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Pharm S1 > EX2 Lecture 6 - Drug Interactions > Flashcards

EX2 Lecture 6 - Drug Interactions Flashcards

1
Q

what are drug interactions

A

The modification of the effect of one drug by the prior accompanying administration of another drug

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2
Q

what things are at risk in drug interactions

A

Risking loss of therapeutic effect, toxicity, unexpected adverse effects, or incompatibility

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3
Q

effect can vary from ____

A

one person to another

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4
Q

what are risk factors of drug interactions?

A

Polypharmacy,
multiple prescribers,
multiple pharmacies,
genetic make up,
special populations (elderly, critically ill)
drug make up (a small therapeutic index, prodrug)

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5
Q

two or more drugs given together, create what

A

an alteration in effect

can be beneficial or harmful

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6
Q

carbidopa and levodopa interaction example

A

Carbidopa inhibits peripheral breakdown of levodopa, which means more levadopa crosses the blood brain barrier, giving additional and lengthened time and ability in the brain

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7
Q

warfarin drug interaction example

A

Metabolism of warfarin is increased by some antibiotics meaning the INR becomes reduced (blood is thicker, clots easier), and the drug provides inadequate anticoagulation

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8
Q

drug-dietary supplement interaction examples

A

prescriptions, OTCs, illicit substances
St johns worts and many drugs
cocaine and antihypertensive

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9
Q

what can drug-food or drink interaction cause? what are two examples?

A

-may cause interaction or prevent appropriate absorption
- doxyycline and milk
- metronidazole and alcohol ( get red in face, feeling very off)

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10
Q

drug-disease interaction examples

A

-some drugs are helpful in one disease but harmful in others
- some beta blockers and asthma
-NSAIDs and heart failure

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11
Q

what does A rated drug interaction severity mean (category, action, explanation)

A

category- unknown
action- no known interaction
explanation- no documentation of interaction

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12
Q

what does B rated drug interaction severity mean (category, action, explanation)

A

category- minor
action- no action needed
explanation- limited clinical side effects, may increase frequency or severity of side effects but generally does not require a major change in therapy

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13
Q

what does C rated drug interaction severity mean (category, action , explanation)

A

category- moderate
action- monitor therapy
explanation- may result in exacerbation of patients condition and/or require therapy alteration

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14
Q

what does D rated drug interaction severity mean (category, action, explanation)

A

category- major
action- consider therapy modification
explanation- may be life threatening and/or require medical intervention to minimize or prevent serious adverse effects

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15
Q

what does X rated drug interaction severity mean (category, action, explanation)

A

category- contraindicated
action- avoid combination
explanation- the drugs are contraindicated for concurrent use

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16
Q

pharmacodynamic drug interaction classification

A

-involves process or change of drugs
- interactions at receptor level

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17
Q

pharmacokinetic drug interaction classification

A

-involves motion of drug through body
- interactions drug moving through body

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18
Q

what are additive effects on same receptor (PD drug interaction) and an example drug and effect

A
  • multiple agonists working on similar receptors = excessive effect

-multiple benzodiazepines (ativan, xanax)
-excessive sedation, breathing issues

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19
Q

what are additive effects on different receptors (PD drug interaction) and example drugs and effect

A

-different agonists work on different receptors with similar adverse effects (causing the same result)

-benzodiazepines and opiods
= excess respiratory depression

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20
Q

PD additive interactions causing increased bleeding risk

A
  • anticoagulants (warfarin, DOACs)
  • antiplatelets (clopidogrel, ticagrelor, prasugrel, aspirin)
  • NSAIDs, SSRIs, SNRIs
  • natural products (garlic, ginko, ginger, ginseng, glucosamine)
  • all these have an increased risk of bleeding but excess when taken together
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21
Q

PD additive interactions causing anticholinergic toxicity, and what are the side effects of this

A

-antihistamines ( diphenhydramine)
- SSRIs, antipsychotics, tricylic antidepressants
- muscle relaxants (baclofen)
- overactive bladder antimuscarinics (oxybutynin)

  • may not have side effect symptoms until given more than one of these together

side effects= dry mouth, dry eyes, urinary retention, constipation

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22
Q

PD additive interaction causing nephrotoxicity

A

-amnioglycosides, vancomyocin, amphotericin B
- NSAIDs
- IV loop diuretics
- chemotherapy (cisplatin, methotrexate) cyclosporine, tacrolimus

