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anticoagulants/anemia/urology Flashcards

1
Q

phases of hemostasis

A 
vascular
platelet
coagulation
common
insoluble
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2
Q

Generally only for arterial or intracardiac thrombosis as these thrombi are rich in platelets

A

antiplatelits

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3
Q

fibrinolytic

A

when the clot is already made and targeted on it’s own

used for acute treatment

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4
Q

anticoagulants can be used to affect platelet aggregation on the venus or arterial side?

A

both

hit’s the factors

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5
Q

thrombi/emboli in the venous sysplatelettem have relatively low count of ____compared to ti arterial thrombosis

A

thrombi/emboli in the venous sysplatelettem have relatively low count of platelets

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6
Q

Dissolve existing thrombus and are for the acute treatment of thrombosis (MI, ischemic stroke, massive PE)

A

fibrinolytic

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7
Q

Anticoagulants inhibit the formation of ______

A

Anticoagulants inhibit the formation of fibrin clots

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8
Q

Three major types of anticoagulants are available

A

heparin and related products, which must be used parenterally; direct thrombin and factor X inhibitors, which are used parenterally or orally; and the orally active coumarin derivatives (eg, warfarin).

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9
Q

heparin MOA

A

Heparin binds to antithrombin via its pentasaccharide sequence. This induces a conformational change in the reactive center loop of antithrombin that accelerates its interaction with factor Xa.

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10
Q

lower molecular weight heparin

A

still big
but only deactivates facot Xa

can not deactivate thrombin

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11
Q

what is necessary in order to induce thrombin inhibition with heparin

A

To potentiate thrombin inhibition, heparin must simultaneously bind to antithrombin and thrombin. Only heparin chains composed of at least 18 saccharide units (MW ~5,400 Da) are of sufficient length to perform this bridging function.

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12
Q

indications of heparin

A

” Prophylaxis & tx of venous thrombosis (DVT/PE) & peripheral arterial embolism
“ Early tx unstable angina (UA) or acute MI, AF w/ embolization
“ Disseminated intravascular coagulation
“ Prevents coagulation as blood passes through extracorporeal circuit in dialysis & arterial/cardiac surgery, coronary angioplasty, coronary stents, lab specimen, catheters
“ Consumptive coagulopathies
“ Prevention of thrombosis in pts with heart valve

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13
Q

factors that heparin affects

A

” Affects primarily factor IIa & Xa (also IXa, Xia, XIIa)

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14
Q

MOA of heparin UFH

A

” Prevents fibrin formation from fibrinogen during active thrombosis
“ Inhibits prothrombin conversion to thrombin
“ Induces secretion of tissue factor pathway inhibitor

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15
Q

dosing of heparin

A

only IV/SQ

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16
Q

clearance of heparin

A
  • Plasma T½: 1-2 hrs í dose dependent
  • T½ prolonged in anepheric pts, severe renal impairment, cirrhosis í no dose adj in RF
  • NO dose adjustment not necessary in RF (renal failure) or HD pts (hemodialysis
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17
Q

dosing of heparin

A

is weight based

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18
Q

monitor therapy with heparin (goal)

A 
blood draw every 30 
(measures activity of thrombin, Xa, IXa)
o	Goal: 1.5-2.5 x control (sec) or hep level 0.3 - 0.7 by antifactor Xa heparin levels
o	Goal for DVT/PE: 60-100 secs 
í risk of bleeding @ 100 secs
o	Goal for AMI: 60-80 secs
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19
Q

what are we worried about

A

heparin induced thrombocytopenia

looks for platelet drop of below 50,000 or >50% decline form baseline

can lead to gangrene

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20
Q

main adverse reaction of heparin

A

bleeding and bruising

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21
Q

antidote for heparin

A

Protamine for unfractionated heparin; protamine reversal of LMW heparins is incomplete

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22
Q

antidote for warfarin

A

Vitamin K1, plasma, prothrombin complex concentrates

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23
Q

LMWH indications

A

” Prevention of venous thrombus (general/orthopedic surgery)
“ Tx of DVT w/ or w/o PE
“ Bridging anticoagulation: continue 24-48hrs after INR therapeutic
“ Need to cover before at full effect

Monitor (less = easier outpt tx):
“ SCr, CBC
“ No need to monitor APTT

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24
Q

advantages of heparin

A

” Increased plasma ½ life
“ Lower incidence of HIT
“ Less risk of osteoporosis
“ No need to monitor APTT - still need CBC, SCr
“ More predictable dose-response relationship
“ Less monitoring “ easy outpt tx option

