Haematology PHARM Flashcards
Most common form of anemia
iron deficiency anemia
Iron stores in the body
hemoglobin 70%
myoglobin
enzymes
liver - ferritin
How much iron is lost per day in the body
1mg of iron is lost by the GI
How much iron is absorbed by the body in a day
10% of iron is absorbed
How much iron is needed if you are
- child
- man
- female, menstruation
- pregnancy
child 10mg
male 10mg
female, menstruation 18mg
pregnancy 27mg
Different causes of anemia (etiology)
- iron deficiency
- vitamin B12 deficiency
- folic acid deficiency
- malabsorption (celiac, crohn’s, UC, alcoholism, drugs)
- diet
- pregnancy
- sickle cell anemia
- Thalassemia
- Sideroblastic anemia (lead poisoning)
- hemorrhagic anemia
- aplastic anemia
What patient population is the highest risk for iron overload?
- infants and children
- sickle cell anemia
- thalassemia
- hemolytic anemia
Clinical signs and symptoms of anemia
pallor, fatigue
tachycardia, dyspnea
kiolonychia, stomatitis, cheilosis, dysphagia, glossitis
dysphagia
PICA
restless leg syndrome
splenomegaly
hepatomegaly
impaired cognition
Types of iron supplements
Iron sulfate 20%
iron fumarate 33%
iron gluconate 11%
iron asparate 16%
Iron supplements
Mechanism of action
Absorption by GI
ferroportin transports iron to plasma
transferrin binds iron transports in plasma to bone marrow
taken up by macrophages and mitochondria and integrated into heme for erythropoesis
also taken up by muscles and made into myoglobin
stored in liver as ferritin
Therapeutic monitoring of iron - when do you see improvements?
1 week reticulocytes, hemoglobin increase
1 month increase hemoglobin by 2g/L
Goal: hemoglobin 15
AE of iron
Nausea, gastritis, heart burn, constipation, stained teeth, black stool
children overdose iron 2g
Prescribing considerations
Iron type determines absorption
sulfate 20%, fumarate 33%, gluconate 11%, asparate 16% ; and dosage
take with 500mg vitamin C to increase absorption
avoid taking with calcium, ant-acids, coffee which decrease absorption
Do not combine with IV iron
PO Iron contraindications
Ulcers
gastritis/enteritis
ulcerative colitis
crohn’s disease
MOA Vitamin B12 (cobalamin)
Activation folate
DNA purine synthesis
Required for growth/development/reproduciton bone marrow cells, cells of mucosa, etc.
Absorption of vitamin B12
H/K ATPase in GI , parietal cells
secretion of intrinsic factor
required for absorption vitamin B12 by small intestine
transported and stored in liver
Causes of low Vitamin B12
alcoholism
malabsorption - ceiliac disease
gastritis, H. pylori infection, lack of intrinsic factor (auto-immune)
Syndromes associated with pernicious anemia
auto-immune destruction parietal cells
anchlorhydria
gastritis
H. pylori infection
type I DM, thyroiditis and hypothyroidism
Signs and Symptoms of Low Vitamin B12
beefy red tongue
glossitis
sallow yellow colour
paraesthesias, hallucinations, memory and mood changes (demyelination)
GI nausea, diarrhea, bleeding
infections
Cells affected by low vitamin B12
demyelination (glial cells)
GI bleeds (mucosa)
pancytopenia (low RBC, WBC, platelets)
What masks low vitamin B12
folic acid supplementsLab
Lab values to test for anemia
Serum iron (< 60)
vitamin B 12 (< 200)
folic acid (< 2)
Cobalamin (Vitamin B12) prescription
Lifelong
PO 1000-2000mg daily
IM 1000mg / month
Therapeutic monitoring for vitamin B12
CBC and diff
- RBC
- WBC
- Platelets
serum Vitamin B12 every 3-6 months
Folic acid
Activation pathways for folic acid
- vitamin B12
- alternative pathway (used with high dosages of folic acid - supplementation can mask vitamin B12 anemia)
Causes of low folic acid
malabsorption - celiac, gastritis
alcoholism, drugs
demand > supply (diet)
pregnancy
hemodialysis
diet
Signs and symptoms of low folic acid
low DNA synthesis in all cells
pancytopenia
- low RBC, WBC, platelets
- infections
- anemia
- bleeding
mucosa irritation
- stomatitis, burning mouth, bleeding
neural tube defects
- spina bifida
colorectal cancer
atheroscelerosis
MOA folic acid
DNA purine syntheiss all cells
bone marrow, mucosa, neural tube
Dosage folic acid
500-1000mcg/day
maintenance 400mcg per day
Prescriber considerations folic acid
masks vitamin B12 deficiency
prophylaxis needed in pregnancy and breastfeeding
MOA Erythropoetin
EPO
made by peritubular cells of proximal tubules in the kidney
