Hematology Pharmac😍

ANTI PLATELET DRUGS

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  • Tikka (Ticagrelor) in a Can (Cangrelor) → Reversible
  • PAR-1 (Protease Activator Receptor) INHIBITOR:
    • AtoPaxar
    • VoraPaxar
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  1. Aspirin
      • Inhibit COX → ↓TXA2
  1. Clopidogrel, Ticlodipine, Prasugrel
      • Reversibly inhibit ADP (P2Y12)
      • It is a pro drug
      • Irreversible P2Y₁₂ Inhibitors
        • Ticagrelor, Cangrelor
  1. Atopaxar/Vorapaxar
    1. notion image
      • Act on PAR-1 receptors of thrombin
      • Mnemonic: PAR → Paxar
  1. Abciximab
      • Tirofiban
      • Eptifibatide
      • Act on GP IIb/IIIa
      • Mnemonic: 2b3a → ab → Abc, fiban, fibatide ()

ANTI COAGULANTS

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These are divided into oral and parenteral anticoagulants.

Oral Anti-Coagulants

  1. Vitamin K inhibitors
  1. Direct thrombin inhibitors
  1. Factor Xa inhibitor

1. Vitamin K inhibitors

  • Includes dicumarol and warfarin

Warfarin:

Warfarin

  • ⛔Epoxide reductase
    • Vitamin K active form
    • gamma carboxylase γ carboxyglutamic acid 
    • Prevent activation of
      • 2, 7, 9, 10
        • Order of decline (fastest → slowest)
        • 7 > 9 > 10 > 2
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      • Protein C protein S
        • Responsible for Prothrombotic action initial days
    • Oral anticoagulant
    • Takes 4-5 days to produce action
    • Mainly used for maintenance purpose
    • Contraindicated in pregnancy →
    • Effect of Warfarin is monitored by PT/INR
      • Target INR for Post valve replacement: 2.5 - 3.5

Warfarin → Fetal Warfarin Syndrome

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  • Disala syndrome
    • Chondrodysplasia
    • Stippled epiphysis
    • Nasal hypoplasia
    • CNS: Corpus callosum agenesis, microcephaly
    • Cataract
  • Mnemonic: War (Warfarin) nu poya Michel (Microcephaly) and salar (Disala Syndrome) nu idi kitti mookilum (Nasal hypoplasia) bone (Stipled epiphysis) ilum cartilage (Chondrodysplasia) ilum and killed his cat (Cataract)

Initial Hypercoagulable State

  • Seen during first 1–2 days of warfarin therapy
  • Causes increased risk of clotting
  • Due to protein C deficiency (genetic or functional)
  • Leads to:
    • Dermal vascular necrosis
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    • Purple toe syndrome

Warfarin Overdose:

  • Overdose of Warfarin causes bleeding.
  • For bleeding tendency/warfarin overdose
    • Vitamin K is antidote and treatment of choice
  • For bleeding
    • TOC → Four Factor complex /Prothrombin Factor complex
      • Active Factors like IIa, VIIa, IXa, X
    • If not available → FFP
    • If not available → whole blood

2. Oral Direct Thrombin Inhibitors

Dabigatran

  • Can be given Orally
  • Does not require monitoring
  • Antidote: Idarucizumab
  • Mnemonic: Da → Direct acting; Tran → Thrombin antagonist

3. Direct factor Xa inhibitors

  • DOAC/NOAC
  • Drugs are:
    • Rivaroxaban
      • RIVAR – REVERSIBLE
      • O – ORAL
      • XA – XA
      • B – BLOCKER (OR)
      • AN – ANTAGONIST
    • Apixaban
    • Edoxaban
    • Betrixaban

Injectable Anti-Coagulants

  • 1. Indirect Thrombin Inhibitors
  • 2. Direct Thrombin Inhibitors

1. Indirect Thrombin Inhibitors [Heparin]

  • All activate antithrombin
  • UFH
    • Inhibit factor IIa = Xa (equal inhibition)
      • Mnemonic: Big size → inhibit 2a
    • Degraded via Reticuloendothelial system
      • Safe in Renal Failure
  • LMWH
    • Inhibit factor Xa > IIa
    • Mnemonic: Lesser size → Less inhibition of 2a
    • Preferred for cancer-related thromboembolism
  • Fondaparinux
    • Only inhibits factor Xa
    • Mnemonic: Lowest size → no inhibiton of 2a
  • Heparins
    • Route → S.C. or IV
    • Activate anti-thrombin 3
    • Immediate Action → Useful in acute conditions
    • Anti-coagulant of choice in pregnancy
    • Monitoring done by APTT
    • Heparin is always Apt
    • Antidote Protamine Sulphate

