Week 12: Hematologic Flashcards
Prototype Hematologic (Anti-anemia and Anticoagulation) Drugs
- Ferrous sulfate (Feosol)
- Vitamin B12 (Cyanocobalamin)
- Folic Acid (Folvite)
- Erythropoietin (Epogen)
- Heparin
- Enoxaparin (Lovenox)
- Protamine Sulfate
- Warfarin (Coumadin)
- Vitamin K (AquaMephyton)
- TPA (Alteplase)
- Aminocaproic Acid (Amicar)
- Transexamic Acid (Lysteda)
- Filgrastim (Neupogen)
What varies between iron supplements
the amount of elemental iron found in the salt
ex: Ferrous sulfate has more iron than Ferrous gluconate
Anemia
A SYMPTOM of an underlying problem
Not a diagnosis by itself usually
The most common anemia …
iron deficiency anemia
Prototype Iron Replacement Drug
ferrous sulfate (Feosol)
Ferrous Sulfate (Feosol)
Class: Iron Replacement
Most common med for increasing Fe stores in people
Action of Ferrous Sulfate
Replace iron in the body whihc is then used in normal fxning- ESP. in aiding O2 carrying capacity of RBC
What route is Ferrous Sulfate usually given
Oral
However it can be given parenterally for those who cannot absorb it thorugh the GI tract
What is interesting about the absorption of ferrous sulfate/iron
If body stores of iron are high already less iron absorption will occur. but when the stores are too low it will absorb more easily
___% of ferrous sulfate is absorbed when body stores are low while ___% is absorbed if the stores are high
15%; 2-3%
What are some things that may increase iron absorption
Vitamin C!!!
Orange Juice (Uncertain)
Low Body Stores of Iron
What is interesting about the Metabolism of Ferrous sulfate/iron
Iron is used in the body and is broken down and usually reutilized or stored
VERY LITTLE IS EXCRETED DAY TO DAY d/t ITS IMPORTANCE
Most health people do not lose a lot and do not need much more daily
4 People at risk for Iron Loss/Iron Deficiency Anemia
- Menstruating Women
- Periods when the body is growing - Puberty and INfancy
- GI BLeeding
- Pregnant women
If a patient is found to be anemic one of the first thing that is checked is…
whether there is small or large bleeding occurring in the GI tract and if its iron deficiency anemia
ADRs of Ferrous Sulfate
- Constipation AND Diarrhea
- GI Effects (when taken orally)
Other: HA, Anorexia, Gastric Pain, NV
What is important to know about ferous sulfate therapy following dips in body iron stores
If there is small dips in iron stores there should be improvement within 2-3 weeks
However if there is severe iron loss and anemia (Empty ferratin stores) it could take almost a year to get iron levels back to normal
How often is the dosage of ferrous sulfate usually taken
1 time a day at 325 mg (sometimes 2 but it increases ADRs)
What is important about the stool of someone on ferrous sulfate
Stools will be black (or green) in color and can appear as though is it blood/old blood
It is not, that is staining that occurs
What is an important consideration about solution/liquid iron
Give it through a straw since it can cause staining
Always keep tablet ferrous sulfate…
AWAY FROM CHILDREN - high doses can be lethal
Never take ___ with iron. Why?
Antacids; They will bind oto the iron and carry it out of the body without any of the iron being absorbed
How does the elemental iron content differ between preparations of: Ferrous Sulfate, Ferrous Gluconate, and Dried Ferrous Sulfate
Ferrous Sulfate - 20% elemental iron (ex: 100 mg pill is 20 mg iron)
Ferrous Gluconate - 12%
Dried Ferrous Sulfate - 30%
When is the best time to take your iron supplement
on an empty stomach
*however this can cause NV so someitmes for the first week you take with food then take without after that
Some people cannot take oral iron due to malabsorption syndromes or issues from age, so they may need it IV or IM. What 2 important things need to be kept in mind regarding this route?
