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PHAR 300 > drug interactions > Flashcards

drug interactions Flashcards

1
Q

There can be interactions between which types of products?

A
  • prescription or over-the counter medications and
  • certain foods or “recreational” drugs, foods, or herbal remedies
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2
Q

With each added agent (drug), there is a __________ of the risk of drug interactions

A

multiplication

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3
Q

Which effects can drug interactions have?

A

either increase or decrease the therapeutic or toxic effect of a particular drug.

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4
Q

The greater the _______ level, the greater the incidence of adverse drug interactions.

A

poverty

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5
Q

When do drug-drug interactions occur?

reasons why you might take mutliple drugs

A
  1. Multiple drugs to treat one disorder.
  2. Multiple disorders requiring different drugs, such as chronic condition + acute infection.
  3. OTC meds, caffeine, nicotine, alcohol
  4. 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.
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6
Q

What are the Factors leading to drug interaction?

A
  • 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.
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7
Q

What are Factors influencing outcomes of drug interactions?

patient factors and drug administration factors

A
  • 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
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8
Q

How do we classify drug interactions?

A

Look at consequence, site, mechanism, interaction type

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9
Q

What are the different consequences of drug interactions?

A

Beneficial or adverse

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10
Q

What are the sites of drug interactions?

A

External or internal

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11
Q

What are the mechanisms of drug interactions?

A
  • 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)
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12
Q

What are the types of interactions used to classify drug interactions?

A
  • 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
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13
Q

Pharmacokinetic drug interactions occur when one drug alters the _____________ of another drug, which means that the ________ concentration is altered.

A
  • absorption, distribution, metabolism or excretion
  • plasma
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14
Q

Pharmacodynamic drug interactions occur when _______

A

two drugs act on the same site

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15
Q

What interacts with tetracycline and by what mechanism?

A
  • milk and antacids
  • prevents absorption by binding to it
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16
Q

Calcium carbonate interacts what what drug? By what mechanism?

A
  • it prevents absorption of thyroxine (synthroid)
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17
Q

What effect do Agents used to stabilize gastric pH (ex. H2-blockers, proton-pump inhibitors) have?

A

alter the gastric pH and reduce the absorption of drugs such as antifungal drug ketoconazole

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18
Q

How can transit time in the small intestine be altered?

A

with diarrhea for instance, the drug can pass through so quickly that it’s not absorbed

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19
Q

How can absorptive surface area in the small intestine be altered?

A

drugs do not affect absorptive surface area, but some diseases do (ex. inflammatory bowel disease)

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20
Q

What are ways that drug absorption in the small intestine can be altered?

A
  1. Transit time
  2. Absorptive surface area
  3. Drug complexes can occur in the intestine
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21
Q

What are the Intestinal transport systems: To circulation and Back into lumen?

A
  • specialized transport proteins
  • p-glycoproteins
22
Q

What are p-glycoproteins?

A

efflux pumps which actively transport drugs out of the enterocyte into the
lumen of the intestine

23
Q

The action of p-glycoproteins is a ________ mechanism

A

Protective

24
Q

Where can p-glycoproteins be found?

A

Small intestines, kidneys, blood-brain barrier, tumour cells etc

25
Q

How are p-glycoproteins affected by tumor cells that are drug resistant?

A

Upregulated

26
Q

How can p-glycoproteins be affected by other drugs and how does this affect other drugs?

A
  • can be inhibited, which would increase absorption and bioavailability of another drug
  • can be activated, which would decrease absorption and bioavailability of another drug
27
Q

What are different interactions based on absorption?

A
  • change in gastric pH
  • change in rate of gastric emptying
  • change is p-glycoproteins
28
Q

What are interactions based on distribution? How often does this occur?

A
  • can be altered by other drugs that compete for binding sites on plasma proteins (could increase bioavailability)
  • rare, it is a “test-tube” phenomenon
29
Q

How many polymorphisms of CYP2D6 and CYP3A4 exists?

A
  • 2D6: 70 alleles
  • 3A4: 4 alleles
30
Q

What can affect CYP2D6 functions?

what drugs affect it and what effect do polymorphisms have?

A
  • 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
31
Q

What are some CYP3A4 inhibitors and what other drugs do they affect?

A
  • 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)
32
Q

What is the effect of enzyme inhibition and induction on drug availability?

A
  • 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
33
Q

How does tobacco affect other drugs and by what mechanism?

A
  • drugs for blood pressure and depression
  • by inducing CYP1A2
34
Q

What is the effect of ethanol on other drugs?

A

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

35
Q

What drugs affects oral contraceptive effectiveness? How?

A
  • 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
36
Q

what effect does St John’s worts have?

A
  • may increase metabolism of certain drugs by inducing CYP3A4
  • can lead to decrease bioavailability or increase effects of drugs activated by this
37
Q

what interactions do garlic supplements have?

A

decreases saquinavir (for AIDS/HIV) levels

38
Q

Grapefruit contains many bioactive agents, including compounds that inhibit ____________ and also stimulates ___________

A
  • CYP3A4 and CYP1A2
  • the function of p-glycoproteins
39
Q

what drugs can grapefruit juice affect? how?

A
  • increase absorption of statins
  • decrease absorption of fexofenadine
  • blocks breakdown of caffeine
40
Q

what affect does THC and CBD have on metabolism?

A
  • THC: CYP1A2 inducer
  • CBD : CYP3A4 inhibitor
41
Q

what are drugs that can interact with warfarin?

A

many including ethanol and aspirin

41
Q

what is inverted drug interaction?

A
  • 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
42
Q

what are ways to study drug interactions?

how to test before clinical trials

A
  • In vitro: cytochrome P450 induction / inhibition
  • Newer strategies: high-throughput robotics allow to predict potential drug interactions and toxic
    metabolites
43
Q

what interacts with lithium? how?

A

Renal clearance of lithium can be decreased by 25% by:
- diuretics (which increase urinary output)
- NSAIDs (which change the pH).

44
Q

what are ways excretion of drugs can be altered?

A

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)

45
Q

what interacts with methotrexate? how?

A

amoxicillin; they compete, which leads to toxic levels of methotrexate in the bloodstream

46
Q

what is Parkinson’s?

A

defect in dopamine in a specific region of the brain (substantia nigra) which leads to tremors and impaired balance

47
Q

what is Levodopa, what is it used for and how does it work? what are some side effects?

A
  • 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
48
Q

what is a drug interaction with Levodopa, what effect does it have?

A
  • Carbidopa is a beneficial drug interaction
  • blocks the peripheral enzyme, but cannot cross the BBB. Thus, more Levodopa is available to enter the brain
49
Q

people with arthritis who take NSAIDs usually also take _________ because __________

A
  • proton pump inhibitors
  • to prevent ulcers
50
Q

Opioids + CNS depressants are a ____________ combination since ___________________

A
  • potential lethal
  • it can lead to respiratory arrest
51
Q

what effect does Monoamine Oxidase Inhibitors (antidepressants) + wine / cheese have?

A
  • 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

PHAR 300 (12 decks)

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