drug interactions and adr's Flashcards
What is a drug interaction?
When one drug alters the effects of another drug.
How can Drug A affect Drug B?
Increased or reduced effect
Slower or more rapid effect
New or increased side effects
What is a precipitant drug?
The drug that causes the interaction.
What is an object drug?
The drug whose effect is altered.
What is the FDA definition of a serious adverse event?
Death
Life-threatening
Hospitalization (initial or prolonged)
Disability (significant, persistent, or permanent)
Congenital anomaly
Requiring intervention to prevent permanent impairment.
How can interactions and adverse reactions be prevented?
Avoid drugs that interact.
Adjust the dose of the object drug.
Change dosing intervals to avoid interactions.
Monitor for early detection.
Provide information on risk factors.
Improve computerized screening systems.
Focus on clinically significant interactions.
Pharmacokinetic interaction
Alters the amount of drug available in circulation.
Most common type of interaction.
Pharmacodynamic interaction
The drug’s effect is altered, but amount of drug in circulation remains the same.
Less common type of interaction.
What are absorption-based drug interactions?
One drug make the absorption of another drug … Faster or slower, Less or more complete
What are the mechanisms that affect drug absorption?
Direct alterations of absorption
Ionization changes (pH alterations)
Changes in gastric emptying and GI motility
Chemical interaction (chelation)
Where are most orally delivered drugs absorbed?
small intestines
How does reduced gut motility affect drug absorption?
increases absorption because the drug spends more time in the small intestine
How does increased gut motility affect drug absorption?
reduces absorption because the drug moves through the intestines more quickly, leading to less time for absorption
How does H-2 blockers (e.g., Zantac) affect ketoconazole absorption?
decrease the dissolution of ketoconazole, resulting in reduced absorption
What is an example of a drug interaction involving gastric pH alteration?
H-2 blockers (e.g., Zantac) + ketoconazole
How do antacids affect drug absorption?
decrease the absorption of acid drugs (e.g., aspirin, anticoagulants) by changing the percent of drug that is ionized
What does pKa represent in drug ionization?
pKa is the pH at which a drug is 50% ionized and 50% unionized.
T or F: The ionization of acid and basic drugs depends on the pH of the environment.
True
How does altered gastric emptying affect drug absorption?
If Drug A alters the rate of gastric emptying, the rate of absorption of Drug B is also altered.
What happens when absorption rate is slower?
Peaks become lower
Peaks are shifted to the right
What is complexation/chelation in drug absorption?
Two drugs bind together in the GI tract
Neither drug is absorbed
What causes interactions from changes in drug distribution?
Displacement of bound drug from blood plasma proteins
T or F: One drug can alter the rate at which a second drug is inactivated or degraded
True
How does one drug affect another in drug distribution?
One drug can displace another from plasma proteins, increasing the free drug concentration
Are interactions from changes in distribution long-term?
No, self-correcting by increased metabolism and excretion if both drugs are taken for an extended period
What can result from altered drug metabolism?
Enhanced or delayed degradation of drugs
Are the effects of altered metabolism always negative?
No, the effects can be either desirable or detrimental
What is liver enzyme induction in drug metabolism?
It is a slow process, taking 1 week or more, where one drug increases the activity of liver enzymes, affecting the metabolism of other drugs
T or F: One drug can change the rate at which a second drug is removed from the body.
True
What happens when drugs compete at liver enzymes?
It results in a more immediate effect, where both drug metabolism slow down
Individual variability in
drug/drug interactions
- Disease state
- Renal & hepatic function
- Serum protein levels
- Urinary pH
- Diet
- Pharmacogenetic factors
- Age
What are pharmacodynamic interactions?
interactions of drugs at the level of the target site of action (receptor interactions).
Three types of pharmacodynamic interactions
Antagonism
Additivity
Synergism
What is an antagonistic interaction?
It’s when the precipitant drug reduces the effectiveness of the object drug.
What is a synergistic drug interaction (potentiation)?
The precipitant and object drug act together to produce an effect greater than the sum of their individual effects (i.e. 1+1=3). 80-100%
What is an additive drug interaction?
The precipitant and object drug act via the same mechanism, and their effects are predicted by adding the effects of both drugs together. (i.e. 1+1=2) 50%
What are the goals of positive synergistic opioid interactions with other analgesics?
Achieve superior analgesia.
Reduce the dose of each drug.
Minimize side effects.
What are two key points about antibiotic interactions?
Combining antibiotics that destroy bacteria in different ways can produce additive or synergistic effects
May reduce the effectiveness of oral contraceptives like amoxicillin and tetracycline
How do benzodiazepines interact with other drugs?
Additive effects with other CNS depressants
Metabolism is reduced by drugs such as cimetidine, oral contraceptives, and valproic acid.
What are the interactions of epinephrine in drug therapy?
Additive in local anesthetics.
It may reduce the effectiveness of nonselective beta blockers and tricyclic antidepressants, potentially causing hypertension.
Why do ADRs (Adverse Drug Reactions) occur?
Two-thirds of patient visits result in a prescription.
Billions of prescriptions are issued each year.