- Proper Z Track is needed to prevent skin staining
2. High risk/rate of anaphylaxis when given IV so they must be monitored
deferoxamine (Desferal)
Antidote for iron/ferrous sulfate
it will bind to iron and allow its removal via the kidneys
The biggest problem for Iron supplement adherence is…
the ADRs (GI GI GI - Constipation, Diarrhea, Abdominal Discomfort, NV, etc)
What 2 prototype drugs are included for Macrocytic Anemia treatment
Vitamin B12 (cyanocobalamin)
folic acid (Folvite)
Vitamin B12 (cyanocobalamin)
Oral/Parenteral vitamin that mostly comes from animal products
Used for RBCs AND Myelin Sheathes in the CNS
Action of Vitamin B12
Restores Vitamin B12 to the body which is needed in formation of RBC (and the myelin sheathe)
Where does most Vitamin B12 come from and why is this a problem
animal products - this then is a problem for vegans and vegetarians
Other than RBC what else does Vitamin B12 work on
the myelin sheathes in the CNS
Main Route of Vitamin B12
IM or Deep SubQ (Parenteral)
Oral can be given but the absorption is poor with only 1-2% of uncomplexed B12 absorbing
ADRs of Vitamin B12
RARE - only concern may be a drop in Potassium (K)
What is the 2 issues with a lack of Vitamin B12
RBC - Macrocytic Anemic
Neurological Impairment/Damage
What is needed in order to absorb and use Vitamin B12 effectively
Intrinsic factor for the parietal cells in the stomach and gastric mucosa
So, gastric modification, illness, or surgery can alter B12 absorption
What must be done while first starting Vitamin b12 therapy
patients must be evaluated for 4-6 months to make sure the therapy is effective
If a patient does not have intrinsic factor how must they take Vitamin B12
Large oral doses to have an effect
Megaloblastic/Macrocytic Anemia
An anemia due to deficiency in folic acid or vitamin B12
Causes Large Cell Aenami where there are large RBCs, fewer RBCs, and they are less useful in O2 delivery
Folic Acid (Folvite)
Vitamin
Plays an essential role in DNA production leading to RBC production
In what foods is folic acid found
green leafy vegetables
liver
milk
eggs
In what kinds of people might folic acid levels and absorption be decreased
those with celiac disease
those ingesting large quantities of alcohol
Action of Folic Acid
plays an active role in development of enzymes which are necessary for DNA production
(If inadequate DNA, erythropoiesis is affected and macrocytic RBC occur)
Absorption and Route of Folic Acid
Usually give oral, can be put in TPN as well
Even if someone has malabsorption issues, they can still be given larger doses of this for effect
ADRs of Folic Acid
NONTOXIC
Rare Allergic Rxns can occur
How does dosage differ for folic acid
depends on the situation
For isntance, if a woman is deficient early in pregnancy she may be given a lot more
Once folate stores return to normal, do you need to continue on folic acid supplements?
No once stores return to normal dietary sources are usually adequate in preventing further issues
Folic acid plays a very important part at what stage of development
It plays an important part in the formation of the unborn fetus because it prevents neural tube defects (NTDs)
How did the government plummet the rate of NTDs in the US
In the 1960s they added folic acid to cereal and grain products
Prototype Drug that is a Biological Response Modifier
erythropoietin (Epogen, Procrit)
erythropoietin (Epogen, Procrit) Classification
biological response modifier
recombinant human erythropoietin
Action of erythropoietin
mimics the effect of natrually made erythropoietin - helps production of RBCs
What type of patient may be receiving synthetic erythropoietin regularly
a chronic renal failure patient
What is an illegal use for erythropoietin that can now be detected
professional cyclers may take it to increase RBC and performance
What route is erythropoietin given?
