MCPHS PA Pharmacology EXAM 3 Thrombolytics Flashcards
Drugs and Mechanics
1
Q
What are the three types of Hematopoietic Agents
A
Erythropoetin Stimulating Agent
Granulocyte Stimulating Agents (G-CSF. GM-CSF)
Platelet Stimulating Agents
2
Q
How do Erythropoetin Stimulating Agents (ESAs) work?
A
Agents that increase RBC production within 2-6 Weeks provided the body has the building blocks (namely Iron).
3
Q
What do Erythropoetic Stimulating Agents (ESAs) treat?
A
Treat Anemia from Renal disease
Used while in Chemotherapy
Used in patients with HIV/AIDS
Used to help reduce the need for transfusion post surgery.
Used by professional athletes (blood doping).
4
Q
Name the ESA agents we have studied in Class.
A
Epoetin
Procrit
Darbepoetin
5
Q
What are Granulocyte Stimulating Agents (GSA)?
A
Granulocyte Colony Stimulating Factor (G-CSF)
Granulocyte Macrophage Colonly Stimulating Factor (GM-CSF)
6
Q
What G-CSFs did we look at and what do they treat?
A
Filgrastim and Pegfilgrastim
Treat neutropenic (low neutraphile) complications in cancer PTs
Nonmyeloid malignancies
HIV
Hepatitis C
7
Q
What do GM-CSF agents treat?
A
Acute Myelogenous Leukemia
Bone Marrow Transplant
Radiation induced Bone Marrow Suppression
8
Q
What are Platelet Stimulating Agents?
A
Agents that increase platelet production.
Onset within a week.
9
Q
How do Platelet Stimulating Agents work, and which ones did we look at in class?
A
Romiplostim and Eltrombopag.
These agents bind to and activate human thrombopoetin receptor increasing platelet production.
10
Q
What can Cause Clot formation?
A
Increase in Venous stasis
Vascular endothelium Damage (Plaque rupture, erosion, trauma, surgery)
Medications
Hormones
Cancer
Genetic Disorder
11
Q
What is Virchow’s triad?
A
A combination of 3 factors that lead to thrombosis. Stasis
Vessel wall injury
Hypercoaguability
12
Q
Explain the Clotting Cascade
A
Intrinsic (involving factors XII, XI, IX, VIII) and Extrinsic (involving factor VII) pathways that lead to a common pathway (factors X, V, II, I, and XIII) that cause clots to form.
13
Q
What are the dangers of clots?
A
Arterial clots affect the left side of the heart and above, can cause heart attack, stroke, ischemic bowel, liver and kidney injury.
Venous clots can cause DVT, and pulmonary embolism.
14
Q
What types of drugs do we use to treat clots?
A
Anticoagulants (prevent propagation of clots, disrupt clotting cascade, Best treatment for Arterial and venous clots)
Antiplatelets (Prevent clots from starting, inhibit platelet activation, most preventitive measure for Arterial clots).
Thrombolytics (Break up current clots by inducing or enhancing bodies natural processes).
15
Q
How are Erythropoetin Stimulating Agents (ESAs) administered, and what needs to be monitored while PTs are on them?
A
While using ensure Hemoglobin and Iron levels are monitiored.
Given IV or SQ.
16
Q
How do the G-CSF Granulocyte Stimulating factors work?
A
G-CSFs increcrease production of Myelblast cells (The progenitor to Basophil, Neutrophil, Esoniphil, and Monocytes). Onset in 2-3 Days.
17
Q
How do the GM-CSF Granulocyte Stimulating factors work?
A
GM-CSFs increase the production of Common Myeloid Progenitors (the Precursors to MegaKaryocytes, Erthrocytes, and Myelblasts), and everything that they create.
Onset in 5-7 Days.
18
Q
How are G-CSF Granulocyte Stimulating factors administered, and how are they monitoted?
A
IV, SQ or Patch.
Monitor absolute neutrphil count (ANC).
Pegfilgrastim - Given once.
Filgrastim - Given daily.
19
Q
How GM-CSF Granulocyte Stimulating factors monitored?
A
Monitor CBC w/ differential.
