drug interactions Flashcards
There can be interactions between which types of products?
- prescription or over-the counter medications and
- certain foods or “recreational” drugs, foods, or herbal remedies
With each added agent (drug), there is a __________ of the risk of drug interactions
multiplication
Which effects can drug interactions have?
either increase or decrease the therapeutic or toxic effect of a particular drug.
The greater the _______ level, the greater the incidence of adverse drug interactions.
poverty
When do drug-drug interactions occur?
reasons why you might take mutliple drugs
- Multiple drugs to treat one disorder.
- Multiple disorders requiring different drugs, such as chronic condition + acute infection.
- OTC meds, caffeine, nicotine, alcohol
- Elderly patients have a high incidence of drug interactions because they commonly take multiple
medications, some of them to sustain life, and they often have age related changes in drug clearance.
What are the Factors leading to drug interaction?
- Lack of information about what the patient is consuming
- Inadequate checking by the prescriber or pharmacist
- Individual variation in pharmacokinetics
- Variation in time of day when drugs are consumed
- Failure to monitor patient response / failure of the patient to report adverse symptoms, or misdiagnosis of a drug reaction.
What are Factors influencing outcomes of drug interactions?
patient factors and drug administration factors
- Patient factors: genetic variation, current diseases, diet, environment, smoking, alcohol, illegal drug use.
- Drug administration: dose, duration , sequence (ie. drug A before B or vice versa), the timing of consumption, route of administration
How do we classify drug interactions?
Look at consequence, site, mechanism, interaction type
What are the different consequences of drug interactions?
Beneficial or adverse
What are the sites of drug interactions?
External or internal
What are the mechanisms of drug interactions?
- Pharmacodynamic (two drugs act on the same receptor site to either magnify / decrease the effect)
- Pharmacokinetic (quite common)
- physiological (increases or decreases a physiological response)
What are the types of interactions used to classify drug interactions?
- Additive 1+1 =2
- Synergistic 1+1 = 3 (one drug magnifies the effect of
the other drug) - Potentiation 1+ 0 = 2
- Antagonism 1+ 0 = 0.5
Pharmacokinetic drug interactions occur when one drug alters the _____________ of another drug, which means that the ________ concentration is altered.
- absorption, distribution, metabolism or excretion
- plasma
Pharmacodynamic drug interactions occur when _______
two drugs act on the same site
What interacts with tetracycline and by what mechanism?
- milk and antacids
- prevents absorption by binding to it
Calcium carbonate interacts what what drug? By what mechanism?
- it prevents absorption of thyroxine (synthroid)
What effect do Agents used to stabilize gastric pH (ex. H2-blockers, proton-pump inhibitors) have?
alter the gastric pH and reduce the absorption of drugs such as antifungal drug ketoconazole
How can transit time in the small intestine be altered?
with diarrhea for instance, the drug can pass through so quickly that it’s not absorbed
How can absorptive surface area in the small intestine be altered?
drugs do not affect absorptive surface area, but some diseases do (ex. inflammatory bowel disease)
What are ways that drug absorption in the small intestine can be altered?
- Transit time
- Absorptive surface area
- Drug complexes can occur in the intestine
What are the Intestinal transport systems: To circulation and Back into lumen?
- specialized transport proteins
- p-glycoproteins
What are p-glycoproteins?
efflux pumps which actively transport drugs out of the enterocyte into the
lumen of the intestine
The action of p-glycoproteins is a ________ mechanism
Protective
Where can p-glycoproteins be found?
Small intestines, kidneys, blood-brain barrier, tumour cells etc
How are p-glycoproteins affected by tumor cells that are drug resistant?
Upregulated
How can p-glycoproteins be affected by other drugs and how does this affect other drugs?
- can be inhibited, which would increase absorption and bioavailability of another drug
- can be activated, which would decrease absorption and bioavailability of another drug
What are different interactions based on absorption?
- change in gastric pH
- change in rate of gastric emptying
- change is p-glycoproteins
What are interactions based on distribution? How often does this occur?
- can be altered by other drugs that compete for binding sites on plasma proteins (could increase bioavailability)
- rare, it is a “test-tube” phenomenon
How many polymorphisms of CYP2D6 and CYP3A4 exists?
- 2D6: 70 alleles
- 3A4: 4 alleles
What can affect CYP2D6 functions?
what drugs affect it and what effect do polymorphisms have?