IV - through hemodialysis or Subcutaneously
Parenteral
What is important to know about the absorption of erythropoietin
It is broken down in the GI tract so it has to be given parenterally
ADRs of Erythropoietin
- HTN
- Increased clotting of AV grafts
- Limb pain and sweating up to 12 hours after injection
Other: Cardiovascular Events (Black Box Warning), NVD, SOB, Rash, Cough, Fatigue, Paresthesia, HA, Encephalopathy, Seizure
Black Box Warning of Erythropoietin
Increased incidence of TIA, MI, and CVA (Thromboemboli production)
You are increasing a hypercoagulable state so there is slower moving blood and pooling occurring
Why does erythropoietin cause HTN
because it makes more volume and a more viscous blood volume due to increasing RBC production
What is the dosage of erythropoietin
50-100 U/kg individualized
Why is erythropoietin dosage individualized
to prevent black box issues like thromboemboli formation
What is the % goal for therapeutic erythropoietin use
Maintain a HCT of 30-36%
HCT and HGB rise within 2-6 weeks (Takes a little bit)
Indications for erythropoietin therapy
Chronic Renal Failure
HIV/AIDS (Esp. if tx with Zidovudine)
Adjunct to cancer chemotherapy
Elective non cardiac or non vascular surgery
Why is erythropoietin only given to elective non cardiac or non vascular surgeries
because vascular and cardiac surgeries try to get the blood moving but this makes it slower and more viscous with risk for clotting
erythropoietin is naturally made in the ____
kidneys
What finding should be monitored for and as a result erythropoietin dose should be lowered if it occurs?
Watch for rapid Hct increases (>4 points in 2 weeks) - the dose will need to be lowered as this leaves the patient predisposed to HTN and clotting
What does synthetic erythropoieting response depend on
the endogenous erythropoietin amount in the plasma
At what levels of endogenous erythropoietin will therapeutic use of synthetic erythropoietin be affected
> 500 U/L - syn. ery. will probably not respond
<500 U/L - syn ery will probably respond
Basically if you make a sufficient amount or some amount it works less than if you made none at all
What is needed concurrently with synthetic erythropoietin treatment
adequate iron supplementation!
You cannot make empty RBCs, you need the iron for it as well
What is another benefit some taking erythropoietin may achieve
increased appetite and wellbeing
originally the company oversold the bonus energy effects for chemotherapy treatment but it does help with anemia
Anticoagulants
Class of drugs
PREVENT blood clotting, NOT break down existing clots
4 Prototype Anticoagulant Drugs
Heparin
Enoxaparin (Lovenox)
Warfarin)
DOACs (Direct Oral Anticoagulants)
Heparin
Anticoagulant
“Standard Heparin” / Unfractionated
Action of Heparin
- Inhibits thrombin mediated conversion of fibrinogen to fibrin - SUPPRESSES FIBRIN
- Markedly potentiates actions of plasma antithrombin (Anti clotting factor) which neutralizes thrombin and Factor Xa
The Outcome of the action of Heparin
2 Prong Approach:
Not much fibrin is being made and thrombin is neutralized leading to the nromal clotting cascade from being inhibited and prevents the action fo factor Xa which inhibits clots
Fibrin
mesh like substance that holds blood clots together
Antithrombin (Thromboplastin)
A naturally occurring ANTI Clotting factor that neutralized thrombin and factor Xa
What route is heparin given and why?
parenteral (SubQ or IV)
It is NOT given orally because it is VERY POLAR and CANNOT CROSS MEMBRANES
What is the distribution of heparin like?
IV Onset = Immediate and lasts 4-6 hours
SubQ Onset - Delayed but lasts 8-10 hours
Half life depends on dose but avg is 1.5 hours
ADRs of Heparin
- HEMORRHAGE (Minor/Major Bleeding)
- Hypersensitivity Reaction (chills, fever, urticaria, anaphylactic shock, hives)
- Mild Thrombocytopenia
What are some of the minor bleeding ADRs of heparin
- GI TRACT BLEEDING
Gu Tract Bleeding
Petechiae
Ecchymosis
What are some fo the majro bleeding ADRs of heparin
- GI TRACT HEMORRHAGE
(CAN KILL)
Death occurring from bleeding in CNS (brain)
Thrombocytopenia
drop in platelet count
Why is mild thrombocytopenia as an ADR of heparin concerning
because it leaves that even MORE risk for bleeding
What are dose and effectiveness of Heparin based on
PTT (Partial thromboplastin time) OR APTT (Activated partial thromboplastin time)
The pt. values then are measured against a heparinized lab standard
How do therapeutic levels vary for heparin
Levels are usually 1.5-2x the control value
ex: If PTT was 30 then the range would be 45-60
Why is heparin NOT given IM
because of risk of local hematoma since muscles are too vascular
Black Box warning for Heparin
epidural or spinal hematomas with spinal anesthesia, etc!!
