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Pharm II > anticoagulants/anemia/urology > Flashcards

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
Q

pregnancy category for heparin

A

b

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26
Q

Protamine

A

UFH Reversal Agent

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27
Q

administration of protamine

A

” Administer SLOWLY í IV injection over 1-3 mins, NTE 50mg in 10 min

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28
Q

Fondaparinux (Arixtra) MOA

A

Synthetic Factor Xa inhibitor

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29
Q

monitoring for LMWH

A

” SCr, CBC

“ No need to monitor APTT

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30
Q

ADE of Fondaparinux (Arixtra)

A
  • Hemorrhage
  • Anemia, (elderly, poor renal fxn, < 50kg higher risk)
  • Fever
  • Nausea

found a pair of neux

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31
Q

half life of heparin
LMW
fondaparinux

A

1-2 h=hep
3-7 h= LMWH
15 h= fonda

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32
Q

clotting factors inhibited by warfarin

A

II
VII
IX
X

2+7=9
missin 1!
10

s
c

all of these are synthesized by the liver

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33
Q

MOA of warfarin

A

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

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34
Q

two flavors of warfarin

A

I and S

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35
Q

DDI w/ warfarin

A

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

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36
Q

two isomers in warfarin

A

S isomer: 5 x more potent
and associated with CYP2C9

R CYP3A4
cyp1a2

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37
Q

enzyme inhibited by warfarin

A

vitamin k oxide reductase needed for activation and conversion

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38
Q

only anticoagulant we can use in pt w/ prosthetic heart valve

A

warfarin

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39
Q

dietary restrictions with warfarifn

A

Vit K intake; TPN —> BEWARE of OTC supplements (MVI, Teas, etc)
- intake: Abx, fat malabsorption

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40
Q

INR

A

international normalized ratio

Sweet spot between thrombotic and hemorrhage

between 2.0-3.0

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41
Q

how frequently do you check INR

A

Daily while inpatient -> twice weekly outpatient, until INR stable -> weekly -> bi-weekly -> monthly

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42
Q

why don’t we front load warfarin anymore

A

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

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43
Q

caution with warfarin should be taken wiht

A

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
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44
Q

CHF caution

A

exacerbation with different doses

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45
Q

(hyperthyroid, fever . considerations

A

increase warfarin sensitivity by increasing catabolism of Vit K-dependent factors

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46
Q

DDI with warfarin

A

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

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47
Q

INR for mechanical prosthetic valves

A
  • INR 2.5-3.5:
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48
Q

INR bioprosthetic valves

A
  • INR 2-3:
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49
Q

Metabolic Variability seen with heparin

A

Hereditary resistance (occurs in rats & humans); Requires 5-20x more vs. average dose d/t ltered affinity of receptor for warfarin

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50
Q

Phytonadione

A

reversal for warfarin

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51
Q

INR of 3.5-5 what do you do

A

lower dose resume at decreased level

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52
Q

INR of 5-9 w/out bleeding what do you do

A

omit 1 or 2 doses then resume at decreased

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53
Q

over 9 no sig bleeding

A

hold war
give vit k 3-5mg
exepect reduce in 24-48 hours

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54
Q

INR over 20

A

hold warfarin

vitamin k 10 mg
slow IV or SQ

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55
Q

de bridging

A

it takes 4 half lifes for the clotting factors to be deactivated
this is a process that takes several days

56
Q

clotting factors with the shortest half life

A

VII and
C

can’t measure these independently

57
Q

Parental direct thrombus inhibitors

A

Lepirudin
Desirudin
Bivalirudin

Recombinant/Modified form of hirudin

Argatroban

58
Q

Synthetic molecules Direct Thrombin Inhibitors

A

oral

  • Dabigatran

parental
Argatroban

59
Q

only alt anticoagulant you can use with hepatic impairement

A

dabigatran

60
Q

DDI of DOACs metabolized by CYP3A4

A

rovaroxaban

apixaban

61
Q

DDI dabigatram

A 
C = Carbamazepine
R = rifampin
A = azoles
P = phenytoin
62
Q

rivaroxaban should be avoided in

A

¢ Avoid use: hepatic impair, ARF, or CrCl<15 for Afib or <30 for DVT

63
Q

indications of dabigatran

A

DVT, AF
Monitor:
Dilute thrombin time (hemoclot)
aPTT, TCT, INR

64
Q

what can you use if your pt has labile INR you need a anticoagulant

65
Q

what would you use if you had a pt with a CrCl<30 you need a anticoagulant

66
Q

what can you use as dual anti platelet tx you need a anticoagulant

67
Q

what can you use for a pt with swallowing difficulty and you need a anticoagulant