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23
Q

PD additive interaction causing QT prolongation examples

A
  • antiarrythmitics- amiodarone, sotalol, dofetilide, ibutilide, procainamide, dronedarone
  • antimicrobials- azoles, fluorquinoles, macrolides

-antipsychotics- haloperidol, quetiapine, ziprasidone

  • antidepressants- SSRIs, SNRIs, TCAs

-methandone, sumatriptan, ondansetron

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24
Q

PD additive interactions of serotonergic agents examples

A
  • mood-altering meds SSRIs, SNRIs, mirtazapine, trazadone, buspirone, TCAs, MAOi, lithium
  • linezolid
    -tramadol, methadone, meperidine
  • dextromethorphan
  • antiemetics (ondansetron)
  • triptans (sumatriptan)
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25
PD additive interaction of hyperkalemia examples
- excess potassium - ACE inhibitors, ARBs, sacubitril/valsartan - K- sparing diuretics - aldosterone antagonists - sulfamethoxazole/ trimethoprim - tacrolimus, cyclosporine
26
what are synergistic effects (PD interaction) and example
-effect of two drugs magnified beyond what would be expected - aminoglycosides and penicillins
27
what are antagonist blocking agonist effects (PD interaction) and example
-antagonist blocks and prevents further activation of receptor -naloxone for opioid overdose
28
Chelation, complex formation, disruption of PK Absorption with drug interactions
-antacids, multivitamins reduce availability of fluroquinolone, tetracycline - cholestyramine binds warfarin, sulfamethoxazole in small intestine
29
change in PH disruption in PK absorption with drug interactions
- increasing pH of stomach (H2 antagonists, PPI, antacids) may decrease absorption of drugs that need acidic environments (itraconazole, ketoconazole)
30
increased motility time, disruption of PK absorption example
- metoclopramide increases gastric emptying, may reduce digoxin levels
31
4th way absorption (PK) is affecte din drug interaction without example ( and list the other three as well)
P- glycoprotien efflux pumps ( chelation- complex formation, change in pH, increased motility time)
32
PK Distribution effects from drug interactions
binding to alpha 1- acid glycoprotein and binding to albumin
33
binding to albumin example- PK distribution disruption
diclofenac has same affinity for albumin as warfarin - displacement of warfarin, increasing plasma concentration
34
how is phase 1 metabolism affected in PK metabolism with drug interaction
-oxidation, reduction, hydrolysis for inactivation - includes cytochrome P450 enzymes
35
how is phase 2 metabolism affected in PK metabolism with drug interaction
-glucuronidation, sulfation, methylation for elimination
36
how is competition for transport in PK elimination affected in drug interaction
-probenecid blocks penicillin renal excretion, increasing therapeutic levels
37
how is change in urinary pH in PK elimination affected in drug interaction
-bicarbonate alkalizes urine, increases methotrexate excretion
38
what are cytochrome (CYP) P450 enzymes and how many are identified and primary break down drugs
- hemeoproteins located in liver - more than 50 identified, 6 primary break down drugs
39
small polymorphisms lead ______
changes in metabolism - poor v extensive v ultrametabolizers
40
drugs can be ____
substrates, inducers, inhibitors
41
what are CYP inducers
-increase enzyme activity and metabolism - often reduce amount of active drug available - full effect may take days to weeks --- require new enzyme production --- washout period may be lengthened
42
SCRAP GPS'S
S- sulfonylureas C- carbazaepine (anti seizure) R- rifampin and rifabutin (antibiotic) A- alchohol use (chronic) P- phenoarbital (anti seizure) G- griseofulvin P- phenytoin (anti seizure) S- smoking S- st johns wort
43
what are CYP inhibitors
- reduce enzymnatic activity and metabolism - often increase active drug availability (by inhibiting enzymes breakdown) - effects noted quickly (prolonged breakdown-x prolonged drug effect- possible side effects quicker) - can be used therapeutically - ritonavir, cobiccistat
44
PACMAN'S GM ( grandma -slow- inhibitors)
P- protease inhibitors (cancer) A- amiodarone C- cyclosporine, chlorophenol, cimetidine M- macrolides (not azithromyocin) (antibiotics) A-azoles (anti fungals) N- non DHP calcium channel blockers S- sodium valproate (anti seizure) G- grapefruit juice M- metronidazole
