ANTICOAGULANTS
Dr Amber
Department of Pharmacology
Anticoagulants
Inhibit:
• Action of coagulation factors
• Interfere with the synthesis of coagulation
factors
CLASSIFICATION
Thrombin inhibitors:
Vitamin K antagonist:
• Heparin Warfarin
• Low molecular weight
Direct thrombin
heparin
inhibitor:
Others: Dabigatran etexilate
• Bivalirudin, Desirudin Abixaban
• Argatroban Betrixaban
• Fondaparinux Edoxaban
Rivaroxaban
HEPARIN & LOW MOLECULAR WEIGHT
HEPARIN
• Heparin indicates un-fractioned form of the
drug
Extracted from porcine intestinal mucosa for
commercial use
Strongly acidic because of presence of
sulphate and carboxylic acid groups
• LMWH(one third size of heparin)
Formed from depolymerization of UF heparin
Enoxaparin and Dalteparin
Heparin
Structure
Mucopolysaccharide
Metabolism:
• Partially in the liver
• 20-50 % is excreted unchanged.
• Administered IV (1hr)or SC (3 hours)
• Heparin should not be given IM (danger of
hematoma formation).
MECHANISM OF ACTION:
Interact with antithrombin III which inhibit
factor proteases, thrombin IIa and Xa
Antidote : Protamine sulphate
Monitor: aPTT (activated partial
thromboplastin)
Clinical uses of UFH
• Acute thrombosis and thromboembolism
• Myocardial infarction
• Ischemia
• Prevention of thrombus formation after
surgeries
• Atherosclerosis
• Autoimmune diseases
• Used in pregnancy(does not cross placenta)
SIDE EFFECTS CONTRAINDICATIONS
• Bleeding • Hemorrhage
• Hematoma • Leukemia
• Micro and • Anemia
macrohematuria • Malignant diseases
• Thrombocytopenia • Gastric ulcer
• Allergy • Hypertension
• Osteoporosis • Severe diseases of liver
• Silvering of hair and kidney
LOW-Molecular-Weight Heparin (LMWH)
Mechanism of Action
• Inhibiting factor Xa, which is higher in the
coagulation cascade than anti thrombin
• LMWH is more efficient than UFH.
•Half life 4 hours, longer dosing interval
•Does not crosses placenta
•Prophylaxis: once a day
•Therapy : twice daily
Unfractionated Heparin
• Unpredictable pharmacokinetics
• Requires regular monitoring
• Infusion
• Higher incidence of HITs (heparin induced
thrombocytopenia)
• Rebound ischemia
Advantages of LMWH over UFH
• No need for laboratory monitoring.
• Higher bioavailability.
• Longer plasma half life.
• Less platelet inhibition.
• Less incidence of thrombocytopenia.
Other Parenteral Anticoagulants
• Argatroban- Direct thrombin inhibitor
• Fondaparinux- Selectively inhibits Factor Xa
• Bevalirudin, Desirudin- Thrombin inhibitor
and are analogs of hirudin
Oral Anticoagulants
Coumarins - warfarin, dicumarol
Structure:
small, lipid-soluble molecules, Structurally
related to vitamin K, isolated from clover
leaves
Mechanism:
• Inhibits production of active clotting factors
• Blocks the Vitamin K-dependent glutamate
carboxylation of precursor clotting factors e.g.
II, VII, IX , X.
Overdose - reversed by vitamin K infusion
Metabolism:
Absorption: rapid, Binds to albumin
Clearance is slow: 36 hours
Delayed onset: 8-12 hours
Use:
•To prevent the formation, recurrence or
extension of DVT & PE
•Not used in pregnant women (cross placenta)
•Not used for arterial thrombi (No effect on
platelets)
Toxicity:
•Bleeding
•Birth defects
Severe Side effects:
• Severe bleeding • Nausea or vomiting
• Bleeding from the rectum • Fever or flu-like
or black stool symptoms
• Skin conditions such as • Joint or muscle aches
hives, a rash or itching • Diarrhea
• Swelling of the face, • Numbness or tingling
throat, mouth, legs, feet • Painful erection lasting
or hands four hours or longer
• Bruising
• Chest pain or pressure
Dabigatrin
• Oral direct thrombin inhibitor
• Used for stroke and systemic embolism and as
prophylaxis for DVT and PE
• AE: Bleeding
• Should be used with caution in renal
impairment
• Abrupt discontinuation should be avoided
Direct Oral Factor Xa Inhibitor
Apixaban, Betrixaban, Rivaroxaban
• Rivaroxaban is oral, fast acting with very few drug
interactions
• Safe for long term therapy.
• Oral bioavailability of 80 to 100%.
• Rivaroxaban reversibly inhibits the intrinsic and extrinsic
pathways of coagulation
• Therapeutic uses include stroke, DVT and PE
• AE: Bleeding
• Abdrupt discontinuation should be avoided
• Cost of the medications, periodic INR
monitoring and need of hospitalisation for
heparin therapy are major factors leading to
nonadherence to standard treatment.
• Disadvantages of rivaroxaban includes,
antidote dexanet alfa not available in Pakistan,
lack of efficacy in obese, inability to monitor
rivaroxaban activity.
THANK YOU
Which of the following anti-coagulant drug has
low-molecular weight
(A) Dicumarol
(B) Enoxaparin
(C) Phenprocoumon
(D) Argatroban
A 61-year-old man with hypertension develops atrial
fibrillation. His medications include simvastatin and
metoprolol. His physician prescribes an anticoagulant for
clot prophylaxis, which directly inhibits thrombin. Which
drug is this?
(A) Aspirin
(B) Dabigatran
(C) Heparin
(D) Warfarin
A 58-year-old man presents to the emergency
department after experiencing a sudden loss of motor
control on his left side accompanied by aphasia. By the
time he reached the ED, his symptoms had already
resolved. He is given a prescription for a drug that binds
platelet ADP receptors to prevent their aggregation.
Which drug is this?
(A) Clopidogrel
(B) Enoxaparin
(C) Eptifibatide
(D) Tirofiban
A 70-year-old woman is diagnosed with nonvalvular
atrial fibrillation. Her past medical history is significant
for chronic kidney disease, and her renal function is
moderately diminished. Which anticoagulant for atrial
fibrillation avoids the need for renal dose adjustment in
this patient?
(A) Apixaban
(B) Dabigatran
(C) Rivaroxaban
(D) Warfarin
A 75-year-old man is brought to the emergency
department with right calf pain and swelling. Three weeks
ago, he underwent a radical cystectomy for invasive
bladder cancer. Ultrasound reveals a right pelvic vein deep
venous thrombosis. Heparin drip was started. One hour
later, he was bleeding profusely from the intravenous site.
The heparin therapy was suspended, but the bleeding
continued. Protamine sulfate was administered
intravenously that works in which of the following ways?
(A) Activates the coagulation cascade
(B) Ionically combines with heparin
(C) Degrades the heparin
(D) Inactivates antithrombin
