2. Anticoagualtion and antiplatelets
Hashem m. mansour

3. Introduction
Thrombosis, the formation of an unwanted clot within a blood vessel.
Thrombotic disorders include acute myocardial infarction (MI), deep vein thrombosis (DVT), pulmonary embolism (PE), and acute ischemic stroke.
These conditions are treated with drugs such as anticoagulants and fibrinolytics.

4. Thrombosis versus embolism
A clot that adheres to a vessel wall is called a “thrombus,” whereas an intravascular clot that floats in the blood is termed an “embolus.
Arterial thrombosis usually consists of a platelet-rich clot.
In contrast, venous thrombosis is triggered by blood stasis or inappropriate activation of the coagulation cascade.

5. D. Platelet aggregation E. Formation of a clot F. Fibrinolysis
Thrombus formation
A. Tissue injury.
B. Platelet adhesion
C. Platelet activation
D. Platelet aggregation
E. Formation of a clot
F. Fibrinolysis

7. Platelet aggregation inhibitors
The platelet aggregation inhibitors inhibit
1) cyclooxygenase-1 (COX-1) or 2)block GP IIb/IIIa or
3)ADP receptors, thereby interfering with the signals that promote platelet aggregation.

8. Aspirin
Mechanism of action:
Aspirin inhibits thromboxane A2 synthesis irreversibly by inhibiting cycloxygenase enzyme.
Thromboxane A2 promotes the aggregation process that is essential for the rapid formation of a hemostatic plug.

10. Aspirin Effect
The inhibitory effect is rapid, and aspirin-induced suppression of platelet aggregation last for the life of the platelet ( 7 to 10 days).
Aspirin is the only antiplatelet agent that irreversibly inhibits platelet function

11. Therapeutic use
Aspirin is used in the prophylactic treatment of transient cerebral ischemia
Reduce the incidence of recurrent MI, and to decrease mortality in the setting of primary and secondary prevention of MI.

12. Adverse effects
Increased incidence of hemorrhagic stroke and gastrointestinal (GI) bleeding.
Bronchospasm .
Renal damage.
Angioedema.
Hepatotxicity.
Nonsteroidal anti-inflammatory drugs, such as ibuprofen, if taken within the 2 hours prior to aspirin, can antagonize platelet inhibition by aspirin.

14. Ticlopidine, clopidogrel, prasugrel, and ticagrelor
Mechanism of action:
These drugs inhibit the binding of ADP to its receptors on platelets and, thereby, inhibit the activation of the GP IIb/IIIa receptors required for platelets to bind to fibrinogen and to each other.
Ticagrelor binds to the P2Y12 ADP receptor in a reversible manner.

16. The maximum inhibition of platelet aggregation is achieved in
Max effects
The maximum inhibition of platelet aggregation is achieved in
1 to 3 hours with ticagrelor.
2 to 4 hours with prasugrel.
3 to 4 days with ticlopidine.
3 to 5 days with clopidogrel.

17. Therapeutic use
Prophylaxis of thrombotic events in acute coronary syndromes and percutaneous coronary intervention (PCI).
Ticlopidine is indicated for the prevention of transient ischemic attacks (TIA) and strokes in patients with a prior cerebral thrombotic event.

18. They undergo hepatic metabolism. Elimination renal and fecal routes.
Pharmacokinetics
They undergo hepatic metabolism.
Elimination renal and fecal routes.
Drugs that inhibit CYP 2C19, such as omeprazole and esomeprazole, should not be administered concurrently with clopidogrel.

19. These agents cause prolonged bleeding.
Adverse effects
These agents cause prolonged bleeding.
Agranulocytosis, thrombotic thrombocytopenic purpura (TTP), and aplastic anemia.
Prasugrel is contraindicated in patients with history of TIA or stroke.

20. Anticoagulants
Heparin and low molecular weight heparins
Mechanism of action:
Heparin anticoagulant effect is due to antithrombin III, with the subsequent rapid inactivation of coagulation factors.
LMWHs complex with antithrombin III and inactivate factor Xa.

21. Therapeutic use Treatment of acute venous thromboembolism (DVT or PE).
Prophylaxis of postoperative venous thrombosis in patients undergoing surgery
The anticoagulants of choice for treating pregnant women.
LMWHs do not require the same intense monitoring as heparin.

