Pharm Heme/onc Flashcards
what are the two main categories of hematologic drugs?
supplements
growth factor stimulants
what are the three categories of drugs under the supplements branch of hematologic drugs?
hematinics: iron
Vitamin B12
nutritionals: folic acid
what are the two categories of drugs under the hematologic growth factor stimulants?
erythrocyte stimulating agents: erythropoetin
myeloid growth factor: filgastrin
what is iron bound to in the blood?
transferrin
when iron (FE) stores are high, where is it diverted to for additional storage? where is it initially stored before going there?
diverted to intestinal mucosal cells
initial stores are in
macrophages in the liver, spleen, and bone
what is ferritin made out of?
iron and apoferritin
what percent of ferrous iron dose is absorbed daily if the pt has ADEQUATE IRON STORES? what about if this same patient had DEPLETED stores?
if adequate iron stores: 5-10%
if depleted, maximum: 25-30%
what is the goal for elemental iron daily?
200-400 mg
what is the max incorperate of iron?
50-100 mg daily
Caution: what should you caution about children and iron?
overdoses are lethal in children
what percent of iron is absorbed?
5-30% depending on the stores
5-10% if stores are adequate
25-30% if stores are depleted
what two things decrease iron absorption?
food and achlorhydria
- age decreases RBC absorption
- impacted by proton pump inhibitors
what part of the intestine absorbes FE via what mechanism
duodenum, jejunum via divalent metal transporter 1 (DMTI)
what is iron administered as?
FESO4
if you administer 325 mg of FESO4 how much elemental iron is released?
65mg
How long does it take for reticulocytosis and increase in hemoglobin/hct after giving pt iron?
reticulocytosis: 5-10 days
increase in hgb: 4-6 weeks
these patients are sicker so it takes longer to see increase in hgb
what happens to the rate of absorption as the FE stores replenish with FESO4 administration?
the rate of absorption decreases
what is the max amount of time you should take iron?
6 months
what is the maximum Hgb on treatment?
12 gm/dl
how long does it take a erythrocyte stimulating agent (ESA) to increase the number of reticulocytes? how long to increase the hemoglobin (Hbg) and hematocrit (Hct) when treated with ESA?
5-10 days to increase # of reticulocytes
2-6 weeks to increase hgb and hct
if giving someone erythropoeitin, the patient is most likely a lot sicker, which is why it takes the Hbg and Hct so much time to increase compared to the normal 2-4 weeks in normal patient
What two things might a patient need to take/increase when being treated with a erythrocyte stimulating agent (ESR)?
iron supplementation
anti-coagulant
think about it…more cells!
what are the four major classes of anti-coagulant drugs?
- indirect thrombin inhibitors
- direct thrombin inhibitors
- coumarin drugs
- direct oral Xa inhibitors
what are the three major classes under anti-hemostasis drugs?
- anti-coagulant drugs
- fibrinolytic drugs
- anti-platelet drugs
what does “white” clot mean?
arterial clots form around activated platelets
what does “red” clots mean?
venous clots form around activated fibrin and RBCs
what drugs are used for arterial clots (white clots)?
anti-platelet drugs
what drugs are used for venous cloths (red cloths)?
anti-coagulants
the prothrombine time PT is a function of what? what factors does it include?
extrinsic factors, primarily k dependent factors
what is the INR?
normalizes the PT across different labs
the active partial thromboplastin time aPTT is a function of what? what factors does it intclude?
intrinsic pathways, both vitamin k dependent factors and contact activated factors
what are the four indirect anticoagulant drugs?
- unfractioned heparin
- low molecular weight heparin (LMWH)
- fonaparinux
- protamine sulfate
what is the name of the oral and IV direct thrombin inhibitors?
dabigatran (PO)
argatroban (IV)
what are the benefits to using a oral direct thrombin inhibitor?
- rapid onstet
- halflife=minutes
- stable pK (body on drug) and bioavaliability
- doesn’t interact with P-450 interacting drugs
what is the first and common clotting factor between the intrinsic and extrinsic clotting pathways?
Factor X
what does factor Xa (activated 10) do?
catalyzes the conversion of prothrombin (II) to thrombin (Ila)
explain where the direct factor Xa inhibitor “rivaroxaban” is metabolized and excreted? by what mechanism? what else is it a substrate of?
70% liver metabolism by CYP34A/5
30% renally excreted
substrate of paraglyocoprotein pump system
what percentage of warfarin is bound in serum?