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25
pregnancy category for heparin
b
26
Protamine
UFH Reversal Agent
27
administration of protamine
" Administer SLOWLY í IV injection over 1-3 mins, NTE 50mg in 10 min
28
Fondaparinux (Arixtra) MOA
Synthetic Factor Xa inhibitor
29
monitoring for LMWH
" SCr, CBC | " No need to monitor APTT
30
ADE of Fondaparinux (Arixtra)
- Hemorrhage - Anemia, (elderly, poor renal fxn, < 50kg higher risk) - Fever - Nausea found a pair of neux
31
half life of heparin LMW fondaparinux
1-2 h=hep 3-7 h= LMWH 15 h= fonda
32
clotting factors inhibited by warfarin
II VII IX X 2+7=9 missin 1! 10 s c all of these are synthesized by the liver
33
MOA of warfarin
Vit K is co-factor for post-translational carboxylation of glutamate residues to -carboxyglutamates on Vit K-dependent proteins Factors II, VII, IX, X require -carboxylation for biologic activity
34
two flavors of warfarin
I and S
35
DDI w/ warfarin
Inhibitors: Bactrim, Flagyl, barbiturates, CBZ, PHT, Cholestyramine, Sucralfate, Vit K, RIF, SJ Wort, Ginseng - doses Potentiating: INH, -azoles, EtOH (liver dz), APAP, NSAID, Statins, amiodarone, TMX-SMX, garlic tabs, gingko biloba, other anticoags í doses
36
two isomers in warfarin
S isomer: 5 x more potent and associated with CYP2C9 R CYP3A4 cyp1a2
37
enzyme inhibited by warfarin
vitamin k oxide reductase needed for activation and conversion
38
only anticoagulant we can use in pt w/ prosthetic heart valve
warfarin
39
dietary restrictions with warfarifn
need to be consistent with dietary VitK provided predominantly by phylloquinone in plant material (leafy green) - Vit K intake; TPN ---> BEWARE of OTC supplements (MVI, Teas, etc) - intake: Abx, fat malabsorption
40
INR
international normalized ratio Sweet spot between thrombotic and hemorrhage between 2.0-3.0
41
how frequently do you check INR
Daily while inpatient -> twice weekly outpatient, until INR stable -> weekly -> bi-weekly -> monthly
42
why don't we front load warfarin anymore
if you give big dose you see a big change in factor 7 but you're also knocking out coagulation and can make them procoagulated ??? 48 mins
43
caution with warfarin should be taken wiht
Hepatic Dysfxn - impaired synthesis of factors ( decrease initial dose; increase INR & albumin) - Hyper-metabolic states (hyperthyroid, fever) --> increase warfarin sensitivity by increasing catabolism of Vit K-dependent factors - CHF - sensitivity
44
CHF caution
exacerbation with different doses
45
(hyperthyroid, fever . considerations
increase warfarin sensitivity by increasing catabolism of Vit K-dependent factors
46
DDI with warfarin
DDI: Inhibitors: Bactrim, Flagyl, barbiturates, CBZ, PHT, Cholestyramine, Sucralfate, increase Vit K, RIF, SJ Wort, Ginseng - decrease doses Potentiating: INH, -azoles, EtOH (liver dz), APAP, NSAID, Statins, amiodarone, TMX-SMX, garlic tabs, gingko biloba, other anticoags --> increase doses
47
INR for mechanical prosthetic valves
- INR 2.5-3.5:
48
INR bioprosthetic valves
- INR 2-3:
49
Metabolic Variability seen with heparin
Hereditary resistance (occurs in rats & humans); Requires 5-20x more vs. average dose d/t ltered affinity of receptor for warfarin
50
Phytonadione
reversal for warfarin
51
INR of 3.5-5 what do you do
lower dose resume at decreased level
52
INR of 5-9 w/out bleeding what do you do
omit 1 or 2 doses then resume at decreased
53
over 9 no sig bleeding
hold war give vit k 3-5mg exepect reduce in 24-48 hours
54
INR over 20
hold warfarin vitamin k 10 mg slow IV or SQ
55
de bridging
it takes 4 half lifes for the clotting factors to be deactivated this is a process that takes several days
56
clotting factors with the shortest half life
VII and C can't measure these independently
57
Parental direct thrombus inhibitors
Lepirudin Desirudin Bivalirudin Recombinant/Modified form of hirudin Argatroban
58
Synthetic molecules Direct Thrombin Inhibitors
oral - Dabigatran parental Argatroban
59
only alt anticoagulant you can use with hepatic impairement
dabigatran
60
DDI of DOACs metabolized by CYP3A4
rovaroxaban | apixaban
61
DDI dabigatram
``` C = Carbamazepine R = rifampin A = azoles P = phenytoin ```
62
