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Heme/Lymph Exam > Anticoagulants & Analgesics > Flashcards

Anticoagulants & Analgesics Flashcards

1
Q

venous thromboembolism (VTE) - hereditary risk factors

A

*factor V Leiden mutation
*Protein C or S deficiency
*hyperhomocysteinemia
*prothrombin gene mutation
*decreased factor VIII levels
*dysfibroginemia
*antithrombin deficiency

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2
Q

venous thromboembolism (VTE) - acquired risk factors

A

*surgery
*trauma
*medical illness
*immobolization
*pregnancy
*contraception/HRT
*indwelling catheters
*malignancy
*air travel

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3
Q

venous thromboembolism (VTE) in malignancy

A

*key risk factor: HYPERCOAGULABILITY
-mucin production by adenocarcinomas
-tissue factor production

*risk is higher in certain tumor types: pancreatic cancer, lung cancer, breast cancer, CNS malignancies

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4
Q

4 classes of anticoagulants

A
  1. heparins
  2. vitamin K antagonists
  3. direct thrombin inhibitors
  4. factor Xa inhibitors
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5
Q

anticoagulant class: heparins - MOA

A

*activates antithrombin, which decreases action primarily of factors IIa (thrombin) and Xa
*has its predominant impact on the intrinsic (PTT) pathway of the coagulation cascade

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6
Q

indications for heparin

A

*immediate anticoagulation for:
-VTE prophylaxis/treatment [pulmonary embolism, DVT]
-acute coronary syndrome
-MI
-percutaneous coronary intervention

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7
Q

heparins - ADEs

A

*heparin-induced thrombocytopenia (HIT)
*bleeding

note - monitor PTT of pts on heparin

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8
Q

what lab test should you monitor in patients on heparin

A

PTT

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9
Q

heparin-induced thrombocytopenia (HIT) - pathophysiology

A

*complication of therapy with heparins
*development of IgG antibodies against heparin-bound platelete factor 4:
-antibody-heparin-PF4 complex binds and activates platelets, leading to removal by splenic macrophages and therefore LOW PLATELET COUNTS

*tx - discontinue heparin and start an alternative anticoagulant

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10
Q

heparin-induced thrombocytopenia (HIT) - diagnosis

A

*serotonin release assay = diagnostic gold standard
*4T score: thrombocytopenia, timing of platelet fall coincides with heparin use, thrombosis, oTher causes (injury, fall, etc)

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11
Q

heparin-induced thrombocytopenia (HIT) - management

A

*stop all heparin products
*initiate therapy with alternative anticoagulant (bivalirudin, argatroban, fondaparinux)
*note - reexposure to heparin should be avoided

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12
Q

low molecular weight heparin - examples

A

*enoxaparin
*dalteparin

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13
Q

low molecular weight heparin - MOA

A

*activate antithrombin → act mainly on decreasing factor Xa

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14
Q

enoxaparin

A

*example of a low molecular weight heparin
*indications:
-VTE prophylaxis/treatment
-acute coronary syndrome
*ADEs: heparin-induced thrombocytopenia, bleeding

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15
Q

dalteparin

A

*example of low molecular weight heparin
*indications:
-VTE prophylaxis/treatment
-myocardial infarction
*ADEs: heparin-induced thrombocytopenia, bleeding

note - not as commonly used in the US

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16
Q

what is the reversal agent for heparin

A

PROTAMINE SULFATE

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17
Q

protamine sulfate

A

*reversal agent of heparin

*MOA: positively charged peptide that binds negatively charged heparin

*indications: unfractionated and low molecular weight heparin overdosage/associated hemorrhage

*ADEs:
-hypersensitivity
-pulmonary hypertension
-dyspnea

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18
Q

vitamin K antagonists (warfarin) - MOA

A

*inhibits vitamin K epoxide reductase
*inhibits vitamin K-dependent clotting factors: factors II, VII, IX, and X
*also inhibits proteins C and S (which are anticoagulants)
*has its predominant impact on the extrinsic pathway of the coagulation cascade

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19
Q

warfarin - MOA

A

vitamin K antagonist (inhibits vitamin K epoxide reductase → decreased production of factors II, VII, IX, and X and proteins C and S)

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20
Q

warfarin - indications

A

*VTE treatment
*chronic anticoagulation

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21
Q

warfarin - onset of action

A

*vitamin K inhibition: takes about 5 days
*HYPERcoagulability for 0-48 hours after 1st dose; therefore, you have to “bridge them”

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22
Q

what lab test should you monitor in patients on warfarin

A

PT/INR

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23
Q

INR monitoring for patients on warfarin

A

*goal of therapy = INR
*INR monitoring:
-weekly during initiation/major dose adjustment
-monthly during maintenance