99%
what type of mixture is warfarin? which is more effective?
racemic mixture
S-warfarin is 4x more potentent than R-warfarin
must consider this in dx-dx reactions
what does warfarin act on?
vitamin K dependent coagulation factors
what does warfarin produce?
biologically inactive molecules
can people be genetically resistant to warfarin? what is this based on?
yes
mutation changes to vitamin K epoxide reductase (VKOR)
what is the delay in drug onset of warfarin? and what is the delay in effect?
8-12 hour delay in drug onset, 48-72 hour delay in effect
what is interesting about warfarin and pregnancy?
crosses placenta readily and is CATEGORY X!!!!!
what are the two fibrinolytic drugs?
streptokinase, alteplase
how long would it take to see the hgb increase when giving oral iron?
2-4 weeks!
in a otherwise normal patient, it would be closer to 2 weeks
does dabigatran require any formal monitoring plan?!
NO!!! it doesn’t!!! give it and don’t have to monitor it!
Although you don’t have to monitor dabigatran, what are the three things you need to check before prescribing to a patient?
H&H, CrCl, and aPTT
how does iron deficient anemia present? what things can cause it?
vegan diet excessive NSAID use (ibuprofen) menorrhagia (heavy periods) fatigue with minimal excertion pale nail beds and skin
what do you treat iron deficient anemia with? whats the dosing?
FeSO4
325 mg 3x daily
what is important to do when treating patients with FeSO4?
uptitrate, can bind people up badly!
can be harsh on the stomache so give 2 times daily and then three, if ELDERLY, start with 1 time daily
what should you do for a elderly patient starting FeSO4?
start 1x a day and then up titrate to get to 2x, and 3x if they can tolerate it. might cause too much N/V/D/contipation in elderly so better to start small!
why do you need to give FeSO4 so much or three times a day?
because by the time you pick up on the anemia, the body has already depleted the stores so the body is unable to conpensate for that. they have gone through all the stores so it takes a lot to get rid of the symptoms and replenish the stores!
how long are people usually required to take FeSO4 for?
6 months
Case: if someone has menorrhagia and have iron deficient anemia what do you need to consider?
need to consider their birth control options and consider uping the dose to decrease the amount of bleeding which causes decreased risk of anemia! helps stablize iron levels!
if someone has iron deficient anemia, what are the two main things you want to consider for reasons?
diet (green and leafy)
bleeding (GI/menorrhagia)
what is the most common cause of blood loss for a otherwise healthy person?
blood loss
if treating a patient with FeSO4 for iron deficient anemia, what should you monitor and in what time frame?
reticulocytes after 2 weeks
H+H after a month
interesting: what is the #1 reason people stop taking FeSO4?
GI complications
N/V/D/constipation
iron deficient anemia, the RBCs appeare….
MICROCYTIC!
B12/folate deficient anemia, the RBCs appeare….
MACROCYTIC!! since dont’ have all the components they are release prematurely!
can you have both B12/folate anemia and iron deficient anemia at the same time?
Yes! you would see micro and macrocytic RBC at the same time!
what does FeSO4 stand for?
ferrous sulphate
what do people use Ferrous sulphate to treat iron deficient anemia? what are the benefits of this drug?
cost effective
has the least side effects
HIGHEST YIELD OF ELEMENTAL IRON
Case: what type of anemia would you suspect in a patient who is using tNAIDs as a bridge therapy for gout? what is important to check in this patient?
GI bleed from extended tNAIDs use, leading to iron deficient anemia
want to check the serum uric acid levels in this patient because if
Case: why is it important to check the uric acid levels of a patient with gout?
if UA is less than 6 then dont have to treat with allpurinol
if you have a patient where bleeding is suspected, what is the next step?
1st-upper GI endoscopy
2nd-colonoscopy
in patients suspect of a GI bleed because of iron deficient anemia, why do you do a upper gastric endoscopy first
because there is statistical evidence upper GI bleeds are more common than lower GI bleeds
what are you looking for in iron deficient anemia where you do a lower endoscopy or colonoscopy?
GI bleed or ulcerative colitis
what is a quick test you can do to check for GI bleed?
guiac stool
tells you if there is a bleed in the GI tract, indicates you should do endoscopy!
Interesting: what is the most common cause for bleeding/iron deficient anemia in women
menorrhagia, HEAVY MENSES
Interesting: what is the most common cause of bleeding/ iron deficient anemia in post menupausal women or men >50?
upper or lower GI bleed if not responding to iron treatment
which is more common upper or lower GI blled?
upper GI bleed statistically
what are four conditions that can lead to anemia of chronic conditions?
