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PPP 249 SPRING QUARTER 2023 > Anticoagulants > Flashcards

Anticoagulants Flashcards

1
Q

What’s the common pathway for coagulation?

Extrinsic Pathway?

Intrinsic pathway?

A

Factor X with cofactor 5 –> Factor 2 aka thrombin –> Factor 1 aka fibrinogen –> Clot with factor 13 that helps crosslink

Tissue damage –> Factor 7 –> common pathway

XII –> XI –> IX with co factor 8 –> Common pathway

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2
Q

Drug Targets for the following?
1. warfarin and citrate (6)
2. Factor Xa inhibitors
3. direct Thrombin inhibs
4. Heparins and Heparinoids

A
  1. IX, X,7, II and Proteins S and C
  2. Factor X
  3. Factor 2
  4. Are ATIII so they indirectly inhib factors X and II
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3
Q

Direct Thrombin Inhibitors
1. Name 3
2. How is it administered?
3. Dosing?
4. type of elim?
5. Half life?

A
  1. Dabigatran , Bivalirudin , Argatroban
  2. Oral, IV, IV
  3. BID, Continuous IV, continuous IV
  4. renal, proteolytic, hepatic
  5. 12-17 hrs, 25 min, 40-50 min
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4
Q

Factor Xa inhibitors

  1. Name 3
  2. Admin?
  3. Dosing
  4. Elim?
  5. Half life?
A
  1. Rivaroxaban, Apixaban, edoxaban
  2. ALL ORAL
  3. Daily or BID, BID, Daily
  4. Hepatic, hepatic, renal AND hepatic
  5. 5-9 hrs, 12 hrs, 10-14 hrs (less effective when CRCL> 95)
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5
Q

Heparins & Heparinoids

  1. Antithrombin III
    - Made by ___, circulates in ?
  2. Weakly inhibs factors __ and __ by binding in ?
  3. Factor Xa not inhib when bound to ?
  4. Factor 2a not inhib when bound to?
A
  1. liver, blood
  2. 2 and 10 , 1:1 complex
  3. platelets
  4. fibrin
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6
Q

Unfractionated Heparin (UFH)
- What is it?
MOA 1?
MOA 2?

A

heterogenous mix of glycosaminoglycan chains

allosteric activation of ATIII
- specific 5 saccharide sequence required
-only present in about 1/3 of heparin molecules

Ternary complex formation with ATIII and thrombin
- min 18 saccharide chain length required

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7
Q

Heparin Induced Thrombocytopenia (HIT)
- Caused by ?
- Ab’s bind ___ and ___ on platelets
-Leads to ?

A

Heparins (UFH or LMWH)

heparin + platelet factor 4

platelet activation, consumption and thrombosis

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8
Q

UFH
1. Has ____ to other targets which is greater for ____
- what binding causes HIT?
- what is used as reversal agent?
- binding to what causes a variable response? requires?
- binding to ___ causes ___ w/prolonged use?

A
  1. high binding, larger molecules

platelets+PF4
Protamine
Plasma proteins , PTT monitoring

osteoblasts , osteopenia

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9
Q

UFH is cleared by ___ which is faster for ____
-___ and ____
-Shorter ___ than ____
- no need for ___

A

reticuloendothelial system , larger molecules

macrophages, endothelial cells
- half life, LMWH
- renal dose adjustments

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10
Q

LMWH : Name 2
- a more uniform mixture of?
-MOA?
- EXCEPTION : ?
- average ___ length, but most are too short to bind
-ratio of Xa : 2a inhibition is about?
-Less effect on ___; monitored with ___ instead?

Most chains are <18 sacchs, which is why there’s less ____ inhibition?

A

Enoxaparin, Dalteparin

depolymerized heparin
similar to heparin

DECR INHIBITION of THROMBIN

17 sacch

3:1

PTT, anti-Xa

thrombin

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11
Q

LMWH : Other properties

  1. Decr binding to other targets
    Describes what happens in the following situations when bound: plasma proteins , platelets , protamine
  2. renal clearance
    - requires?
    -Longer ___, allows for?
  3. more uniform sequence
    - more consistent ____ effect , less monitoring
A
  1. More consistent half life , less monitoring required
    - lower incidence of HIT
    - reversal is LESS EFFECTIVE
  2. Renal dose adjustment
    half life, q12/q24 hr dosing
  3. Anticoag
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12
Q

Fondaparinux
- Synthetic _____
MOA : _____ only
- Does not inhib ___
-monitoring is similar to ____ with anti ___ NOT ___
- ___ clearance ?
-Longest ____
- Does not cause _____
-Not reversed by ____

A

5 saccharide analog (heparinoid)

factor Xa inhibition

thrombin

LMWH , Xa, PTT

renal

half life with q24h dosing

HIT

Protamine

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13
Q

Protein targets for Warfarin + Citrate? (5)

A

Factors 9, 10, 2, protein S&C, 7

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14
Q

What are the vitamin K dependent clotting factors?

produced as ____
Glutamic acid (Glu) is converted to ?
factors are now functional and localize to membranes via __

A

II, VII, IX, X, S, C

inactive proteins

Gamma-carboxyglutamic acid (Gla)

calcium

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15
Q

Why are they considered Vitamin K Dependent?

