Chapter 9: Blood disorders Flashcards
What drugs are used to treat anemia?
Iron
Folic acid
B6
Anemia: HGB levels
<13 in men
<12 on period
<11 if pregnant
How does Iron prevent/treat anemia
Help with production of HGB
when should iron supplements be avoided?
iron overload syndromes:
hemosiderosis
hemochromotosis
what patients often become anemic?
chronic renal failure
Iron mechanism of action
molecule of iron becomes incorporated into a heme
one heme unit attaches to a globin protein
4 heme-globin subunits combine to make one unit of HGB
Iron: Absorption
the major control point
mainly in jejunum
5-10% of oral intake
Iron: distribution
remains in the body for many months
will ceoss placenta and enter breast milk
90%protein bound
Iron: metabolism
recycled daily
iron: excretion
small daily losses through sweat, desquamination, urine, and bile (unless there is a massive blood loss)
how long is therapy needed to replace depleted stores of iron
3-6 months
Iron Side effects: DERM
flushing, uticaria
Iron sifeeffects: GI
heartburn
nausea
diarrhea/constipation
abdominal cramps
what can help ease GI side effects of iron?
start with small dose and work up over several days or weeks
iron side effects: MISC
pan at IM site
phlebitis at IV site
metallic taste
Iron side effects: NEURO
seizures, dizziness, syncope, headache
delayed side effects of iron
hemosiderosis
lymphadenopathy
myalgia, fatigue,
arthralgia and fever
anaphylactoid reaction
What medications decrease iron’s effect
Thyroxine
any drug that changes gastric pH
what other substances decrease iron’s effectiveness
coffee, tea, fiber/bran
Iron increases the absorption of what?
tetracyclines, OCN, quinolones
what should be considered with iron deficiency anemia past age 50?
eval for GI cancers
What should you consider if iron therapy does not resolve anemia?
incorrect diagnosis
complicating illness
non-compliance
inadequate dose
continuing iron loss
iron malabsorption
What enhances the absorption of iron?
Vitamin C
meat
what hinders absorption of iron?
calcium
fiber
tea
coffee
wine
Typical causes of iron deficiency
poor dietary intake
loss of blood
poor absorption
Risk factors for iron deficiency anemia
African American or Mexican
blood donation
poor
pregnant and post patum
child/adolescent obestity
vegetarian diet
what lab should be drawn before begining iron therapy?
serum ferritin
What should be used for iron therapy in patients on dialysis?
Iron sucrose
Serum ferritin level in iron deficiency anemia
<25mcg/L
>100mcg/L rules it out
Patient education for iron therapy
encourage compliance
possible black stools
avoid foods that reduce iron absorption
What does folic acid stimulate?
production of protein synthesis needed for RBCs, WBCs, and platelet formation
What is folic acid used for?
prevent or treat folate deficiency
Why is folic acid recommended for pregnant women?
reduces the incidence of neural tube defects in the offspring
dietary sources of folate
green leafy vegetable, meats, yeasts, nuts, beans, organ juice, dairy products, grains, cereals
serum levels to indicate folate deficiency
< 2.5 mcg/L
< 5mcg/L in older adults
Folic acid: absorption
well absorbed within 30-60 minnutes in the proximal small intestine
(oral)
folic acid: distribution
1/2 circulates through enterohepatic circulation
other 1/2 circulates bound to protein
folic acid: metabolism
converted by the liver to an active metabolite
folic acid: excretion
excess amounts excreted unchanged by kidney
folic acid: half-life
unknown
Folic acid side effects: DERM
rashes
folic acid side effects: MISC
fevers
which medication does folate interact with?
phenytoin
(which is associated with folate deficiency in and of itself)
Folic acid contraindications
No known
make sure there are adequate B12 strores before prescribing
Folic acid: patient education
may turn urine yellow
report any rash
eat a balanced diet
What is vitamin B12?
coenzyme for many metabolic processes
not produced by the body so it must be supplemented
what is required for GI absorption of B12?