20
Q
Which GM-CSF agent did we look at in class?
A
Sargramostim
21
Q
How do Anticoagulants work?
A
Reduce the formation of thrombin by inhibiting clotting factor activity or synthesis.
22
Q
What Heparin and Heparin like Anticoagulants did we cover in Class?
A
Unfractioned Heparin (UFH)
Low Moleculra Weight Heparin (LMWH)
- Dalteparin (LMWH)
- Enoxaparin (LMWH)
Fondaparinux
23
Q
What is Unfractioned Heparin (UFH) method of action to prevent coagulation?
A
UFH inhibits Factor Xa and thrombin equally.
UFH binds Xa and preventing prothrombin from making more thrombin, and it binds thrombin in such a way that it is unable to change fibrinogen to fibrin.
24
Q
What are the indications to use Unfractioned Heparin (UFH)?
A
Treatment and Prevention of THrombosis.
25
What are the onset and route of administration for Unfractioned Heparin (UFH)?
Onset - Minutes to Hours
Route of Admin - IV or SQ
26
How is Unfractioned Heparin (UFH) Metabolised?
It is Metabolized hepatically then metabolites are cleared by the kidney.
27
How is Unfractioned Heparin (UFH) Dosed?
Bolus + continuous infusion for Clot treatment.
-Determined by Units / KG
28
How is Unfractuioned Heparin Usually monitired?
aPTT of anti-XA
Generally monitred va aPTT, checked every 4-6 Hrs until stable.
1.5-2x baseline seconds (can vary dependent on analyzing method)
29
What are the Adverse Effects of Unfractioned Heparin (UFH)?
Bleeding (PT needs to be monitored for blood loss i.e. decreased BP, increased HR, black tarry stool, red colored urine, headache, somnolence, and abdominal pain.
Spinal / epidural Hematoma (Can reduce risk by eliminating wpidural catheters, multiple anticoagulants/ antiplatelets)
Heparin induced Thrombocytopenia (HIT).
30
What is Heparin induced Thrombocytopenia (HIT)?
Type 1 is a transient drop in platelets approx 1-2 days post exposure that the PT will recover from.
Type 2 usually occurs approx 4-7 days post exposure and is indicated by a \> 50% drop in platelets over time. It can cause a worry for thrombosis.
31
How does Type 2 Heparin Induced Thrombocytopenia (HIT) raise the concern for thrombosis when there is an indicated \>50% drop in platelets?
In type 2 HIT the Body develops antibodies to heparin-PF4 (Platelet Factor 4). This forms a complex which can result in a thrombosis.
32
Is there a test for Heparin Induced Thrombocytopenia (HIT)?
A HIT antibody test can be completed with SRA assay.
33
What is the treatment for Heparin Induced Thrombocytopenia (HIT)? Can Heparin ever be used again?
Discontinue heparin
Initiate argatroban
May rechallenge if \> 100 days since the event.
34
What is an aPTT test?
An aPTT test is a test of the activated Partial THromboplastin Time. It is a measure of the time it takes for the blood to clot.
The Greater the aPTT the more anticoagulation.
35
What is an anti-Xa test?
The anti-Xa test shows what the amount of Xa not bound by heparin is.
The Higher the level the more anticoagulation present.
36
Is there a tool to assess the likelihood of developing HIT?
The 4T test assesses the following with a rating of 0, 1, or 2.
**T**hrombocytopenia (% fall in platelet count)
**T**iming of platelet count fall (between 1 and 10)
**T**hrombosis or other sequelae (presence of thrombosis)
O**T**her cause for thrombocytopenia (definite / possible / none)
37
What can be done to reverse Bleeding with Unfractionated Heparin (UFH).
Protamine binds to Heparin immediately and lasts for 2 hours.
1 mg of protamine per 100 units of Heparin, max dose 50mg.
Give plasma or blood (if Hg\<7 or Hypotensive)
38
What is Protamine, and what is it used for?
A highly positively charged molecule first isolated from fish sperm that binds with Heparin so it cannot bind with antithrombin.
39
What are Low-Molecular Weight Heparins (LMWH)?