Ciraparantag

  • Universal reversal agent for anticoagulants
  • Antidote for heparin, LMWH, DOACs
    • NOT FOR Fondaparinux
  • No known drug-drug interactions.
  • Safer profile: No anaphylaxis, pulmonary hypertension, or hypotension risks.
  • Cira paran → cheera () for parama (universal) problems

WARFARIN vs HEPARIN Table:

Feature
Warfarin
Heparin
Route
Oral
S/C or IV
MOA
Inhibit vitamin K
Activate AT – III
Onset
4-5 days
Immediate
Use
Maintenance
Acute condition
Pregnancy
C/I
DOC
Monitoring
PT/INR
aPTT
Antidote
Vitamin K
Protamine Sulphate

2. Injectible Direct Thrombin Inhibitors (DTI)

  • Mnemonic: Din, Tran, Troban
  • injectable DTI.
    • Bivalirudin
    • argatroban
    • melagatran
      • Troban and Tran → DOC for HIT
  • Hirudin and lepirudin are not used now.

ANTIDOTES OF ANTI-COAGULANTS

Antidote vs Anticoagulant Table
Anticoagulant
Antidote
Monitoring
Warfarin
Vitamin K
PT/INR
Heparin
Protamine sulfate
aPTT

Not required for
DOACs,
LMWH,
Fondaparinux

Dabigatran
Idarucizumab

Mnemonic: Dabbakkullil (Dabi) Idara (idaru)
Rivaraoxaban or
Apixaban
Andexanetalfa

Mnemonic:
Riverer → and
PT
Edoxaban
Adexanetalfa

Mnemonic:
Ed → Ad
Fibrinolytics/Thrombolytics
EACA > Tranexamic Acid

FIBRINOLYTIC DRUGS

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  • Drugs:
    • S – Streptokinase
    • U – Urokinase
    • R – Reteplase
    • A – Alteplase
    • T – Tenecteplase
  • Antidotes:
    • Epsilon AminoCaproic Acid [EACA]
    • Tranexamic Acid.
  • Tissue plasminogen activators.
  • tPA converts plasminogen to plasmin → breaks the thrombus.
  • For acute STEMI, acute stroke and acute DVT.
  • Overdose of thrombolytics → Leads to bleeding

DRUGS AFFECTING BLOOD CELLS

  1. Hematinics
  1. Growth factors

1. HEMATINICS

These are nutritional substances which help in formation of blood. e.g.
  • 1. Iron (Fe)
  • 2. Folic acid (FA)
  • 3. Vitamin B12

Iron Deficiency Anemia

  • Treatment of choice is Oral iron.

Oral Iron Therapy (First Line)

  • Ferrous sulphate (200 mg):
    • Contains 60 mg elemental iron ~10% absorption.
      • Absorption increases to ~20% in deficiency.
    • Only 6 mg absorbed from a normal dose.
  • Ferrous Fumarate
  • ferrous gluconate
  • Side effect: black stool
  • Tabs or drops
    • Dropsdeep in mouth
      • As they cause skin pigmentation.
  • Earliest response - Reticulocytosis.
  • Adequate response → Hb ↑ by 0.5 g/dl/week
  • Factors affecting:
    • Ascorbic acid : Increase Absorption
    • Phytates, Tannate and oxalates : Decrease Absorption
  • Iron deficiency anemia:
    • Always continue iron for 3 months after Hb normalizes
      • To replenish iron stores

Parenteral Iron therapy

  • Ferrous Sucrose (200 mg)
  • Ferric Carboxy Maltose
    • 1 gm single dose IV
  • Iron Isomaltose
    • 1 gm single dose IV

Other Preparations of injectable iron are:

  • Iron Dextran – Can be given IV as well as IM
    • Mnemonic: Dextran → dual route
  • Iron Sorbital citrate (Used IM only)
    • Mnemonic: Sorbitol → Sirf IM
  • IM iron is given by Z-tract technique to avoid pigmentation.

2. HEMATOPOIETIC GROWTH FACTORS

Cells vs Growth Factor vs Drug vs Indications Table
Cells
Growth Factor
Drug
Indications
RBC
Erythropoietin
Darbopoietin
Anemia due to chronic renal failure

Anemia due to bone marrow suppression
WBC
G-CSF
(Granulocyte - stim)

GM-CSF
(Gra - Mo - Stim)
Filgrastim


Sargramostim
Leukopenia due to bone marrow suppression
Platelets
IL-11

Mnemonic:
11 Plate for OPERA
Oprelvekin

(
Kin → Interleukin)
(oprELEVEkiN → Eleven)

Fostamatinib
Eltrombopag
Romiplostim
Thrombocytopenia due to bone marrow suppression
  • Thrombopoietin receptor agonists - TPO agonists
    • Eltrombopag (Oral).
    • Romiplostim (Subcutaneous injections).