Hematopoiesis Stimulating Agents & Hematinics

Hematopoietic agent

stimulates red blood cell production

• ex: EPO

Hematinic Agents

Agents that provide the essential substances required for cell growth and formation

• ex: folic acid, iron, and vitamin B12

What stimulates EPO release?

Hypoxia inducible factor

When would there be a deficiency of EPO?

chronic renal disease

When is EPO replacement therapy indicated?

• nonregenerative anemia associated with CKD

True or False: There is a veterinary approved EPO product.

FALSE

What are some complications of EPO use?

• anti-EPO Antibody destruction

  • Minimize with glycosylated EPO → epoetin & darbepetin

• Hypertension

• Pure red cell anemia

  • Darbepoetin has lower risk

What drug is used in cats suffering from non-regenerative anemia due to CKD?

Molidustat

What is the mechanism of action of molidustat?

HIF=PB inhibitor to stimulate EPO production

How do anabolic steroids increase EPO?

• increases cellular energy production to increase EPO

• Increase erythroid progenitor proliferation

• Increase RBC production

Anabolic steroids are related to:

testosterone but have less androgenic activity

What position is stanozolol alkylated to produce less androgenic effects?

C17

Nandrolone has a _____ androgenic effect due to:

small; esterification

When are anabolic steroids indicated?

• nonregenerative anemia associated with CKD

• Appetite

• Increase strength and vitality

True or False: All steroids undergo hepatic metabolism

TRUE

What are the adverse effects of anabolic steroids?

• hepatotoxicity

• Virilization: androgenic effect

• Behavioral changes

• Reproductive disorders

True or False: Anabolic steroids undergo hepatic products are widely available.

FALSE - most discontinued and have restrictions

How can you become deficient in B12?

• malnutrition (rare)

• Poor absorption from GI disease

Why is vitamin B12 important for RBC production?

• cofactor for methionine cycle To synthesize purine and pyrimidine in DNA methylation

• Cofactor for succinyl CoA synthesis to produce hemoglobin

Aka maturation factor

What is the Labratory finding for B12 deficiency?

Macrocytic RBC

• megaloblastuc anemia or pernicious anemia

What protects vitamin B12 from oxidation in the stomach?

R protien

What complex is necessary for Ileal absorption of B12?

cobalamin-intrinsic factor complex

How long can it take for vitamin B12 deficiency to be clinically relevant?

months to a year due to liver storage

What are the two forms of administered vitamin B12?

• Cyanocobalamin - supplements

• Hydroxocobalamin - injectable form

What is the active coenzyme form of cobalamin?

methylcobalamin

Whayt is the active mitochondrial coenzyme form of cobalamin?

adenosylcobalamin

True or False: Methycobalamin may be useful when combined with other analgesics for treating neuropathic pain.

TRUE

What drugs may decrease vitamin B12 absorption?

• Proton pump inhibitiors

• H2 receptor antagonists

Conversion of folic acid to the active form, tetahydrofolate, requires:

vitamin B12

Where is folic acid absorbed?

Jejunum

When is folic acid contraindicated?

• patients with undiagnosed anemia

• Megaloblastic anemias where vitamin B12 is deficient

Deficiency of _____ can cause neuropathy due to lack of maintanence of the myelin sheath.

vitamin B12

True or False: Folic acid will mask megaloblastic anemia from vitamin B12 deficiency.

TRUE

When is iron indicated?

• iron deficiency anemia

  • Excessive blood loss

  • Chronic blood loss (parasites)

• Neonatal IDA in piglets

What is the laboratory finding associated with IDA?

hypochromic, microcytic RBC

What type of iron contributes to the development of free radicals and damages tissue?

free or unbound

What are the four iron-protein complexes?

• hemoglobin: Fe2 with globin - carries O2

• Ferritin: Fe3 with apoferritin and non-toxic storage form

• Hemosiderin: ferritin with protien and lipid, toxic storage form

• Transferrin: Fe3 with globulin and carries to different organs via blood circulation

What has an intrinsic catalytic activity that oxidizes ferrous iron into ferric iron?

Apoferritin

Where is iron absorbed?

duoednum and proximal jejunum

What is the unabsorbed and insoluble form?

Ferric iron (Fe3)

What causes ferrous iron to be rapidly oxidized to the insoluble form?

physiological pH

What vitamin enhances iron absorption by chelating with ferric iron?

Ascorbic acid

What distributes iron into circulation?

ferroportin

What are the side effects of iron and iron salts?

• overdose

  • Vomiting / diarrhea

• Anaphylaxis with IV

What drugs does iron interact with?

fluroquinolones, tetracyclines, antacids, and foods

When is iron contraindicated?

hemolytic anemia