intrinsic factor and calcium
most common cause of B12 deficiency
inability of patient to split the R factor from B12 in foods
Risk factors for B12 deficiency
those taking medications that alkalize stomach pH
surgical resection of the stomach or ileum
vegan diet
Clinical uses for B12
B12 deficiency anemia
neurologic complications
demetia
B12: distribution
stored in the liver
B12: metabolism/excretion
any excess is excreted unchanged in the urine
B12: half-life
6 days
B12 side effects: CV
peripheral vascular thrombosis
B12 side effects: DERM
itching, urticaria, swelling
B12 side effects: GI
diarrhea, N/V
B12 side effects: META
hypokalemia with heavy dosing d/t intracellular shift of the potassium ion
B12 side effects: MISC
pain at injection site, hypersensitivity reactions
(including anaphylaxis)
B12 side effects: NEURO
headache, anxiety
B12 contraindications
Those with Leber’s optic nerve atrophy
What if vitamin B12 deficiency goes undiagnosed?
can lead to irreversible neurological damage
What other labs should be monitored when a patient is on B12
HCT
reticulocyte count
folate/iron levels
How does erythropoietin induce RBC production?
stimulating division and differentiation of erythroid precursor cells in the bone marrow
what does erythropoietin do?
induces RBC production
Induces release of reticulocytes from marrow into bloodstream
erythropoietin contraindications
nonspecific anemia, uncontrolled HTN. albumin allery
Normal levels of erythropoietin
5-30 mU/mL
erythropoietin: absorption
rapidly absorbed from subQ sitesand is taken up by bone marrow, liver, and kidneys
Erythropoietin: distribution
unknown
Erythropoietin: metabolism/excretion
metabolized by liver to inactive metabolites
small amounts excreted unchanged into urine
eruthropoietin: half-life
4-13 hours
erythropoietin’s effect is dependent on what?
its dose
erythropoietin side effects: CV
can precipitate hypertensive crisis (id BP poorly controlled)
HTN/seizures (if HCT rises too rapidly)
MI, chest pain, vascular thrombosis (hemodialysis patients)
erythropoietin clinical uses
anemia associated with renal failure
(HCT should be 100ng/dL
and transferrin saturation should be >20-30%)
erythropoietin sidef effects: DERM
transient rashes
erythropoietin sidef effects: ENDO
restored fertility, resumption of menses
erythropoietin sidef effects: GI
diarrhea, nausea
erythropoietin sidef effects: HEM
thromboembolism
erythropoietin sidef effects: ONCOLOGY
lower survival rates
erythropoietin sidef effects: MS
paresthesias
erythropoietin sidef effects: NEURO
seizures, headache
erythropoietin sidef effects: PULM
upper respiratory infection
erythropoietin interacts with which drugs
None
erythropoietin: conscientious prescribing
Page 142 in text
heparin: mechanism of action
binds to antithrombin converting it to a powerful anticoagulant
Heparin: absorption
Not absorbed orally
must be given IV or SQ
heparin: clinical uses
prevention of venous thromboembolism
treatment of venous or arterial thromboembolism
unfractionate heparin v. low molecular weight heparins
LMWHs have a longer half life and can be given 1-2 daily doses
UH mst be given as cont IV infusion or multiple daily SQ injections
Things to watch for in patients taking heparin
hepatitis
bleeding
heparin-induced thrombocytopenia (HIT)
heparin induced thrombocytopenia
serious and potentially life threatening condition caused by antibodies to platelets
labs used to monitor Heparin
aPTT
ACT
heparin contraindications
history of peptic ulcer disease
poorly controlled HTN
diabetic retinopathy
if patient has ever experienced heparin induced thombocytopenia
NSAIDs and heparin
Increased bleeding risk
When is INR needed with heparin
If coadministered with coumadin
OTC products to avoid while on heparin
ginko, garlic, gimseng, vitamin E, fish oil
Baseline labs for heparin
PT/PTT
HGB/HCT
platelets
labs to monitor during heparin therapy
PTT
periodic platelet count
monitor for signs of bleeding
Patient education: heparin
signs of bleeding
use soft toothbrush and electric razors
wear a medical alert bracelet
LMW heparin drug names
danaparoi (Orgaran)
enoxaparin (Lovenox)
dalteparin (Fragmin)
fondaparinux (Arixtra)
tinzaparin (Innohep)
LMW heparin: mechanism of action
inhibits factor Xa more that it does thrombin
LMW heparin: absorption
parenteral administration as they are destroyed by enzymes in the bowel
LMW heparin: metabolism/excretion
some ar artially metabolized or not at all, excreted renally
LMW heparin: half lives
enoxaparin: 3-6hrs
dalteparin: 2hr
danaparoid: 24hrs
tinzaparin: 4hrs
fondaparinux: 17hr (21hrs in elderly)
LMW heparin: clinical uses
prevention/treatment of DVT/PE
acute coronary syndrome
(more effective and safe than heparin for this)
LMW heparin side effects: DERM
local skin reactions
LMW heparin side effects: GI
diarrhe, nausea
LMW heparin side effects: HEM
bleeding
most serious sites are: CNS, GI tract, and retroperitoneal space
LMW heparin side effects: META
elevated tranaminases
LMW heparin side effects: MS
long term use may cause osteoporosis
LMW heparin contraindications
spinal or epidural catheters
(risk for spinal and epidural hematoma that can cause paralysis)
how long after removal of a spinal or epidural catheter must you wait before administering LMW heparin
at least 4 hours
how is LMW heparin administered
SQ not IM
Are heparin, LMW heparins, and fondaparinux interchangeable?