Smaller pieces of Polysaccharides that bind to antithrombin and inactivate factor Xa (only, does not bind thrombin).
Indicated for treatment and prevention of thrombosis.
40
What Formulations of Low-Molecular Weight Heparin (LMWH) were presented to us in class?
Tinzaparin
Enoxaparin
Dalteparin
41
What are the routes of administration and Onset of Low-Molecular Weight Heparin (LMWH)?
Onset 12-18 Hours
Admin - Intermittent SQ injections
-mg/kg or unit / kg doses
42
How are Low-Molecular Weight Heparins (LMWH) monitored and cleared?
Monitor - anti-Xa
Renally cleared (cannot be used on PT's with acute Kidney injury or Hemodialysis)
43
What are the adverse effects of Low-Molecular Weight Heparin (LMWH)?
Bleeding (less compared with UFH)
Spinal / Epidural hematoma
Thrombocytopenia (Similar to HIT)
- Antibody mediated less likely
- Discontinue Medication treat with Argatroban
44
What can be done to reverse bleeding with Low-Molecular Weight Heparin (LMWH)?
Protamine can be used (not as effective only binds about 80% of LMWH)
0.5MG per 1 mg LMWH (max dose 100MG)
Give within 12 or 24 hours after last dose LMWH
Give plasma or blood (if Hg \<7 or hypotensive)
45
Does Unfractionated Heparin (UFH) have better Efficacy than Low-Molecular Weight Heparin (LMWH) for treatment of Clots?
No they have equal Efficacy
46
Does Low-Molecular Weight Heparin (LMWH) have any advantages over Unfractionated Heparin (UFH) for treatment of Clots
It deosn't require hospitalization
Requires no routine monitoring
And can be Self administered
Due to ease of administration usually preferred for treatment / prevention of venous thrombosis.
47
Does Unfractionated Heparin (UFH) have any advantages over Low-Molecular Weight Heparin (LMWH) for treatment of Clots?
It's Cheaper than LMWH
It can be used with an Acute Kidney Injury.
48
What are the disadvantages of Unfractionated Heparin (UFH) treatment?
It requires Hospitalization
It has to be routinely monitored
It cannot be self administered
49
What are the disadvantages of Low-Molecular Weight Heparin (LMWH) treatment?
It costs more than UFH
It cannot be used with an Acute Kidney Injury
50
What is Fondaparinux's method of action to prevent coagulation?
Fondaparinux inhibits Factor Xa by binding to Antithrombin
51
How is Fondaparinux administered?
Admin:SQ with a fixed dose based on weight.
Can be used in Patients with a History of HIT.
52
How is Fondaparinux Cleared?
Renally eliminated (cannot use in acute kidney injury or hemodialysis)
53
What are Fondaparinux's indications?
DVT/PE treatment and prevention.
54
What are the adverse effects of Fondaparinux?
Bleeding
55
What can be done to reverse bleeding with Fondaparinux?
Give plasma or blood (if HG\<7 or hypotensive).
56
What Vitamin K Antagonist Anticoagulants did we cover in Class?
Warfarin
57
What is Warfarin's method of action to Prevent clots?
Warfarin inhibits clotting factor synthesis that require Vitamin K (inhibits Vit K epoxide reductase complex 1 and vit K reductase)
-Inhibit production of: Prothrombin (FactorII), VII, IX, X, protein C and S.
**2**+**7**=**9** and 1 more is **10 C&S**
58
How is Warfarin administered and what is it's onset?
Admin: PO or IV
Onset: Delayed, takes approx 2 days to start decreasing clotting factors.
- Usually takes several days to achieve full therapeutic effect.
- If drug stopped, effects linger.
59
Why does Warfarin linger even after discontinuing the medication?
Warfarin is extensively bound to albumin, and cannot be metabolized until it is unbound.
60
Where is Warfarin Metabolized?
Warfarin is metabolized in the liver by CYP2C9.
61
How is Warfarin Monitored?
International Normalized Ratio (INR)
Prothrombin time (PT)
62
What are Warfarin's Goal INRs?
Normal INR is 1.8
Warfarin wants between 2-3 for
Acute MI, AFIB, Valvular heart disease, Pulmonary embolism, DVT, and Tissue Heart Valve.