- heart failure
- chronic kidney disease
- Diabetes
- RA
Interesting: what happens in a chronic inflammatory state that can contribute to anemia of chronic disease?
in chronic inflammatory state you don’t absorb iron as well, leading to anemia
Intersting: what can you co administer with iron to increase iron absorption? how long should you wait before trying this?
Co administer vitamin C, increases absorption because it makes the environment more acidic!
try regular iron for 2 weeks and then try this!
what should you do when administering FeSO4 to limit the potential for negative effects?
taper up to 3x a day!
what is the order of iron administration you should try to eliminate negative effects? (3)
- FeSO4 oral
- FeSO4 with vitamin C
- FeSO4 IV, watch for anaphylaxis
what is a negative side effect you must be concious with when administering IV iron?
anaphylaxis
but recently with medications the risk of this has been decreasing but still want to know this!
Interesting: what does metformin do? why is this influential in diabetics?
inhibits B12 absorption
increases diabetics risk for B12 deficient anemia!
Interesting: explain why kidney disease increases the risk for anemia?
In anemia the kidneys can’t sense the concentration of oxygen so can’t effectively secrete erythropoetin. if this isn’t secreted effectively you don’t get adequate production of RBC….ANEMIA
Case: when do you worry about CKD increasing the risk for anemia? what is the corresponding ml/min?
Stage 4 and below
why don’t elderly respond as well to anemia treatment?
usually they have more than one type, so you fix one but don’t fix them all. their anemia is usually more complex and may need more than one type of treatment.
Interesting: which drug for anemia do you only want to use if the patient is on dialysis?
epoetin alfa, H+H
what is an interesting side effect of B12 deficient anemia that can help differentiate it from folate deficient anemia?
Neurological side effects with paresthesia, numbness and tingling in the extremities.
periphreal neuropathy
epoetin alfa increases the risk of…. (3)
MI, cloths, TIA
why do you ALWAYS want to check both a B12 and a Folate when testing for deficient anemia?
BECAUSE ONE CAN MASK THE SIDE EFFECTS OF THE OTHER NEED TO ALWAYS CHECK BOTH SO YOU MAKE SURE YOU AREN’T MISSING ANYTHING!!
Interesting: what is one thing you MUST check before starting epotein alfa?
need to check their iron concentration because you want to make sure they have enough to make the RBC (I’m assuming this is talking about in the form of ferritin)
Interesting: what is the target concentration of hbg in patient being treated with epoetin alfa?
12 gm/dl
what happens to the MCV in B12/folate deficiency?
increases since cells are macrocytic
Case: what are three things that can decrease the folic acid levels?
methotrexate, alcohol, phenytoin
Case: how can you tell the difference between folate/B12 anemia and alcoholic anemia?
get a SMEAR!!
macrocytic RBC=folate/B12
microcytic=alcohol/chronic
what does phenytoin decrease in regards to anemia?
B12 AND folate!! both!!
interesting: how is folate acquired?
only through diet
what are three things that folic acid is essential for?
DNA synthesis, cell division, reticulocyte formation
Interesting: if you suspect a B12 absorption deficiency, what test should you use? what are you looking for?
Schillings test you why B12 isn’t absorbed.
Tells you if the problem is secondary to a lack of intrinsic factor needed to absorb B12 or terminal ilieum disease like crohns
what anemia deficiency can lead to permanent neurological deficits?
B12 deficient anemia
Interesting: how long does it take for the H=H to change in response to an acute bleed?
24-48 hours
what are the four stages in depletion of iron stores and what is the significance of this?
- normal
- iron depletion
- iron-deficient erythropoiesis
- iron-deficient anemia
This last step is the time the lab work reflect an iron deficient anemia, this means by this point there is significant depletion and the body can’t compensate here
NEED TO KNOW!! Explain why there is HYPERcoagulation seen intially when the patient takes WARFARIN?
First it knocks out proteins C & S which have ANTICOAGULATION effects, so by wiping them out you make the blood thicker and hypercoagulated!
then II and IIa are inactivated by the warfarin which significantly decreases the clotting/thickness
SO the NET is hypocoagulation or thinner blood
what is the function of proteins C and S in the clotting cascade? what are they targeted by?
they ask as checks and balances and are anti clotting components!
they are targeted in wafarin
Factor II and IIa stand for what?
