This document discusses drugs used to treat deep vein thrombosis (DVT). It outlines platelet aggregation inhibitors, anticoagulants, and thrombolytic drugs - their mechanisms of action, uses, and adverse effects. Platelet aggregation inhibitors work by inhibiting cyclooxygenase-1 or blocking platelet receptors. Anticoagulants like heparin and warfarin prevent clotting by suppressing clotting factors. Thrombolytic drugs dissolve blood clots by activating plasminogen to form plasmin, which breaks down fibrin in clots. While these drugs can effectively treat DVT, they may increase bleeding risk as a side effect.

1. Anticoagulants and drugs for treatment of DVT
OUTLINE :
1. Platelet aggregation inhibitors
( Mechanism – use – adverse effects )
2. Anticoagulants
( Mechanism – use – adverse effects )
3. Thrombolytic drugs
( Mechanism – use – adverse effects )
4. Anistreplase
( Mechanism – use – adverse effects )

2. What is Thrombosis?
Thrombosis is the formation of a blood clot, known as a
thrombus, within a blood vessel. It prevents blood from flowing
normally through the circulatory system.

3. What is deep vein thrombosis (DVT) ?
Deep vein thrombosis occurs when a blood clot forms in a major vein,
usually in the leg. This blood clot stops blood from flowing easily through
the vein, which can lead to swelling, discoloration, and pain in the leg. It is
often diagnosed with an ultra sound.
Signs and symptoms of DVT include :
Discomfort, heaviness, pain, aching, throbbing, itching, or warmth
in the legs.
Skin changes in the leg, such as discoloration, thickening, or
ulceration.
Swelling of the legs, ankles, or feet.
Patients with DVT are at risk for developing post-thrombotic syndrome
(PTS). PTS can involve chronic leg swelling, calf pain, calf heaviness/fatigue,
skin discoloration, and/or venous ulcers.

4. Risk factors that contribute to thrombosis include:
Immobilization
Hypercoagulability
Vessel wall damage
Age
Surgery (especially orthopedic surgery and total knee replacement)
Cancer
Heredity (including the Factor V Leiden genetic mutation)
Pregnancy
Increased estrogen levels (due to oral contraception or hormone replacement
therapy)
Obesity
Smoking
Crohn’s Disease

5. platelet aggregation inhibitors
Platelet aggregation inhibitors decrease the formation of a platelet-rich clot or
decrease the action of chemical signals that promote platelet aggregation
The platelet aggregation inhibitors described below inhibit cyclooxygenase-1 (COX-1) or
block GP IIb/IIIa or ADP receptors, thereby interfering with the signals that promote
platelet aggregation.
Because these agents have different mechanisms of actions, synergistic or additive
effects may be achieved when agents from different classes are combined.
Classified into :
1- Irreversible cyclooxygenase inhibitors
2- Adenosine diphosphate (ADP) receptor inhibitors
3- Glycoprotein IIB/IIIA inhibitors
4- Thromboxane inhibitors
5- Phosphodiesterase inhibitors
6- Protease-activated receptor-1 (PAR-1) antagonists
7- Prostaglandin analogue (PGI2)

6. Irreversible cyclooxygenase inhibitors
1-Aspirin
Mechanism of action :
•Stimulation of platelets by thrombin, collagen, and ADP results in activation of platelet membrane
phospholipases that liberate arachidonic acid from membrane phospholipids.
•Arachidonic acid is first converted to prostaglandinH2 by COX-1, ProstaglandinH2 is further
metabolized to thromboxane A2 , which is released into plasma.
•Thromboxane A2 (TXA2) promotes the aggregation process that is essential for the rapid formation of
a hemostatic plug.
Aspirin inhibits thromboxane A2 synthesis by acetylation of a serine residue on the active site of COX-1,
thereby irreversibly inactivating the enzyme.
This shifts the balance of chemical mediators to favor the antiaggregatory effects of prostacyclin,
thereby preventing platelet aggregation.
The inhibitory effect is rapid, and suppression of thromboxane A2 and the resulting suppression of

