2 – Drugs Affecting Blood Cells/Function

Question 1

Drugs affecting WBCs

Answer 1

• Goal: increase WBC numbers and function
• Recombinant granulocyte colony stimulating factors (g-CSF)
  o Involved in increasing neutrophils

Question 2

What are the uses of drugs affecting WBCs?

Answer 2

• increase circulating neutrophil counts
• activate neutrophil function (phagocytosis)

Question 3

What are the example of drugs that affect WBCs?

Answer 3

• *filgrastim, pegfilgrastim
• Humans: Neupogen, Neulasta
  o Used for neutropenic patients during CHEMOTHERAPY
  o Occasionally used in canine oncology patients
  o *HIGHLY CONSERVED BETWEEN SPECIES (issue if used repeatedly)

Question 4

Neulasta

Answer 4

• Pegfilgrastim form
• LASTS LONGER

Question 5

Drugs affect RBCs

Answer 5

• *erythropoietin and variants
• NEW: mollidustat
• Pentoxifylline

Question 6

Erythropoietin (EPO, ‘epoetin’)

Answer 6

• Produced by kidney peritubular interstitial cells
• Injectable formulations only (it is a small peptide hormone)

Question 7

What are the uses of EPO?

Answer 7

• Anemia due to chronic kidney disease
• Myelodysplasia
• Performance-enhancing drug (ex. Armstrong)

Question 8

When do you use antithrombotic drugs?

Answer 8

• Prevent thrombosis (but not so much to cause hemorrhage!)
  o Arterial or venous thrombosis
  o Pulmonary thrombosis and embolism
  o DIC

Question 9

Sub-endothelial tissue exposed, steps that occur..

Answer 9

• Vessel constricts
• Platelet adhere
• Platelets aggregate to form platelet plug
• *activation of coagulation pathway results in activation of thrombin which catalyzes fibrinogen (soluble) into FIBRIN (insoluble)=stabilizes plug (THROMBUS)

Question 10

“Drug” examples affecting coagulation (anti-coagulants)

Answer 10

• Heparin
• Calcium chelators
• Vit K analog (warfarin, dicoumarol)

Question 11

What are some examples of calcium chelators?

Answer 11

• Sodium citrate
• Sodium oxalate
• EDA
• Sodium fluoride

Question 12

What are calcium chelators used for?

Answer 12

• Blood collection and storage
  o IMPACTS fibrin clot formation
• *NOT as an anticoagulant drug

Question 13

Where is heparin produced?

Answer 13

• In mast cells (proteoglycan)

Question 14

**What is heparin?

Answer 14

• Glycosaminoglycan (GAG), negatively-charged polyanion
• Significant anticoagulant activities
• *used in multiple types of antithrombotic drugs
  o Give IV or SC

Question 15

What are the anticoagulant activities of heparin?

Answer 15

• Inactive factor IX, X, XI, XII (along with anti-thrombin)
• Prevents conversion of prothrombin to thrombin
• Prevents conversion of fibrinogen to fibrin
• Prevents stabilization of fibrin clots (inhibition of factor XIII)

Question 16

**Coumarin derivatives (dicoumarol, warfarin)

Answer 16

• Interfere with Vit K-dependent coagulation factors (lots!)
• Long term oral administration may be required
• Dose modification based on observed prothrombin time (PT)
• *used in humans, lots of toxicity in animals

Question 17

What do thrombolytics do?

Answer 17

• Enhance clot breakdown (fibrinolysis) by stimulating conversion of plasminogen to plasmin
• *not used much in vet med (except in referral practices)

Question 18

Drug examples affecting clot formation (thrombolytics)

Answer 18

• Streptokinase
• Tissue-type plasminogen activator (tPA)

Question 19

Drug examples affecting platelets (antiplatelet drugs)

Answer 19

• Thromboxane inhibitor: aspirin (ASA)(NSAID)
• Clopidogrel: therapy for IMHA
• *not much in vet med (maybe referral practices)
• *decrease platelet aggregation and plug formation