Drugs Affecting Coagulation

Anticoagulant, Antiplatelet, and

Thrombolytic Drugs
Hemostasis
Stage 1 Formation of Platelet Plug
Platelet aggregation
Stage 2 Coagulation
Intrinsic system
Extrinsic system
You tube video

https://www.youtube.com/watch?feature=pla
yer_embedded&v=xNZEERMSeyM

Process of Coagulation

Blood Vessel Injury

Local vasoconstriction seals off small injury
Platelet aggregation forms a platelet plug
Hageman factor is activated
Intrinsic pathway converts prothrombin to thrombin to
seal system
Extrinsic pathway clots the blood that has leaked out
of the vascular system

Damaged Vessel Endothelium Stimulates

Platelets to Cause Platelet Adhesion

Types of Blood Disorders

Thromboembolic disorder

Conditions that predispose a person to the

formation of clots and emboli

Hemorrhagic disorder

Condition in which excess bleeding occurs

Anticoagulant Therapies
A. Antiplatelet
1. Aspirin
2. Thienopyridines

Clopidogrel (Plavix), Prasugrel (Effient) ,Tichlopidine (Tichlid)

3. GP IIb/IIIa Inhibitors

Abciximab (Reopro),Eptifibitide (Integrilin) ,Tirofiban (Aggrastat)

B. Anticoagulants
1. Unfractionated Heparin
2. LMWH

a. Enoxaparin (Lovenox) b. Dalteparin (Fragmin)

3. Direct Thrombin Inhibitors
a. Bivalrudin (Angiomax)
b. Argatroban
4. Factor Xa Inhibitors

a. Fondaparinux (Arixtra)
5. Vitamin K Antagonists
(Warfarin, Coumadin)
C. Fibrinolytics

Actions of Anticoagulants
Antiplatelet

Alter the formation of the platelet plug

Anticoagulants

Interfere with the clotting cascade and thrombin

formation

Thrombolytic drugs

Break down the thrombus that has been formed by

stimulating the plasmin system

Classification of
Cyclooxygenase Inhibitors
Drugs with anti-inflammatory properties

NSAIDs (nonsteroidal anti-inflammatory

drugs)

Aspirin, celecoxib, ibuprofen, and naproxen

Drugs without anti-inflammatory properties

Acetaminophen

Antiplatelet Drugs
Aspirin (ASA)
Inhibition of cyclooxygenase
Ticlopidine (Ticlid)
ADP receptor antagonists
Tirofiban (Aggrastat)
GP IIb / IIIa receptor antagonists

Antiplatelets-Aspirin
Action

Inhibit platelet adhesion and aggregation by blocking receptors sites on

the platelet membrane-irreversible inhibition of cycloxyenase, an enzyme
required by platelets to synthesize thromboxane A2 (TXA2)

Anagrelide: blocks the production of platelets in the bone marrow

Indications

Reduce risk of recurrent TIAs or strokes; reduces death or nonfatal MI;

MI and anginal prophylaxis; anti-inflammatory, analgesic, and antipyretic
effects
Pharmacokinetics
Well absorbed and bound to plasma proteins
Metabolized in the liver and excreted in the urine

Aspirin
Nonselective inhibitor of cyclooxygenase
Therapeutic uses
Analgesic, antipyretic, anti-inflammatory
Suppression of platelet aggregation

Protects in thrombotic disorders

Dysmenorrhea
Cancer prevention
Prevention of Alzheimers disease

Antiplatelet (cont.)
Contraindications

Allergy,

Pregnancy, and lactation

Anemia, postpartum hemorrhage, may prolong labor

Caution

Reyes syndrome

Bleeding disorder, recent surgery, closed head injury

Adverse effects

Bleeding

Headache, dizziness, and weakness

GI distress

Drug-to-drug interaction
Anticoagulants: warfarin and heparin
Glucocorticoids
Alcohol
Ibuprofen
ACE inhibitors and ARBs

Clopidogrel (Plavix)
Therapeutic uses
Prevents blockage of coronary artery stents
Reduces thrombotic events in patients with
acute coronary syndromes

MI, ischemic stroke, and vascular death

Similar adverse effects to those of aspirin

Use with caution in combination with other
drugs that promote bleeding

Direct Thrombin Inhibitors

Direct inhibition of thrombin

(unlike heparin, which enhances the activity of antithrombin)

Dabigatran- Etexilate (2010)

Oral prodrug- GI Conversion to Dabigatran
Advantages:
doesnt require monitoring of anticoagulation
little risk of adverse interactions
same dose can be used for all patients regardless of age
or weight

Other Antiplatelet Drugs

Dipyridamole
Dipyrindamole + aspirin
Aggrenox
Cilostazol

Anticoagulants
Argatroban (Acova)

Used to treat thrombosis in heparin-induced

thrombocytopenia

Bivalirudin (Angiomax)