NO
herbals to avoid while on heparin
dong quai, evening primrose, garlic, ginger, ginko, ginseng, green tea
Coumadin mechanism of action
interferes with synthesis of vitamin K-dependent clotting factors by inhibiting vitamin K epoxide reductase
vitamin K-depedent clotting factors
2, 7, 9, 10
How is coumadin administered
Oral only
how long does it take for coumading to stabilize in the body?
5-6 days
coumadin: clinical uses
reduce risk of stroke or peripheral embolism in those with non-valvular a-fib
prevent/treat DVT/PE
patients with metal cardiac valves
short term use after placement of bioprosthetic cardiac valves
therapeutic range for coumadin
2-3
coumadin: absorption
nearly 100% bioavailability orally
coumadin: distribution
crosses placenta but does not enter breast milk because it is 99% protein bound
coumadin: metabolism/excretion
hepatic metabolism
coumadin: half-life
1/2 day - 3 days
what dose should you start coumadin at
5mg if also on heparin, otherwise 2.5mg
Coumadin side effects: DERM
skin necrosis and gangrene d/t paradoxical local thrombosis
rare
often shows in limbs, penis, or breast
Coumadin side effects: HEM
bleeding
Coumadin side effects: MS
long term use associated with osteoporosis
drugs that decrease effectiveness of coumadin
antithyroid drugs
barbituates
carbamazepine
phenytoin
rifampin
cholestyramine
Coumadin: conscientious considerations
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Pradaxa: clinical use
prevention of stroke or peripheral embolism in patients with a-fib
pradaxa mechanism of action
directly inhibts production of thrombin (Final step in the clotting cascade)
Pradaxa comes in what forms
PO and IM
How long does it take for PO Pradaxa to reach peak
serum concentration
2 hours
Pradaxa: absorption/distribution
3-7% is rapidly absorbed
Pradaxa: metabolism/excretion
metabolized to active metabolite in the liver with elimination by kidneys
converting from coumadin to pradaxa
d/c coumadin and start pradaxa when INR falls below 2
converting from pradaxa to coumadin
CrCl >50 mL/min
start coumadin 3 days before stopping pradaxa
converting from pradaxa to coumdain
CrCl 31-50mL/min
start coumadin 2 days before stopping pradaxa
converting from pradaxa to coumdain
CrCl 15-30 mL/min
start coumadin 1 day before stopping pradaxa
converting from heparin to pradaxa
start pradaxa 0-2 hours before next heparin dose is due
discontinuing pradaxa prior to surgery
CrCl >50 = 1-2 days prior
CrCl <50 = 3-5 days prior
Pradaxa side effects: GI
dyspepsia, abdominal pain
Pradaxa side effects: HEM
bleeding
what drug does pradaxa interact with
rifampin
(reduces the concentration of pradaxa)
when is anti-platelet therapy indicated
all acute coronary syndromes
after noncardioembolic stroke/TIA
patients with peripheral artery disease after CABG or carotid endarterectomy
primary prevention (if multiple risk factors)
anti-platelet: aspirin
mechanism of action
potent irreversible inhibitor of cyclo-oxygenase (COX-1)
Aspirin: absorption
rapidly absorbed in stomach and upper bowel
how long does it take for platelet inhibition
by aspirin to be detectable?
