Haematopoietic Pharmacology Flashcards
(141 cards)
1
Q
EPO (epoetin Alfa, epogen, procrit)
A
Recombinant growth hormone similar to human epo and stimulates the production of rbc in bone marrow
2
Q
Indication for epo
A
Anemia secondary to health conditions such as chronic renal failure or chemotherapy treated cancers.
3
Q
Epo MOA
A
Simulated rbc production in bone marrow. This increases patients hemoglobin, hematocrit, and reticulocyte counts
4
Q
Patients on epo require adequate intake of what
A
Iron, folic acid, b12
5
Q
Indications for epo
A
Chronic renal failure
Anemia
6
Q
Why chronic renal failure need epo
A
It is made in kidney
7
Q
Anemia wanting epo may be caused by what
A
HIV meds, cancer, chronic renal failure
8
Q
Side efects epo
A
Increased risk of thrombosis
Pelvic and limb pain
Hypertension
9
Q
Epo may accelerate tumor progression
A
Yikes
10
Q
Warfarin
A
In patients requiring chronic anticoagulation such as those with history of DVT, PE, a fib, or artificial heart valves
11
Q
How does warfarin work
A
Inhibiting epoxied reductase, leading to interference int he synthesis of vitamin K dependent clotting factors
12
Q
What are the vitamin dependent clotting factors
A
II, VII, IX, X, C< and S
13
Q
Side effects warfarin
A
Bleeding, which necessitates the monitoring of patients INR as well as necrosis which is more common in protein C deficient patients..
14
Q
What causes warfarin necrosis
A
Initial prothrombin state caused by the rapid decline in proteins C and S and manifests as gangrene and massive skin necrosis
15
Q
How is warfarin metabolized
A
P450 pathway and providers should be cautioned of other medications effecting this pathway.
16
Q
Pregnancy and warfarin
A
Teratogen
17
Q
MOA warfarin : clotting factors
A
Interferes with vit k dependent clotting factors
Warfarin inhibits epoxied reductase, so vitamin k unable to reduced to its active form-hydroquinone (vitamin KH2). Prevents gamma-carboxylation of glutamic acid on the clotting factors II, VII, IX, X and C and S. Can’t bind to endothelium and become biologically inactive
18
Q
Warfarin MOA: extrinsic pathway
A
Acts on extrinsic pathway by preventing the activation of vitamin k , which reduces production of II, VII, IX< and X
19
Q
Why does the effect of warfarin take several days
A
Half lives of already activated factors
20
Q
Warfarin MOA: bridge with heparin
A
Usually administered with warfarin to prevent thrombosis. This is because for the first 4-5 days, though warfarin is preventing active factors from being formed, the previously formed factors must degrade. After give,it causes a decline in factor VII, but takes more time to decrease factor II. Furthermore, proteins C and S are decreased, leading to a prothrombin state initially
21
Q
Indications for warfarin
A
Chronic anticoagulation
22
Q
What ailments might require chronic anticoagulation
A
Fibrillation, artificial heart valves, previous pulmonary embolism and previous DVT
23
Q
Side effects warfarin
A
Bleeding
Necrosis
Cytochrome p450
24
Q
Hemorrhage is the most common side effect of warfarin. What do physicians monitor
A
PT and INR to make sure only 2-4 times the normal range
25
Necrosis and warfarin
Can lead to massive thrombus formation, causing skin necrosis and gangrene.
26
Why get necrosis from warfarin
Initial inhibition of proteins C and S leading to a prothrombin state when starting this medication.
27
Who is more susceptible to necrosis when on warfarin
Patients who are protein c deficient
28
Cytochromep45O inhibitors
May lead to too much warfarin
29
Antidote to too much warfarin (or severe bleeding, reversal before surgery)
FFP and vitaminK
30
Warfarin/Coumadin
Oral anticoagulant used int he prevention of thrombosis and embolism
31
How does warfarin work
Inhibits vitamin k epoxied reductaseand leads to depletion of active vitamin K to be used by blood coagulation proteins.
32
Antidotes to warfarin
Vitamin K and fresh frozen plasma
33
Vitamin K antidote to warfarin
Involved int he production of coagulation factors II, VII, IX, X , protein C and S.
34
Are the effects of vitamin K reversal on warfarin immediate
No
35
Fresh frozen plasma (FFP)
Liquid portion of human blood that has been frozen and preserved after a blood donation . It replaces II, VII, V, IX, X, and helps to reverse warfarin effects much quicker than vitamin K
36
Vitamin K1 (phytonadione)
Essential component in the synthesis of prothrombin and clotting factors II, VII, IX, X which allow the blood to coagulate
37
Indication for vitamin K1
Hypoprothrombinemia, warfarin overdose, and prophylaxis of hemorrhage in new borne
38
Side effects vitamin K1
Bilirubin induced brain dysfunction (kernicterus), and hypersensitivity reactions such as shock and cardiac arrest.