Used with aspirin to prevent ischemic events in

patients undergoing trans luminal coronary
angioplasty

Direct Thrombin Inhibitors

Hiruden Analog: Bivalirudin (Angiomax)

Prevents clot formation (combined with aspirin) in patients with

unstable angina who are undergoing coronary angioplasty

Mechanism of action
Facilitates the actions of antithrombin
Prevents conversion of fibrinogen to fibrin
Prevents activation of factor XIII

Adverse effects
Bleeding
Back pain
Nausea, headache

Other Direct Thrombin Inhibitors

Lepirudin (Refludan)
Argatroban (formerly known as Acova)
Desirudin (Ipravask)
Dabigatran (Pradaxa)

Selective Factor Xa Inhibitors

Produce selective inhibition of factor Xa
Fondaparinux
Activation of antithrombin
Injection

Rivaroxaban
Binds directly with factor Xa to cause
inactivation
Oral

Rivaroxaban (Xarelto)
Oral anticoagulant approved in 2011
Does not require laboratory monitoring
Patients who received rivaroxaban were
found to be much less likely to experience
DVT, VTE, PE, or death

Anticoagulants
Warfarin (Coumadin)

Maintains a state of anticoagulation when the patient is

susceptible to potentially dangerous clot formation

Heparin (generic)

Inhibits the conversion of Prothrombin to thrombin

Antithrombin (Thrombate III)

Used for hereditary Antithrombin III deficiencies and

replacement therapy in congenital Antithrombin III
deficiency

Anticoagulants
Action

Interfere with the normal cascade of events involved in the clotting

process

Pharmacokinetics

Vary based on the drug

Contraindications

Allergy and conditions that could be compromised by increased

bleeding tendencies

Pregnancy, renal, and hepatic disorders

Cautions

CHF, thyrotoxicosis, senility, and psychosis

Anticoagulants (cont.)
Adverse effects

Bleeding
GI upset
Hepatic dysfunction
Alopecia, dermatitis, bone marrow suppression, and
prolonged and painful erection

Drug-to-drug interactions

Heparin and oral anticoagulants, salicylates,

penicillins, and cephalosporins
Heparin and nitroglycerine
Warfarin: number of documented interactions

Heparin
Rapid acting anticoagulant
Uses
Pulmonary embolism
Stroke
Vein thrombosis
Adverse Effects
Hemorrhage
Thrombocytopenia
Hypersensitivity reactions

Low-Molecular-Weight Heparins
Inhibit thrombus and clot formation by blocking factors Xa
and Iia
Do not greatly affect thrombin, clotting, or prothrombin times;
therefore, they cause fewer systemic adverse effects
Block angiogenesis, the process that allows cancer cells to
develop new blood vessels
Are indicated for specific uses in the prevention of clots and
emboli formation after certain surgeries or bed rest

Warfarin (Coumadin)
Oral anticoagulant
Antagonist Vitamin K
Effects synthesis - Factors VII, IX, X, and
prothrombin
Uses

Prevents thrombosis formation

Adverse Effects

Hemorrhage

Coumadin(Warfarin)
https://www.youtube.com/watch?featur
e=player_embedded&v=ucP1OEOGO5E
Patient education video for monitoring and
taking Coumadin.

Thrombolytic Drugs
Streptokinase
Binds plasminogen
Uses
Myocardial infarction
Deep vein thrombosis
Massive pulmonary emboli
Adverse Effects
Bleeding
Hypotension
Fever

Thrombolytic Therapy
Action to dissolve clots
Thrombolytics
Alteplase -Tissue plasminogen activator
Reteplase
Streptokinase
Urokinase
Anistreplase

Thrombolytic Agents
Action
Activate plasminogen to plasmin, which in turn breaks down fibrin
threads in a clot to dissolve a formed clot
Indications
Acute MI, pulmonary emboli, and ischemic stroke
Pharmacokinetics

Drugs must be injected and are cleared from the body after liver
metabolism
Contraindications
Allergy

Any condition that worsens through dissolution of clots

Pregnancy and lactation

Streptokinase (Streptase)
Binds to plasminogen to form active complex
Therapeutic uses

Acute coronary thrombosis (acute MI)

Deep venous thrombosis (DVT)
Massive pulmonary emboli

Adverse effects

Bleeding excessive fibrinolysis can be reversed with IV

aminocaproic acid (Amicar)
Antibody production
Hypotension
Fever

Thrombolytic Drugs
Streptokinase (Streptase); Alteplase (tPa)
Major adverse effect bleeding (minor
oozing to life-threatening amount)

Likely sites of bleeding

Recent wounds, needle puncture sites, invasive

procedure sites

Anticoagulants increase the risk for

hemorrhage
Blood replacement may need to be considered

Thrombolytic Agents (cont.)

