L21 Drug Interactions Flashcards
How many drugs do hospitalized patients usually receive? What are they given for
More than 20
anxiety, blood pressure, infection, pain, anesthetics
The relationship between the number of drugs taken and the number of patients experiencing side effects is…
linear
TF: Drug interactions always decrease therapeutic effects of a drug
False, interactions can increase or decrease therapeutic or toxic effects of a drug
TF: There is a link between poverty and the increase of adverse effects due to drug interactions
True
This is due to lack of professional advice/monitoring and the tendency to seek out cheaper alternatives
Roasted coffee is a mixture of _ bioactive compounds
> 1000
The _ in red wine sometimes triggers headaches in certain people
tyramine
When do drug-drug interactions occur (4)
- multiple drugs to treat one disorder
- Multiple disorders requiring different drugs e.g. chronic conditions + acute infection
- OTC meds, caffeine, nicotine, alcohol
- Elderly patients have high incidence of drug interactions due to amount of medications they take and their age related changes in drug clearance
What are factors that lead to drug interaction (5)
- Lack of info about what the patient is consuming
- inadequate checking by prescriber or pharmacist
- Individual variation in pharmacokinetics
- Variation in time of day when drugs are consumed
- failure to monitor patient response/failure of patient to report adverse symptoms, or misdiagnosis of a drug reaction
What are some factors that can influence outcomes of drug interactions
patient factors: genetic variation, current diseases, diet, environment, smoking, alcohol, illegal drug use
drug administration: dose, duration, sequence, timing of consumption, route of administration
TF: drug interactions are usually external
False, interactions are rare for topical medications
Drug interactions can be… (4)
additive (1+1=2)
synergistic (1+1=3)
potentiation (1+0=2)
antagonism (1+0=0.5)
Describe what pharmacokinetic drug interactions are. What are the consequences of such interactions
they are interactions that occur when one drug alters the absorption, distribution, metabolic, or excretion of another drug (ADME)
The drug is closer to toxicity or further from efficacy in the context of therapeutic index and window
Describe what pharmacodynamic drug interactions are
they are interactions that occur when two drugs act on the same site
drug A can affect the action of drug B through competition or blockage (alteration of effects)
Which better describes pharmacokinetics:
alter blood concentration of a given drug
or
modulate drug effect at given plasma concentration
alter blood concentration of a given drug
Which better describes pharmacodynamics:
alter blood concentration of a given drug
or
modulate drug effect at given plasma concentration
modulate drug effect at given plasma concentration
What is the main site of absorption for oral drugs?
GIT
How does gastric pH alter drug absorption?
weak acids are better absorbed at acidic pH as they will be unionized and lipid soluble
thus, drugs that can alter gastric pH may have an effect on drug absorption
e.g. asprin is a weak acid
TF: milk helps the absorption of tetracycline (antibiotic)
False, the calcium carbonate in milk or in antacid binds to tetracycline which can no longer be absorbed
Calcium carbonate inhibits _ absorption
thyroxine (forms a drug complex in intestine)
thyroxine absorption is inhibited by _
calcium carbonate (forms a drug complex in intestine)
*tums (thyroxine = T4, thyroid hormone)
What happens if you take calcium carbonate and thyroxine at the same time?
hypothyroidism and increased TSH
What are some agents that are used to stabilize gastric pH?
H2 blockers, proton-pump inhibitors
Altering the gastric pH can reduce the absorption of which anti fungal drug?
ketoconazole
How can diarrhea affect drug absorption?
The drug passes through the SI so quickly that it is not absorbed
TF: drugs that affect the absorptive surface are can cause drug interaction
False, although diseases that affect absorptive surface area can cause drug interaction, there are no drugs that cause this
What are P-glycoproteins?
efflux pumps that actively transport drugs Out of the enterocyte and into the lumen of the intestine (protective mechanism)
Where can P-glycoproteins be found?
intestine, kidneys, blood-brain barrier, tumour cells
TF: P-glycoproteins interact with select chemical structures only
False, they interact with a wide variety of chemical structures (promiscuous)
_ of p-glycoproteins in tumour cells are in involved with drug resistance
upregulation
What happens when a drug is ejected from the enterocyte by p-glycoproteins?
it is excreted in the feces
Drug A which induces p-glycoproteins would have what effect on drug B?
