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PHAR300 > L21 Drug Interactions > Flashcards

L21 Drug Interactions Flashcards

(88 cards)

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1
Q

How many drugs do hospitalized patients usually receive? What are they given for

A

More than 20

anxiety, blood pressure, infection, pain, anesthetics

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2
Q

The relationship between the number of drugs taken and the number of patients experiencing side effects is…

A

linear

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3
Q

TF: Drug interactions always decrease therapeutic effects of a drug

A

False, interactions can increase or decrease therapeutic or toxic effects of a drug

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4
Q

TF: There is a link between poverty and the increase of adverse effects due to drug interactions

A

True

This is due to lack of professional advice/monitoring and the tendency to seek out cheaper alternatives

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5
Q

Roasted coffee is a mixture of _ bioactive compounds

A

> 1000

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6
Q

The _ in red wine sometimes triggers headaches in certain people

A

tyramine

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7
Q

When do drug-drug interactions occur (4)

A
  1. multiple drugs to treat one disorder
  2. Multiple disorders requiring different drugs e.g. chronic conditions + acute infection
  3. OTC meds, caffeine, nicotine, alcohol
  4. Elderly patients have high incidence of drug interactions due to amount of medications they take and their age related changes in drug clearance
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8
Q

What are factors that lead to drug interaction (5)

A
  • 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
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9
Q

What are some factors that can influence outcomes of drug interactions

A

patient factors: genetic variation, current diseases, diet, environment, smoking, alcohol, illegal drug use

drug administration: dose, duration, sequence, timing of consumption, route of administration

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10
Q

TF: drug interactions are usually external

A

False, interactions are rare for topical medications

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11
Q

Drug interactions can be… (4)

A

additive (1+1=2)
synergistic (1+1=3)
potentiation (1+0=2)
antagonism (1+0=0.5)

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12
Q

Describe what pharmacokinetic drug interactions are. What are the consequences of such interactions

A

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

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13
Q

Describe what pharmacodynamic drug interactions are

A

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)

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14
Q

Which better describes pharmacokinetics:

alter blood concentration of a given drug
or
modulate drug effect at given plasma concentration

A

alter blood concentration of a given drug

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15
Q

Which better describes pharmacodynamics:

alter blood concentration of a given drug
or
modulate drug effect at given plasma concentration

A

modulate drug effect at given plasma concentration

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16
Q

What is the main site of absorption for oral drugs?

A

GIT

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17
Q

How does gastric pH alter drug absorption?

A

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

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18
Q

TF: milk helps the absorption of tetracycline (antibiotic)

A

False, the calcium carbonate in milk or in antacid binds to tetracycline which can no longer be absorbed

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19
Q

Calcium carbonate inhibits _ absorption

A

thyroxine (forms a drug complex in intestine)

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20
Q

thyroxine absorption is inhibited by _

A

calcium carbonate (forms a drug complex in intestine)

*tums (thyroxine = T4, thyroid hormone)

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21
Q

What happens if you take calcium carbonate and thyroxine at the same time?

A

hypothyroidism and increased TSH

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22
Q

What are some agents that are used to stabilize gastric pH?

A

H2 blockers, proton-pump inhibitors

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23
Q

Altering the gastric pH can reduce the absorption of which anti fungal drug?

A

ketoconazole

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24
Q

How can diarrhea affect drug absorption?

