially occurring?

<p>Calcium carbonate decreases the absorption of levothyroxine (D)</p> Signup and view all the answers

What two effects are listed for drug interactions?

<p>Decrease drug metabolism and increase concentration (B), Increase drug metabolism and decrease concentration (C)</p> Signup and view all the answers

Which of these factors is NOT mentioned as being important to consider when faced with a potential drug interaction?

<p>Frequency of the interaction (C)</p> Signup and view all the answers

What is the object of the drug interaction in the case presented?

<p>Simvastatin (D)</p> Signup and view all the answers

Based on the provided information, what type of drug interaction is likely occurring in the case presented?

<p>Inhibition (D)</p> Signup and view all the answers

How soon after the last dose of an inhibitor drug are concentrations likely to return to normal?

<p>3-4 half-lives (B)</p> Signup and view all the answers

A patient is taking simvastatin and is prescribed clarithromycin. What is the potential interaction?

<p>Clarithromycin slows down the metabolism of simvastatin. (B)</p> Signup and view all the answers

What is the recommended course of action when a patient is taking simvastatin and is prescribed clarithromycin?

<p>Consider an alternative antibiotic or statin. (D)</p> Signup and view all the answers

A patient is taking sertraline and starts taking St. John's Wort. This interaction is classified as:

<p>An antagonistic interaction. (B)</p> Signup and view all the answers

What is the primary concern regarding the interaction between St. John's Wort and sertraline?

<p>Decreased effectiveness of sertraline. (C)</p> Signup and view all the answers

What is the main factor driving the interaction between clarithromycin and simvastatin?

<p>Both medications are metabolized by the same enzyme. (C)</p> Signup and view all the answers

Which of these is a direct example of a drug interaction that is described in the provided content?

<p>Clarithromycin and simvastatin. (C)</p> Signup and view all the answers

Which of the following is a common concern associated with drug interactions mediated by CYP450 enzymes?

<p>Increased risk of drug toxicity. (B)</p> Signup and view all the answers

Which of the following best describes the interaction between clarithromycin and simvastatin, based on the information provided?

<p>Clarithromycin inhibits the metabolism of simvastatin. (C)</p> Signup and view all the answers

The patient is taking simvastatin. What potential food-drug interaction should be considered when discussing red yeast rice with him?

<p>Red yeast rice is a known inhibitor of CYP3A4, which is the primary enzyme responsible for metabolizing simvastatin. (D)</p> Signup and view all the answers

What is a key principle in patient counseling related to natural product use?

<p>Actively inquire about OTC and herbal supplements used by patients during each visit. (B)</p> Signup and view all the answers

Which of the following natural product interactions has the most prolonged effect?

<p>Grapefruit juice increasing the concentration of certain drugs. (A)</p> Signup and view all the answers

Which category of patients is particularly vulnerable to adverse effects from natural products?

<p>Patients with chronic illnesses and polypharmacy. (B)</p> Signup and view all the answers

Which of the following enzymes is most commonly inhibited by grapefruit juice?

<p>CYP3A4 (D)</p> Signup and view all the answers

What does the text refer to when it mentions "food-drug interactions"?

<p>The impact of food on the absorption, metabolism, and excretion of drugs. (B)</p> Signup and view all the answers

What is the key takeaway from the patient's case scenario regarding red yeast rice and simvastatin?

<p>Red yeast rice may not be a suitable supplement for patients taking simvastatin due to potential drug interactions. (B)</p> Signup and view all the answers

Flashcards

Pharmacokinetic Interactions

Interactions where one drug alters another's pharmacokinetic parameters (ADME).

ADME

The four main pharmacokinetic processes: Absorption, Distribution, Metabolism, Elimination.

Absorption

The process by which a drug enters the bloodstream from its site of administration.

Distribution

The dispersion or spreading of substances throughout the fluids and tissues of the body.

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Metabolism

The chemical alteration of drug by the body, mainly done by the liver.

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Excretion

The removal of the substances from the body, typically via urine or feces.

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Bioavailability

The proportion of a drug that enters circulation when introduced into the body and is available for action.

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Drug Interaction Management Goal

To keep plasma concentrations of affected drugs relatively unchanged despite interactions.

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P-glycoprotein (P-gp)

A drug transporter that regulates the absorption and elimination of medications in the body.

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P-gp inhibitors

Substances that increase the concentration of drugs transported by P-glycoprotein.

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P-gp inducers

Compounds that decrease the concentration of drugs transported by P-glycoprotein.

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Organic Anion Transporting Polypeptides (OAT-P)

Transporters in the liver that facilitate the uptake of drugs and endogenous compounds.

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Enzyme Inhibition

A common drug interaction leading to decreased drug metabolism and increased bioavailability.

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Levothyroxine TSH Result

High TSH levels indicate insufficient levothyroxine absorption despite medication adherence.

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Absorption Interactions

Interactions affecting how a drug enters the body, often involving solubility and chelation effects.

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Drug Distribution

The process by which drugs are transported throughout the body post-absorption.

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Protein-Bound Drugs

Drugs that are attached to proteins in the blood, making them inactive therapeutically.

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CYP450 Enzymes

Enzymes in the liver and intestines that metabolize drugs; can be inhibited or induced.

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Induction

A process where drug metabolism is increased, leading to decreased drug concentration.

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Inhibition

A process where drug metabolism is decreased, leading to increased drug concentration.

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Interaction Timing

Refers to the speed of onset for drug interactions, either slow (induction) or fast (inhibition).