- Inhibited by a variety of drugs (fluoxetine, haloperidol, paroxetine, quinidine)
- some people don’t have it so they aren’t affected by morphine or tamoxifen
What are some CYP3A4 inhibitors and what other drugs do they affect?
- ketoconazole and grapefruit juice
- affect calcium channel blockers, benzodiazepines, HIV protease inhibitors and statins (will greatly increase statin plasma level which can lead to toxicity)
What is the effect of enzyme inhibition and induction on drug availability?
- enzyme inhibition: increases the amount of a drug in circulation or can decrease the therapeutic effect of a drug if it needs to be metabolized to do its job
- enzyme induction: decreases the amount of a drug in circulation
How does tobacco affect other drugs and by what mechanism?
- drugs for blood pressure and depression
- by inducing CYP1A2
What is the effect of ethanol on other drugs?
induces CYPs & depletes glutathione which is involved with the second stage of deactivating acetaminophen so it isn’t toxic, so increases the risk of acetaminophen toxicity
What drugs affects oral contraceptive effectiveness? How?
- antibiotics (altering the GI flora & thus altering the enterohepatic estrogen recycling and may also increase liver inactivation of the estrogen )
- Anticonvulsants and anti-infectives have same effect
what effect does St John’s worts have?
- may increase metabolism of certain drugs by inducing CYP3A4
- can lead to decrease bioavailability or increase effects of drugs activated by this
what interactions do garlic supplements have?
decreases saquinavir (for AIDS/HIV) levels
Grapefruit contains many bioactive agents, including compounds that inhibit ____________ and also stimulates ___________
- CYP3A4 and CYP1A2
- the function of p-glycoproteins
what drugs can grapefruit juice affect? how?
- increase absorption of statins
- decrease absorption of fexofenadine
- blocks breakdown of caffeine
what affect does THC and CBD have on metabolism?
- THC: CYP1A2 inducer
- CBD : CYP3A4 inhibitor
what are drugs that can interact with warfarin?
many including ethanol and aspirin
what is inverted drug interaction?
- When a patient stops taking an enzyme inhibitor or inducer after long duration of use, a rebound and opposite effect can occur ⇒ it is important to reduce the administration dose slowly before stopping the medication completely.
- Discontinuation of enzyme-inducing drugs is equivalent to adding a enzyme inhibitor
- Discontinuation of enzyme-inhibiting drugs is equivalent to adding an enzyme-inducer
what are ways to study drug interactions?
how to test before clinical trials
- In vitro: cytochrome P450 induction / inhibition
- Newer strategies: high-throughput robotics allow to predict potential drug interactions and toxic
metabolites
what interacts with lithium? how?
Renal clearance of lithium can be decreased by 25% by:
- diuretics (which increase urinary output)
- NSAIDs (which change the pH).
what are ways excretion of drugs can be altered?
change renal clearance by altering:
- urinary output
- alter the urinary pH which can alter the ionization
state of drugs that are weak acids or bases (leading to changes in renal tubular reabsorption)
what interacts with methotrexate? how?
amoxicillin; they compete, which leads to toxic levels of methotrexate in the bloodstream
what is Parkinson’s?
defect in dopamine in a specific region of the brain (substantia nigra) which leads to tremors and impaired balance
what is Levodopa, what is it used for and how does it work? what are some side effects?
- is a dopamine precursor used to treat Parkinson’s
- converted to dopamine by dopa decarboxylase.
- must penetrate the BBB to be converted to dopamine in the brain.
- However, most of the drug is converted to dopamine in the periphery and never reaches the brain - peripheral dopamine causes side effects
what is a drug interaction with Levodopa, what effect does it have?
- Carbidopa is a beneficial drug interaction
- blocks the peripheral enzyme, but cannot cross the BBB. Thus, more Levodopa is available to enter the brain
people with arthritis who take NSAIDs usually also take _________ because __________
- proton pump inhibitors
- to prevent ulcers
Opioids + CNS depressants are a ____________ combination since ___________________
- potential lethal
- it can lead to respiratory arrest
what effect does Monoamine Oxidase Inhibitors (antidepressants) + wine / cheese have?
- Red wine and many cheeses contain tyramine, which releases neurotransmitters in the synapse
- if you’re blocking monoamine oxidase with MAOIs and increasing the release neurotransmitters from the presynaptic terminals (because of tyramine), then you’re flooding your adrenergic terminals in the brain and periphery with noradrenaline
- leads to a hypertensive crisis (significantly increased blood pressure) which can cause a stroke