upregulation of p-glycoproteins > decreased absorption and bioavailability of drug B
TF: weak bases are better absorbed in highly acidic environments
True, since it will be in its un-ionized form
TF: weak acids are better absorbed in highly acidic environments
True (since they are in their unionized form)
*weak acid form depends on its environment unlike strong acids
How fast the drug gets into the intestine will depend on…
the rate of gastric emptying
Once in the blood, drugs get to the liver through…
the portal vein
TF: Once absorbed, drugs circulate freely in the blood to bind to tissue receptors
False, there is an equilibrium between free drugs and drugs bound to plasma proteins
only the free drugs can bind to tissue receptors
Distribution of a drug can be altered by drugs that…
compete for binding sites on plasma protein
This changes the concentration of free drug circulating in the blood
TF: interactions based on distribution and binding are common and dangerous
false, they are rare (but yes, can be dangerous)
What is the largest and most important group of enzymes that metabolize drugs?
cytochrome p450 family of enzymes
cytochrome p450s are mostly found where?
liver
what are isozymes
different forms of an enzyme that catalyze the same chemical reaction but have distinct structural or genetic characteristics
Which CYP450 enzymes are very important for drug metabolism?
CYP2D6: antidepressants (e.g., fluoxetine, paroxetine), antipsychotics (e.g., haloperidol), beta-blockers (e.g., metoprolol), and opioids (e.g., codeine, tramadol)
CYP3A4: statins (e.g., simvastatin), immunosuppressants (e.g., cyclosporine), antivirals (e.g., ritonavir), and some opioids (e.g., fentanyl)
and CYP2C19, CYP2C9, CYP1A2
TF: CYP450 enzymes can be down regulated by inflammation
True
How many alleles does CYP2D6 have?
70 alleles
Why do people who lack CYP26D not respond to codeine for pain relief
CYP2D6 activity is necessary to convert codeine to morphine
Why do people who lack CYP2D6 not respond to tamoxifen (breast cancer drug)
CYP2D6 activity is necessary to convert tamoxifen to its active form
Classify the following as antidepressants, antipsychotics, beta-blockers, and opioids:
fluoxetine, paroxetine, metoprolol, haloperidol, tramadol, codeine
antidepressants: fluoxetine, paroxetine
antipsychotics: haloperidol
beta-blockers: metoprolol
opioids: codeine, tramadol
how many alleles does CYP34A have
4
What is ketoconazole
an antifungal (-ole) that is metabolized by many CYP450 enzymes (including CYP2D6 and CYP3A4)
it is also a powerful inhibitor of some CYP enzymes such as CYP3A4
Which drug or food inhibits CYP3A4? What are the consequences of this
ketoconazole and grapefruit juice, affects metabolism of calcium channel blockers, benzodiazepines, HIV protease inhibitors and more (any drug that is metabolized by CYP3A4)
blocking CYP3A4 can also cause statin toxicity (increased statin levels in blood) an myopathy
ketoconazole:antifungal
How can enzyme inhibition increase the amount of drug?
by decreasing the drug clearance
TF: CYP450 enzyme induction leads to decreased drug availability
True,
if drug A induces p450s, drug B will have lower bioavailability thus decreasing its therapeutic effect
TF: A competitive inhibitor will have a lower Km but the same Vmax
False, competitive = higher Km, same Vmax
unless it binds irreversibly, then Vmax would decrease, Km would increas
TF: A non-competitive inhibitor will have the same Km but lower Vmax
True
TF: During enzyme induction, Km will be higher while Vmax stays the same
False
the expression and activity of enzymes are increased in response to the presence of specific substances, often substrates or inducers. Therefore:
enzyme induction = same Km, higher Vmax (increased enzyme activity)
Vmax: rate of reaction (higher = faster)
Km: substrate affinity
Why should you not smoke tobacco while taking blood pressure meds or depression meds
tobacco metabolizes CYP1A2, an enzyme that breaks down drugs for blood pressure and depression
Why does ethanol increase risk of acetaminophen toxicity
ethanol induces a CYP450 enzyme and depletes glutathione. Thus, the body is unable to metabolize and detoxify acetaminophen
Why do antibiotics impair oral contraceptive efficacy
GI flora is altered by antibiotics thus altering enterohepatic estrogen recycling (decrease half-life)
it may also increase liver inactivation of the estrogen in oral contraceptives
What kinds of drugs should not be taken when relying on oral contraceptives?
