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Year 1: Patho/Pharm > Haematology PHARM > Flashcards

Haematology PHARM Flashcards

(92 cards)

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1
Q

Most common form of anemia

A

iron deficiency anemia

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2
Q

Iron stores in the body

A

hemoglobin 70%
myoglobin
enzymes
liver - ferritin

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3
Q

How much iron is lost per day in the body

A

1mg of iron is lost by the GI

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4
Q

How much iron is absorbed by the body in a day

A

10% of iron is absorbed

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5
Q

How much iron is needed if you are
- child
- man
- female, menstruation
- pregnancy

A

child 10mg
male 10mg
female, menstruation 18mg
pregnancy 27mg

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6
Q

Different causes of anemia (etiology)

A
  • 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
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7
Q

What patient population is the highest risk for iron overload?

A
  • infants and children
  • sickle cell anemia
  • thalassemia
  • hemolytic anemia
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8
Q

Clinical signs and symptoms of anemia

A

pallor, fatigue
tachycardia, dyspnea
kiolonychia, stomatitis, cheilosis, dysphagia, glossitis
dysphagia
PICA
restless leg syndrome
splenomegaly
hepatomegaly
impaired cognition

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9
Q

Types of iron supplements

A

Iron sulfate 20%
iron fumarate 33%
iron gluconate 11%
iron asparate 16%

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10
Q

Iron supplements
Mechanism of action

A

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

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11
Q

Therapeutic monitoring of iron - when do you see improvements?

A

1 week reticulocytes, hemoglobin increase

1 month increase hemoglobin by 2g/L

Goal: hemoglobin 15

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12
Q

AE of iron

A

Nausea, gastritis, heart burn, constipation, stained teeth, black stool

children overdose iron 2g

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13
Q

Prescribing considerations

A

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

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14
Q

PO Iron contraindications

A

Ulcers
gastritis/enteritis
ulcerative colitis
crohn’s disease

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15
Q

MOA Vitamin B12 (cobalamin)

A

Activation folate
DNA purine synthesis
Required for growth/development/reproduciton bone marrow cells, cells of mucosa, etc.

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16
Q

Absorption of vitamin B12

A

H/K ATPase in GI , parietal cells
secretion of intrinsic factor
required for absorption vitamin B12 by small intestine
transported and stored in liver

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17
Q

Causes of low Vitamin B12

A

alcoholism
malabsorption - ceiliac disease
gastritis, H. pylori infection, lack of intrinsic factor (auto-immune)

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18
Q

Syndromes associated with pernicious anemia

A

auto-immune destruction parietal cells

anchlorhydria

gastritis

H. pylori infection

type I DM, thyroiditis and hypothyroidism

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19
Q

Signs and Symptoms of Low Vitamin B12

A

beefy red tongue
glossitis
sallow yellow colour
paraesthesias, hallucinations, memory and mood changes (demyelination)
GI nausea, diarrhea, bleeding
infections

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20
Q

Cells affected by low vitamin B12

A

demyelination (glial cells)
GI bleeds (mucosa)
pancytopenia (low RBC, WBC, platelets)

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21
Q

What masks low vitamin B12

A

folic acid supplementsLab

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22
Q

Lab values to test for anemia

A

Serum iron (< 60)
vitamin B 12 (< 200)
folic acid (< 2)