45
3A4 (enzyme) substrates
-analgesics ( buprenorphine, tramadol) - anticoagulants (warfarin) - antiplatelets (ticagelor) - antidiabetics (saxigliptin) - cardiovascular drugs (amiodorine) - immunosuppressants (tacrolimus) - statins (atorvastatin) - HIV drugs (ritonavir) -PDE-5 inhibitors (sildenafil) -others (benzos, buspirone)
46
2C8/9 (enzyme) substrates
amiodarone, pioglitazone, carvedilol, alosetron, celecoxib, diazepam, glyburide, glipizide, glimepiride, phenytoin, warfarin, ramelteon, zolpidem
47
2C19 (enzyme) substrates
clopidogrel, phenytoin, voriconazole
48
2D6 (enzyme) substrates
- analgesics ( codeine, oxy) - antidepressants/ antipsychotics ( doxepin) - others ( carvedilol, tamoxifen)
49
key point: many drugs affected by _____ enzymes
CYP450 enzymes
50
a pt is taking fluconazole (for prophalaxis of AML) and developed MDD for which he was prescribed citalopram 40mg - what will occur with this reaction
fluconazole is a CYP inhibitor so it slows CYP enzyme so you dont get as much of the inactive metabolite fro citalopram - more citalopram available in the body - additive effect of QT prolongation *prolonged QTc
51
a patient was in hospital due to STEMI, got two stents placed in cath lab and has sicne started aspirin and ticagrelor (to keep stent open). He also started OTC st johns wort 2 weeks before MI- what could the implications be
st johns wort is a cyp inducer - adds an extra enzyme so breaks drug down faster so there will be increased risk of thrombosis as the stent wont be able to stay as open
52
to monitor or to take action in drug interactions
important to consider implication of interaction - if one is way higher priority and for known causes besst to keep that and discontinue others -some cases not very clear - consider each interaction and make clinical decision based on best judgement
53
pt has PMH of hypolipedemia (HDL) being treated with atorvastatin, he recently got a juicer and makes grapefruit juice - what are the possibel implications of this new habit
grapefruit juice is a cyp inhibitor so in is going to make metabolism slower increased risk of muscle aches (side effect of statins) increased atorvastatin levels
54
what percent of drugs are metabolized by non CYP enzymes? what kind of reaction is it?
33% of top 200 drugs mainly by phase II elimination
55
two facts about non cyp p450 enzymes
drug interactions less common isoniazid toxicity can occur through some pathways
56
3 examples of non cyp p450 enzymes
UDP- glucuronosyl transferase (UGT) N- acytytransferase (NAT) Monoamine oxidase (MAO)
57
where are P-glyxoprotein (PGP) Efflux pumps found and what is their role
found around the body pump substrates to prevent activity (OAT efflux pumps)
58
p-glycoprotein efflux pump substrates
- anticoagulants ( apixaban, rivaroxaban, dabigatran) - antineoplastics ( docetaxel, vincristine) -immunosupressants (cyclosporin, tacrolimus) - macrolides (clarithromyocin) -HIV drugs (dolutegravir) -digoxin
59
p-glycoprotein efflux pump inducers
-st johns wort - rifampin - carbamazepine - phenytoin - phenobarbital
60
p-glycoprotein efflux pump inhibitors
- antibiotics (clarithromyocin, itraconazole, posaconazole) - HIV drugs (cobicistat, ritonavir) -cardio drugs ( verapamil, amiodarone, dronedarone, dilitiazem) -cyclosporine, ticagrelor
61
67 YOF w PMH of T2DM, HTN, on metformin, lisinopril, verapamil recently developed Afib and was prescribed dabigatran what is the risk associated with this drug interaction adn are there potential alternatives
dabigatran is an anticoagulant so there is an increased risk of bleeding due to the use of a p-gp inhibitor (veraprimil) could switch and use different agents
62
what is a prodrug, what do they use to activate, what do they risk
- utilize CYP enzyme to activate drug (first pass metabolism) -can be used to increase bioavailability, avoid drug abuse - risk lack of activity or potential toxicity
63
what is first pass metabolism in prodrugs
converts mediation to pharmacologically active formulation (must occur to have an effect)
64
metabolite of codeine
morphine
65
Metabolite of clopidogrel
active metabolite
66
metabolite of lisdexamphetamine
dexamphetamine
67
metabolite of fosphenytoin
phenytoin
68