Adverse effects

Bleeding
Cardiac arrhythmias
Hypotension
Hypersensitivity: rash, flushing, bronchospasm, and
anaphylactic reaction

Drug-to-drug interactions

Anticoagulants
Antiplatelet

Bleeding Disorders Treated With

Clotting Factors
Hemophilia

Genetic lack of clotting factors that leaves the patient

vulnerable to excessive bleeding from any injury

Liver disease

Clotting factors and proteins needed for clotting are not

produced

Bone marrow disorders

Platelets are not formed in sufficient quantity to be

effective

Antihemophilics
Actions

Replace clotting factors that are either genetically

missing or low in a particular type of hemophilia

Indications

Prevent blood loss from injury or surgery and to treat

bleeding disorders

Pharmacokinetics

Replace normal clotting factors; they are processed as

such by the body

Antihemophilics (cont.)
Contraindications

Allergy

Factor IX in the presence of liver disease

Lactation

Caution

Pregnancy

Adverse effects

Risks associated with use of blood products

Headache, flushing, fever, chills, and lethargy

Nausea and vomiting

Stinging, itching, and burning at the site of injection

Systemic Hemostatic Agents

Action

Stop the natural plasminogen clot-dissolving

mechanism by blocking its activation or by directly
inhibiting plasmin

Indication

Prevent or treat excess bleeding in hyperfibrinolytic

states

Pharmacokinetics

Vary for each drug

Systemic Hemostatic Agents

Contraindications

Allergy

Acute DIC

Caution

Cardiac disease, renal or hepatic dysfunction,

pregnancy, and lactation

Systemic Hemostatic Agents

Adverse effects

Excessive clotting

CNS: hallucinations, drowsiness, dizziness, headache, and

psychotic states

GI: nausea, cramps, and diarrhea

Weakness, fatigue, malaise, and muscle pain

Aprotinin: cardiac arrhythmias, MI, CHF, and hypotension

Drug-to-drug interactions

Heparin

Oral contraceptives and estrogen

Drugs for Deficiency Anemia

Anemia decrease in erythrocytes (RBC)
Number
Size
Hemoglobin content

Causes
Blood loss
Hemolysis
Bone marrow dysfunction

Red Blood Cell Development

Stage 1 Proerythroblasts

Lacks hemoglobin

Stage 2 Erythroblasts

Gains hemoglobin

Stage 3 Reticulocytes

Immature erythrocytes

Stage 4 - Erythrocytes

Maturity

Iron Deficiency Anemia

Most common nutritional anemia
Iron essential to hemoglobin
Daily requirements
Dietary sources
Iron supplements

Iron Deficiency Anemia-Causes

Imbalance in iron uptake and iron demand
Microcytic, hypochromic anemia
Causes
Pregnancy
Infancy and early childhood
Chronic blood loss

Iron Preparations
Ferrous Sulfate
Indications
Administration
Drug Interactions

Adverse Effects
GI disturbances
Staining of teeth
Toxicity

Dosage Formula for Iron

Mg Iron =
0.66 x kg body weight x
hemoglobin value in g/dl)
14.8

(100-

Vitamin B12 Deficiency

Vitamin B12 (Cobalamins)
Essential for synthesis of DNA
Absorption requires intrinsic factor
Daily requirement
Dietary sources
Diagnostic tests

Vitamin B12 Deficiency Causes

and Consequences
Causes
Regional enteritis
Celiac disease
Lack of intrinsic factor

Consequences
Megaloblastic anemia
Neurologic damage
GI disturbances

Vitamin B12 Preparations Cyanocobalamin

Cyanocobalamin
Administration
Oral, parenteral, intranasal
Adverse Effects
Hypokalemia
Long term treatment
With lack of intrinsic factor, Vitamin B12
lifelong

Folic Acid Anemia

Folic Acid
Found small intestine
Daily requirements
Dietary sources
Administration

Folic Acid AnemiaCauses and Consequences

Causes
Poor

diet
Malabsorption syndrome
Consequences
Megaloblastic

anemia
Neural tube defects

Hematopoietic and Thrombopoietic

Growth Factors
Acts on bone marrow to stimulate formation
of blood cells
Types
Hematopoietic growth factor
RBCs, WBCs
Thrombopoietic growth factor
Platelets

Epoetin Alfa (Erythropoietin)

Epoetin alfa (Epogen)
Hematopoietic growth factor
Recombinant DNA technology

Uses
Chronic renal failure
HIV-infected patients
Chemotherapy

Adverse Effects

Hypertension

Filgrastim (Neupogen)
Filgrastim
Hematopoietic growth factor
Recombinant DNA technology
Uses
Chemotherapy
Bone marrow transplant
Chronic neutropenia
Adverse Effects
Bone pain

Oprelvekin (Interleukin 11)

Oprelvekin (Neumega)
Thrombopoietic growth factor
Recombinant DNA technology

Uses

Chemotherapy

Adverse Effects
Fluid Retention
Cardiac Dysrhythmias