8. ANTIPLATELET drugs
• ANTIPLATELETS ARE THE DRUGS WHICH DECREASE THE AGGREGATION
OF PLATELETS AND INHIBIT THE THROMBUS FORMATION.
• ASPIRIN is an Antiplatelet drug and it produces ANTIPLATELET ACTIVITY
IN LOWER DOSES (75-100 MG DAILY), WHILE HIGHER DOSE OF ASPIRIN
(UP TO 3600 MG DAILY IN DIVIDED DOSES) IS REQUIRED FOR IT’S
ANALGESIC EFFECTS.
• ANTIPLATELETS CAN INTERACT WITH PRESCRIPTION DRUGS, OVER-
THE-COUNTER (OTC) MEDICATIONS, HERBAL PRODUCTS, DIETARY
SUPPLEMENTS, VITAMINS, FOODS, AND GENETICS.
• Antiplatelet drugs can reversibly or irreversibly inhibit the process involved in
platelet activation resulting in decreased tendency of platelets to adhere to one
another and to damaged blood vessels' endothelium.

9. Aspirin is the "gold standard" antiplatelet agent for prevention of arterial thromboses. The
optimum dose of aspirin as an antithrombotic drug can differ in different organ circulations.
Therapeutic use:
 In the prophylactic treatment of transient cerebral ischemia
 To reduce the incidence of recurrent Myocardial infarction
 And to decrease mortality in the setting of primary and secondary prevention of MI.
 Complete inactivation of platelets occurs with 75 mg of aspirin given daily.
Some Antiplatelet drugs
Dual antiplatelet therapy
Often a combination of aspirin plus an ADP/P2Y inhibitor (such
as clopidogrel, prasugrel, ticagrelor, etc) is used in order to obtain greater effectiveness than
with either agent alone.
Aspirin

10. Adverse effects:
- Bleeding time is prolonged by aspirin treatment, causing complications that include an
increased incidence of hemorrhagic stroke and gastrointestinal (GI) bleeding, especially at
higher doses of the drug.
- Indigestion and stomach aches – taking your medicine with food may help reduce this risk
- Hives : a raised, itchy rash.
- Tinnitus : hearing sounds that come from inside your body.
- Breathing difficulties or an asthma attack.
Missed or extra doses
If you're taking aspirin to reduce your risk of blood clots and you forget to take a dose, take
that dose as soon as you remember and then continue to take your course of aspirin as
normal.
If it's almost time for the next dose, skip the missed dose and continue your

11. What is Plavix?
Plavix (clopidogrel) prevents platelets in your blood from sticking together to form an unwanted blood
clot that could block an artery.
Plavix is used to lower your risk of having a stroke, blood clot, or serious heart problem after you've
had a heart attack, severe chest pain (angina), or circulation problems.
Before taking this medicine
You should not use Plavix if you are allergic to clopidogrel, or if you have:
Any active bleeding
A stomach ulcer or bleeding in the brain (such as from a head injury).
Plavix side effects
Plavix increases your risk of bleeding.
pale skin, purple spots under your skin or in your mouth
jaundice (yellowing of your skin or eyes)
fast heartbeats, shortness of breath;
headache, fever, weakness, feeling tired;
little or no urination;
Plavix

12. What is Effient?
Effient is used to prevent blood clots in people with acute coronary
syndrome who are undergoing a procedure after a recent heart attack or stroke,
and in people with certain disorders of the heart or blood vessels.
Effient is not expected to be harmful to an unborn baby. However, aspirin is usually given with
Effient, and aspirin can cause bleeding when it is taken during the last 3 months of pregnancy.
Aspirin can also cause side effects in a newborn baby.
Effient side effects
hives; dizziness, chest pain, difficulty breathing; swelling of your face, lips, tongue,
or throat,pink or brown urine.
signs of stomach bleeding - bloody or tarry stools, coughing up blood or vomit that looks like
coffee grounds; or
Effient