antibiotics, anticonvulsants, anti-infectives
What do PM, EM, and URM stand for
PM: poor metabolizers
EM: efficient metabolizers
URM: ultra-rapid metabolizers
which CYP450 enzyme does St-John’s wort induce? why is this dangerous
CYP3A4
can cause rapid metabolism of life-saving drugs, which can be lethal
or
increase the activity of a drug if it is activated by CYP34A leading to overdose
garlic supplements decrease _ levels
saquinavir (inverse) 51% decrease
this is a HIV protease inhibitor, so garlic supplements pose a serious risk for individuals taking meds for HIV/AIDS
What bioactive agent does grapefruit contain that might inhibit CYP3A4 (and CYP1A2)
furanocoumarins
such as naringin and naringenin
TF: Grapefruit juice can increase drug absorption of statins and caffeine
True
What effect does grapefruit juice have on p-glycoproteins
it enhances the function of p-glycoproteins thus leading to decreased intestinal absorption, lower penetration of BBB and increased renal excretion
What are the effects of grapefruit juice on metabolism and absorption
metabolism: inhibits CYP3A4 (which breaks down statin) up to 3 days
absorption: stimulates p-glycoproteins thus decreasing absorption
Which CYP450 does THC act on? Does it induce or inhibit it?
THC is a CYP1A2 inducer
Which CYP450 does CBD act on? Does it induce or inhibit it?
CBD is a CYP3A4 inhibitor
TF: Cannabis is safe to take with other drugs
False, it may potentially affect metabolism of drug resulting in potentially dangerous drug interactions
THC - CYP1A2 inducer
CBD - CYP3A4 inhibitor
What is warfarin and what is it used for
it is an anticoagulant used in exceptional cases as it has a very small therapeutic index
What are some potential drug interactions with warfarin
ethanol and aspirin
warfarin + aspirin = potentiation
TF: When a patient stops taking an enzyme inhibitor or inducer after long duration of use, a rebound and opposite effect can occur
True
TF: Discontinuation of enzyme-inducing drug is equivalent to adding enzyme inhibitor
True
TF: Discontinuation of enzyme-inhibiting drug will have no after effects
False, it will be the equivalent to adding enzyme-inducer
What is a new way to study drug interactions
high-throughput robotics allow to predict potential drug interactions and toxic metabolites
What does drug reabsorption depend on (for renal clearance)?
whether the drug is lipid-soluble and on the pH of the proximal tubule
Renal clearance of lithium can be decreased by … (2)
diuretics and NSAIDS
dangerous since lithium has low safety factor
For diuretics: since lithium shares transport mechanisms with sodium, increased sodium reabsorption can lead to decreased lithium excretion.
outerwhise, diuretics usually increase renal clearance
Drugs that alter _ can lead to changes in tubular reabsorption and thus excretion
urinary pH
Which two drugs can compete and lead to toxic levels of methotrexate in the bloodstream
amoxicillin and methotrexate
TF: Pharmacodynamic interaction alter the dose-response curve left or right by involving the action of drug at the receptor site
False, it alters the curve up or down, not left or right
In which region of the brain is there a defect in dopamine for individuals suffering from Parkinson’s disease
substantia nigra
What is the current therapy for PD? How does it work
Levodopa (dopamine precursor) which is converted to dopamine by dopa decarboxylase
levodopa must penetrate BBB to reach substantial nigra (where dopamine is required)
It is given in combination with Carbidopa which blocks the peripheral dopa decarboxylase and cannot cross the BBB. This way, more levodopa is available to enter the brain
> Levodopa + Carbidopa
Individuals who take NSAIDs (e.g. aspirin) regularly also take which drugs to counter NSAID side effects such as ulcers?
aspiring + proton pump inhibitor
TF: Drug interactions can be beneficial
True
Why don’t aspirin and ibuprofen mix well?
ibuprofen will prevent aspirin activity therefore ibuprofen must be taken after aspirin has taken effect
*note aspirin must be taken in low doses to prevent infarcts so increasing aspiring dosage is not a good idea
Opioids should not be taken with…
CNS depressants
leads to respiratory arrest
CNS depressants should not be taken with…
opioids
leads to respiratory arrest
What foods should not be taken with MAOIs (antidepressants, monoamine oxidase inhibitors)
wine and cheese
both contain tyramine which releases neurotransmitters in the synapse
taking both would flood adrenergic terminals in the brain and periphery with noradrenaline which can lead to hypertensive crisis (increase B) which can cause a stroke
