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Year 1: Patho/Pharm > Haematology PHARM > Flashcards

Haematology PHARM Flashcards

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
Q

Activation pathways for folic acid

A
  1. vitamin B12
  2. alternative pathway (used with high dosages of folic acid - supplementation can mask vitamin B12 anemia)
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26
Q

Causes of low folic acid

A

malabsorption - celiac, gastritis
alcoholism, drugs
demand > supply (diet)
pregnancy
hemodialysis
diet

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27
Q

Signs and symptoms of low folic acid

A

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

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28
Q

MOA folic acid

A

DNA purine syntheiss all cells
bone marrow, mucosa, neural tube

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29
Q

Dosage folic acid

A

500-1000mcg/day
maintenance 400mcg per day

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30
Q

Prescriber considerations folic acid

A

masks vitamin B12 deficiency

prophylaxis needed in pregnancy and breastfeeding

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31
Q

MOA Erythropoetin

A

EPO
made by peritubular cells of proximal tubules in the kidney
stimulate bone marrow to make RBC

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32
Q

SE erythropoetin

A

CVE - HTN, MI, stroke
Oncology - tumour progression and death

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33
Q

Indication EPO

A

end stage renal disease
oncology patient palliative
- reduce number of transfusions

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34
Q

AE erythropoetin

A

RBC aplasia
antibodies against EPO
no longer produces RBC

tumour progression

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35
Q

Prescribing considerations

A

keep hemoglobin < 11
rate of rise <1gm/dL

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36
Q

Drugs prescribed for neutropenia

A

filgastrim (G-CSF)

Sargramostim (GM-CSF)

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37
Q

MOA filgastrim

A

granulocyte colony stimulating factor

myeloid stem cell -> granulocyte –> neutrophils, eosinophils, basophils

38
Q

SE filgastrim

A

flu like symptoms - HA, N/V, diarrhea
Muscle and bone aches

39
Q

filgastrim indications

A

neutropenia
< 500

40
Q

hydroxyurea indication

A

sickle cell anemia
beta thalassemia

41
Q

Hydroxyurea
MOA

A

ribonucleotide reductase inhibitor - stops the nucleotide pool and hematopoesis

results in increase in hemoglobin F (fetal)

prevents polymerizatino of hemoglobin S - decrease sickle

42
Q

SE hydroxyurea

A

teratogenic
infertility
myelosupression, pancytopenia

43
Q

Laboratory monitoring
Hydroxyurea

A

CBC and diff
2-3 months
*takes 1 year to be active

44
Q

Aspirin
MOA

A

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
Q

SE Aspirin

A

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
Q

Contraindications ASA

A

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
Q

Indications ASA

A

ACS: acute coronary syndrome (MI, stroke)
325mg PO

Anti-platelet therapy: arterial thrombus, coronary stents, atrial fibrillation
81mg PO

48
Q

P2Y12 ADP receptor antagonists

A

Clopidogrel
Ticagrelor

49
Q

MOA Clopidogrel

A

blocks ADP receptor
prevents platelet activation IIb/IIIa and aggregation/fibrinogen cross linking

50
Q

Contraindications clopidogrel

A

Liver disease
requires CYP2C19 for activation

pregnancy

History of thrombocytopenia

GI issues

51
Q

SE Clopidogrel

A

GI: dyspepsia, N/V, bleeding

TTP: bleeding, clotting, hemolytic anemia

teratogenic

52
Q

Drug interactions clopidogrel

A

Drugs that block the CYP2C19 enzyme block clopidogrel activation

  • AZOLE antifungals
  • SSRIs
  • H2 receptor antagonists
  • PPIs
53
Q

Drug monitoring clopidogrel

A

Thrombotic thrombocytopenic purpura (TTP)
- first 2 weeks of taking drug
- hemolytic anemia
- kidney damage

54
Q

Antidote clopidogrel

A

platelet transfusion
irreversible inhibition of the P2Y12 ADP receptor
lifespan of the platelet

55
Q

Indications Clopidogrel

A

ACS
- MI, stroke

Secondary prevention
- stent

56
Q

Ticagrelor MOA

A

blocks the P2Y12 ADP receptor
prevention platelet IIb/IIIa activation, aggregation, plug formation

57
Q

SE Ticagrelor

A

Bleeding

SOB, irregular RR, bradycardia

HA

Gout - hyperuricemia

teratogenic

58
Q

List of Anti-coagulants

A
  • heparin (Anti-thrombin activator)
  • LMWH
  • warfarin (block vitamin K CF)
  • rivaroxaban, apixaban (Xa inhibitors)
  • dabigatran (thrombin II inhibitor)
59
Q

Indication anti-coagulants

A

Venous thromboembolisms
PE
DVT
prevention complications MI, STEMI, NSTEMI, unstable angina

60
Q

Heparin
MOA

A

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
Q

Pharmakokinetics heparin

A

activation within minutes
half life 60-90 minutes
D/C 4 hours before surgery or lumbar puncture

62
Q

Antidote heparin

A

protamine sulfate
1U protamine sulfate for 100U heparin

63
Q

SE heparin

A

Bleeding

HIT
heparin induced
thrombocytopenia

S&S: fever, chills, HTN, clots, bleeds, purpura, SOB, chest pain etc.

