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Drug Action > Drug Interactions > Flashcards

Drug Interactions Flashcards

1
Q

How many drugs are people likely to receive in the hospital, for what?

A

Patients often receive more than 20 drugs in hospital
Control: pain, anesthesia, muscle relaxant, blood pressure, control infection, anti-anxiety

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2
Q

Drug interactions using prescription drugs?

A

Over the counter medication, with prescription or herbal remedies, (drug interactions could be dangerous)

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3
Q

What is the relationship between the number of drugs and side effects due to interactions?

A

Amount of side effects goes up as you increase the amount of drugs

Not too significant side effects with 0-5 drugs but goes up for 6-10 drugs and then significantly higher for 11-15 drugs and very high for 16-20 drugs

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4
Q

Why is poverty a major risk factor for drug interactions?

A

buy a lot of things OTC or try herbal remedies, take some stuff without consulting a doctor, so they are more at risk since they don’t have the money to ask a professional

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5
Q

Are drug interactions positive or negative?

A

Both, We usually look at the negatives since we want to avoid them, and some can lead to death
There are some positive ones that give a benefit when taking together

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6
Q

What does beetroot do?

A

Beetroot: urine turns red, the dye in beets is not absorbed

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7
Q

Red wine interactions?

A

Red wine: over 1000 chemicals, some interact, some can give headaches on their own like tyramine

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8
Q

What are factors influencing drug interaction outcomes?

A

Patient factors: genetics, disease, diet, environment, smoking, alcohol
Drug administration: dose, duration, dosing times (the times you take the different drugs, A vs B first) , sequence, route, dosage form

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9
Q

There is a high variability in drug interactions between people

A

Just because person A can take a certain combination doesn’t mean person B will be able to take that combination, it has to be varied for each person individually

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10
Q

Classification of drug interactions: Consequence?

A
  • Beneficial or adverse
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11
Q

Classification of drug interactions: site?

A
  • External or internal (usually internal)
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12
Q

Classification of drug interactions: Mechanism?

A
  • Pharmacodynamic (two drugs act on same receptor site to magnify or decrease an effect)
  • Pharmacokinetic (increase or decrease metabolism)
  • Physiological (increase or decrease a physiological response)
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13
Q

Types of interactions? (4)

A
  • Additive (drugs d o a similar thing, 1+1=2)
  • Synergistic (one drug magnifies the effect of another (1+1=3))
  • Potentiation (one drug does nothing by itself but can magnify the effect of another one) (1+0=2)
  • Antagonism (one drug antagonizes the effect of another drug) (1+0= 0.5)
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14
Q

Pharmacokinetic mechanisms of drug interactions?

A

One drug can alter the absorption, distribution, metabolism, or excretion of another drug
Alter blood concentration of a given drug, more or less of it available in the blood

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15
Q

Pharmacodynamic mechanism of drug interactions?

A

Two drugs are acting on the same site, one drug can compete with it, block it, alter it
Modulate drug effect at a given plasma concentration (the blood concentration stays the same but the effect on receptors is different for the same concentration)

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16
Q

Altering the plasma concentration of a drug? (pharmacokinetics

A
  • Get a higher concentration of the drug, the level is closer to the toxic level, more side effects
  • Get a lower concentration of the drug, there will not be enough for an effective level
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17
Q

How can drug absorption be altered?

A

Gastric pH will alter the absorption of some drugs (tetracycline, antibiotic, on empty stomach good absorption, but with milk the calcium carbonate binds to the tetracycline so it will not be absorbed)
Calcium Carbonate inhibits Thyroxine absorption (girl separated her doses morning and night)

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18
Q

What drugs affect the gastric pH?

A
  • Omeprazole, lansoprazole, H2-antagonists alter gastric pH, reduce absorption of ketoconazole, delavirdine
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19
Q

What factors (3) effect drug absorption?

A

Transit time, absorptive surface area, complex formation
Some people have reduced absorptive surface area due to diseases like inflammatory bowel disease
Transit time altered if someone has diarrhea the blood can pass through very rapidly
A complex formed in the intestine, so the drug can’t be absorbed

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20
Q

What do p-glycoproteins do?

A

P glycoproteins prevent drug from getting into the portal vein, kicks it back out to intestinal lumen
(prevents drug accumulation in cells)

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21
Q

Drug effect on p-glycoproteins and absorption?

A

If a drug inhibits the p-glycoprotein, more of another drug will be absorbed into the blood, can get an overdose of the second drug
Can also upregulate the p glycoprotein, so have less of a second drug in the blood, so it will no longer be effective

22
Q

What drug interactions can alter distribution?

A

Unbound drugs are also the ones that can be metabolized
Drug interaction regarding plasma protein binding
A second drug kicks the first one off of plasma proteins so there is much more free drug in circulation and there can be an overdose of it, pretty rare in reality, usually enough plasma proteins and they don’t kick each other off
(usually a balance of unbound to plasma protein bound drugs)

23
Q

What are the 2 main cytochrome P450s that break down drugs, how can they be altered by drug interactions?

A

P450 enzymes, CYP3A4, CYP2D6 very important to metabolize drugs
For each of the different types of P450 enzymes their activity can be altered by many things, inhibition, it can be induced, inhibited, polymorphisms for different people

24
Q

Ketoconazole (anti-fungal) drug interaction making it less active?

A

It is metabolized by many CYP450s, CYP3A4
Enzyme inhibition,
Since Ketoconazole needs to be broken down to its active intermediate to cause an effect, there is decreased amount of the effective drug

25
Q

Why can inducing CYP3A4 be dangerous?