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24
Q

warfarin drug-drug interactions

A

*CYP2C9 inhibitors/inducers (fluconazole, amiodarone, rifampin)
*chemotherapy agents (capecitabine, aprepitant)
*oral contraceptives

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25
warfarin food interactions
*green, leafy veggies (kale, turnip greens, iceberg lettuce) *cereal *lamb essentially, you would need to eat these regularly and in consistent amounts; if not, there will be INR fluctuations
26
warfarin ADEs
*teratogenic effects *skin/tissue necrosis (due to hypercoagulable state) *vasculitis
27
reversal of warfarin
*Vitamin K (slow reversal) *Kcentra (rapid reversal): -4 factor prothrombin complex -ADEs: headache, N/V, arthralgia, hypotension, stroke, DVT,PE
28
examples of direct thrombin inhibitors
*bivalirudin *argatroban *dabigatraban
29
bivalirudin - MOA
*directly inhibits thrombin (factor IIa)
30
bivalirudin - indications & ADEs
*indications: percutaneous coronary intervention; treatment of HIT *ADEs: back pain, bleeding
31
argatroban - MOA
*directly inhibits thrombin (factor IIa)
32
argatroban - indications & ADEs
*indications: percutaneous coronary intervention, treatment of HIT *ADEs: hypotension, bleedingg *note - with co-administration with warfarin, argatroban can cause artificially high INR but it is purely lab artifact
33
dabigatran - MOA
*directly inhibits thrombin (factor IIa)
34
dabigatran - indications & ADEs
*indications: primary or secondary VTE prevention *ADEs: dyspepsia, bleeding, drug interactions
35
dabigatran - reversal
*idarucizumab *monoclonal antibody that binds dabigatran and its metabolites
36
examples of factor Xa inhibitors
*apixaban *edoxaban *rivaroxaban *fondaparinux *betrixaban note - naming convention: usually have an "x" in them or end with "-xaban"
37
fondaparinux - MOA
*directly inhibits factor Xa
38
rivaroxaban - MOA
*directly inhibits factor Xa
39
apixaban - MOA
*directly inhibits factor Xa
40
edoxaban - MOA
*directly inhibits factor Xa
41
betrixaban - MOA
*directly inhibits factor Xa
42
fondaparinux - indications & ADEs
*indications: VTE prophylaxis/treatment, acute coronary syndrome, treatment of HIT *ADEs: fever, nausea, bleeding
43
rivaroxaban - indications & ADEs
*indications: VTE prevention/treatment *ADEs: bleeding, increased liver enzymes
44
apixaban - indications & ADEs
*indications: prevention/treatment of VTEs *ADEs: increased liver enzymes, bleeding
45
what is the reversal agent of factor Xa inhibitors
andexanet alfa
46
andexanet alfa
*factor Xa inhibitor reversal agent *MOA: recombinant inactive form of factor Xa that acts as a decoy to bind anticoagulant *ADEs: thromboembolic events, infusion site reaction
47
pain classification: nociceptive pain
*musculoskeletal conditions *inflammation *direct tissue injury
48
pain classification: neuropathic pain
*result of damage to nervous system *acquired in most cases
49
pathogenesis of acute cancer pain
1. most related to iatrogenic sources (diagnostic tests/procedures or treatment of disease) 2. can be related to the disease itself: -bone pain from pathologic fracture -visceral pain from acute obstruction 3. adverse effects of treatment for cancer: -mucositis from chemotherapy or radiation -chemo induced neuropathy
50
pathogenesis of chronic cancer pain
1. tumor-related somatic pain: -bone pain from bone metastases -visceral pain from organ/soft tissue metastases 2. tumor-related neuropathic pain: -leptomeningeal metastases -paraneoplastic syndromes (osteoarthropathy)
51
challenges in treatment of cancer pain
*route of administration (mechanical and physiologic challenges) *drug-seeking vs. true pain *acute variance in pain *adverse effect management
52
WHO pain management algorithm ladder
*mild to moderate pain [scores 1-3]: treat with non-opioid analgesics (NSAIDs, acetaminophen) *moderate to severe pain [scores 4-6 or 7]: mild opioids (e.g. codeine) *severe pain [scores 7-10]: strong opioids (e.g. morphine)
53
classes of analgesic agents
1. non-opioid analgesics (acetaminophen, NSAIDs) 2. opioid analgesics 3. anticonvulsants 4. antidepressants
54
acetaminophen - MOA, drug class, indication
*MOA: prostaglandin blockade/inhibition *drug class: non-opioid analgesics *indication: mild to moderate pain [scores 1-3]
55
acetaminophen - ADEs
*hepatotoxicity! *masks a fever (important in oncology population)
56
NSAIDs - examples
