Drugs for Anemia & Hemostasis – INI-CET Essentials

Antiplatelets

Uses

• To treat MI (Acute coronary syndrome)
• Ischemic stroke or transient ischemic attack
• Peripheral vascular disease- Intermittent claudication – Seen in Buerger's disease
• DOC in all above-mentioned diseases: Aspirin
• Dual antiplatelet therapy (DAPT). Aspirin + other add-on drug: Dual antiplatelet therapy

Antiplatelets Drugs

Aspirin

Other name: 

Irreversible COX inhibitor (suicide inhibitor/hit-andrun drug)

Binds with covalent bonds.

Mechanism of action

• Inhibits COX-1 enzyme in platelets
• Reduces production of TxA2
• Inhibits platelet attachment

Uses

Drug of choice (DOC) for the following conditions:

• MI (Myocardial infarction)
• Stroke
• Buerger's disease

Side effects

• Should be stopped 7 days before surgery
• It gives time for new platelet formation
• This helps prevent excess blood loss during surgery

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Vorapaxar

• PAR inhibitor (Protease activating receptor)
• The PAR receptor on platelets is a receptor of thrombin. No attachment of thrombin on blocking these receptors leads to no platelet aggregation
• Recently approved as an add-on drug to aspirin in MI

Dazoxiben

Thromboxane A2 synthase inhibitor 

• Under trial for MI
• Prostaglandin G2 is present inside the  platelets and is produced from arachidonic acid by the COX-1 enzyme.
• PG-G2 converts to TxA2 by thromboxane A2 synthase.
• Aspirin blocks COX-1

Pro-Platelet Drugs

Romiplostim

• Recombinant form of thrombopoietin
• Given as a subcutaneous injection
• Treatment of idiopathic thrombocytopenic purpura (ITP)

Eltrombopag

• Thrombopoietin receptor agonist
• Present on megakaryocyte
• Oral drug
• Treatment of ITP and chronic liver disease
• Similar drugs – Avatrombopag, Lusutrombopag

Oprelvekin

• Recombinant from of IL-11
• Given as a subcutaneous injection
• DOC in chemotherapy-induced thrombocytopenia

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Anticoagulants

Anticoagulant drugs

Vitamin K Antagonists

• Also known as Coumarins (A poison that inhibits the action of Vit K)
• Drugs
  • Warfarin
  • Acenocoumarin
  • Bishydroxycoumarin
  • Dicumarol

Direct factor Xa inhibitors

• Ends with Xaban
• Drugs
  • Apixaban
  • Rivaroxaban (Longest acting)
  • Edoxaban
  • Betrixaban

Direct thrombin inhibitors

• Ends with Gatran
• Drugs
  • Dabigatran
  • Ximelagatran (banned due to hepatoxicity)

Warfarin

Mechanism of Action

Anticoagulants in Pregnancy

DOC- Heparin (LMWH or ULMWH)

Do not cross placenta

Antidotes of Anticoagulants

• Warfarin (coumarins)—Vitamin K1
• Apixaban, Rivaroxaban- Andexate a
• Dabigatran- Idarucizumab
• HMW heparin- Protamine sulfate

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Parenteral Anticoagulants

Direct thrombin Inhibitors: ROA- IV

Indirect thrombin Inhibitors: Heparin

Direct Thrombin Inhibitors- Parenteral

• Name of the drugs ends with 'irudin'
• Hirudin
  • Obtained from the saliva of leeches
• Synthetic hirudin derivatives:
  • Desirudin
  • Bivalirudin
  • Lepirudin—Safe in liver disease patients
• Argatroban—Non hirudin
  • Renal safe drug

Indirect Thrombin Inhibitors: Heparins

In blood vessel

↓

Heparin binds to antithrombin 3 protein

↓

Change in the structure of antithrombin 3

↓

Conformational changes: inhibits factor X

Structural changes: inhibit factor X and II

Types of Heparin

Three types of Heparins

• High molecular weight (HMW) heparin
• Low molecular weight (LMW) heparin
• Ultra Low molecular weight (ULMW) heparin

Heparin Induced Thrombocytopenia (HIT)

• Caused by HMWH >>> LMWH
• Fondaparinux- Do not cause HIT
• Increased risk of thrombosis: Venous > Arterial
  • Venous thrombosis—DVT/PE
  • Arterial thrombosis—MI/Stroke

Anticoagulants also used as In-vitro anticoagulants

• Hirudin (direct thrombin inhibitor) is used
• Heparin + thrombin 3 (adjuvant) is used
• Heparin: Not used - It is an indirect thrombin inhibitor
• Warfarin: Not used - Inhibits vitamin K

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Thrombolytics And Anti Thrombolytics

Fibrinolytics (Thrombolytics)

MOA

• Activate plasminogen into plasmin
• Degrades deposited fibrin

Antifibrinolytics

• Drugs
  • Tranexamic acid
  • Epsilon amino caproic acid

Given to stop active internal bleeding

• DOC for Antidote for fibrinolytics
• Epsilon amino caproic acid
  • Most potent drug
  • Antidote for fibrinolytic
• Tranexamic acid - Used in
  • Menorrhagia
  • Bleeding esophageal varices
  • Haematuria

Hematinic

Hematinic are the agents that increase the formation of blood cells

Drugs that promote RBC growth

• Erythropoietin
• Darbepoetin alpha and epoetin alpha
• Peginesatide

Side effects of erythropoietin-like drug

• Hypertension
• Increased viscosity of the blood due increased WBCs - Causes thromboembolism (MI and strokes)

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