Session 6_Pharmacokinetics Of Drug Interactions Flashcards
What is a drug interaction?
A modification of the expected drug response in the patient as a result of exposure to another drug or substance.
What types of drug interactions are there?
- Drug-drug interactions
- Food-drug interactions
- Chemical-drug interactions
What can cause an alteration in pharmacokinetics due to drug interactions?
- Absorption
- Distribution
- Elimination
What are drug-drug interactions (DDI)?
A serious concern in pharmacotherapy where the pharmacological effect of a victim drug is exaggerated or suppressed by a perpetrator drug.
How can pharmacokinetic interactions be classified?
- Absorption interactions
- Distribution interactions
- Metabolism interactions
- Excretion interactions
What are absorption interactions?
Interactions where the absorption of a drug is altered, commonly occurring in the gastrointestinal tract.
List the factors that can alter gastrointestinal absorption.
- Altered pH
- Altered intestinal flora
- Complexation or chelation
- Drug-induced mucosal damage
- Altered motility
What effect does altered gastric pH have on drug absorption?
Non-ionized forms of drugs are more lipid soluble and more readily absorbed than ionized forms.
How do antibiotics affect intestinal flora and drug absorption?
Antibiotics can kill normal intestinal flora, influencing the absorption of other drugs.
What is complexation or chelation in drug interactions?
It occurs when one drug interacts with another to form insoluble complexes, reducing absorption.
What is the impact of altered GI motility on drug absorption?
- Increased motility decreases bioavailability
- Decreased motility Decreases gastric emptying time, reducing bioavailability
What are distribution interactions?
Interactions that occur due to displaced protein binding, affecting the free levels of drugs in the plasma.
What is enzyme inhibition in metabolism interactions?
A decrease in the rate of metabolism of a drug by another, leading to increased concentration of the target drug.
What is enzyme induction?
A drug may induce the enzyme responsible for the metabolism of another drug, potentially increasing its clearance.
What is the role of CYP450 enzymes in drug metabolism?
CYP450 enzymes are the major metabolizing enzymes involved in phase I metabolism.
Which CYP450 enzyme metabolizes the largest percentage of drugs?
CYP3A4, metabolizing approximately 60% of drugs.
What happens during renal excretion interactions?
Drugs can be actively secreted or reabsorbed in the proximal tubules, affecting their elimination.
What is pharmacokinetic boosting?
A strategy to optimize therapeutic properties of a drug by inhibiting enzymes or enhancing absorption.
What are the management options for drug interactions?
- Avoiding the combination
- Adjusting the dose
- Spacing dosing times
- Monitoring for early detection
- Providing information on patient risk factors
- Using computerized drug interaction screening systems
What factors affect the likelihood of drug interactions?
- Genes
- Physiology
- Age
- Lifestyle
- Underlying diseases
- Drug doses
- Duration of therapy
- Timing of administration
What is the ‘dose-related reference range’ in therapeutic drug monitoring?
The mean ± SD range of the trough concentration of a drug under steady-state conditions.
What does the concentration to dose ratio (C/D) indicate?
It is used to analyze pharmacokinetic abnormalities and estimate the dose required to achieve a target concentration.
What is the metabolite to parent compound ratio (MPR)?
It measures the activity of metabolizing enzymes in vivo and helps identify abnormal metabolism.
What is an example of a serious drug interaction with warfarin?
Warfarin plus ciprofloxacin, clarithromycin, erythromycin, or metronidazole increases the effect of warfarin.
True or False: Pharmacokinetic interactions can only occur with drug-drug interactions.
False, they can also occur with food-drug and chemical-drug interactions.
Fill in the blank: The liver is the major site of _______.
[drug metabolism]
What is the Clinical Global Impressions (CGI-I) scale used for?
Assessment of patient improvement or response to treatment.
What are the low and high DRC factors for venlafaxine?
Low = 0.12; High = 0.36.
What are the low and high DRC factors for O-desmethyl venlafaxine?
Low = 0.78; High = 1.3.
What are the low and high DRC factors for N-desmethyl venlafaxine?
Low = 0.15; High = 0.33.
Is venlafaxine a substrate of CYP2D6 and CYP2C19?
Yes.
What is the expected metabolite to parent compound ratio (MRP) of O-desmethyl venlafaxine to venlafaxine?
2.7 to 7.7.
What is the expected metabolite to parent compound ratio (MRP) of N-desmethyl venlafaxine to venlafaxine?
0.28 to 0.85.
What is levomepromazine known for?
GIT disturbance.
What enzyme does smoking induce?
CYP1A2.
What was the active moiety concentration of venlafaxine plus O-desmethyl venlafaxine in Clinical Case 1?
419 ng/mL.
What is the therapeutic reference range for the active moiety concentration?
100 to 400 ng/mL.
What is the expected dose-related reference range for venlafaxine at a dose of 225 mg/day?
27 - 81 ng/mL.
What is the expected dose-related reference range for O-desmethylvenlafaxine at a dose of 225 mg/day?
176 - 293 ng/mL.
What is the MPR of O-desmethylvenlafaxine to venlafaxine in Clinical Case 1?
1.49.
What does an MPR below the expected range indicate regarding CYP2D6?
Inhibition of the phenotype of CYP2D6.
What is the MPR of N-desmethylvenlafaxine to venlafaxine?
0.85.
What can be inferred from a higher than expected concentration of N-desmethylvenlafaxine?
PM phenotype of CYP2D6.
Can adverse drug reactions (ADRs) be linked to high concentrations of venlafaxine?
Yes, likely due to drug-drug interaction and old age.
What recommendation was made to manage the case?
Dose reduction of venlafaxine or replacement of levomepromazine.
Fill in the blank: The expected active moiety concentration should amount to ______.
203-374 ng/mL.
True or False: Levomepromazine is a CYP inhibitor.
True.