1 hour
optimal aspirin dose for prevention of MI/stroke
50-100mg daily
optimal aspirin dosage for acute conditions
(acute coronary syndrome, stroke)
160-325mg
aspirin dsage for chronic use
no reason to exceed 81mg
aspirin side effects: GI
dose related bleeding
aspirin side effects: HEM
low risk of intracranial bleeding
aspirin side effects: EENT
tinnitus
aspirin interactions
coadministration with traditional NSAIDs can negate cardioprotective effect
what if a patient has cardiovascular disease but gets GI bleeds with aspirin
combination therapy with esomeprazole 20mg and low dose aspirin 75mg
clopidogrel (Plavix)
mechanism of action
blocks platelet activation by selectively and irreversibly blockng the binding of ADP to the platelet
this prevents the ADP-dependent activation of Gp IIb-IIIa complex
Plavix: absorption
well absobed orally
Plavix: metabolism
quickly metabolized by the liver into an active metabolite
Plavix: excretion
50% in urine
45% in feces
Plavix: half-life
Active metabolite 8hrs
When should plavix be used along with aspirin?
management of acute coronary syndrome, including unstable angina and acute MI
in patients undergoing angioplasty with either bare metal or drug eluting stents
how long should you wait to d/c plavix after ACS is relieved?
indefinite if treated with stents
after 1 year if treated without stents
When should aspirin alone be used
vascular disease without prior MI or stents
(stable CAD, prior TIA or CVA, peripheral artery disease)
when should aspirin be used prophylactically
no established heart disease but lots of risk factors
Plavix side effects: CV
chest pain, edema, HTN
Plavix side effects: DERM
pruritis, purpurea, rash
Plavix side effects: HEM
bleeding
thrombotic thrombocytopenic purpura (rare)
Plavix side effects: GI
abdominal pain, N/V, constipation
Plavix side effects: NEURO
headache, dizziness, depression, fatigue, generalized pain
Which drugs decrease effectiveness of plavix
atorvastatin, clarithromycin, erythromycin
which drugs increase effect of plavix
rifampin and other antiplatelets and anticoagulants
plavix contraindications
prior/active bleeding events
prasugrel (Effient)
second thienopyridine approved as an antiplatelt drug
effient mechanism of action
binds to ADP receptor on platelet surface and irreversibly inhibits platelet activity
why is effient a “pro-drug”
it undergoes metabolic activation by intestinal esterases and then through liver’s CYPA34 and 2B6 systems
when is effient indicated?
acute coronary syndromes who are undergoing primary coronary interventions
effient contraindications
patients older than 75 or those weighing less than 60kg
patients with history of stroke
why should effient not be routinely used
higher efficiency but also higher side effects (increased bleeding risk)
effient: absorption
rapid within 30 minutes of oral administration
effient: distribution
plasma proteins
effient: metabolism
hepatic cytochrome P450 isoenzymes
(CYP3A4, CYP2C9. CYP2C19, CYP2B6)
effient: excretion
mostly in urine, some in feces
effient: half-life
7 hours
onset of platelet activity 30 minutes
steady state reached in 3 days
effient dosage and administration
page 153
Aggrenox
50mg of aspirin with 200mg ER dipyridamole
Aggrenox: clinical use
prevention of vascular events
(most commonly used to prevent strokes)
IV Aggrenox
used by cardiologists to cause maximal coronary vasodilation
Aggrenox contraindications
patients with bronchospasm
when is aspirin preferable to aggrenox
patients with establish CAD or PAD
fibrinolytic (thrombolytic) agents
drugs that lyse blood clots
(all are forms of tissue plasminogen activator tPA)
fibrinolytic agents: mechanism of action
tPA binds to fibrin and convert plasminogen to plasmin which causes local fibrinolysis, dissolving clots
how are fibrinolytics administered
IV only
fibrinolytics: clinical uses
treatment of ST-segment elevation MI
acute massive PE, acute ischemic stroke
to open clotted central venous access devices (alteplase only)
Fribrinolytic drug names
Alteplase (Activase, cathflo activase)
reteplase (Retavase)
tenecteplase (TNKase)