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Clarithromycin Interaction

Clarithromycin can increase the concentration of drugs like simvastatin through inhibition.

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Clinical Judgment

The application of knowledge and experience to assess the seriousness of drug interactions.

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Natural Product Concerns

Issues related to the use of natural supplements like unclear mechanisms, interactions, and side effects.

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High Risk Patients

Groups that may suffer adverse effects from supplements, including elderly, pregnant, infants, and those on multiple medications.

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Food-Drug Interactions

Effects of food on the absorption and effectiveness of medications, altering drug levels in the body.

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Grapefruit Juice Effect

Inhibits enzymes in the gut, increasing the bioavailability of certain drugs for up to 72 hours.

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Red Yeast Rice

A natural supplement that can help lower cholesterol but may interact with medications like statins.

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Vitamin K Interactions

Green leafy vegetables can affect warfarin effectiveness due to high vitamin K content.

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Potassium and Salt Substitutes

Excess potassium from substitutes can cause issues in patients on potassium-increasing medications, like ACE inhibitors.

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Mechanism of Action

The specific biochemical interaction through which a substance produces its effect.

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Clarithromycin

An antibiotic that inhibits simvastatin metabolism.

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Simvastatin

A medication used to lower cholesterol that can be affected by inhibitors.

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Inducer

A substance that speeds up drug metabolism, decreasing levels in the body.

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Sertraline

An antidepressant that may interact with St John's Wort.

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St John's Wort

A natural supplement that can reduce the effectiveness of antidepressants.

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Drug Interaction

A situation where one drug affects the action of another drug.

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Treatment Alternatives

Options to replace a drug due to an interaction, maintaining patient safety.

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Study Notes

Basics of Drug Interactions

  • Drug interactions can cause significant harm.
  • 48.6% of people using at least one prescription drug in the past 30 days.
  • 24.0% of people using three or more prescription drugs in the past 30 days.
  • 12.8% of people using five or more prescription drugs in the past 30 days.
  • 15% risk of interaction for two medications.
  • 40% risk of interaction for five medications.
  • 80% risk of interaction for seven or more medications.

Learning Objectives

  • Describe the types of drug interactions.
  • Recognize substrates, inhibitors, and inducers involved in interactions.
  • Identify tools that can assist in identifying and managing drug interactions.
  • Develop strategies to manage different types of drug interactions.

Drug-Drug Interactions

  • A drug can be changed by the presence of another drug, herbal supplement, food, or beverage.
  • Drug-drug interactions can affect either pharmacodynamics or pharmacokinetics.

Pharmacodynamics Interactions

  • Interaction between either shared or competing mechanisms of drug action.

Agonist vs Antagonist

  • Agonist: activation
  • Antagonist: inhibition

Pharmacodynamic Interactions Examples

  • Warfarin (inhibits vitamin K) and Vitamin K: decreased effect of both drugs.
  • Warfarin (anticoagulant) and Apixaban (anticoagulant): increased bleed risk.
  • Ondansetron and Haloperidol: increased risk of QT prolongation/Torsades de pointes.
  • NSAIDS and ACE-I/ARBs: risk of acute kidney injury.
  • Midodrine (alpha-1 agonist) and Terazosin (alpha-1 antagonist): potential consequences of orthostatic hypotension or BPH worsening.

Pharmacokinetic Interactions

  • Interactions where one or both drug's pharmacokinetic parameters are altered by the presence of the other drug.
  • Interactions interfere with ADME: absorption, distribution, metabolism, and excretion/elimination.

Absorption Interactions

  • Increased absorption interactions can be influenced by pH effects. Levothyroxine absorption is decreased by antacids. Spacing doses.
  • Altered bacterial flora: Long-term antibiotics may affect absorption.
  • Altered gastrointestinal tract motility: Some medications increase peristalsis, decreasing absorption time.

Patient Case #1

  • 52-year-old woman taking levothyroxine 100 mcg daily and calcium carbonate 600 mg twice a day.
  • High TSH level (83 mIU/L) despite consistent levothyroxine.
  • Calcium may decrease levothyroxine absorption; separate doses.

Patient Case #2

  • 40-year-old woman taking lisinopril, hydrochlorothiazide, and simvastatin.
  • Considering prescribing Biaxin (clarithromycin).
  • Clarithromycin and simvastatin, an interaction is possible (avoid)

Patient Case #3

  • Patients using oral hormonal contraceptives should switch to a non-oral or barrier method for 4 weeks after starting or escalating tirzepatide.
  • Tirzepatide may delay gastric emptying, reducing oral contraceptive absorption.

Patient Case #4

  • 32-year-old woman taking sertraline.
  • Starting St John's Wort.
  • Strongly discourage this combination; serotonin syndrome risk. St John's Wort could increase or decrease the effectiveness of the serotoneric agents.

What if our patient is on a natural supplement not listed on LexiDrug?

  • Many areas of natural supplements are not well-defined (mechanism of action, disease interactions, drug interactions, adverse effects).
  • High-risk patients include elderly, infants, pregnant or lactating women, or those on polypharmacy.
  • Lexi-Drug database
  • Natural Medicines Database
  • Liverpool Drug Interaction Checker (for HIV or COVID medications)
  • Personal team pharmacist

Key concepts

  • Pharmacodynamics, pharmacokinetics, and bioavailability interactions.
  • Dose spacing, induction, and inhibition.
  • Drug interactions with food and supplements.
  • Tools for checking drug interactions (Lexi-Drug database, Liverpool checker).

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Drug Interactions PA_Ray_2025 HANDOUT PDF

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