For mechanical heart Failure we want between 2.5-3.5
63
What are the adverse effects of Warfarin?
Bleeding
64
What can be done to reverse uncontrolled bleeding while on Warfarin?
Phytonadione (Vitamine K) can be administered.
Can give Plasma or prothrombin complex concentrate (PCC) or Factor VII (Novoseven)
*If you give PCC VIT K is needed as well PO preferred.*
65
When reversing uncontrolled bleeding while on Warfarin how should Vit K be administered?
PO preferred, but IV will be used in life threatening conditions.
Takes 2-6 hours to start revesing effects, with a total effect within 24 hours.
66
What is Prothrombin Complex Concentrate(PCC)?
PCC - contains major clotting factors II, VII, IX, and X, all of which are low in patients treated with warfarin or other VKA anticoagulants, as well as the antithrombotic proteins C and S
67
Warfarin interactions, which drugs increase INR?
Bactrim
Amiodarone
Cimetidine
Acetaminophen
Metronidazole
Azol Antifungals
68
Warfarin interactions, which drugs decrease INR?
Phenobarbital
Rifampin
Phenytoin
Carbamazepine
69
What Method of action do Direct Thrombin inhibitors use to prevent Coagulation?
Direct thrombin inhibitors inhibit thrombin (IIa) to prevent conversion of fibrinogen to fibrin.
70
What direct Thrombin inhibitors did we talk about in class?
Bivalirudin
Argatroban
Dabigatran
71
How is Dabigatran administered?
PO
72
How is Argatroban administered?
IV
73
How is Bivalirudin Administered?
IV
74
What are the indications to use Dabigatran?
Prophylaxis for non-valvular AFIB, treatment of DVT/PE.
75
What is the onset for Dabigatran?
Rapid onset prodrug converted by blood esterases.
76
How is Dabigatran eliminated?
Renally eliminated and dose adjusted for CKD. (Most common, but cannot use with Hemodialysis PTs)
77
What can be done to reverse bleeding while on Dabigatran?
Treat life threatening bleed with Praxbind.
Dabigatran can also be removed with hemodialysis treatment.
Plasma can be given.
78
What are the indications for Argatroban use?
HIT treatment, and Cardiac Catheterization (PCI).
Artofocially raises INR.
79
How is Argatroban eliminated?
Metabolized by liver (Dose adjustments for Chronic Liver Disease).
80
How is Argatroban monitored?
Monitor aPTT.
81
What are the adverse events associated with Agatroban?
Bleeding
No specific anidote, can only give plasma.
82
What are the indications for Bivalirudin use?
PCI with acute or remote history of HIT.
83
How is Bivalirudin Eliminated?
Eliminated by the Kidneys (dose adjust for Renal Dysfunction).
84
How is Bivalirudin monitored?
Monitor aPTT.
85
What are the adverse events associated with Bivalirudin?
Bleeding (No antidote can only give plasma).
86
What Direct Xa Inhibitors did we talk about in class?
Rivaroxaban
Apixaban
Edoxaban
Betrixaban
-**_Xa_**ban
87
How are Direct Xa inhibitors administered and Monitored?
Admin: PO
No monitoring
88
What is the onset for direct Xa inhibitors?
Rapid Onset
89
What are the indications for Apixaban?
DVT/PE treatment
Stroke Prophylaxis in non-valve AFIB
Post op DVT Prophylaxis
90
What are the indications for Rivaroxaban?
DVT/PE treatment
Stroke Prophylaxis in non-valve AFIB
Post op DVT Prophylaxis
91
What are the indications for Edoxaban?
DVT / PE treatment
Stroke prophylaxis in non-valve AFIB
92
What are the indications for Betrixaban?
Prohylaxis for VTE
93
Which direct Xa inhibitor can be used on PTs undergoinf Hemodialysis?
Apixaban
94
What can be done to reverse uncontrolled bleeding while on Direct Xa inhibitors?
Administer Andexxa
Hemodialysis does not remove drug
95
Which Xa inhibitors can be used on PT's with Renal insufficiency?
