Hematopoiesis but Make It Pharmaceutical ( drugs acting on blood hematopoiesis)

What is another name for Erythrocyte deficiency?

anemia

Many diseases can cause erythrocyte deficiency and are grouped into what THREE things?

1) conditions cause blood loss: trauma, heavy infestation of blood-sucking parasites, tumors, or blood clotting disorder

2) diseases cause hemolysis

3) diseases cause bone marrow suppression

T/F For long-term management, the common condition of chronic anemia is an insufficient supply of substances required for normal production of erythrocytes or hematopoietic growth factors.

True

_____-____ ___(ESAs) are used for the pharmacological management of certain types of anemia by supplementing the substances necessary for blood cell formation.

Hematopoiesis-stimulating agents

•Hematopoietic agents stimulates what?

Stimulating red blood cell production

What is the key regulator regulator of red blood cell formation?

Erythropoietin (EPO)

What is a medication used to treat anemia by stimulating the production of red blood cells?

Darbepoetin

What is an example of a medication that is an oral EPO inducer?

Molidustat

What are TWO examples of Anabolic or Androgenic Steroids?

Stanozolol, Nandrolone

What agents provide the essential substances required for cell growth and formation?

Hematinic Agents

What are the TWO things that are crucial for cell maturation?

Vitamin B12 and folic acid

What is necessary for the production of heme, which in turn supports hemoglobin development in mature erythrocytes.

iron

When is a case where hematopoietic agents are essential for treatment?

bone marrow suppression

T/F The most critical substances that are likely to become deficient include vitamin B12, folic acid, and iron, all of which are necessary for cell synthesis and hemoglobin formation.

True

What is the name of the peptide hormone that is a growth factor for erythroid stem cells?

Erythropoietin (EPO)

This protein hormone is synthesized primarily in the ____ ____ ; hypoxia or anemia will ____ its synthesis

renal cortex

increase

Once released into circulation, it binds to receptors of erythroid progenitor cells, where it does what?

it initiates proliferation and differentiation of erythroid precursor cells and subsequent release of mature reticulocytes from the bone marrow

What is an instance where there would be an EPO deficiency?

Chronic renal disease

In the face of renal disease, erythropoietin synthesis ____, resulting in what?

decreases

anemia

Anemia related to kidney disease indicates using ___ by replacing the erythropoietin with an exogenous erythropoietin injection.

EPO

T/F There is veterinary-approved EPO product available

False, there is none

What is is used in animals. "r" hEPO is synthesized using recombinant techniques

rhEPO

Although the rhEPO peptide has cross-reaction for erythropoiesis, the rhEPO peptide is sufficiently foreign to animals that _____ ____ resulting in premature destruction and a loss of efficacy.

antibody production

The ____ of position refers to "alpha" and "beta" EPO products

glycosylation

T/F Adding carbohydrates or glycosylating to the protein disguises it somewhat, thus increasing antibody formation response

False, decreased antibody formation

What are TWO examples of alpha products?

Epogen and darbepoetin

_____, a model drug, is an example of a 2nd generation erythropoietin that has been hyperglycosylated

Darbepoetin

A hyperglycosylated product not only _____ antigenicity but stabilizes the product as well as prolongs elimination.

decreases

The primary indication for recombinant erythropoietin is what?

chronic renal disease

T/F. EPO therapy might not be necessary to manage non-kidney-related anemia

True

Chronic anemia results in lower __ stores, as erythropoiesis increases

iron

What are some adversities associated with erythropoietin therapy? (3)

Hypertension

Pure red cell anemia (PRCA)

Polycythemia (unlikely)

Anemia induced by EPO therapy is called what?

Pure red cell anemia

How long does recovery take after EPO is discontinued?

2-4 months

T/F Darbepoetin has less incidence of PRCA than epoetin.

True

EPO use in humans shows a high incidence of hypertension as well as the use in what animal?

cats

What is the drug that is the first oral drug to receive conditional approval for use in cats suffering from nonregenerative anemia due to chronic kidney disease?