39
To prevent a life threatening hypersensitivity reaction, vitamin K1 should not be given ___ unless other routes are contraindicated
IV
40
MOA vitamin K1
Essential in synthesis of prothrombin and clotting factors II, VII, IX, and X, whicha loow the blood to coagulate
41
Indications of vitamin K1
Hypoprothrombia (newborn prophylaxis)
| Bleeding from warfarin overdose
42
Babies are born with a _ defiency
Vitamin K
43
In order to prevent hemorrhage in newborns what are they given
Single dose of vitamin K1 to increase prothrombinleavels and preventbleeding
44
Side effects vitamin K1
Shock (hypersensitivity), kernicterus (causes serum bilirubin levels to rise), cardiac arrests not give though IV)
45
___ __ are required for intestinal absorption of vitamin K1
Bile salts
46
Increased risk of __ with IV administration of vitamin K1
Hypersensitivity reaction
47
Heparin
Anticoagulant medication, which is a cofactors for antithrombin, working to inactivate the coagulation factors IIa (thrombin ) and Xa
48
Indication for heparin
Acute coronary syndrome, a fib, pulmonary embolism, and prophylaxis in hypercoagulable states.
49
Does heparin cross the placenta
No
50
Who is heparin commonly used in
Anticoagulat in pregnant patients
51
Indications for heparin
Acute coronary syndrome (STEMI NSTEMI-help break down clots in cases of non ST elevation)
Prophylaxis (against thrombosis(DVT risk))
Pulmonary embolism (prevent thrombi)
April fibrillation 9stop stroke and embolism)
Used in pregnancy
52
Why is heparin used during pregnancy
Doesn’t cross placenta no risk to fetus
Pregnant patients may become hypercoagulable as a physiologic mechanismto prevent post partum hemorrhage
53
Heparin
Anticoagulant which is a cofactors for antithrombin , working to inactivate the coagulation factors IIa (thrombin and Xa
54
Indication for heparin
Acute coronary syndrome, a fib, pulmonary embolism, prophylaxis in hypercoagulable states
55
Half life of heparin
Short so administered frequently or as continuous infusion
56
MOA heparin
Acting as a cofactor for antithrombin activation. As antithrombin is activated, it acts to decrease activation of factor IIa, or thrombin, as well as factor Xa.
57
Side effects heparin
Bleeding, thrombocytopenia(HIT)
58
Antidote to heparin therapy
Positively charged reversal agent, protamine sulfate, which binds to the negatively charged heparin
59
MOA heparin
Half life 1 hour
Binds to inhibitor antithrombin III, causing its activation.
Antithrombin now activated, leading to the inactivateion of thrombin (factor IIa) and other proteases involved in blood clotting, most notable Xa
60
Antithrombin effects are increased _ fold due to the activation via heparin, leading to vastly decreased coagulability
1000
61
Side effects heparin
Bleeding
| HIT
62
Bleeding with heparin
If too much
| Monitor PTT
63
Heparin induced thrombocytopenia (HIT)
5-10 days after heparin—-leading to pathological platelet activation and clearance, causing thrombocytopenia
64
Antidote to heparin
Protamine sulfate
65
Protamine sulfate
For rapid reversal of heparin, protamine sulfate is used as an antidote. It is highly positively charged, and binds to negatively charged heparin.
Low molecular weight heparin is not easily reversible
66
HIT incidence
.2-5% in patients who have been treated for greater than 4 days
67
__ heparin is more likely to cause HIT tha ______
Unfractionated
| Low molecular weight heparin (LMWH)
68
When does HIT occur
5-10 days after initiation of heparin therapy
69
Early onset HIT
10 hours, patients who have receives heparin therapy recently and have persistent antibodies to the complex of heparin and platelet factor 4
70
Heparin platelet factor 4 complex
Platelet factor 4 is released from the alpha granules of platelets upon platelet activation and binds to heparin
71
__, __, and __ autoantibodies form against heparin platelet factor 4 complex
IgG IgA, IgM
72
Heparin platelet factor 4 antibody complex binds __
Platelets—>platelet aggregation and thus thrombocytopenia and procoagulant product which can lead to thrombosis
73
Platelet aggregation
Heparin platelet factor 4 antibody complex bound to platelets results in platelet aggregation, subsequent removal from circulation and thus thrombocytopenia
74
Procoagulatn release HIT
Platelet aggregation also results in the release of progcoagulants which can cause thrombosis
75
Symptoms of HIT
Thrombocytopenia
76
Diagnosis of HIT
Serotonin release assay (SRA)
77
SRA
High serotonin release occurs as this is a marker of platelet activation.