II=prothrombin
IIa=thrombin
prothrombin (II) is dependent on what?
vitamin K dependent factor
prothrombin (II) is a target for which two drugs?
unfractioned heparin and wafarin
Proteins C and S are a target for what drug?
wafarin
when is an exception that you would transfuse a patient if their hgb was above 8.5?
if the person is bleeding out, for instance with a ruptured spleen, and needs to have emergency surgery and they will continue to bleed until they have the surgery!!
what do you do for an INR above therapeutic range
reduce or skip warfarin dose, monitor INR until INR is therapeutic
what do you do for an INR 4.5-10?
hold 1 to 2 doses of warfarin, resume warfarin at lower dose when INR therapeutic
what do you do for an INR >10?
hold warfarin and give vitamin K 2.5-5 mg
if trying to get someones INR to lower, what is an interesting thing you can do with the IV formulation of vitamin K?
give it orally if you mix with orange juice to get rid of bad taste
what is serum ferritin in equilibrium with?
macrophage ferritin
how long does it take to replenish B12 stores?
3-5 years
what organs is iron specifically toxic to in children? what do you need to treat or do about it?
kidneys, liver, iron
need to treat with iron chelator because it is FATAL!!! esp in kids!!
how long will a patient with B12 need to be treated with B12 supplements?
likely indefininetly!!
Case: what is the DOC of choice for a patient post AMI for prophylaxis?
ASA! (sometimes combined with clopidogrel, don’t be concerned with this)
what is the ideal dose for ASA in post AMI prophylaxis? what is the maximum limit you are supposed to use and why?
optimal dose: 81 mg
Max dose: 325 mg
*if more than 325 mg it inhibits prostaglandin A2 which is a ANTICOAGULANT!!! if the goal is to anticoagulate the blood, the last thing you want to do is inhibit the bodies natural anticoagulants!! THINK ABOUT IT
Case: what is the DOC for a patient post AMI prophylaxsis who is allergic to the original DRUG ASA because they have an aspirin allergy?
clopidogrel alone!
when should you be concerned with the risk of stroke?
CHAD2 score >2, its arterial and you need to do something about it!!
Case: What is the drug to prevent stroke/CVA in a patient with NON-VALVULAR A FIB!! (this part is key!!)
dabigatran
Case: what is the DOC in a post ischemic stroke patient for a SECONDARY anticoagulant? what do you need to do if this patient takes asprin?
warfarin
need them to stop taking ASA!! in studies leaving the patient on asprin when combined with warfarin has no proven benefits but definitely makes them more likely to bleed, so stop it!
Case: what is the DOC for a RA patient that has COPD? what would be the original DOC?
original DOC would be methotrexate.
can’t use in this patient because of their COPD. methotrexate is contraindicated because it leads to pulmonary fibrosis!!!
USE ETANERCEPT FOR THIS PATIENT INSTEAD!!
Case: if you have a patient with a 7/22 H+H and a positive guiac who is going to be going to surgery, do you or do you not transfuse if asymptomatic?
YOU TRANSFUSE
because they are going to surgery they are loosing a lot of blood and so you need to treat them like they will loose more….if you don’t, they could drop a lot during surgery and it would be unsafe!!
Case: if patient has a 8.5 hemoglobin with anemia of chronic disease do you transfuse them if they are symptomatic vs. asymptomatic?
typically you would say don’t transfuse for 8.5 since above threshold, HOWEVER, if they are symptomatic then transfuse!!
Case: how does claudication PVD present in a patient?
difficult walking for more than 25 yards, pain in the legs, periphreal pulses not felt, carotid bruits felt
Case: what is the DOC for PVD? what is important to combine with this drug for effective treatment and why?
DOC: Cilostazol and WALKING PROGRAM!!!
this drug actually sucks and need to combine with walking program to actually help the issue (explained on another flashcards)
why are walking programs important for patients with PVD?
walk till discomfort, rest, walk again when better
pain in legs is caused by ischemia from lack of blood flow and o2 to the muscles, walking increases COLLATERAL CIRCULATION, or the formation of little tiny arterioles. this allows the muscles to get more oxygen!! the more walking the more ateriole formation and decreased symptoms! THIS DOESN’T FIX ATHROSCLEROSIS BUT HELPS WITH PROFUSION AND SYMPTOMS
what are carotid bruits a strong indication for?
PVD!!! atherosclerosis
when you hear CLAUDICATION, what should you relate it to?
ARTERY AND PLATELET CLOTS (collateral artery stimulation)
CLAUDICATION=PLATELETS=ARTERY ISSUE
BOOM!
what is the MOA of cilostazol?
inhibits platelet phosphodiesterase “stickiness” of platelets, so it prevents their aggregation
what do you need to avoid when taking cilostazol?