A

Gamma carboxylation requires vitamin K
- this reaction oxidizes vitamin K to vitamin K epoxide
vitamin K must be restored by VKOR or dietary intake

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16
Q

Warfarin MOA

  1. Inhibs?
  2. Depletes?
  3. Prevents synthesis of?

half lives of factors 7, C, IX, S, X, II?

A
  1. VKOR
  2. vitamin K
  3. functional clotting factors II, VII, IX, X, S, C

4-6 hrs, 8 hrs, 24 hrs, 30 hrs, 48 hrs, 72 hrs

17
Q

Day 1 of Warfarin Initiation
- Describe what happens?

Day 2-4 what begins to rise?
- factor __ has shortest half life but greatest effect on ___
-patient is NOT ____ bc factors ____ remain
-patient MAY BE ___ bc protein __ and __ are depleted

A

Liver produces fewer active clotting factors (30-50% less)
Factors alrdy in circulation NOT AFFECTED by warfarin

INR

7, INR

Anticoagulated, 9,10, 2

hypercoagulable, c and s

18
Q

Day 5 : ____Achieved
- factor __ has longest half life and may take longer to reach steady state

A

anti coagulation
II

19
Q

Warfarin can also cause the following (7)
S, T, S, G, D, D, D

A

skin necrosis
teratogenicity
stereoisomers
genetics
drug-drug interactions
disease and population interactions
dietary interactions

20
Q

Teratogenicity
Category ___, Categ D for mechanical heart valves
- In 1st trimester causes what?
-2nd or third trimester causes?

A

X

skeletal defects, nasal and limb hypoplasia

CNS and ophthalmic defects, hearing loss, heart disease, growth restriction, hemorrhage, death

21
Q

Warfarin’s Stereoisomers : S and R
1. WHich is better at VKOR inhibition?

  1. Describe each isomer’s CYP metabolism
A
  1. S
  2. S –> CYP 2C9
    R –> 3A4, 1A1, 1A2
22
Q

Genetics :
VKORC1 variants lead to increased?
More common in ?
Reduce dose in this way for hetero vs homozygotes ?

CYP2C9*2 or *3 lead to ?
Reduce dose how?

A

warfarin sensitivity

asians>caucs>africans

hetero reduce dose 25%, homo reduce dose 50%

incr warf sensitivity
25% for hetero, 50% for homozygs

23
Q

Drug interactions : state what happens to INR, Clinical risk, and Examples

  1. CYP inducers
  2. CYP inhibitors
  3. ANticoags and antiplatelets
A
  1. decr INR
    incr clotting
    carbamazepine, phenytoin, rifampin, phenobarb, chronic alcohol
  2. incr INR
    -incr bleeding
    amiodarone, fluconazole, ACUTE alcohol
  3. same INR
    incr bleeding
    aspirin, clopidogrel, LMWH,
24
Q

Disease and Population Interactions
1. Name conditions that are warfarin sensitive (6)

  1. Conditions that make u warfarin resistant (2)
A
  1. Catabolic conditions such as acute illness or surgery, hyperthyroidism, decompensated heart failure
    - liver disease
    -malnourish
    -low albumin
    -elevated baseline INR
    - low body weight
  2. hypothyroidism
    - high body weight
25
Q

Dietary Interactions
- depends on ?
Variations in ___ leads to variations in warfarin sensitivity

A

vitamin K content

diet

26
Q

Citrate is ?
What happens?

A

Calcium chelator

binds calcium, no more calcium to coordinate with functional proteins (Clotting factor deficient)

27
Q

Use of citrate
- for ?
Citrate is infused AFTER ___
Calcium infused as ____
Requires constant ___ and __

A

anticoag of extracorporeal blood circuits
blood leaves patient
blood returns to pt

monitoring of iCA, lactate, dose adjustment

28
Q

Use of citrate also for ?
Citrate content can cause ___ w/ massive ___
treatment is __

A

anticoag of blood stored for transfusion
coagulopathy , transfusions
calcium

PPP 249 SPRING QUARTER 2023 (11 decks)

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