13. Anticoagulant
How Blood Clots:
- Hemostasis is the body's way of stopping injured blood vessels from
bleeding.
- Hemostasis includes clotting of the blood.
- Too much clotting can block blood vessels that are not bleeding.
Consequently, the body has control mechanisms to limit clotting and dissolve
clots that are no longer needed. An abnormality in any part of this system
that controls bleeding can lead to excessive bleeding or excessive clotting,
both of which can be dangerous.
- When clotting is poor, even a slight injury to a blood vessel may lead to
Coagulation process

14. Clogged vessels in the brain can cause strokes, and clogged
vessels leading to the heart can cause heart attacks.
Pieces of clots from veins in the legs, pelvis, or abdomen
can travel through the bloodstream to the lungs and block
major arteries there (Pulmonary Embolism).

15. Anticoagulant : Any drug that, when added to blood, prevents it from clotting.
Anticoagulants achieve their effect by suppressing the synthesis or function of various clotting
factors that are normally present in the blood.
Such drugs are often used to prevent the formation of blood clots (thrombi) in
the veins or arteries or the enlargement of a clot that is circulating in the bloodstream.
Conditions commonly treated with anticoagulants include deep-vein thrombosis, in which clots form
in so-called deep veins, such as those of the legs.
pulmonary embolism: in which a clot obstructs the pulmonary artery or one of its branches;
coronary thrombosis: in which a clot obstructs a coronary artery in the heart;
and disseminated intravascular coagulation, a systemic activation of the coagulation system that
leads to the consumption of coagulation factors and hemorrhage.
Anticoagulants are also used in drawing and storing blood.
Anticoagulants generally are of two types: heparin, which is given by injection, and derivatives
of coumarin or indandione, which are administered orally.

16. Heparin, used primarily in hospitalized patients, is a mixture of Mucopolysaccharides that
promote the activity of antithrombin III, a blood plasma protein that inactivates thrombin
(an enzyme that promotes clotting).
Because it is not well absorbed from the GIT, heparin is given intravenously
to inhibit coagulation immediately, or it is given subcutaneously. Heparin is not bound to
plasma proteins, it is not secreted into breast milk, and it does not cross the placenta.
The drug’s action is terminated by metabolism in the liver and excretion by the kidneys. The
major side effect associated with heparin is hemorrhage; thrombocytopenia (reduced number
of circulating platelets) and hypersensitivity reactions also may occur. When oral anticoagulants
are given with heparin, additional anticoagulant effects occur.
Heparin-induced hemorrhage may be reversed with the antagonist protamine, a positively charged
Heparin

17. Structurally, the coumarin derivatives resemble vitamin K, an important element in the
synthesis of a number of clotting factors.
Interference in the metabolism of vitamin K in the liver by coumarin derivatives gives rise
to clotting factors that are defective and incapable of binding calcium ions (another important
element in the activation of coagulation factors at several steps in the coagulation cascade).
The other group of oral anticoagulants, the synthetic indandione derivatives (e.g.,
anisindione), are thought to work by a similar mechanism of action.
When anticoagulants are taken orally, several hours are required for the onset of the
anticoagulant effect because time is required both for their absorption from the gastrointestinal
tract and for the clearance of biologically active clotting factors from the blood.
Warfarin, a coumarin derivative and the most commonly used oral anticoagulant, is rapidly and
almost completely absorbed.
Oral Anticoagulants

18. Oral anticoagulants differ from heparin primarily in their longer duration of
action, which is the result of extensive binding to plasma proteins, giving these
agents relatively long plasma half-lives.
Oral anticoagulants are metabolized by the liver and excreted in the urine and
feces.
They may cross the placenta to cause fetal abnormalities or hemorrhages in
newborns; however, their appearance in breast milk apparently has no adverse
effect on nursing infants.
Hemorrhage is the principal toxic effect during oral anticoagulant therapy.
Vitamin K, when given intravenously to promote the synthesis of functional
clotting factors, stops bleeding after several hours.
Plasma that contains normal clotting factors is given to control serious bleeding.