stimulate bone marrow to make RBC
SE erythropoetin
CVE - HTN, MI, stroke
Oncology - tumour progression and death
Indication EPO
end stage renal disease
oncology patient palliative
- reduce number of transfusions
AE erythropoetin
RBC aplasia
antibodies against EPO
no longer produces RBC
tumour progression
Prescribing considerations
keep hemoglobin < 11
rate of rise <1gm/dL
Drugs prescribed for neutropenia
filgastrim (G-CSF)
Sargramostim (GM-CSF)
MOA filgastrim
granulocyte colony stimulating factor
myeloid stem cell -> granulocyte –> neutrophils, eosinophils, basophils
SE filgastrim
flu like symptoms - HA, N/V, diarrhea
Muscle and bone aches
filgastrim indications
neutropenia
< 500
hydroxyurea indication
sickle cell anemia
beta thalassemia
Hydroxyurea
MOA
ribonucleotide reductase inhibitor - stops the nucleotide pool and hematopoesis
results in increase in hemoglobin F (fetal)
prevents polymerizatino of hemoglobin S - decrease sickle
SE hydroxyurea
teratogenic
infertility
myelosupression, pancytopenia
Laboratory monitoring
Hydroxyurea
CBC and diff
2-3 months
*takes 1 year to be active
Aspirin
MOA
Aspirin
Acetylsalicylic acid
Blocks COX 1 (dosage < 325mg) and/or COX 2 (dosage > 325mg)
Prevents conversion arachadonic acid to thromboxane A2, preventing activation of the GPIIb/IIIa receptor preventing platelet activation, adhesion and aggregation
Irreversible inhibition for the life of the platelet 7-11 days
SE Aspirin
GI: increase ulcers and bleeds (decrease mucous blood flow, mucous, increase acid secretion, decrease bicarb
Cardio: HTN, stroke, clots (inhibition PGI2 (vasodilator, platelet inhibitor))
Kidney: decrease blood flow leading to AKI
Reye’s syndrome: children with viral infection results in brain swelling and lipid deposit in liver/liver failure and death
Acidosis: older adults, first sign is tinnitis
Premature closure of ductus artereosus and still birth in pregnancy
Contraindications ASA
pregnancy (ductus artereosus, still births)
Older adults (Salicylism)
BP > 150 (MI, stroke)
Smoking, alcoholics (Hemorrhages)
Children (Reye’s syndrome)
Cancer (bleeding)
Anti-coagulant therapy
RAAS inhibitors (kidney damage) ; AKI ; CKD
GI gastritis, ulcers, etc.
Indications ASA
ACS: acute coronary syndrome (MI, stroke)
325mg PO
Anti-platelet therapy: arterial thrombus, coronary stents, atrial fibrillation
81mg PO
P2Y12 ADP receptor antagonists
Clopidogrel
Ticagrelor
MOA Clopidogrel
blocks ADP receptor
prevents platelet activation IIb/IIIa and aggregation/fibrinogen cross linking
Contraindications clopidogrel
Liver disease
requires CYP2C19 for activation
pregnancy
History of thrombocytopenia
GI issues
SE Clopidogrel
GI: dyspepsia, N/V, bleeding
TTP: bleeding, clotting, hemolytic anemia
teratogenic
Drug interactions clopidogrel
Drugs that block the CYP2C19 enzyme block clopidogrel activation
- AZOLE antifungals
- SSRIs
- H2 receptor antagonists
- PPIs
Drug monitoring clopidogrel
Thrombotic thrombocytopenic purpura (TTP)
- first 2 weeks of taking drug
- hemolytic anemia
- kidney damage
Antidote clopidogrel
platelet transfusion
irreversible inhibition of the P2Y12 ADP receptor
lifespan of the platelet
Indications Clopidogrel
ACS
- MI, stroke
Secondary prevention
- stent
Ticagrelor MOA
blocks the P2Y12 ADP receptor
prevention platelet IIb/IIIa activation, aggregation, plug formation
SE Ticagrelor
Bleeding
SOB, irregular RR, bradycardia
HA
Gout - hyperuricemia
teratogenic
List of Anti-coagulants
- heparin (Anti-thrombin activator)
- LMWH
- warfarin (block vitamin K CF)
- rivaroxaban, apixaban (Xa inhibitors)
- dabigatran (thrombin II inhibitor)
Indication anti-coagulants
Venous thromboembolisms
PE
DVT
prevention complications MI, STEMI, NSTEMI, unstable angina
Heparin
MOA
Heparin binds to anti-thrombin
conformational change more actively binds to
- intrinsic pathway: XII, XI, IX, X
- common pathway: II
Most strongly binds X and II
prevents conversion fibrinogen to fibrin / reinforcement platelet clot
Pharmakokinetics heparin
activation within minutes
half life 60-90 minutes
D/C 4 hours before surgery or lumbar puncture
Antidote heparin
protamine sulfate
1U protamine sulfate for 100U heparin
SE heparin
Bleeding
HIT
heparin induced
thrombocytopenia
S&S: fever, chills, HTN, clots, bleeds, purpura, SOB, chest pain etc.