A CBC is always performed to determine the degree of thrombocytopenia
78
Treatment of HIT
Stop heparin, start direct thrombin inhibitor
79
Example of a direct thrombin inhibitor
Bivalirudin
Argatroban
80
Aspirin
Ok
81
ENOS Paris (lovenox)
First LMW heparin in the US.
82
Use of enoxaparin (lovenox)
Prevents DVT while patients are int he hospital or it can be used as a bridge medication for patients starting warfarin
83
What are some other LMW heparin
Dalteparin (fragmin)
| Tinzaparin (innohep)
84
Benefits of LMW heparin
Can be administered outpatient and do not require PTT minotoring
85
MOA enoxaparin
LMW heparin only inactivated factor XA (standard heparin inactivated IIa and Xa)
It binds to antithrombin, forming a complex which irreversibly inactivated clotting factor Xa
86
Indications for LMW heparin
Clot formation prevention (prevent DVT, patients with unstable angina or an acute STEMI)
87
Side effects LMW heparin
HIT
| Bleeding
88
Consideration for LMW heparin
Educate patient on side effects
| If going home on enoxaparin need to demonstrate administration.
89
How is enoxaparin administered
Subcutaneously 2 inches away from umbilicus or any abdominal incision
90
Why give enoxaparin 2 inches away from umbilicus or incision
Have more scar tissue and don’t absorb normally
91
Antidotes for enoxaparin
Protamine sulfate binds directly to the free heparin in the bloodstream and inactivated it, immediately preventing further inactivation of clotting factors
92
Clopidogrel (plavix)
Antiplatelt medication that works as an ADP receptor antagonist to prevent platelet aggregation.
93
Indication for clopidogrel
Treatment of coronary syndrome and in order to prevent thrombotic events
94
Side effects clopidogrel (plavix)
Coronary syndrome and in order to prevent thrombotic events.
95
Side effects clopidogrel
Hemorrhage, abdominal pain, thrombotic thrombocytopenic purpura, and pancytopenia
96
Why not give clopidogrel before surgery
Prevent increased bleeding
97
MOA clopidogrel
Antagonizing ADP receptors in order to prevent ADP mediated aggregation. IRREVERSIBLE and last the full lifespan of the platelet
Prevents platelet activation
98
Lifespan of platelet
3-7 days
99
Indications for clopidogrel
Acute coronary syndrome (prevents blockages from forming within coronary arteries)
Prevention of thrombotic events (MI and ischemia)
100
Side effects clopidogrel
Bleeding, Thrombotic Thrombocytopenic Purpura (TTP), pancytopenia, abdominal pain
101
Thrombotic thrombocytopenic purpura
Cause small blood clots to form within the small vessels of the body leading to issues related to organ function. Monitor for bruising, kidney failure, fever, anemia, thrombocytopenia, and neurological symptoms
102
Pancytopenia
Includes thrombocytopenia, leukopenia, and anemia
103
Why abdominal pain on clopidogrel
Absorbed in the GI tract; therefore, it may cause abdominal pain related to GI bleeding. Patients taking clopidogrel should be monitored for abdominal pain and other signs of GI bleeding, such as blood in the feces
104
Do not give clopidogrel _ days before surgery
5
105
Abciximab and tirofiban and eptifibatide (GP IIb/IIIa inhibitors)
Glycoproteins iIb/IIIa receptor inhibitors that work by inhibiting platelet glycoproteins IIb/IIIa receptors, preventing the binding of fibrinogen
106
MOA GP IIb/IIIa inhibitors
Prevent binding of fibrinogen, prevent aggregation of platelets, thereby preventing clot formation.
107
The inhibition of platelet aggregation caused by GPIIb/IIIa receptor inhibitors can be reversed. How
Stopping the medication, unlike medications such as asprin and ticlopidine, which cause irreversible inhibition of platelet aggregation
108
Indications for GP IIb/IIIa receptor inhibitors used to prevent thrombotic events in patients after percutaneous coronary intervention (PCI) or in those with acute coronary syndrome (ACS)
Ok
109
Side effects of GP IIb/IIIa receptor inhibitors
Bleeding, espicially GI hemorrhage
110
GPIIBIIIa receptor inhibitors are often administered with what
Heparin and asprin
111
MOA IIb/IIIa receptor inhibitors
IIb/IIIa receptor inhibitors which prevents binding to fibrinogen, preventing platelet aggregation of platelets thereby preventing clot formation
Inhibit platelet aggregation
112
Are abciximab, tirofiban and epitibatide irreversible? Do they irreversibly inhibit GPIIb/IIIa receptor
Abciximab-irreversible
| Tirofiban and eptifibatide-reversible by stopping medication of daily zing the patient
113
Indications for IIb/IIa receptor inhibitors
Thrombotic event prevention short term
- acute coronary syndrome
- percutaneous coronary intervention (PCI)
114
Acute coronary syndrome
These patients experience a disruption of arterial plaque causing complications such as unstable angina, and MI. Treatment with GP/IIb?IIIa receptor inhibitors, with heparin and asprin decreases the likelihood that the patient will experience a thrombotic event sue to the disruption of plaque
115
Percutaneous coronary intervention (PCI)
Wall of artery is damaged, increasing the risk of platelet aggregationa nd blood clot formation
116
Side effects GP IIb/IIIa inhibitors
Bleeding
| Espicially GI hemorrhage. If bleeding or hemorrhage occurs, the infusion should be stopped immediately
117
Considerations GP IIb/IIIa inhibitors
Expensive, combination drug therapy( heparin and asprin!!!!!)