Molidustat (Varenzin-CA1)

What is the MOA for Molidustat (Varenzin-CA1)?

EPO is produced by stimulating of

Hypoxia-inducible factor (HIF) alpha and HIF beta binding at Hypoxia-Response Element (HRE). HIF-alpha is produced continuously

Under normal oxygen conditions, what happens to HIF-α,?

Prolyl hydroxylase breaks down HIF-α so it can't join with HIF-β.

How does molidustat change this process to ultimately increase erythropoietin (EPO) production?

Molidustat blocks this enzyme, letting HIF-α stay intact and bind to HIF-β. Together, they turn on genes that make more erythropoietin (EPO).

A HIF-PB inhibitor does what to EPO and RBC production?

increases both

What is an indication for giving Molidustat (Varenzin-CA1)?

Anemia from chronic kidney disease in cats

Anabolic Steroids are drugs that mimic what?

the effects of testosterone

How do anabolic steroids produce their effects at the cellular level?

Anabolic steroids enter the target cell, bind to receptors in the cytosol, and move into the nucleus. There, they attach to nuclear receptors that activate DNA synthesis and stimulate production of specific proteins.

In the ____ ___, the effect is to differentiate stem cells into erythroid cells and subsequent stimulation

bone marrow

In the kidney, they also stimulate ___ formation and release.

EPO

Anabolic steroids promote ____ release

oxygen

Where does erythropoietin (EPO) act, and what does it bind to?

EPO acts on target cells in the bone marrow and binds to cytosolic receptors inside those cells

What cellular effects occur after EPO binds to its receptor?

Binding enhances glycolysis to increase energy and promotes greater oxygen release from red blood cells

What happens after the receptor complex moves into the nucleus?

The complex stimulates the formation of effector proteins, leading to increased EPO synthesis, stem cell proliferation, and differentiation into mature red blood cells.

Anabolic steroids are synthetic compounds structurally related to _____

testosterone

Anabolic steroids result in a ___- protein balance, and, in contrast to testosterone, anabolic steroids have less ____ ____

positive

androgenic effects

___-____ relationships indicate a potency of an anabolic effect compared to an androgenic effect

Structure-activity

Changing the ___ ____ of the molecule alters the balance between anabolic and androgenic effects and improves how the drug is processed in the body.

C17 position

_____, a modified form of testosterone with alkylation at the C17 position, serves as an example—it has strong anabolic activity but very little androgenic effect.

Stanozolol

Testosterone (or any other steroids) has a first-pass effect from ___ administration

oral

Stanozolol has better oral absorption compared to testosterone and impairs _____ ____ , thus prolonging elimination.

hepatic metabolism

_____ is an esterification structure from testosterone in the same position and has a small level of androgenic effect and has an extended absorption from parenteral sites

Nandrolone

T/F Synthetic testosterone-like drugs are designed to have stronger anabolic effects than androgenic ones.

True

What does Alkylation at the C17 position do?

enhances absorption, reduces hepatic metabolism, and prolongs the drug's half-life.

What does Esterification do?

slows absorption, further extending the drug's duration of action.

Anabolic steroids are formulated as ___-____ products to prolong parenteral absorption and, thus, further action duration.

oil-based

T/F . All steroids must be metabolized, generally by the liver, and many metabolites are active.

True

What type of anabolic steroid is more likely to cause Hepatotoxicity?

The C-17 alkylated (methylated) products

What is an adverse effect associated with androgenic effects?

Masculinization

What are the indications for anabolic steroids?

countering the catabolic effects of renal disease or cancer chemotherapy

Because of abuse and harm, anabolic steroids are regulated by the ___ ___ ___ ___ schedule ___ substances under the Controlled Substances Act

Drug Enforcement Agency: Schedule III

What are the TWO indications for Anabolic Steroids?

•Renal disease

•Bone marrow stimulation

Why are drug testing limits important for anabolic steroids in animals?