Therapeutic monitoring heparin
platelets
3x per week for 3 weeks
monthly
monitoring for HIT
HIT PF4 antibody
aPTT time
60-80 seconds (2x normal)
Contraindications heparin
previous history HIT
hemorrhages
- pelvic abdominal pain
- hematuria
- black stools etc.
Alternative to heparin
Dabigatran
Argatroban
*use if history of HIT and pregnancy
Low molecular weight heparins LMWH
enoxaparin
daltiparin
fondaparinux
MOA of LMWHs
LMWH pentasaccharide sequence binds and activates anti-thrombin
affinity for factor Xa > IIa
protamine sulfate works less well as antidote
Pharmacokinetics LMWH
metabolized by liver
excreted by kidney
- dangerous accumulation in elderly
half life 6 hours
stop 24 hours before surgery
subcutaneous injection
Therapeutic monitoring LMWH
no monitoring
dose = serum concentration
SE LMWH
bleeding
*higher risk than heparin
protamine sulfate less effective (works better on II)
*highest risk fondaparinux (targets X)
Contraindications LMWH
HIT
lumbar puncture, surgery
NSAIDS or anti-platelet therapy
Older population ( do not clear heparin, LMWH well)
Osteoporosis
Kidney disease CrCL < 30mL/min
Non-heparin anti-coagulants
Warfarin (not safe in preganncy)
Direct IIa (thrombin) inhibitor
- dabigatran (safe in preganncy)
Warfarin
Indication
DVT, PE
atrial fibrillation
prosthetic heart valves
Warfarin MOA
inhibits VKORC1
vitamin K epoxide reductase complex 1
prevents formation of vitamin K = preventions formation vitamin K dependent clotting factors
VII, IX, X, II
extrinsic pathway
Warfarin SE
bleeding, hemorrhage
must wear medic alert bracelet
large number of drug interactions and food interactions
teratogenic
thrombocytopenia
Vitamin K deficiency
liver disease
Warfarin pharmacokinetics
half life 3 days
takes many days to become peak therapeutic
bridge with heparin
Drugs that increase warfarin levels
tylenol
Azoles
amiodarone
cimetidine
Trimethoprim-sulfamethazole
NSAIDS
DOACs
glucocorticoids
Drugs that decrease warfarin levels
AEDs - carbamazepine, phenytoin, rifampin, phenobarb
oral contraceptives
vitamin K
bile acid sequestrants
Antedote of warfarin
Vitamin K
phytonadione
DOAC
Direct oral anti-coagulant
dabigatran (thrombin inhibitor)
rivaroxaban (Xa inhibitor)
Indications dabigatran
VTE, PE
a fib
heart valves
*same as warfarin
Pharmacokinetics
same dose for everyone
not weight based
half life 15 hours
stop 2 days before surgery
Prodrug - requries liver to activate
SE dabigatran
liver disease - not activated
bleeding
GI: dyspepsia, N/V, bleed, bgastritis
*prescribe with PPI
*similar to clopidogrel
teratogenic
Contraindications
liver disease
low creatinine clearance
P-glycoprotein inhibitors (amiodarone, CCB, azole antifungals)
*alternatives
LMWH
heparin
Antidote dabigatran
Idaricuzumab
monoclonal antibody against dabigatran
Direct Xa inhibitors
rivaroXABAN
edoXABAN
ApiXABAN
MOA direct Xa inhibitors
directly bind to Xa
MOA dabigatran
binds to thrombin (II) free and clot
inactivates XIII (soluble fibrin clot)
antidote
Direct Xa inhibitors
andexanet alfa
SE
Direct Xa inhibitors
accumulates with P-glycoprotein inhibitors, liver, and kidney disease
teratogenic