GRAPEFRUIT JUICE
Case: what is the DOC for a patient with valvular afib to prevent against DVT/PE?
warfarin!! valvular is the key here!
this patient can’t take the newer drugs!
Case: what is the DOC in NON-VALVULAR afib to prevent DVT/PE?
Rivaroxaban or dabigatron
what is the goal PTINR for a patient with afib on warfarin for DVT/PE prophylaxis? When should you check the INR?
2-3
but closer to 2 if elderly
CHECK AFTER 3 DAYS OF ADMINISTRATION!
Case: what do you do if a patient has a INR >10?
- hold warfarin and start vit K 2.5 mg
- check the INR daily
- monitor till it goes back down and then warfarin again
don’t want to give the patient a bigger dose unless they are severely bleeding
what happens when a patient is on warfarin and they eat some great leafy vegetables?!
the INR goes DOWN
blood gets THICKER!
warfarin resistance:
can happen if the patient is given too much vitamin k, makes the blood too thick and then the warfarin takes longer to work or is resistant
this can occur for 1-2 weeks!! not good for the patient!
what is the DOC for surgical prophylaxis if you want to give it to the patient after surgery? what is the down side to this drug?
rivaroaxaban
Benefit: relatively short halflife (7-11H) compared with wafarin (25-60H), so it can be given after the surgery and work quickly
down side: since it works so quickly if a elderly patient misses a dose because they forget it can lead to HYPERCOAGULATION! this is BAD!! less forgiving than warfarin
what is the halflife of warfarin?
20-60H, long time!!
Takes 2-3 days to work
Case: what is the DOC for surgical prophylaxis if you want to dose it before surgery? (3 drugs)
warfarin
LMWH
fondaparinux
what drug is used as a bridge therapy for coumadin? why do you need a bridge therapy?
LMWH
coumadin takes 2-3 days to work so need to anticoag before then!
coumadin test?
PTINR
heparin test?
PTT
explain the difference between a provoked and unprovoked DVT? causes for each?
Provoked: known cause (BC, known DVT, sitting in the car for a long time)
unprovoked: don’t know where DVT came from! usually comes from proximal thigh, iliac, pelvic/thigh region, but since don’t know for sure need to treat aggressively!!!
what percent of people is the source of a DVT unprovoked?
1/3, don’t know the source in these
Case: what are the two DOCs for a patient with a PE who is on BC? what do you need to get this patient to do?
PROVOKED by BC
treat with heparin (more control over dosing) OR LMWH (less control since standardized dose)
STOP THE BC!!! INCREASED RISK!!
Case: what is the new DOC in a patient with a PE that is on birthcontrol and they had an EPISODE OF THROMBOCYTOPENIA during the last heparin administration?
Fondaparinux!
still an indirect thrombin inhibitor but doesn’t contain heparin
what is the MOA of ASA?
- irreversible inactivation of cyclo-oxygenase
- inhibits thromboxane A2 (platelet aggregation and vasoconstriction)
inactivates for the entire life of the platelet~5days
what is the MOA of clopidogrel?
irreversibly blocks ADP receptor on the platelets preventing platelet/fibringogen binding and platelet aggregation
case: what is the DOC for a post 3 day PE patient who is being discharged from the hospital? (2 options)
coumadin/rivaroxaban
Case: what is the DOC for a patient who had a PE and were treated with heparin, and when they came back to have aPTT, they were WAY TOO COAGULATED?
protamine sulfate
inactivates heparin, thickens the blood, wait, and then restart more appropriate dose of heparin
** big increase aPTT means you gave too much!**
white clots form in the______. they consist of _______. This pathway is most common with 4 general conditions…name them!
white clots form in the ARTERIES, they consist of PLATELETS.
Concern with:
- stroke (CVA)
- AMI
- PAD
- coronary stenting
Red clots form in the ______. they consist of______. this pathway is most common with 3 general conditions. what are they?
Red clots form in the VENOUS SYSTEM they consist of RBC AND FIBRIN.
Three conditions:
- DVT/PE
- both afib types
- surgical prophylaxsis
explain why venous thrombus form?
pro and anti coagulants arent mixed well like in the arterial system where the flow is faster. since the flow in the venous systems is slower, the pro and anti coagulants don’t mix well. the imbalance between the two cause spontaneous activation of clotting mechanisms and clots to form with the RBC and fibrinogen
what type of medications do you use for venous thrombus?
anticoagulation factors!!
what type of medications do you use for the aterial system?
antiplatelets!
unfractioned heparin is the most common cause of______. what percent of people experience this?
Heparin induced thrombocytopenia! (HIT)
3% of people