They ensure drug residues stay within safe tolerance levels, which is especially important for food-producing animals.

How long are the typical withdrawal times for these drugs?

Withdrawal times can range from weeks to months, depending on the drug and animal species.

How are residues commonly detected, and where can they persist the longest?

Residues are most often detected through urine testing, where they can remain longer than in other tissues, posing a risk of meat residue contamination

Vitamin B12 or ____ is a cobalt-centered porphyrin and is naturally found in animal products

cobalamin

T/F Dogs and cats are carnivorous, so that the deficiency of vitamin B12 from malnutrition is rare

True

Anemia relating to vitamin B12 deficiency in animals often is from ____ ____ ____ , causing poor absorption

chronic gastrointestinal diseases

Vitamin B12 acts as a cofactor in the ___ cycle, where it helps synthesize purines and pyrimidines and regulates ___ ____

methionine

DNA methylation

VIT B12 serves as a cofactor in the production of ____ __, which is essential for hemoglobin synthesis. Because of its key role in red blood cell maturation, vitamin B12 is often referred to as the “maturation factor.”

succinyl CoA

Because of its key role in red blood cell maturation, vitamin B12 is often referred to as the what?

maturation factor.

The deficiency of Vitamin B12 can lead to what?

unable to develop mature erythrocytes and to accumulate hemoglobin.

What happens to red blood cell development when vitamin B12 is deficient?

Red blood cells fail to mature properly and cannot accumulate enough hemoglobin, making them unable to carry oxygen efficiently.

How does vitamin B12 deficiency lead to hypoxia and increased erythropoiesis?

The lack of oxygen (hypoxia) caused by immature RBCs triggers the release of erythropoietin (EPO), which stimulates the bone marrow to produce more RBCs, including immature ones.

What are the typical laboratory findings for vitamin B12 deficiency anemia?

A macrocytic red blood cell pattern is seen, often detected during a routine CBC.

T/F Vit B12 def can cause Megaloblastic anemia or "Pernicious anemia

True

What does Vit B12 combine with in the stomach to protect oxidation from gastric acid?

R protein

What splits the cobalamin-R-protein complex in the duodenum, where cobalamin binds to the intrinsic factor

pancreatic enzyme

Parietal cells produce an ___ ___ , and its secretion is stimulated via the same pathways to stimulate gastric acid secretion

Intrinsic factor

A cobalamin-intrinsic factor complex moves along a small intestinal tract, and absorption occurs where?

ileum

How is vitamin B12 absorbed and distributed in the body after binding with intrinsic factor?

Vitamin B12 binds to intrinsic factor and is absorbed in the ileum. It then attaches to transcobalamin, which carries about half to the bone marrow for use and the rest to the liver for storage.

Where is Vit B12 stored?

liver

T/F Elimination occurs in the bile, resulting in enterohepatic circulation, or urine

True

Vitamin B12 also undergoes ____ ____ , allowing it to be reused.

enterohepatic circulation

What are the four forms of Vit B12 and how would you describe them?

1.(Cyano)-cobalamin: semi-synthetic

2.Hydroxocobalamin: microbial synthesis

3.Methylcobalamin: active forms

4.Adenosylcobalamin: unstable form

Because a lack of oral absorption is usually the cause for vitamin B12 deficiency, treatment generally reflects injectable products as which TWO forms

cyanocobalamin or hydroxocobalamin.

T/F There is an abundance of oral medications of B12

False, limited

What type of drug interactions does Vit b12 have

anti gastric drugs

What is the role of Folic Acid?

DNA and RNA synthesis

Folate is absorbed in the gastrointestinal tract after undergoing what THREE processes?

hydrolysis, reduction, and methylation

T/F To be converted into its active form, tetrahydrofolate (THF), vitamin B12 is required

True

Where is folic acid mainly absorbed?

jejunum

What is the contraindication for Folic acid?

undiagnosed anemia

What does Vit B12 help maintain? Deficiency can cause what?

myelin sheath

neuropathy