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23
Q

Cobalamin (Vitamin B12) prescription

A

Lifelong
PO 1000-2000mg daily
IM 1000mg / month

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24
Q

Therapeutic monitoring for vitamin B12

A

CBC and diff
- RBC
- WBC
- Platelets

serum Vitamin B12 every 3-6 months
Folic acid

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25
Activation pathways for folic acid
1. vitamin B12 2. alternative pathway (used with high dosages of folic acid - supplementation can mask vitamin B12 anemia)
26
Causes of low folic acid
malabsorption - celiac, gastritis alcoholism, drugs demand > supply (diet) pregnancy hemodialysis diet
27
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
28
MOA folic acid
DNA purine syntheiss all cells bone marrow, mucosa, neural tube
29
Dosage folic acid
500-1000mcg/day maintenance 400mcg per day
30
Prescriber considerations folic acid
masks vitamin B12 deficiency prophylaxis needed in pregnancy and breastfeeding
31
MOA Erythropoetin
EPO made by peritubular cells of proximal tubules in the kidney stimulate bone marrow to make RBC
32
SE erythropoetin
CVE - HTN, MI, stroke Oncology - tumour progression and death
33
Indication EPO
end stage renal disease oncology patient palliative - reduce number of transfusions
34
AE erythropoetin
RBC aplasia antibodies against EPO no longer produces RBC tumour progression
35
Prescribing considerations
keep hemoglobin < 11 rate of rise <1gm/dL
36
Drugs prescribed for neutropenia
filgastrim (G-CSF) Sargramostim (GM-CSF)
37
MOA filgastrim
granulocyte colony stimulating factor myeloid stem cell -> granulocyte --> neutrophils, eosinophils, basophils
38
SE filgastrim
flu like symptoms - HA, N/V, diarrhea Muscle and bone aches
39
filgastrim indications
neutropenia < 500
40
hydroxyurea indication
sickle cell anemia beta thalassemia
41
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
42
SE hydroxyurea
teratogenic infertility myelosupression, pancytopenia
43
Laboratory monitoring Hydroxyurea
CBC and diff 2-3 months *takes 1 year to be active
44
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
45
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
46
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.
47
Indications ASA
ACS: acute coronary syndrome (MI, stroke) 325mg PO Anti-platelet therapy: arterial thrombus, coronary stents, atrial fibrillation 81mg PO
48
P2Y12 ADP receptor antagonists
Clopidogrel Ticagrelor
49
MOA Clopidogrel
blocks ADP receptor prevents platelet activation IIb/IIIa and aggregation/fibrinogen cross linking
50
Contraindications clopidogrel
Liver disease requires CYP2C19 for activation pregnancy History of thrombocytopenia GI issues
51
SE Clopidogrel
GI: dyspepsia, N/V, bleeding TTP: bleeding, clotting, hemolytic anemia teratogenic
52
Drug interactions clopidogrel
Drugs that block the CYP2C19 enzyme block clopidogrel activation - AZOLE antifungals - SSRIs - H2 receptor antagonists - PPIs
53
Drug monitoring clopidogrel
Thrombotic thrombocytopenic purpura (TTP) - first 2 weeks of taking drug - hemolytic anemia - kidney damage
54
Antidote clopidogrel
platelet transfusion irreversible inhibition of the P2Y12 ADP receptor lifespan of the platelet
55
Indications Clopidogrel
ACS - MI, stroke Secondary prevention - stent
56
Ticagrelor MOA
blocks the P2Y12 ADP receptor prevention platelet IIb/IIIa activation, aggregation, plug formation
57
SE Ticagrelor
Bleeding SOB, irregular RR, bradycardia HA Gout - hyperuricemia teratogenic
58
List of Anti-coagulants
- heparin (Anti-thrombin activator) - LMWH - warfarin (block vitamin K CF) - rivaroxaban, apixaban (Xa inhibitors) - dabigatran (thrombin II inhibitor)
59
Indication anti-coagulants
Venous thromboembolisms PE DVT prevention complications MI, STEMI, NSTEMI, unstable angina
60
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
61
Pharmakokinetics heparin
activation within minutes half life 60-90 minutes D/C 4 hours before surgery or lumbar puncture
62
Antidote heparin
protamine sulfate 1U protamine sulfate for 100U heparin
63
SE heparin
Bleeding HIT heparin induced thrombocytopenia S&S: fever, chills, HTN, clots, bleeds, purpura, SOB, chest pain etc.
64
Therapeutic monitoring heparin
platelets 3x per week for 3 weeks monthly monitoring for HIT HIT PF4 antibody aPTT time 60-80 seconds (2x normal)
65
Contraindications heparin
previous history HIT hemorrhages - pelvic abdominal pain - hematuria - black stools etc.
66
Alternative to heparin
Dabigatran Argatroban *use if history of HIT and pregnancy
67
Low molecular weight heparins LMWH
enoxaparin daltiparin fondaparinux
68
MOA of LMWHs
LMWH pentasaccharide sequence binds and activates anti-thrombin affinity for factor Xa > IIa protamine sulfate works less well as antidote
69
Pharmacokinetics LMWH
metabolized by liver excreted by kidney - dangerous accumulation in elderly half life 6 hours stop 24 hours before surgery subcutaneous injection
70
Therapeutic monitoring LMWH
no monitoring dose = serum concentration
71
SE LMWH
bleeding *higher risk than heparin protamine sulfate less effective (works better on II) *highest risk fondaparinux (targets X)
72
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
73
Non-heparin anti-coagulants
Warfarin (not safe in preganncy) Direct IIa (thrombin) inhibitor - dabigatran (safe in preganncy)
74
Warfarin Indication
DVT, PE atrial fibrillation prosthetic heart valves
75
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
76
Warfarin SE
bleeding, hemorrhage must wear medic alert bracelet large number of drug interactions and food interactions teratogenic thrombocytopenia Vitamin K deficiency liver disease
77
Warfarin pharmacokinetics
half life 3 days takes many days to become peak therapeutic bridge with heparin
78
Drugs that increase warfarin levels
tylenol Azoles amiodarone cimetidine Trimethoprim-sulfamethazole NSAIDS DOACs glucocorticoids
79
Drugs that decrease warfarin levels
AEDs - carbamazepine, phenytoin, rifampin, phenobarb oral contraceptives vitamin K bile acid sequestrants
80
Antedote of warfarin
Vitamin K phytonadione
81
DOAC
Direct oral anti-coagulant dabigatran (thrombin inhibitor) rivaroxaban (Xa inhibitor)
82
Indications dabigatran
VTE, PE a fib heart valves *same as warfarin
83
Pharmacokinetics
same dose for everyone not weight based half life 15 hours stop 2 days before surgery Prodrug - requries liver to activate
84
85
SE dabigatran
liver disease - not activated bleeding GI: dyspepsia, N/V, bleed, bgastritis *prescribe with PPI *similar to clopidogrel teratogenic
86
Contraindications
liver disease low creatinine clearance P-glycoprotein inhibitors (amiodarone, CCB, azole antifungals) *alternatives LMWH heparin
87
Antidote dabigatran
Idaricuzumab monoclonal antibody against dabigatran
88
Direct Xa inhibitors
rivaroXABAN edoXABAN ApiXABAN
89
MOA direct Xa inhibitors
directly bind to Xa
90
MOA dabigatran
binds to thrombin (II) free and clot inactivates XIII (soluble fibrin clot)
91
antidote Direct Xa inhibitors
andexanet alfa
92
SE Direct Xa inhibitors
accumulates with P-glycoprotein inhibitors, liver, and kidney disease teratogenic

Year 1: Patho/Pharm (45 decks)

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