19. Anticoagulants medicines are used if your blood is clotting too quickly. When this happens, blood clots
can form in the wrong places. These clots can break off and block a blood vessel, disrupting the flow of
blood around your body.
This can lead to several, serious medical conditions, including :
Strokes - when a blood clot restricts the flow of blood to your brain, causing brain cells to
die and possibly resulting in permanent brain damage or death,
Transient ischaemic attacks (TIAs) - or 'mini-strokes', with symptoms similar to a
stroke, but the effects usually only last 24 hours,
Heart attacks - when a blood clot blocks part of your heart, starving it of oxygen and
causing chest pain and sometimes death,
Deep vein thrombosis (DVT) - when a blood clot forms in one of the deep veins in
your body, usually your legs, causing pain and swelling, and
Pulmonary embolism - when a blood clot blocks one of the blood vessels around the
lungs, stopping the supply of blood to your lungs.
Uses of anticoagulants

20. A possible side effect of anticoagulants is excessive bleeding (haemorrhage), because these medicines increase
the time it takes for blood clots to form.
Some people also experience other side effects.
Excessive bleeding
Signs of excessive bleeding can include:
Passing blood in your pee
Passing blood when you poo or having black poo
Severe bruising
Prolonged nosebleeds (lasting longer than 10 minutes)
Bleeding gums
Vomiting blood or coughing up blood
Sudden severe back pain
Difficulty breathing or chest pain
Side effect

21. Bleeding. You will bleed more easily when taking anticoagulants, even from minor bumps, scrapes or cuts.
Take care when shaving or tooth brushing. Bleeding can be serious, so make sure you take your
anticoagulants as directed by your doctor and pharmacist, and have regular monitoring with your doctor.
Other medicines. Many anticoagulants are affected by medicines that are used to treat other conditions,
potentially increasing your risk of bleeding or clotting. Check with your doctor before starting any new
medicines, including complementary medicines.
Surgery. If you need to have surgery, it’s important that your surgeon and doctor are aware that you are
taking anticoagulation medicines. The dose and timing of your anticoagulants will most likely need to be
adjusted before surgery.
Precautions when taking anticoagulants

22. Dental procedures - Let your dentist know that you are taking anticoagulants
before any dental procedures that may put you at risk of bleeding.
Pregnancy - Some anticoagulant medicines, such as warfarin, are not suitable for use in
pregnancy. If you are pregnant or planning a pregnancy, see your doctor.
Emergency medical ID - It’s a good idea to wear or carry some medical ID that
lists the medicines you are taking, and the name of your doctor. Available options include
bracelets (such as MedicAlert) and other jewellery, or cards for your purse or wallet.

23. Thrombolytic drugs
Mechanism of action
Thrombus

24. 1-tissue plasminogen activator (tPA)
Alteplase short life time (5 min) So administrated IV
Retaplase genetically engineered, smaller derivative of recombinant tPA that has increased
potency and is faster acting than Alteplase
Tenecteplase longer half life action and greater binding affinity
2- Streptokinase
3- Urokinase
Thrombolytic drugs dissolve bloodclots by activating plasminogen (pro enzyme) by cleaving the
R561/V562 peptide bond which forms a cleaved product called plasmin (active form) .
There are 3 types of thrombolytic drugs :

25. Plasmin is a proteolytic enzyme that is capable of breaking cross-links between
fibrin molecules(protein), which provide the structural integrity of bloodclots
forming soluble degradation products
Because of these actions, thrombolytic drugs are also called "plasminogen
activators" and "fibrinolytic drugs."