These hematomas are in the CNS and lead to bleeding around the spinal cord
What population is reported more sensitive to heparin
elderly women
What does Heparin NOT have an effect on regarding clotting
platelet aggregation- there is no effect on platelet function at all but it can lower the numbers
What is a potentially fatal condition from heparin use
HIT - Heparin induced thrombocytopenia
Protamine Sulfate
antidote for heparin (1mg/100units of heparin)
Binds heparin and stops it from working
Also acts as an anticoagulant itself
What is the antidote to heparin
protamine sulfate
Why can heparin be given during pregnancy
because it cannot cross membranes and hurt the fetus
Prototype Low molecular weight heparin/anti-coagulant drug
enoxaparin (Lovenox)
enoxaparin (Lovenox)
Anticoagulant/Low molecular weight heparin
It is a smaller molecule than standard heparin that is given SubQ and does not generally need lab monitoring
Made by depolymerizing standard heparin
Action of enoxaparin (Lovenox)
Preferentially inactivates factor Xa MORE than thrombin
Prevents clots from forming by preferentially inactivating Factor Xa ONLY
When is the peak of enoxaparin (Lovenox) experienced after a SubQ injection?
3-5 hours after - given once daily
What route is enoxaparin usually given
subQ
ADRs of Enoxaparin (Lovenox)
- Bleeding (Minor/Major - but since its not IV major is more rare)
- HIT (less so than standard heparin)
Other: Edema, Rash, Pain at injection site, ANGIOEDEMA
What is the dosage of enoxaparin like
It is given 1-2x daily infixed doses based on body weight and generally does NOT need lab monitoring
What is the big difference between long term enoxaparin and heparin therapy
you need to monitor APTT/PTT and lab values when taking heparin but you dont need to watch lab values with enoxaparin
What is interesting about the dose of enoxaparin once on it
It is never really changed once you learn what dosage is needed
What may be found in the name of a drug that is a portion/type of heparin
-parin
Avoid enoxaparin use in patients with …
increased risk of hemorrhage
When is enoxaparin given after surgery
usually the initial does is not given until 12-24 hours post op if hemostasis is stable and they are not bleeding
What is enoxaparin approved for following Hip and Knee Replacements
prophylaxis and treatment of DVT and PE
Protamine Sulfate
Heparin (and enoxaparin) antidote
What route is protamine sulfate usually given
IV for rapid effect - instantaneous
occasionally IM
When is protamine sulfate used
usually in emergency bleeding situations otherwise you can just stop IV and SubQ infusions
Where does protamine sulfate come from
Fish - so it is important to know if the person is allergic to fish
What is an interesting secondary effect of protamine sulfate other than beign an antidote
It is a mild anticoagulant itself if given alone but neutralizes other anticoagularn activities
Action of protamine sulfate
Combines with heparin/enoxaparin and each neutralize the anticoagulant activity of the other
Has antithromboplastin actvity not as active as in heparin which causes its anticoagulant effects
ADRs of Protamine Sulfate
Only in cases of Rapid Injection
Dyspnea
Flushing
Bradycardia
Hypotension (Perhaps from Histamine Release)
OVERDOSE - causes anticoagulation leading to hemorrhage
What is the dosage of protamine sulfate like
Varies and depends on amount of heparin given in the last 3-4 hours
Given slowly over IV and is 1mg/100units of heparin remaining in the body
What is an important consideration with protamine sulfate
Can cause hypersensitivity reactions in pts allergic to fish as it comes from the sperm and testes of certain fish
Prototype Oral Anticoagulant and Vitamin K Antagonist
Warfarin (Coumadin)
Action fo warfarin (Coumadin)
Blocks Vitamin K Dependent clotting factors by competitively interfering with Vitamin K
NO effect on platelet function
Stops vitamin K to prevent coagulation cascade
Route of warfarin (coumadin)
oral - very good absorbs from small intestine
Food will decrease its rate of absorption but not extent of absorption - just takes longer
What is important to know about the distribution of warfarin (Coumadin)
it is highly protein bound so only 1% is every working at one time since 99% is always protein bound
This means it takes a long time to get to therapeutic levle, but it also has a 2 day half life so it takes a while to get rid of as well
This means there can be trouble when dosing
ADRs of warfarin (Coumadin)
- Hemorrhage - Minor to Life threatening
- Diarrhea
- Leukopenia occasionally
* Similar to other anticoagulants
What is warfarin dose and effectiveness determined by