metabolite of enalapril
enalaprilat
69
metabolite of valacyclovir
acyclovir
70
metabolite of cortisone
cortisol
71
metabolite of prednisone
predisolone
72
metabolite of primidone
phenobarbital
73
metabolite of tramadol
active metabolite
74
metabolite of levadopa
dopamine
75
metabolite of diazepam
oxazepam
76
how is codeine converted to morphine how does it affect UM and PM
converted via CYP2D6 UM- potential toxicity PM (or patients taking CYP2D6 inhibitor)- lack of pain relief
77
how is clopidogrel converted to active metabolite how does it affect PM what can be used alternatively for PM
converted via CYP2C19 PM- reduced platelet inhibition( bc drug not getting activated); use alternative P2Y12 inhibitor
78
what are CYP2C19 inhibitors
reduce platelet inhibition; avoid combination with clopidogrel omeprazole esomeprazole
79
narrow therapeutic index drugs
aminoglycosides vancomyocin digoxin warfarin tacrolimus mycophenolate cyclosporine phenytoin valproic acid carbamazepine theopylline lithium levothyroxine
80
what is one of the most noted medications effected by drug interactions
warfarin
81
metabolic interactions with warfarin
-substrate of CYP 2C9 - CYP3A4, CYP1A2, CYP2C19 also play a role
82
vitamin K interactions of warfarin
-prescription meds - OTC products - foods
83
what drugs increase bleeding risk of warfarin
anticoagulants, antiplatelets NSAIDs SSRIs
84
what drugs increase metabolism interference of warfarin
ABCDEF rifampin
85
what drugs have a reduced vitamin k production by gut flora when taken with warfarin
antibiotics
86
what drugs interrupt vitamin K cycle when taken with warfarin
acetaminophen (1.5-2.5 g chronically)
87
Common drugs that change warfarin metabolism from highest INR to lowest INR
A- amiodarone (highest INR-thinnest blood) B- bactrim C- cipro (and other FQ) D- diflucan (and other azoles) E- erythromyocin (and other macrolides) F- flagyl (all above inhibit warfarin breakdown, prolonging activity) R- rifampin (only one that decreases INR- inducer- thicker blood)
88
effects of warfarin and amiodarone interaction (commonly seen)
decrease warfarin brekadown increase bleeding increase INR
89
if already on amiodarone and starting warfarin what shoudl you do to the dose
reduce starting dose of warfarin by 30-50%
90
if already on warfarin and starting amiodarone what should you do to the dose
reduce warfarin dose by about 50%
91
amiodarone and digoxin interaction
used to control rate and rhythm in patients with Afib digoxin is a p-gp substrate and amiodarone is a p-gp inhibitor gives a risk of digoxin toxicity, reduced HR, electrolyte abnormalities
92
if on amiodarone, used first, and starting digoxin, what should you do to the dose
start digoxin at a lower dose
93
if on digoxin, used first, and starting amiodarone what should you do to the dose
decrease digoxin dose by 50% (so basically always decrease digoxin with amiodarone because amiodarone can prolong activity of digoxin)
94
what are carbamazepine and lamotrigine and what happens when used together
they are antiepileptics carbamazepine is an enzyme inducer and lamotrigine is a substrate used together you risk breakthrough seizures - start at a higher dose
95
what are lamotrigine and valproic acid and what happens when used together
lamotrigine is a substrate and valproic acid is an enzyme inhibitor risk lamotrogine toxicity (serious skin reactions) - start at lower dose (becasue you have extended exposure of lamotrigine due to inhibition of its breakdown)
96
pde-5 inhibitors (give examples) and nitrates (give examples) side effects when used together
pde-5 inhibitors like sildenafil and tadalafil nitrates like nitroglycerin and isosorbide cause excessive vasodilation and severe hypotension concomitant use is CONTRAINDICATED **even PRN nitrates**
97
when should you check for drug interactions
any new medications any medications on list that give you red flags any med on pt list with narrow TI any new adverse effects that may be additive
98
clinical impact of drug interactions to consider
are there a lot of potential drug interactions are they all clinically relevant (is someone drinking 15L of grapefruit juice to cause an interaction) when do drug interactions require action ( based on clinical judgement)
99

Pharm S1 (18 decks)

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