26. Clot buster drugs, also known as thrombolytic therapy, are a type
of heart medication given in the hospital through an IV to break up blood
clots.
Heart attack and ischemic stroke are the two main conditions that clot
busters are used for.
These powerful heart disease drugs are given to :
Prevent the ongoing damage of heart attacks.
Halt ongoing damage from ischemic stroke.
Clot Buster Drugs

27. There are several drugs to break up clots, including:
Tissue plasminogen activator (tPA)
Alteplase
Urokinase
Reteplase
Streptokinase
Who Shouldn't Take Them?
Some people aren't able to take clot busters.
if you have any of the following conditions:
- Previous hemorrhagic stroke or bleeding in the brain
- Known cerebral vascular lesion or tumor
- Previous allergic reaction to a clot buster, or other allergies
- Pregnancy
- high blood pressure
- Bleeding disorder, or recent history of bleeding in any part of the body
- Recent surgery (less than 2 weeks ago)

28. Should I Be Concerned About Food and Drug Interactions With Clot Busters?
Certain drugs may increase your risk of bleeding if you are prescribed clot busters.
- Blood thinners (warfarin or Coumadin)
- Anti-inflammatory medications or pain relievers such as acetaminophen and ibuprofen
What Are the Side Effects?
- Bleeding or oozing from cuts or around where you got your shot
- Allergic reaction
- Fever
- Low blood pressure
- Signs of bleeding from other sites within the body, such as blood in the urine, black tarry
stools, nose bleeds, and bleeding from the gums

29. Anistreplase
(anisoylated plasminogen-streptokinase activator complex, APSAC)
- It is a complex of purified human plasminogen and bacterial streptokinase that
has been acylated to protect the enzyme's active site
- It is a prodrug:
APSAC is deacylated to SK-Plasminogen complex
- The plasma half life of anistreplase is 80 -112 minutes
So it’s longer duration than other thromblytic drug
- Hospital cost is 1700$

30. Mechanism of action
After deacylation, which begins immediately after injection, the streptokinase-
plasminogen complex promotes thrombolysis by speeding the conversion of
plasminogen to plasmin.
Like other Thromblytic drug anistreplase induces a systemic fibrinogenolytic
state
This drug is contraindicated with corticosteroid (Prednisone) & aspirin & Blood
thinner (warfarin) & aminocaproic acid (drug for hypertension)
Drug used for arthritis
- NSAIDS: like naproxen
- sulfinpyrazone
Drug –Drug interaction

31. Route of administration
By IV injection
Side effect
Bleeding
irregular heart rhythm
itching,fever,chillss
sweating headache
dizziness
Precaution
This drug shouldn’tbe used with patient suffering from :
Bleeding
blood vessel abnormalties
Brain tumor
patient with hypertension
patient with bleeding urinary tract
history of stroke recent surgery

32. Anistreplase
Uses of Anistreplase
Anistreplase is used in the treatment of:
- prevents blood from clotting. effective in reducing the risk of death following heart attack.
- An acute heart attack.
- Myocardial Infarction
- Pulmonary Embolism
Anisoylated plasminogen activator complex.
Anistreplase is a preformed complex of streptokinase and plasminogen and it is
considered to be a prodrug.
Advantages:
- Rapid IV injection may be given
- Greater clot selectivity.
- More thrombolytic activity.

33. Side Effects
Hematologic
Hemorrhage or hematoma formation
Purpuric rashes
Thrombocytopenia
Megaloblastic anemia
Cardiovascular
Reperfusion arrhythmias
Bradycardia
Hypotension
Serious ventricular arrhythmias
Ventricular fibrillation
Hypersensitivity
Rash or Photosensitivity
Anaphylaxis

34. Gastrointestinal
Nausea or vomiting
Musculoskeletal
Musculoskeletal back pain
Metabolic
Metabolic changes and hypokalemia
Renal
Musculoskeletal back pain
Nervous system
Hemorrhagic stroke
Headache
Dizziness
Fatigue and syncope

35. Thank You