PT -prothrombin time - and the INR (international normalized ratio)
Patient values are measured against the control INR
Where do we want people’s INR to be
between 2-3
Higher means they are more likely to bleed and below indicated clotting
Therapeutic levels of warfarin are determined…
by going 1.5-2.0 times the control value
Antidote to warfarin
Vitamin K
Can warfarin be used in pregnancy
NO it can cross membranes
What are the benefits of new DOACs (Direct oral anticoagulants) like pradaxa, xarelto, and eliquis over something like warfarin
- Eating a lot of vitamin K (like in green elafy vegis) can negate warfarin but theres no diet restriction on these
- The DOACs act on Factor Xa similar to enoxaparin
- all given orally
- prevent blood clots and PE and all have their own antidote
- rapid onset and offset
- do not need blood monitoring
* one issue is that BID dosing leads to reduced compliance though*
Antidote to DOACs
Factor Xa (they are its competitive antagonist so more will over come them)
Prototype Drug that is a Vitamin, Hemostatic Agent, and Warfarin Antidote
Vitamin K (phytonadione - Aqua Mephyton)
Vitamin K action
essential for hepatic synthesis of prothrombin and factors VII, IX, and X
Never give Vitamin K what route
IV (unless emergency because of risk of anaphylaxis and shock)
ADRs of Vitamin K
relatively non toxic
What is important to keep in mind about giving a patient Vitamin K when they may need warfarin
It will render the patient resistant to warfarin for 10-14 days (2 weeks) and this can occur either from administering Vitamin K or a high vitamin K diet
What normally makes vitamin K
normally synthesized by enteric bacteria
need bile to aid absorption from the intestine though
Thrombolytics
Break down formed blood clots!!!!
Includes t-Pa (tissue plasminogen activator) and streptokinase (older drug)
“Clot Busters”
What has to be done prior to giving a thrombolytic
you MUST rule out intracranial bleeding via CT scan before use
When must a thrombolytic be given
ASAP after onset of symptoms
esp in evolving MI or CVA
Prototype Thrombolytic Agent
Tissue Plasminogen Activator (t-Pa) (Activase, Alteplase)
-ase means
enzyme
Action of t-Pa
Enzyme that selectively binds to the fibrin in a thrombus (already existing clot) and converts entrapped plasminogen into plasmin
Plasmin then initiates fibrinolysis (pac man) which chews up the fibers of the clot
Route of t-Pa
IV
Dosage of t-Pa
given in an IV bolus usually in decreasing amounts after the loading dose, 30 minutes, then 60 minuutes
ADRs of t-Pa
- Internal bleeding - GI, GU, retroperitoneal, intracranial
- Superficial bleeding - at distrubed sites like venipuncture, catheter insert sites, oozing blood when brushing teeth
- Dysrhythmias
Other: N/V, higher stroke incidence than if streptokinase was used
What about t-Pa causes dysrhythmias
it causes irritability for the heart if its breaking down a blood clot from an MI - but this effect tells us the heart muscle is still alive and working at least
There is electrical instability from the reperufsion in 80% of patients
Indications/Uses for t-Pa
Management of acute MI and CVA
When should t-Pa be initiated for use
as soon as possible after symptom onset (not at ER, but when symptoms started - WITHIN 6 HOURS) - use when suspecting MI or stroke
Contraindications for t-Pa
ACTIVE INTERNAL BLEEDING
CVA within the last 2 months
Intracranial or intraspinal surgery or trauma
Known bleeding problems
Severe uncontrolled HTN (high risk for hemorrhagic stroke)
CPR (couldve broken a rib)
Pregnancy
What is often given simultaneously with t-Pa
Heparin to prevent new clot formation - but this is expensive
Important administration notes for t-Pa
Mix with sterile water (not bacteriostatic) and dilute with D5W or NS and do not give with other meds
Can be used to clean a PICC line
very expensive
Prototype thrombolytic antidote and hemostatic agent/Antifibrinolytic
aminocaproic acid (Amicar)
Uses for aminocaproic acid (Amicar)
antidote to thrombolytics like t-PA but also in bleeding conditions can be used to stop bleeding very well in conditions where there is trouble stopping it - like acute leukemia bleeding
Action of aminocaproic acid
COMPETITIVE ANTAGONIST to Plasminogen which prevents plasmin generation (stops thrombolytic action)
Also directly inhibits plasmin to a lesser degree
Route of aminocaproic acid
oral - tablet or syrup ; can also be IV
What is important about the IV dosage of aminocaproic acid
it is 4-5 g given OVER 1 HOUR then 1 g over 8 hours or unti,l desired response obtained
ADRs of aminocaproic acid
MOST DONT OCCUR IF GIVE SLOW/CORRECTLY IV!!!