118
What are GP IIbIIIa inhibitors given with
Heparin and asprin
119
Ticlopidine (ticlid)
Antiplatelet medication designed to inhibit platelet aggregation, thereby preventing thrombotic events
120
Though closely related to clopidogrel, ticlopidine causes what
More adverse hematologic effects, such as neutropenia and thrombotic thrombocytopenic purpura TTP
121
Other side effects of ticlopidine
Diarrhea, abdominal pain, flatulence, nausea, heart burn, rash
122
Patients taking ticlopidine should have their ___ monikered every two weeks for the first three months
CBC
123
It is important to remember that ticlopidine must be withheld prior to surgery. Why
Risk of bleeding
124
MOA ticlopidine
ADP receptor antagonist-prevents GP IIb/IIIa expression on platelets leading to an inability of platelet aggregation by inhibiting fibrinogen from binding
Irreversibly inhibits platelet aggregation -
125
Bc ticlopidine inhibition of platelet aggregation is irreversible so antiplatelet action will continue until when
Until death or destruction of the platelet occurs
126
Indications for ticlopidine
Thrombotic event prevention-bc a clump of platelets makes up the center of a thrombus or clot, use of ticlopidine to inhibit platelet aggregation will ultimately work to prevent a thrombotic event.
127
Ticlopidine should only be used for patients who have not responded to ___ or can not tolerate the use of asprin
Asprin
128
Side effects ticlopidine
Neutropenia. This condition increases a patients risk of infection; however it is not permanent.
TTP-causes clot formation throughout the body.
GI distress
Rash
129
TTP presentation
Fever and changes in neurological function. Lab results may also reveal low platelet counts, anemia, and kidney problems
130
Considerations of ticlopidine
Not before surgery!
- due to increased risk of bleeding. Keep in mind that the effects of the drug remain int he body for 7-10 days after last dose, so ample time must be planned for the discontinuation of the drug prior to surgery
- monitor CBC for neutropenia
131
Alteplase
Thrombocytopenic medication that dissolves blood clots by fibrin lysis..known as a clot buster
132
What is alteplase similar to
TPA
133
What does tPA do
Breaks down the fibrin found in blood clots.
134
Alteplase inc ontraindicated in who
History of bleeding.
135
Antidote to alteplase
Apical
136
Alteplase MOA
Fibronolytic medication by converting plasminogen into enzyme plasmin. Plasmin breaks down blood clots by destroying fibrin structure and therefore dissolving blood clot
137
Indications for alteplase
Thrombosis (bc it breaks down an already formed thrombus or blood clot and is used in acute situations. The formation of a blood clot within a blood vessel or within the heart may obstruct normal blood flow and tissue perfusion. The thrombus may result in acute MI , acute ischemic stroke, or acute pulmonary embolism. In addition this drug may be given to dissolve a thrombus causing central venous Cather blockage
138
Side effects alteplase
Bleeding
139
Contraindications alteplase
Intracranial hemorrhage
-bc it prevents clot formation and potentiates the risk of hemorrhage
Internal hemorrhaging
-since bleeding is a major complication...the med may destroy pre existing clots and instigate bleeding in previously healing sites of injury. May also destroy clotting factors and prevent future clot formation in blood vessels
140
Considerations alteplase
Minimize bleeding
-avoid giving anticoagulants, maintain tissue integrity by avoiding invasive procedures and needles related to subcutaneous or intramuscular injections
, monitor for shock
-internal bleeding may cause hypovolemic shock in the patient receiving alteplase.
-significant intravasculature fluid loss prevents the heart from pumping an adequate supply of blood and oxygen to the organs. It is important to frequently monitor the patient for symptoms of shock. Be alert for changing vital signs such as decreased bp, increased hr, and decreased body temperature. Assess the patient for increasing anxiety, confusion, shallow breathing, refuse sweating and weak pulse
141
Antidote to alteplase if suspect bleeding
Stop thrombocytopenic therapy and administer aminocarproic acid (amicar) as an antidote to prevent further bleeding. This antifibrolytic drug prevents the conversion of plasminogen to plasmin and avoids fibrinoyltic activity that results in bleeding