rivaroxaban should be avoided in
¢ Avoid use: hepatic impair, ARF, or CrCl<15 for Afib or <30 for DVT
63
indications of dabigatran
DVT, AF Monitor: Dilute thrombin time (hemoclot) aPTT, TCT, INR
64
what can you use if your pt has labile INR you need a anticoagulant
warfarin
65
what would you use if you had a pt with a CrCl<30 you need a anticoagulant
warfarin
66
what can you use as dual anti platelet tx you need a anticoagulant
warfarin
67
what can you use for a pt with swallowing difficulty and you need a anticoagulant
rivaroxaban edoxaban warfarin
68
Idarucizumab
Dabigatran reversal
69
Pipeline
Andexanet - reversal of anti-Xa agents Arapazine/Ciraparantag – reversal of all DOACs and heparin products
70
antiplatelets
ASA glycoprotein llb ADP inhibitors PDE adenosine uptake inhibitors
71
how do most anti-platelet agents work
by binding to specific receptors the platelets can not be activated
72
Glycoprotein IIb/IIIa receptor inhibitors: | 3
Abciximab Tirofiban Eptifibatide
73
P2Y12 Inhibitors: | 5
``` Clopidogrel Prasugrel Ticagrelor Cangrelor Ticlopidine ```
74
Inhibitors of phosphodiesterase 3: | 2
Cilostazol
75
4 A's of ASA
Antithrombotic Analgesic Antipyretic Anti-inflammatory
76
indications of ASA
Prevention of CVD Acute treatment of stroke/TIA, acute coronary syndrome Analgesia Anti-inflammatory
77
ASA MOA
Aspirin inhibits synthesis of thromboxane A2 irreversibly. Plts anuclear, so cannot regenerate enzyme Other NSAIDs inhibit enzyme, but action is reversible
78
ASA has profession efficacy for 2ndry prevention of
Proven efficacy for secondary prevention MI, stroke; primary prevention benefit offset by increased risk GIB
79
Glycoprotein IIb/IIIa inhibitors INDICATIONS
during high risk PTCA; | acute coronary syndrome
80
Indications of Glycoprotein IIb/IIIa inhibitors
inhibit GP IIb/IIIa receptor on platelet, inhibiting platelet aggregation
81
Restoration of normal hemostasis with Glycoprotein IIb/IIIa inhibitors (3)
Abciximab 72 Eptifibatide 3-4 Tirofiban 4hr
82
which P2Y12 inhibitors are prodrugs
Clopidogrel | Prasugrel
83
why would you not want to use clopidogrel in acute situation
Gradually over 5-10 days same with prasugrel
84
which P2Y12 inhibitors is best for acute setting
Cangrelor IV
85
which P2Y12 inhibitors is the only IV
Cangrelor
86
which P2Y12 inhibitors have irreversible binding
Clopidogrel | Prasugrel
87
3 major types of fibrinolytic drugs
Tissue plasminogen activators (tPA) Streptokinase (SK) Urokinase (UK)
88
Fibrinolytic drugs indications
dissovle blood clots For acute MI: given within 2 hours (ideally)
89
: absence of adequate Fe, small erythrocytes w/ insufficient Hgb are form (low MCV)
- Microcytic anemia
90
absence of adequate vit B12 or folic acid, large erythrocytes w/ insufficient Hgb are formed (ETOH, high MCV
- Macrocytic anemia
91
: inability to produce erythropoietin (chronic dz, CA, renal dysfxn) results in inadequate #s of normal-sized erythrocytes (normal MCV)
- Normocytic anemia
92
how do we classify anemia
- Classify anemia on size (microcytic, normocytic, macrocytic) and physiologic mechanism (IDA, anemia of chronic kidney dz - micro, hemolytic anemia - normo, pernicious anemia - vit B12 = macro)
93
risk factors for Iron Deficiency Anemia
``` Premature infants Children in rapid growth periods Pregnant and lactating women Hemodialysis Gastrectomy Small bowel disease Menstruation Occult GI bleeding ```
94
classifying Iron Deficiency Anemia
Acute vs. chronic blood loss vs. insufficient intake | Very small amounts of Fe are eliminated each day
95
tx of iron deficiency anemia
Oral iron supplementation Diet Parenteral iron
96
ADE of iron
GI: nausea, epigastric discomfort, abdominal cramps, constipation, diarrhea Lower dose or take with food Black stools
97
oral iron supplements
200-400 Ferrous sulfate – 300 mg tabs (60 mg of elemental Fe) Ferrous gluconate – 300 mg tab (37 mg elemental Fe) Ferrous fumarate – 100 mg tabs (33 mg elemental Fe) Polysaccharide iron complex – 150 mg (150 mg elemental Fe)
98
when do we use Parenteral iron
Iron malabsorption Intolerance of oral therapy Chronic non-compliance
99