64
Q

Therapeutic monitoring heparin

A

platelets
3x per week for 3 weeks
monthly
monitoring for HIT

HIT PF4 antibody

aPTT time
60-80 seconds (2x normal)

65
Q

Contraindications heparin

A

previous history HIT

hemorrhages
- pelvic abdominal pain
- hematuria
- black stools etc.

66
Q

Alternative to heparin

A

Dabigatran
Argatroban
*use if history of HIT and pregnancy

67
Q

Low molecular weight heparins LMWH

A

enoxaparin
daltiparin
fondaparinux

68
Q

MOA of LMWHs

A

LMWH pentasaccharide sequence binds and activates anti-thrombin

affinity for factor Xa > IIa

protamine sulfate works less well as antidote

69
Q

Pharmacokinetics LMWH

A

metabolized by liver
excreted by kidney
- dangerous accumulation in elderly

half life 6 hours
stop 24 hours before surgery
subcutaneous injection

70
Q

Therapeutic monitoring LMWH

A

no monitoring
dose = serum concentration

71
Q

SE LMWH

A

bleeding
*higher risk than heparin
protamine sulfate less effective (works better on II)
*highest risk fondaparinux (targets X)

72
Q

Contraindications LMWH

A

HIT

lumbar puncture, surgery

NSAIDS or anti-platelet therapy

Older population ( do not clear heparin, LMWH well)
Osteoporosis

Kidney disease CrCL < 30mL/min

73
Q

Non-heparin anti-coagulants

A

Warfarin (not safe in preganncy)

Direct IIa (thrombin) inhibitor
- dabigatran (safe in preganncy)

74
Q

Warfarin
Indication

A

DVT, PE
atrial fibrillation
prosthetic heart valves

75
Q

Warfarin MOA

A

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
Q

Warfarin SE

A

bleeding, hemorrhage
must wear medic alert bracelet

large number of drug interactions and food interactions

teratogenic

thrombocytopenia

Vitamin K deficiency

liver disease

77
Q

Warfarin pharmacokinetics

A

half life 3 days
takes many days to become peak therapeutic
bridge with heparin

78
Q

Drugs that increase warfarin levels

A

tylenol
Azoles
amiodarone
cimetidine
Trimethoprim-sulfamethazole
NSAIDS
DOACs
glucocorticoids

79
Q

Drugs that decrease warfarin levels

A

AEDs - carbamazepine, phenytoin, rifampin, phenobarb
oral contraceptives
vitamin K
bile acid sequestrants

80
Q

Antedote of warfarin

A

Vitamin K
phytonadione

81
Q

DOAC

A

Direct oral anti-coagulant

dabigatran (thrombin inhibitor)
rivaroxaban (Xa inhibitor)

82
Q

Indications dabigatran

A

VTE, PE
a fib
heart valves
*same as warfarin

83
Q

Pharmacokinetics

A

same dose for everyone
not weight based
half life 15 hours
stop 2 days before surgery
Prodrug - requries liver to activate

84
Q
A
85
Q

SE dabigatran

A

liver disease - not activated

bleeding

GI: dyspepsia, N/V, bleed, bgastritis
*prescribe with PPI
*similar to clopidogrel

teratogenic

86
Q

Contraindications

A

liver disease
low creatinine clearance
P-glycoprotein inhibitors (amiodarone, CCB, azole antifungals)

*alternatives
LMWH
heparin

87
Q

Antidote dabigatran

A

Idaricuzumab
monoclonal antibody against dabigatran

88
Q

Direct Xa inhibitors

A

rivaroXABAN
edoXABAN
ApiXABAN

89
Q

MOA direct Xa inhibitors

A

directly bind to Xa

90
Q

MOA dabigatran

A

binds to thrombin (II) free and clot
inactivates XIII (soluble fibrin clot)

91
Q

antidote
Direct Xa inhibitors

A

andexanet alfa

92
Q

SE
Direct Xa inhibitors

A

accumulates with P-glycoprotein inhibitors, liver, and kidney disease

teratogenic

Year 1: Patho/Pharm (39 decks)

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