BIIC Pharmacology Lecture 2_Pharmacology of Disorders of Hemostasis and Coagulation

Question 1

What coagulation factor is deficient in Hemophilia A? How common is it?

Answer 1

Factor VIII. It affects 1 in 5000 males.

Question 2

What coagulation factor is deficient in Hemophilia B? How common is it?

Answer 2

Factor IX. It effects 1 in 30,000 people

Question 3

What coagulation factor is deficient in Hemophilia C? How common is it?

Answer 3

Factor XI. It affects 1 in 100,000 people

Question 4

What are the clinical manifestations of Hemophilia?

Answer 4

• Palpable ecchymosis (bruises)
• Hemarthrosis (Bleeding into joint spaces)
• Muscle hemorrages
• Excessive bleeding after surgery or trauma

Question 5

Which Clinical manifestation of hemophilia is distinct from ITP and Von Willebrands?

Answer 5

Hemarthrosis

Question 6

When treating hemophilia, what is the benefit of Recombinant factors vs Plasma factors.

Answer 6

Recombinant have a lower risk of transmitting infection. Plasma derived factors are less expencive

Question 7

What is the:

MOA:
Half Life:
Indication: 
Side effects:
Considerations:

Of Recombinant factor VIII?

Answer 7

MOA: It is not derived from human blood, and it temporarily replaces the missing clotting factor VIII
Half Life: 10-14 hours
Indication: Hemophilia A, Factor VIII inhibitor disorder
Side effects: Antibody development
Considerations: Patient can develop inhibitory antibodies against factor VIII. This is often treated by giving higher doses of factor VIII

Question 8

What is the:

MOA:
Half Life:
Indication: 
Side effects:
Considerations:

Of Recombinant factor IX?

Answer 8

MOA:It is not derived from human blood, and it temporarily replaces the missing clotting factor IX
Half Life: 18-25 hours
Indication: Hemophilia B
Side effects: Antibody development
Considerations:Patient can develop inhibitory antibodies against factor IX. This is often treated by giving higher doses of factor IX

Question 9

How are patients with high titer inhibitors (antibodies) to Coagulation factors treated?

Answer 9

They are given prothrombin and activated prothrombin. This bypasses the deficient coag factor in the cloting casscade

Question 10

What is von Willebrand factor’s role in the coagulation cascade?

Answer 10

It is released from endothelium after vessel injury. It then promotes platelet adhesion and binds Factor VIII, taking it to the site of injury.

Question 11

What are the clinical manifestations of von Willebrand Disease?

Answer 11

• Bleeding of nose and gums
• Easy brusing
• Postoprative bleeding

Question 12

What clinical manifestation of von Willebrand Disease differs from hemophilia?

Answer 12

Bleeding nose and gums

Question 13

What is the:

MOA:
Half Life:
Indication: 
Side effects:
Considerations:

Of Recombinant factor Recombinant von Willebrand Factor?

Answer 13

MOA: Prolongs factor VIII half life by acting as a carrier and mediates platelet adhesion
Half Life: 19-22 hours
Indication: Von Willebrand Disease hemmorage
Side effects: Vertigo, deep venous thrombosis
Considerations: Inhibitory antibodies against von Willebrand factor can develop

Question 14

What is the:

MOA:
Half Life:
Indication: 
Side effects:
Black Box:
Considerations:

Of Desmopressin?

Answer 14

MOA: Leads to water retention by acting as a synthetic analouge to antidiuretic hormone vasoppressin. This increases Plasma factor VIII activity
Half Life: 1-3.4 hours (52% renally excreted unchanged)
Indication: Von Willebrand Disease type 1, Hemophilia A with factor VIII levels less than 5%
Side effects: Fatigue, xerostomia
Black Box: can cause fatal hyponatremia
Considerations: Preferred over plasma products

Question 15

What is the main indication of ITP

Answer 15

Low platelet count (everything else is secondary to that)

Question 16

What are the three approches to treating ITP?

Answer 16

1) Decrease antibody production
2) Decrease platelet destruction
3) Increase platelet production

Question 17

What is the:

MOA:
Half Life:
Indication: 
Side effects:
Black Box:
Considerations:

Of Prednisone, Methylprednisolone, Dexamethasone?

Answer 17

MOA:Inhibit numerous steps in the inflammatory response such as inhibition
of antigen presentation to T lymphocytes, inhibit prostaglandins and
leukotriene synthesis, inhibit neutrophil and monocyte superoxide radical
generation
Half Life:Half-life: Prednisone- 2-3 hours; dexamethasone – 4 hours; methylprednisolone -18-36
hours
Indication: Rheumatoid arthritis, immune thrombocytopenic purpura
Side effects: Glucose intolerance and risk of infection
Black Box:
Considerations:Can increase glucose levels and insulin resistance

Question 18

What is the:

MOA:
Half Life:
Indication: 
Side effects:
Black Box:
Considerations:

Of Rituximab?

Answer 18

MOA:monoclonal antibody against the protein CD20, which is primarily found on the surface of immune system B cells
Half Life: 14-62 days
Indication: ITP, Lymphomas and leukimias, graft-verses-host disease
Side effects: Progressive leukoencephalopathy
Black Box: Fatal infusion rxn can occure
Considerations: Avoid vacciens. Wait 12 months to get pregnant

Question 19

What is the:

MOA:
Half Life:
Indication: 
Side effects:
Black Box:
Considerations:

Of Immune Serum Immune Globulin?

Answer 19

MOA: Blocks the Fab receptor on macrophage bound anibodies. This prevents the auto immune dystruction of platlets
Half Life: 6 days
Indication: ITP, Myasthenia gravis
Side effects: typical stuff
Black Box: Thrombosis
Considerations: Increased platelet count indicates efficacy