``` Iron Dextran (INFeD®, DexFerrum®) Iron Sucrose (Venofer®) -1st choice Ferric Gluconate (Ferrlecit®) Ferumoxytol (Fereheme) ``` are all what class
Parenteral iron
100
Iron Dextran administration
deep IM buttock not arm or slow IV infusion or undiluted
101
black box with iron dectran
anaphylaxis; deaths reported (black box warning!) need to test first
102
Iron Sucrose adm
Can only be given IV by infusion (15 minutes) or slow injection (2 to 5 minutes)
103
when do we see Iron Sucrose used
CKD
104
ADE of Iron Sucrose
: Hypotension (39.4%) and muscle cramps (29.4%) few reports of anaphylaxis
105
treatment for adults and pediatric patients (age>6) undergoing chronic HD and receiving hematopoietic growth factors
Iron Gluconate
106
sxs of iron toxicity
``` Necrotizing gastroenteritis shock Lethargy Dyspnea Metabolic acidosis Coma/death ```
107
Vitamin B12 and Folic Acid is used for the tx of
Macrocytic anemia (abnormal DNA synthesis) cells can not divide or break apart and are getting big
108
sources of b12 AND FOLIC ACID
Vit B12 – cyanocobalamin and hydroxycobalamin – found in meat, eggs, dairy products (no plant foods unless fortified) Folate – yeast, liver, kidney, leafy green vegetables
109
Average dietary B12
Average diet 5-30 mcg/day (1-5mcg absorbed);
110
daily requirement of b12
2mcg/day will be stored in the liver and eliminated
111
what populations do we see poor b12 in
Strict vegans could have dietary def. Bariatric surgery Crohn’s / celiac dz
112
tx for b12 deficiency
cyanocobalamin or hydroxycobalamin (more tightly bound) iM response in 3-4 days
113
average dietary intake of folic acid
Average diet 500-700 mcg/d (50 – 200 mcg absorbed); 5-20 mg stored in liver
114
why do we give folic acid to pregnant women
prevention of spina bifida
115
Erythropoietin mOA
growth factor produced in the kidneys that stimulates the production of red blood cells
116
ADR of erythropoietin
d/t rapid increase H/H; hypertension, thrombosis, seizures, hypersensitivity, nausea, tumor progression, CVA, MI, hypertensive encephalopathy
117
Human granuloctye colony stimulating factor
Filgrastim
118
Filgrastim mOA
: stimulates production of neutrophils in bone marrow
119
indications for Filgrastim
Myelosuppressive chemotherapy (outcomes variable) Bone marrow transplant Severe chronic neutropenia
120
ADE of filgrastim
bone pain (24%), N/V (57%)
121
: non-myeloid malignancies receiving myelosuppressive therapy associated with a significant risk of febrile neutropenia
Pegfilgrastim | G-CSF (PEG Conjugate)
122
Selective competitive inhibitor of cGMP (PDE5) - degradation of cGMP
Phophodiesterase inhibitors
123
Phophodiesterase inhibitors
Sildenafil (viagra) Verdenafil (Levitra) Tadalafil (Cialis)
124
pharmakokinetics of PDE5
Well absorbed PO - CYP3A4, 2C9 - Start low in >65, hep/renal insufficiency, DI
125
DDI with PDE5
- Nitrates: significant HOTN - HIV PI, Macrolide, azole, cimetidine - Alpha blockers: vardenafil, tadalafil " contraindicated
126
cheeseburger +viagra
might not work
127
what PDE5 can you eat and drink whatever
Cialis)
128
ADE of PDE5
HA, flushing, nasal congestion, dyspepsia, diarrhea, abnormal vision, rash, dizziness
129
Alprostadil (PGE1)
injected
130
Yohimbine (Aphrodyne, others)
OTC 5. 4 mg TID PO - elevated BP & HR, incr motor activity - Nervousness, irritatbility, tremor - Has effects on mood - may incr anxiety
131
Finasteride (Proscar, propecia) MOA
inhibits 5a-reductase, blocks peripheral conversion of testosterone to DHT
132
Finasteride indications
Reduces size of prostate over 6 mos
133
Dutasteride (Avodart) mOA
Inhibits 5a-reductase, blocks peripheral conversion of testosterone to DHT - Similar to finasteride, rare immune hypersensitivity rxn, & rarely angioedema - Preg cat X - DDI: 3A4 inhibitors: cimetidine, 3A4 inducers: PHT, Carbamazepine), etc
134
Finasteride (Proscar, propecia) ADE
- ED, decr libido - Preg cat X (abnormalities in external genitalia of male offspring - females of child bearing age shouldn't handle tablets)
135
Selective alpha blocker used for BPH
Sildosin (Rapaflo)
136
ldosin (Rapaflo)
- Dizziness, ortho HOTN, retrograde ejaculation (28.1%) | - Contra in severe hep/reanl

Pharm II (16 decks)

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