A

Drug A binds a receptor and induces the enzyme CYP3A4, there will be more metabolism of drug B, therefore less of drug B
If drug B is important like warfarin (anticoagulant) at risk of a blood clot, heart attack…

26
Q

What cytochrome P450 does smoking induce?

A

Smoking induces CYP1A2
Breakdown more drugs, less effective, some important for controlling blood pressure and depression

27
Q

What P450 does ethanol induce?

A

Ethanol inducs CYP2E1 and depletes gluthathione (involved in the second stage of acetaminophen metabolism so it is not toxic)
Risk of acetaminophen toxicity, CYP2E1, metabolises acetominophen to its toxic metabolite, and less able to detoxify these intermediates

28
Q

What CYP does Ketoconazole inhibit?

A

CYP3A4

29
Q

Effects of CYP3A4 inhibitors on statin serum concentrations?

A
  • Statin toxicity: myopathy … if severe can be fatal
  • Statins: taken to lower risk of heart attacks
  • If inhibit 3A4, increase statin blood levels, overdose of statin result in muscle injury that can be fatal
30
Q

How does CYP2D6 vary between ethnic groups?

A
  • Absent in 7% of Caucasians, 1-2% in non-Caucasians
  • Hyperactive in up to 30% of east Asians
31
Q

What doe CYP2D6 catalyze the primary metabolism of?

A
  • Catalyzes primary metabolism of :
    o Codeine (to morphine)
    o Many beta blockers
    o Many tricyclic antidepressants
32
Q

What is a CYP2D6 inhibitor?

A

o Fluoxetine
o Haloperidol
o Paroxetine
o Quinidine

33
Q

CYP2D6 and breast cancer treatment?

A

Tamoxifen treat breast cancer, needs to be converted to active form by 2D6

34
Q

What CYP does St/ John’s Wort induce?

A

CYP3A4 inducer, can die from taking St. John’s Wort and metabolizing a drug too fast so it is no longer effective
Also increase the effect of a drug activated by 3A4

35
Q

What do garlic supplements decrease?

A

Garlic supplements decrease saquinavir (invirase) levels
- Garlic supplements have a very concentrated amount of the chemical
- Risk to HIV patients

36
Q

What components of the grapefruit inhibit Cytochrome P450s?

A
  • Contains naringin, naringenin
  • Inhibits CYP3A4, CYP3A3, and CYP1A2
  • Furanocoumarins strongly inhibit CYP 3A4
37
Q

Grapefruit juice effect on p-glycoproteins

A
  • Grapefruit juice enhances p-glycoproteins, lower penetration of BBB and the kidney
  • Decrease drug absorption of other drugs by affecting P-glycoproteins, too little drug that you need
38
Q

What drugs can Grapefruit juice inhibit the breakdown of?

A
  • Can inhibit the breakdown of some drugs like statins and cause a statin overdose
  • Morning grapefruit juice increased the levels of evening Lovastatin
  • Blocks the metabolism of caffeine, get a bigger reaction from coffee
39
Q

Grapefruit and metabolism?
Major effect and how long it lasts?

A
  • Major effect is blocking CYP3A4
  • Last up to 3 days
40
Q

Grapefruit and absorption?

A
  • Inhibits transport proteins in intestinal wall
  • Stimulates p-glycoproteins
41
Q

THC and CBD on cytochrome P450s?

A

THC: CYP1A2 inducer
CBD: CYP3A4 inhibitor
May potentially affect the metabolism of many drugs
333 drugs known to interact with cannabis, 24 major drug interactions

42
Q

Warfarin, inverted drug interactions?

A
  • Discontinuation of enzyme-inducing drugs
    o Equivalent to adding an enzyme inhibitor
  • Discontinuation of enzyme-inhibiting drugs
    o Equivalent to adding an enzyme inducer
    May take some time to get back to normal
43
Q

What effects drug excretion?

A

Adrenal drug clearance
Reabsorbed based on lipid soluble
Acidify urine, increase excretion of weak base

44
Q

How can lithium clearance be altered?

A

Renal clearance of lithium can be decreased by 25%, by diuretics and some NSAIDS

45
Q

Principles of Pharmacodynamics of drug interactions?

A
  • Alter the concentration response curve
  • Have an altered effect based on the same concentration
46
Q

Parkinson’s Disease cause and treatment?

A

Defect in dopamine in the substantia Nigra in the brain, tremor, shuffle
Therapy: try to replace dopamine

47
Q

Levodopa mechanism of action to treat Parkinson’s?

A

Levodopa: precursor of dopamine
Converted to dopamine by dopa decarboxylase
Levodopa must cross the BBB to be active in the brain, if it is converted in the periphery get more side effects

48
Q

Drug interaction: levodopa and Carbidopa?

A

Therapy: beneficial drug interaction
Give levodopa with Carbidopa
Carbidopa: blocks peripheral enzyme, but can’t cross BBB
More levodopa available to enter the brain
Need lower dose, fewer side effects

49
Q

opioids and CNS depressants cause?

A

Respiratory arrest

50
Q

Ibuprofen briefly prevents ASA from binding cox 1

A

h

51
Q

Antidepressants with wine and cheese?

A

Red wine and cheese both contain tyramine
tyramine induces the release of neurotransmitters
MOAI (anti depressants) block the neurotransmitter reuptake and prevent their inactivation
this combined results in a hypertensive crisis
flooding adrenergic pathways In the brain, blood pressure goes way up

Drug Action (18 decks)

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