All of them can be dose adjusted, but only Apixaban can be used with dialysis PTs.
96
What drug interactions does Apixaban have?
Strong CYP 3A4 or PGP inhibitors or inducers.
What drug interactions does Apixaban have?
97
What drug interactions does Rivaroxaban have?
Strong CYP 3A4 or PGP inhibitors or inducers.
98
What drug interactions does Edoxaban have?
Strong CYP 3A4 or PGP inhibitors or inducers.
99
What drug interactions does Betrixaban have?
Strong PGP inhibitors
100
How do antiplatlets prevent Arterial Thrombosis?
Cox inhibition
Increase plasma adenosine
Phosphodiesterase-3 (PDE-3) inhibition
P2Y12 ADP inhibition
Glycoprotein IIb/IIIa inhibition
101
Which COX inhibitors did we talk about in class?
Asparin
102
What is the MOA for a COX inhibitor?
Irrisistable inhibition of cyclooxygenase (the enzyme responsible for making Thromboxane A2 (TXA2) which causes platelets to aggregate).
103
What is the duration of the antiplatelet effect of Asparin?
The life of the platelet (7-10 days)
104
What is the MOA of P2Y12 inhibitors?
THey Prevent platelet activation by inhibiting ADP binding to P2Y12 receptors.
105
What monitoring is donw of P2Y12 inhibitors?
Monitor with Platelet assay Tests
106
Which P2Y12 inhibitors are irreversible?
Clopidogrel
Prasugrel
Ticlopidone
107
Which P2Y12 inhibitors are reversible?
Ticagrelor
Cabgrelor (IV)
108
What P2Y12 Inhibitors did we cover in class?
Clopidogrel
Prasugrel
Tclopidone
Ticagrelor
Cangrelor (IV)
109
What are the indications for Clopidogrel?
Prevent coronary stent thrombosis
Ischemic stroke
Peripheral Vascular disease
110
What is the onset for Clopidogrel?
2 hours after dose
111
What is the duration of action of Clopidogrel
5 days
112
Clopidogrel is a Prodrug, what is it metabolized by?
CYP2C19 (genetic varience)
113
What is Clopidogrel's dosing?
mg (usually load given for PCI)
114
What are the adverse events associated with Clopidogrel?
Bleeding
Thrombotic Thrombocytopenia (TTP)
*TTP usually occurs within the first 2 weeks of treatment. Low platelets, hemolytic anemia, fever, and renal dysfunction.*
115
Does Clopidogrel have any DDIs?
There are many drug interactions with CYP2C19 (the metabolizer for this prodrug)
116
Do you need to alter a Clopidogrel prescription prior to any surgeries?
Must hold medications 5 days prior to any major surgery / procedures.
117
What are the indications for Prasugrel?
Acute coronary syndromes
118
What is the onset for Prasugrel?
30 minutes after loading dose
119
Prasugrel is a Prodrug, where is it converted?
The Liver (no DDIs)
120
What adverse events are associated with Prasugrel?
Bleeding
Angioedema (rare)
121
Are there any precautions for the use of Prasugrel?
Avoid use in PTs \>75 Y/O, or with a historu of stroke / TIA.
122
What are the dosing instuctions for Prasugrel?
Adjust dose if PT weighs \<60kg
123
Do you need to alter a Prasugrel prescription prior to any surgeries?
Hold 5 days prior to surgery.
124
What are the indications for Ticlopidine?
Prevention of thrombotic Stroke
Reduce instent thrombosis
125
What is the onset for Ticlopidine?
48hrs after dose
126
What are the adverse effects of Ticlopidine?
Beutropenia / TTP
bleeding
*Monitor WBC every 2 weeks for 12 weeks after initiation.*
127
Is there an antidote to P2Y12 inhibitors?
No, give platelets and possibly Blood.
128
What are the indications for Ticagrelor?
ACS
129
What is the onset of action for Ticagrelor?
1.5 Hours
130
Is Ticagrelor a Prodrug?
No
131
What are the adverse effects associated with Ticagrelor?
Bleeding
Dyspnea
Ventricular Pauses
132
What DDIs does Ticagrelor have?