A

rivaroxaban
edoxaban
warfarin

68
Q

Idarucizumab

A

Dabigatran reversal

69
Q

Pipeline

A

Andexanet - reversal of anti-Xa agents

Arapazine/Ciraparantag – reversal of all DOACs and heparin products

70
Q

antiplatelets

A

ASA
glycoprotein llb
ADP inhibitors
PDE adenosine uptake inhibitors

71
Q

how do most anti-platelet agents work

A

by binding to specific receptors the platelets can not be activated

72
Q

Glycoprotein IIb/IIIa receptor inhibitors:

3

A

Abciximab
Tirofiban
Eptifibatide

73
Q

P2Y12 Inhibitors:

5

A 
Clopidogrel
Prasugrel
Ticagrelor
Cangrelor
Ticlopidine
74
Q

Inhibitors of phosphodiesterase 3:

2

A

Cilostazol

75
Q

4 A’s of ASA

A

Antithrombotic
Analgesic
Antipyretic
Anti-inflammatory

76
Q

indications of ASA

A

Prevention of CVD
Acute treatment of stroke/TIA, acute coronary syndrome
Analgesia
Anti-inflammatory

77
Q

ASA MOA

A

Aspirin inhibits synthesis of thromboxane A2 irreversibly.

Plts anuclear, so cannot regenerate enzyme

Other NSAIDs inhibit enzyme, but action is reversible

78
Q

ASA has profession efficacy for 2ndry prevention of

A

Proven efficacy for secondary prevention MI, stroke; primary prevention benefit offset by increased risk GIB

79
Q

Glycoprotein IIb/IIIa inhibitors

INDICATIONS

A

during high risk PTCA;

acute coronary syndrome

80
Q

Indications of Glycoprotein IIb/IIIa inhibitors

A

inhibit GP IIb/IIIa receptor on platelet, inhibiting platelet aggregation

81
Q

Restoration of normal hemostasis with Glycoprotein IIb/IIIa inhibitors

(3)

A

Abciximab 72
Eptifibatide 3-4
Tirofiban 4hr

82
Q

which P2Y12 inhibitors are prodrugs

A

Clopidogrel

Prasugrel

83
Q

why would you not want to use clopidogrel in acute situation

A

Gradually over 5-10 days

same with prasugrel

84
Q

which P2Y12 inhibitors is best for acute setting

A

Cangrelor IV

85
Q

which P2Y12 inhibitors is the only IV

86
Q

which P2Y12 inhibitors have irreversible binding

A

Clopidogrel

Prasugrel

87
Q

3 major types of fibrinolytic drugs

A

Tissue plasminogen activators (tPA)
Streptokinase (SK)
Urokinase (UK)

88
Q

Fibrinolytic drugs indications

A

dissovle blood clots

For acute MI: given within 2 hours (ideally)

89
Q

: absence of adequate Fe, small erythrocytes w/ insufficient Hgb are form (low MCV)

A
  • Microcytic anemia
90
Q

absence of adequate vit B12 or folic acid, large erythrocytes w/ insufficient Hgb are formed (ETOH, high MCV

A
  • Macrocytic anemia
91
Q

: inability to produce erythropoietin (chronic dz, CA, renal dysfxn) results in inadequate #s of normal-sized erythrocytes (normal MCV)

A
  • Normocytic anemia
92
Q

how do we classify anemia

A
  • 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
Q

risk factors for Iron Deficiency Anemia

A 
Premature infants
Children in rapid growth periods
Pregnant and lactating women
Hemodialysis
Gastrectomy 
Small bowel disease
Menstruation 
Occult GI bleeding
94
Q

classifying Iron Deficiency Anemia

A

Acute vs. chronic blood loss vs. insufficient intake

Very small amounts of Fe are eliminated each day

95
Q

tx of iron deficiency anemia

A

Oral iron supplementation
Diet
Parenteral iron

96
Q

ADE of iron

A

GI: nausea, epigastric discomfort, abdominal cramps, constipation, diarrhea
Lower dose or take with food
Black stools

97
Q

oral iron supplements

A

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
Q

when do we use Parenteral iron

A

Iron malabsorption
Intolerance of oral therapy
Chronic non-compliance

99
Q 
Iron Dextran (INFeD®, DexFerrum®)
Iron Sucrose (Venofer®) -1st choice
Ferric Gluconate (Ferrlecit®)
Ferumoxytol (Fereheme)

are all what class

A

Parenteral iron

100
Q

Iron Dextran administration

A

deep IM buttock not arm or slow IV infusion or undiluted

101
Q

black box with iron dectran

A

anaphylaxis; deaths reported (black box warning!)