1. salicylates (aspirin) 2. propionic acids (ibuprofen, naproxen, ketoprofen) 3. acetic acids (diclofenac, etodolac, sulindac, indomethacin, ketorolac) 4. oxicams (meloxicam, piroxicam)
57
NSAIDs - MOA, drug class, indications
*MOA: COX inhibitors *drug class: non-opioid analgesics *indications: mild to moderate pain [scores 1-3]
58
NSAIDs - ADEs
*platelet inhibition *gastrointestinal insult *renal insult
59
COX-2 inhibitor
*celecoxib is the only agent approved *MOA: selective for COX-2 inhibition *ADEs: peripheral edema, myocardial infarction, nephrotoxicity
60
tramadol - MOA and drug class
*MOA: mu-receptor binding, serotonin/norepinephrine reuptake blockade *drug class: mild opioid *indication: moderate to severe pain [score 4-7/7]
61
tramadol - ADEs
*nausea *constipation *headache
62
opioid analgesics - MOA
*work on 3 different receptors: Mu, delta, and kappa (activates the Mu receptor predominantly) *Mu receptors are concentrated in midbrain and dorsal horn
63
opioid analgesics - class ADEs
*sedation (tolerance develops) *nausea/vomiting (tolerance develops) *constipation (tolerance does NOT develop; prevention is key) *euphoria/dysphoria - related to rate of administration
64
opioid-induced constipation
*result of Mu-receptor activation in the gut *prophylaxis is a must (stimulant laxatives + stool softener)
65
extended-release opioids: REMS
*all extended-release opioids require enrollment by the prescribed and the pharmacy in the REMS program *purpose = heighten awareness of risks of inappropriate use *require medication guide dispensing at each fill of a prescription by pharmacy
66
mild opioids: indications & examples
*indication: first-line agents for patients with moderate to severe pain [score: 4-6/7] *examples: -codeine -hydrocodone
67
morphine: drug class & indications
*drug class: strong opioid *indication: severe pain [score: 7-10]
68
oxycodone: drug class & indications
*drug class: strong opioid *indication: severe pain [score: 7-10]
69
hydromorphone: drug class & indications
*drug class: strong opioid *indication: severe pain [score: 7-10]
70
oxymorphone: drug class & indications
*drug class: strong opioid *indication: severe pain [score: 7-10]
71
fentanyl: drug class & indications
*drug class: strong opioid *indication: severe pain [score: 7-10]
72
fentanyl dosage forms available
*IV/IM *transmucosal *transdermal *buccal film *sublingual liquid/spray *buccal tablet *oral lozenge *intranasal solution *sublingual tablet
73
methadone: MOA & drug class & indications
*MOA: Mu activation/NMDA-receptor inhibition *drug class: strong opioid *indication: severe pain [score: 7-10], OPIATE DETOXIFICATION *available forms: oral tablet, oral solution, injection
74
buprenorphine: drug class, indication
*drug class: partial opioid agonist *indication: chronic severe pain *ADE: QTc prolongation
75
naloxone - MOA, indication
*used for opioid REVERSAL *MOA: competes and displaces opioids at all Mu receptor sites
76
what drug is used for opioid reversal
naloxone
77
anticonvulsants - MOA, indications, ADEs
*MOA: bind to voltage-gated calcium channels and block GABA receptor *used in treatment of NEUROPATHIC PAIN *ADEs: dizziness, somnolence
78
gabapentin: drug class, indications, MOA
*drug class: anticonvulsant *indications: used effectively in post-herpetic neuralgias, but also used in new onset neuropathies *MOA: bind to voltage-gated calcium channels and block GABA receptor note - SLOW onset of improvement
79
pregabalin: drug class, indications, MOA
*drug class: anticonvulsant *indications: used effectively in post-herpetic neuralgias, but also used in new onset neuropathies *MOA: bind to voltage-gated calcium channels and block GABA receptor note - works faster than gabapentin
80
antidepressant pain MOA
*serotonin-norepinephrine reuptake inhibitors possess analgesic qualities *full mechanism not understood, but effects on NEUROPATHIC pain are well established
81
venlafaxine: drug class, indication, ADEs
*drug class: antidepressant *indications: neuropathic pain *ADEs: cardiac conduction abnormalities, hypertension *note - SLOW onset of improvement
82
duloxetine: drug class, indication, ADEs
*drug class: antidepressant *indications: neuropathic pain - chronic low back pain, osteoarthritis, diabetic peripheral neuropathy *ADEs: nausea, dry mouth, insomnia, constipation *note - SLOW onset of improvement

Heme/Lymph Exam (38 decks)

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