HA, Dizziness, NV, Abdominal Pain, Diarrhea, Tinnitus, Malaise, Stuffy Nose, thrombophlebitis, GRAND MAL SEIZURE
If given too rapidly parenterally - hypotension, bradycardia, arrhythmias
What is a newer anti-fibrinolytic / hemostatic used sometimes in the place of aminocaproic acid
Transexamic Acid (Lysteda)
What differentiates transexamic acid from aminocaproic acid
it is 8-10 times more potent
stills inhibits plasminogen and plasmin in conditions where clots are broken down quickly, but it works better and can be given oral for excessive menstrual bleeding, and uncontrolled post op bleeding
Both Transexamic Acid and Aminocaproic acid are for what conditions
uncontrolled hemorrhage
whether associated with trauma/post op bleeding, excessive menstrual bleeding or dental procedures for those with hemophilia
What are the ADRs of transexamic and aminocaproic acid like
htey are both generally well tolerated with MILD ADRs
What is one thing to watch for when giving transexamic or aminocaproic acid
watch for increased thrombosis!!! - increased clotting - if they bleed somewhere like the urinary tract for example it can clot and cause an obstruction
Prototype granulocyte colony stimulating factor
filgrastim (Neupogen/Neulasta (long acting form))
Action of filgrastim
acts in bone marrow to increase production of neutrophils
stimulates granulocyte colony growth by functioning the same as a granulocyte colony stimulating factor (G-CSF)
Route for filgrastim
IV or SubQ
Oral is destroyed in the digestive tract
ADRs of filgrastim
- BONE PAIN (Mild to Moderate - bone marrow is squeezing stuff out) - mostly occurs in the 1-2 days after chemo
Other: Increases in uric acid, lactate dehydrogenase, and alkaline phosphatase
When is filgrastim given
at least 24 hours after the end of chemotherapy
What is important to know about the vials and doses of filgrastim
only 1 dose per vial should be used
Neulasta
the long acting form of filgrastim
OnPro
a new formulation of filgrastim put on a patient that automatically injects medicine 24 hours late eliminating need to return to the chemo center for one injection
If a patient with severe iron deficiency anemia is prescribed iron, how long might it take to return to normal body stores?
a. Within 72 hours
b. Within 2-3 weeks
c. Over 6-10 months
d. Within 1-3 months
C. Over 6-10 months
See effect in 2-3 weeks but the rise and stores dont go back for a while when severe
A thrombolytic agent like t-PA could be safely used in the setting of
a. CVA within the last 2 months
b. Acute MI beginning within the last 3 hours
c. Recent, serious GI bleeding
d. Obstetrical delivery
B. Acute MI beginning within the last 3 hours
To monitor a patient’s response to filgrastim (Neupogen) you would assess which lab finding
A. H&H
B. WBC and/or ANC
C. Serum electrolytes
D. RBC Count
B. WBC and/or ANC