A

The drug passes through the SI so quickly that it is not absorbed

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25
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
26
What are P-glycoproteins?
efflux pumps that actively transport drugs Out of the enterocyte and into the lumen of the intestine (protective mechanism)
27
Where can P-glycoproteins be found?
intestine, kidneys, blood-brain barrier, tumour cells
28
TF: P-glycoproteins interact with select chemical structures only
False, they interact with a wide variety of chemical structures (promiscuous)
29
_ of p-glycoproteins in tumour cells are in involved with drug resistance
upregulation
30
What happens when a drug is ejected from the enterocyte by p-glycoproteins?
it is excreted in the feces
31
Drug A which induces p-glycoproteins would have what effect on drug B?
upregulation of p-glycoproteins > decreased absorption and bioavailability of drug B
32
TF: weak bases are better absorbed in highly acidic environments
True, since it will be in its un-ionized form
33
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
34
How fast the drug gets into the intestine will depend on...
the rate of gastric emptying
35
Once in the blood, drugs get to the liver through...
the portal vein
36
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
37
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
38
TF: interactions based on distribution and binding are common and dangerous
false, they are rare (but yes, can be dangerous)
39
What is the largest and most important group of enzymes that metabolize drugs?
cytochrome p450 family of enzymes
40
cytochrome p450s are mostly found where?
liver
41
what are isozymes
different forms of an enzyme that catalyze the same chemical reaction but have distinct structural or genetic characteristics
42
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
43
TF: CYP450 enzymes can be down regulated by inflammation
True
44
How many alleles does CYP2D6 have?
70 alleles
45
Why do people who lack CYP26D not respond to codeine for pain relief
CYP2D6 activity is necessary to convert codeine to morphine
46
Why do people who lack CYP2D6 not respond to tamoxifen (breast cancer drug)
CYP2D6 activity is necessary to convert tamoxifen to its active form
47
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
48
how many alleles does CYP34A have
4
49
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
50
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
51
How can enzyme inhibition increase the amount of drug?
by decreasing the drug clearance
52
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
53
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
54
TF: A non-competitive inhibitor will have the same Km but lower Vmax
True
55
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
56
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
57
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
58
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
59
What kinds of drugs should not be taken when relying on oral contraceptives?
antibiotics, anticonvulsants, anti-infectives
60
What do PM, EM, and URM stand for
PM: poor metabolizers EM: efficient metabolizers URM: ultra-rapid metabolizers
61
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
62
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
63
What bioactive agent does grapefruit contain that might inhibit CYP3A4 (and CYP1A2)
furanocoumarins such as naringin and naringenin
64
TF: Grapefruit juice can increase drug absorption of statins and caffeine
True
65
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
66
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
67
Which CYP450 does THC act on? Does it induce or inhibit it?
THC is a CYP1A2 inducer
68
Which CYP450 does CBD act on? Does it induce or inhibit it?
CBD is a CYP3A4 inhibitor
69
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
70
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
71
What are some potential drug interactions with warfarin
ethanol and aspirin | warfarin + aspirin = potentiation
72
TF: When a patient stops taking an enzyme inhibitor or inducer after long duration of use, a rebound and opposite effect can occur
True
73
TF: Discontinuation of enzyme-inducing drug is equivalent to adding enzyme inhibitor
True
74
TF: Discontinuation of enzyme-inhibiting drug will have no after effects
False, it will be the equivalent to adding enzyme-inducer
75
What is a new way to study drug interactions
high-throughput robotics allow to predict potential drug interactions and toxic metabolites
76
What does drug reabsorption depend on (for renal clearance)?
whether the drug is lipid-soluble and on the pH of the proximal tubule
77
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
78
Drugs that alter _ can lead to changes in tubular reabsorption and thus excretion
urinary pH
79
Which two drugs can compete and lead to toxic levels of methotrexate in the bloodstream
amoxicillin and methotrexate
80
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
81
In which region of the brain is there a defect in dopamine for individuals suffering from Parkinson's disease
substantia nigra
82
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
83
Individuals who take NSAIDs (e.g. aspirin) regularly also take which drugs to counter NSAID side effects such as ulcers?
aspiring + proton pump inhibitor
84
TF: Drug interactions can be beneficial
True
85
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
86
Opioids should not be taken with...
CNS depressants leads to respiratory arrest
87
CNS depressants should not be taken with...
opioids leads to respiratory arrest
88
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

PHAR300 (13 decks)

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