Asparin doses \> 100 mg/day (make drug less effective)
CYP3A4 inhibitors / inducers
\>40 mg a day of simvastatin or lovastatin
Digoxin levels may increase (PGP inhibitor)
133
Are there any specific reasons not to use Ticagrelor outside of DDIs / Adverse effects?
Don't use if concerned about adherence
134
Do you need to alter Ticagrelor use prior to Surgery?
Hold 1 day prior.
135
What are the indications for the use of Cangrelor?
Approved for PCI
136
How is Cangrelor administered?
Admin: IV
137
Do you continue Cangrelor use after IV admin?
No, transition to oral P2Y12 inhibitors post IV admin.
138
Are there any dose adjustments for Cangrelor?
No
139
How is Cangrelor Dosed?
30 mcg / kg bolus followed by infusiom 4 mcg / kg / min
140
What adverse effects are associated with Cangrelor?
Bleeding
141
Which GP IIb/IIIa inhibitors did we cover in class?
Abciximab
Eptifbatide
Tirofiban
142
What is the onset of GP IIb/IIIa inhibitors?
Immediate
143
What are the adverse effects associated with GP IIb/IIIa inhibitors?
Bleeding
144
Is there an antidote available for GP IIb/IIIa inhibitors?
No, give platelets.
145
What antiplatelets did we discuss in class that were not Cox / P2Y12 / GP IIb/IIIa inhibitors?
Dipyridamole
Cilostazol
Pentoxifylline
146
What is the MOA of Dipyridamole?
Inhibits platelets by increasing plasma levels of adenosine
147
Is Dipyridamole ever given with another drug?
Dipyridamole is always given with asparin (Aggrenox).
148
What are the indications for Dipyridamole?
Used in combonation with ASA for Heart Valve replacement or stroke.
149
What adverse events are associated with Dipyridamole?
Bleeding
Dyspepsia
150
Is there an antidote for Dipyridamole?
No, give platelets.
151
What is the MOA of Cilostazol?
It is a PDE-3 inhibitor.
152
What is the onset of Cilostazol?
Full onset of action at 12 weeks.
153
What are the adverse events associated with Colostazol?
Headache
154
What are the Contraindications to use Cilostazol?
Heart Failure
155
What drug interactions does Cilostazol have?
CYP3A4 inhibitors
156
What is the MOA of Pentoxifylline?
Increases cAMP in RBCs, leading to increased RBC flexibility and decreased Viscosity.
157
What adverse events are associated with Pentoxifylline?
Nausea, Vomiting, and Leukopenia.
158
Does Pentoxifylline have any risk of bleeding?
There is no significant risk of bleeding?
159
What are the clinical uses of Pentoxifylline?
Intermittant Claudication, liver disease, vasculitis, etc
160
What are Thrombolytics?
Agents given to remove thrombi that have already formed.
161
What are the Conraindications to use thrombolytics?
There are no absolute contraindications, must be considered on a case by case basis.
162
What formulatiuons of Thrombolytics did we talk about in class?
Atlepase (tPA)
Tenecteplase
Reteplase
163
What is the MOA of Alteplase?
Identical to plasminogen activator, binds with plasminogen to form active complex.
Complex catalyzes conversion of other plasminogen molecules into plasmin.
-Digests Fibrin meshwork.
164
What are the Therapeutic uses of Alteplase?
Acute ischemic stroke, acute MI, Acute massive PE
165
How is Alteplase Dosed?
Single Dose
Amount Varies based on indication
166
What adverse events are associated with Alteplase?
Bleeding
Angioedema
167
What are the indications to use Tenecteplase or Reteplase?
Acute MI
168
How is Tenecteplase Dosed?
Single Dose
169
Does Tenecteplase have any special characteristics?
It has a longer Halflife
170
What are the adverse events associated with Tenecteplase?
Bleeding
171
How is bleeding associated with Thrombolytics handled?
There is no Antidote, you can only give plasma.
172
Does Reteplase have any special characteristics?
Short Half-life
173
How is Reteplase dosed?
Given as 2 intermittent injections.
Complex dosing makes it less favorable then Tenectplase ot Alteplase
174
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176
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