ADRs increase exponentially with 4 or more medications.
Why are many adverse drug reactions unknown until a medication enters clinical usage?
often not identified until after a drug is marketed, as only an average of 1500 patient exposures occur before FDA approval.
How many patient exposures are needed to generate a signal for rare drug toxicity?
More than 100,000 patient exposures
T or F: it is not possible to identify all adverse effects of drugs before they are marketed, and that 51% of approved drugs have serious side effects not detected prior to approval.
True
Who is at greatest risk for adverse drug reactions?
elderly
young people
chronic diseases that affect the vital organs such as the kidneys and liver.
Why are the elderly at increased risk for adverse drug reactions (ADRs)?
- sensitivity to medications
- side effects secondary to the presence of chronic diseases
- the presence of multiple disease processes
- polypharmacy
- complex dosing schedules
What are Type A adverse drug reactions (ADRs)?
most common (85-95%), predictable, and dose-related. They typically involve drug toxicity or “overdose.”
What are Type B adverse drug reactions (ADRs)?
reactions are less common, more dangerous, unpredictable, and not dose-related. They include idiosyncratic reactions and immunological drug reactions.
What are other types of adverse drug reactions (ADRs)?
include teratogenic drug effects, carcinogenic drug effects, and immune suppressive drug effects.
What is drug toxicity or “overdose”?
occurs when the drug’s effect is more pronounced than clinically desirable due to higher than desirable dosage.
Are drug toxicity(overdose) predictable, dose-related, and acts on the target organ or physiological process.
Yes
What is the therapeutic index (TI) in toxicological evaluation?
difference between the LD50 (lethal dose) and the ED50 (effective dose).
Are drugs with a higher therapeutic index (TI) safer than drugs with a lower TI?
Yes
Local Anesthetic Toxicity can cuase?
Depression of the CNS
What are idiosyncratic drug effects?
abnormal reactivity to a drug, usually genetically determined, and sometimes predictable in a predisposed population. They may also be dose-related.
What is an allergic drug reaction?
an adverse reaction to a drug resulting from previous sensitization to that same drug or a closely related drug
What is “crossallergenicity” in the context of drug reactions?
refers to allergic reactions to a related drug, caused by previous sensitization to that drug or a closely related one.
What are the characteristics of allergic drug effects?
occur infrequently, are not generally predictable, are not dose-related, and are caused by drug effects on the immune system.
What happens during subsequent drug exposure in allergic drug effects?
“eliciting” drug exposure, an antigen-antibody interaction occurs.
What are the characteristics of Type I (Immediate anaphylactic) reactions?
potentially life-threatening and cause vasodilation, edema, and inflammatory responses.
They target the bronchioles in the lungs and skin, leading to rhinitis, asthma, hypotension, bronchospasm, urticaria, and dermatitis.
What mediates Type I (Immediate anaphylactic) reactions?
immunoglobulin E (IgE)
What drugs can produce Type I (Immediate anaphylactic) reactions?
Penicillin, ester local anesthetics, and aspirin can produce Type I reactions.
How common are allergic reactions to local anesthetics?
less than 1% of cases
What causes allergic reactions to local anesthetics?
preservatives or metabolites of esters
What immunoglobulin is involved in Type II (cytotoxic/cytolytic) allergic reactions?
immunoglobulin G (IgG)
What are the symptoms of allergic reactions to local anesthetics?
rash and bronchospasm
What effect does a Type II allergic reaction have on blood cells?
cause blood cell lysis, leading to hemolytic anemia
Which type of drugs can produce Type II allergic reactions?
Antibiotics, such as penicillin
What immunoglobulin is involved in Type III (Arthus) allergic reactions?
immunoglobulin G (IgG)
What are the symptoms of serum sickness in Type III allergic reactions?
urticarial skin eruptions, arthralgia, arthritis, lymphadenopathy, and fever.
What immune cells are involved in Type IV delayed-hypersensitivity reactions?
mediated by T-lymphocytes and macrophages
Which drugs can produce Type III (Arthus) allergic reactions?
Some antibiotics, including penicillins and sulfonamides
What is the outcome of a Type IV delayed-hypersensitivity reaction?
inflammatory reaction
Which substances can cause Type IV delayed-hypersensitivity reactions?
poison ivy, topical benzocaine, and penicillin
What are teratogenic effects?
induce fetal abnormalities, which can also be caused by environmental factors.
Can you name some drugs that have teratogenic effects?
thalidomide, anticancer agents, vitamin A analogs, ethanol, and piperazine antihistamines
What are immunosuppressive drug effects?
occur when drugs impair naturally occurring immune responses.
Which drugs are known to have immunosuppressive effects?
corticosteroids, opioids, and ethanol.
To who are immunosuppressive drug effects of particular concern?
patients with compromised immune systems.
We should Assume that all women of childbearing age that can become pregnant are
pregnant until informed otherwise.
Yes
Which pregnancy categories were repaired with new drug labeling for pregnancy and lactation in 2015?
Pregnancy (including labor and delivery)
Lactation
Females and males of reproductive potential
