Ger 7 Drug Interactions Flashcards
What is a drug-drug interaction?
The effect that one drug has on another
What are the 2 types of drug-drug interactions?
- Pharmacokinetic (what the body does to the drug)
2. Pharmacodynamics (what the drug does to the body)
What is a pharmacokinetic drug interaction?
The effects of one drug on the absorption, distribution, metabolism, or excretion of another drug
What can pharmacokinetic drug interactions result in?
Changes in serum drug concentrations and might change clinical response
What is most frequently involved in pharmacokinetic drug interactions?
- CYP P450
- P-Glycoprotein
- Organic anion transporters
What is a pharmacodynamic drug interaction and what is the outcome?
- Related to the pharmacological activity of interacting drugs
- The outcome is an amplification or decrease in the therapeutic effects or side effects of a specific drug
What are other types of drug interactions?
- Drug-Food
- Drug-Alcohol
- Drug-Herbal Product
- Drug-Nutritional Status
- Drug-Disease or Drug-Patient interactions
* Review Chart in Objectives for Specific Examples
When do drug-disease or drug-patient interactions occur?
They take place when a drug has the potential to exacerbate and underlying disease or medical disorder
What are the 3 new groups of patients at risk for drug-drug interactions?
- Organ transplant
- Mental-health problems
- HIV patients that survived to late life
What are 3 common drug interactions?
- Patients taking drugs with a narrow therapeutic index
- Patients taking drugs that are substrates, inhibitors, or inducers of CYP450 isoenzymes
- Drug-Disease Interactions
What are examples of drugs with a narrow therapeutic index involved in drug-drug interactions?
- Digoxin
- Phenytoin
- Warfin
What are examples of drugs that are substrates, inhibitors, or inducers, of CYP450 isoenzymes commonly involved in drug-drug interactions?
- CYP3A4
2. CYP2D6
What diseases are common to cause drug-disease interactions?
- Constipation
- Dementia
- Postural Hypotension
When are complex interactions seen?
Patients with 9 or more drugs and 5 or more comorbidities
-Although the choice of drugs individually makes sense to treat the patient, the total combination could yield unwanted results (drug-drug interactions and drug-disease interactions)
What is the increased risk of drug interactions due to in elderly patients?
- Patient factors
- Prescriber factors
- Difficulties within the health-care system (Inefficient communication between health professionals and patients)
- All of these need to be considered for prescribing medications for elderly patients
What are patient factors that can increase the risk of drug interactions in elderly patients?
Age related pharmacokinetic and pharmacodynamic changes (these can potentially increase the risk of adverse effects from drug interactions)
What 3 things decrease as you age than can affect pharmacokinetics and pharnacodynamics?
Cellular, organ, and systems reserves
What results in heterogeneity between people as they age?
Individual genetics, lifelong living habits, and environment
Will all 85 year old women react to the same specific dose of a drug in the same way?
NO
Can you use a prototypical male (80kg) that models adult medicine in prediction of treatment for the elderly population?
No
What is a prescriber factor?
- Physicians are often not aware of all the drugs that the elderly patients are taking
- Physician was unaware that the patient was not following the doctor’s orders by not taking a drug prescribed to them
What is a big problem physicians face?
Incomplete documentation of past medical history and active drug profile
What happens as a result of incomplete documentation of past medical history and active drug profile?
EM physicians aren’t considering interactions as a possible cause of presenting complaints of patients
–> This results in a typical presentation of disease or vague presenting complaints such as confusion, falls, urinary incontinence, and weakness masking or confusing the detection of drug interactions
What are 2 of the difficulties within the health system?
- Receive prescriptions from several physicians
2. Take prescriptions to be filled at many pharmacies
What is the risk of receiving and inappropriate drug combination directly related to?
The number of physicians prescribing drugs for that elderly patient
Describe cascading interactions.
- Prescribing cascade begins when an adverse drug reaction is misinterpreted as a new medical disorder
- Another drug is then prescribed, and the patient is placed at risk of developing additional adverse effects related to this potentially unnecessary treatment
- This can produce pharmacokinetic or pharmacodynamic interactions
With regards to cascading interactions, what are patients at increased risk of receiving who had dementia and were dispensed cholinesterase inhibitors?
An anticholinergic drug to manage new urinary incontinence
What is usually diagnostic with regards to drug interactions?
A complete and careful history of the onset of a patient’s symptoms and recent treatment changes are usually diagnostic
What is the best elderly patient care?
Elderly patients usually do better when their care is managed by multidisiplinary team that practives the principles of geriatric care
What is the optimum drug management tearm?
A physician (geriatrician), nurse, and pharmacist (communication between these professionals is crucial for success)
What % of preventable prescribing errors detected in ambulatory patients involve drug interactions?