need to test first

102
Q

Iron Sucrose adm

A

Can only be given IV by infusion (15 minutes) or slow injection (2 to 5 minutes)

103
Q

when do we see Iron Sucrose used

104
Q

ADE of Iron Sucrose

A

: Hypotension (39.4%) and muscle cramps (29.4%) few reports of anaphylaxis

105
Q

treatment for adults and pediatric patients (age>6) undergoing chronic HD and receiving hematopoietic growth factors

A

Iron Gluconate

106
Q

sxs of iron toxicity

A 
Necrotizing gastroenteritis
shock
Lethargy
Dyspnea
Metabolic acidosis
Coma/death
107
Q

Vitamin B12 and Folic Acid is used for the tx of

A

Macrocytic anemia (abnormal DNA synthesis)

cells can not divide or break apart and are getting big

108
Q

sources of b12 AND FOLIC ACID

A

Vit B12 – cyanocobalamin and hydroxycobalamin – found in meat, eggs, dairy products (no plant foods unless fortified)

Folate – yeast, liver, kidney, leafy green vegetables

109
Q

Average dietary B12

A

Average diet 5-30 mcg/day (1-5mcg absorbed);

110
Q

daily requirement of b12

A

2mcg/day

will be stored in the liver and eliminated

111
Q

what populations do we see poor b12 in

A

Strict vegans could have dietary def.
Bariatric surgery
Crohn’s / celiac dz

112
Q

tx for b12 deficiency

A

cyanocobalamin or hydroxycobalamin (more tightly bound)
iM

response in 3-4 days

113
Q

average dietary intake of folic acid

A

Average diet 500-700 mcg/d (50 – 200 mcg absorbed); 5-20 mg stored in liver

114
Q

why do we give folic acid to pregnant women

A

prevention of spina bifida

115
Q

Erythropoietin mOA

A

growth factor produced in the kidneys that stimulates the production of red blood cells

116
Q

ADR of erythropoietin

A

d/t rapid increase H/H; hypertension, thrombosis, seizures, hypersensitivity, nausea, tumor progression, CVA, MI, hypertensive encephalopathy

117
Q

Human granuloctye colony stimulating factor

A

Filgrastim

118
Q

Filgrastim mOA

A

: stimulates production of neutrophils in bone marrow

119
Q

indications for Filgrastim

A

Myelosuppressive chemotherapy (outcomes variable)
Bone marrow transplant
Severe chronic neutropenia

120
Q

ADE of filgrastim

A

bone pain (24%), N/V (57%)

121
Q

: non-myeloid malignancies receiving myelosuppressive therapy associated with a significant risk of febrile neutropenia

A

Pegfilgrastim

G-CSF (PEG Conjugate)

122
Q

Selective competitive inhibitor of cGMP (PDE5) - degradation of cGMP

A

Phophodiesterase inhibitors

123
Q

Phophodiesterase inhibitors

A

Sildenafil (viagra)
Verdenafil (Levitra)
Tadalafil (Cialis)

124
Q

pharmakokinetics of PDE5

A

Well absorbed PO

  • CYP3A4, 2C9
  • Start low in >65, hep/renal insufficiency, DI
125
Q

DDI with PDE5

A
  • Nitrates: significant HOTN
  • HIV PI, Macrolide, azole, cimetidine
  • Alpha blockers: vardenafil, tadalafil “ contraindicated
126
Q

cheeseburger +viagra

A

might not work

127
Q

what PDE5 can you eat and drink whatever

128
Q

ADE of PDE5

A

HA, flushing, nasal congestion, dyspepsia, diarrhea, abnormal vision, rash, dizziness

129
Q

Alprostadil (PGE1)

130
Q

Yohimbine (Aphrodyne, others)

A

OTC

  1. 4 mg TID PO - elevated BP & HR, incr motor activity
    - Nervousness, irritatbility, tremor
    - Has effects on mood - may incr anxiety
131
Q

Finasteride (Proscar, propecia) MOA

A

inhibits 5a-reductase, blocks peripheral conversion of testosterone to DHT

132
Q

Finasteride indications

A

Reduces size of prostate over 6 mos

133
Q

Dutasteride (Avodart) mOA

A

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
Q

Finasteride (Proscar, propecia) ADE

A
  • ED, decr libido
  • Preg cat X (abnormalities in external genitalia of male offspring - females of child bearing age shouldn’t handle tablets)
135
Q

Selective alpha blocker used for BPH

A

Sildosin (Rapaflo)

136
Q

ldosin (Rapaflo)

A
  • Dizziness, ortho HOTN, retrograde ejaculation (28.1%)

- Contra in severe hep/reanl

Pharm II (16 decks)

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