22. Heparin administered subcutaneously or intravenously.
Pharmacokinetics
Heparin administered subcutaneously or intravenously.
The LMWHs are administered subcutaneously.
In renally impaired, pregnant, and obese patients, monitoring of factor Xa levels is recommended with LMWHs.

23. Adverse effects Bleeding.
Excessive bleeding managed by discontinuing the drug or with protamine sulfate.
chills, fever, urticaria, and anaphylactic shock.
Heparin-induced thrombocytopenia (HIT) is a serious condition, in which circulating blood contains an abnormally low number of platelets

24. Adverse effects
Heparin therapy should be discontinued when patients develop HIT or show severe thrombocytopenia.
osteoporosis
Heparin and LMWHs are contraindicated in patients who have bleeding disorders, or who have had recent surgery of the brain, eye, or spinal cord.

26. Rivaroxaban and apixaban
Mechanism of action: Rivaroxaban and apixaban are oral inhibitors of factor Xa.
Therapeutic use: Rivaroxaban is approved for treatment and prevention of DVT and PE and for the prevention of stroke in nonvalvular atrial fibrillation.
Apixaban is used for stroke prevention in nonvalvular atrial fibrillation.

27. Bleeding is the most serious adverse effect.
Adverse effects
Bleeding is the most serious adverse effect.
As both drugs are eliminated renally. neither drug should be used in severe renal dysfunction (creatinine clearance less than 15 mL/min).
Abrupt discontinuation of these agents should be avoided.

28. It work by antagonizing the effects of Vit K
Warfarin
Mechanism of action:
Factors II, VII, IX, and X require vitamin K as a cofactor for their synthesis by the liver.
It work by antagonizing the effects of Vit K

29. Warfarin con.
The anticoagulant effects of warfarin may be delayed for 72 to 96 hours.
The anticoagulant effects of warfarin can be overcome by the administration of vitamin K.
Reversal following administration of vitamin K takes approximately 24 hours.

30. Therapeutic use
Warfarin is used in the prevention and treatment of DVT and PE, stroke prevention,
Stroke prevention in the setting of atrial fibrillation and/or prosthetic heart valves and antiphospholipid syndrome.

31. Warfarin is rapidly absorbed after oral administration
Pharmacokinetics
Warfarin is rapidly absorbed after oral administration
Readily crosses the placental barrier.
Metabolized by liver.
Excreted in urine and feces.
Warfarin has numerous drug interactions.

32. Adverse effects
The principal adverse effect of warfarin is hemorrhage,
Skin lesions and necrosis are rare complications of warfarin therapy.
Purple toe syndrome, a rare, painful, discoloration of the toe caused by cholesterol emboli.
Warfarin is teratogenic and should never be used during pregnancy.

33. Recent CNS and eye surgery Threatened abortion and eclampsia
Contraindication
Bleeding
pregnancy
Recent CNS and eye surgery
Threatened abortion and eclampsia
Spinal puncture
Malignant hypertension
Hypersensitivity
Pt with high level of non compliance

34. D X Apixaban Mifepristone Drug interaction Phenobarbital Prasugrel
Protamine
Sulfamethoxazole
Testosterone
Vit k
Apixaban
Mifepristone

35. Drug interaction D Allopurinol Amiodarone Abciximab Azithromycin
Antithrombin III
Bezafibrate
Carbamazepine
Cefazoline
metronidazole
Cefpodoxime
Ceftriaxone
Cefuroxime
Ciprofloxacin
Clarithromycin
Clotrimazole
Erythromycine
Itraconazole
Levothyroxine

36. Implication in physiotherapy
Anticoagulants and antiplatelet are very important drugs in medicine.
Also they are dangerous drugs due to their side effects especially bleeding.
Most of these drugs need continuous follow up, monitoring and education.
P.T should be aware for the above mentioned issues.

37. Implication in physiotherapy
Before starting Physio-Therapy session you should ask the patient about the last follow up especially for those on warfarin.
Elevated INR may expose patient to bleeding during exercise.
The exercise should be done gently, since extraneous exercise increase the risk of bleeding such as ecchymosis and petechia.
Be aware of any sharp material near the patient during exercise.

38. Implication in physiotherapy
You can educate the patient about the proper way of using these drugs.
Sterile pads should be available to cover any accidental injury.
Remember these drugs are used in serious cases as stroke, cardiac, or pulmonary disease, so you must take this into your consideration.