13%
In one of the studies presented, what % of elderly outpatients had at least 1 potential clinically significant drug-drug interaction and what % of these was regarded as high severity?
46%, 10%
What % of elderly patients in the psyc ward were prescribed drugs involving cytochrome 2D6? 3A4? and what is the importance of this?
25% 2D6
11% 3A4
-These drugs allow the potential for drug-drug interactions to occur
In the memory clinic study, what % of patients were using concomitant alcohol and alcohol-interactive prescription drugs?
9%
In the study of frail elderly patients in the hospital, what % of patients had a potential drug-disease interaction
15-40%
In the study of frail elderly patients in the hospital what there the 3 most common drug-disease interactions?
- Ca-Blockers in patients with heart failure
- B-Blockers in those with diabetes
- Aspirin in those with peptic ulcer disease
What is significantly associated with having one or more potential drug-disease interactions?
Several drugs and high comorbidity index
Why is it important to look at drug-drug results cautiously?
Large variability in how drug interactions are defines, their clinical importance, and the sources used to detect them
Can potential drug interactions never lead to actual clinical effects?
YES
In one study presented, what % of the study population have a potential high-risk drug-drug interaction, with not one adverse drug event that was identied being caused by a drug interaction?
31%
Are drug-interaction databases geriatrics specific?
No
Is the validity of criteria of drug-disease interactions (like B-blockers and diabetes) debatable?
Yes
What can affect the outcomes of studies on drug interactions?
Studies enrolled patients with varying comorbidities
What are 2 examples of drug-drug pharmacokinetic drug interactions?
- Gatifloxacin + caclium and Antacid
2. Ciprofloxacin + Olanzapine
What is the MOA and outcome with Gatifloxacin+ calcium and Antacid?
- Decrease in absorption of gatifloxacin
- Treatment failure
What is the MOA and outcome with Ciprofloxacin+Olanzapine
- Ciprofloxacin inhibits CYP1A2 leading to an increase in CP of olanzapine
- Rigidity, Falls
What are 2 examples of drug-drug pharmacodynamic interactions?
- Ciprofloxacin + glibenclamide
2. Anticholingeric drug + Donepezil
What is the MOA and outcome with ciprofloxacin + glibenclamide?
- Synergy (hypoglycaemic effect)
- Profound hypoglycaemia
What is the MOA and outcome with Anticholingeric drug + donepezil?
- Antagonism
- Decreased effect of donepezil
What is an example of a drug-nutritional status interaction?
Low albumin + phytoin
What is the MOA and outcome of low albumin + phenytoin?
- Increase in free phenytoin concentration
- Confusion, somnolence, ataxia
What is an example of a drug-herbal production interaction?
Gingko + Apsirin
What is the MOA and outcome of gingko + Aspirin?
- Decrease in platelet function and adhesion
- Increased risk of bleeding
What is an example of a drug-alcohol interaction?
Alcohol + Chronic use of bromazepam
What is the MOA and outcome of alcohol + Chronic use of bromazepam?
- Synergy
- Increased risk of falls
What is an example of a drug-disease or drug patient interaction?
Metoclopramide for gastric dysmotility in a patient with Parkinson’s disease
What is the MOA and outcome for metoclopramide for gastric dysmotility in a patient with Parkinson’s disease
- Increase in dopamine receptor blockade
- Worsening Parkinson’s disease
What is the drug interaction between clarithromycin and warfarin?
Risk of increased anticoagulant effect
What is the drug interaction between clarithromycin and ciclosporin?
Risk of increased concentrations of ciclosporin and nephrotoxicity
What is the drug interaction between calcium carbonate and levothyroxine?
Decreased absorption of levothyroxine if given at the same time
What is the drug interaction between ginkgo biloba and warfarin?
Increased risk of heaemorrhage
What do donepezil, ciclosporin, and losaratn have in common?
All substrates of CYP3A4 (potential risk of interaction)
What so losartan and gliclazide have in common?
Substrates of CYP2Cp (potential risk of interaction)
What is clarithromycin an inhibitor of?
CYP3A4
What 2 disease can prednisone cause a drug-disease interaction with?
- Diabetes
- Congestive heart failure
What SE can paroxetine and haloperidol cause and what are they substrates of?
- Extrapyramidal side effect (can lead to tremors)
- Both substrates of CYP2D6
What is the effect of paroxetine and haloperidol both being substrates of CYP2DP?
Haloperidol can inhibit paroxetine metabolism and increase the serum concentration of paroxetin (leading to side effects)
What might you give for someone who had tremors (and you didn’t know they were from paroxetine and haloperidol)
Levodopa and carbidopa
What might you give for CNS SE from levodopa and carbidopa?
Risperidone (which can cause extapyramidal SE)
-This is also a substrate of CYP2D6 like haloperidol and paroxetine
