ch 49 anemia pharm 2

blood is made of

liquid plasma + formed elements (leukocytes, platelets, erythrocytes).

waht are formed elements

(leukocytes, platelets, erythrocytes).

non-nucleated, biconcave cells that carry oxygen to tissues and remove CO2.

Erythrocytes (RBCs)

lifespan eryhtrocytes

120 days

erythrocytes hemolysis in

spleen liver bone marrow

How the body makes more RBCs:

Kidneys sense low oxygen. They release erythropoietin (a hormone). It travels to the bone marrow and tells the stem cells: "make more red cells!"

when renal tissue oxygenation drops,

juxtaglomerular nephron cells increase release of the glycoprotein hormone erythropoietin. It travels via blood to bone marrow, binds hemocytoblast receptors, and stimulates stem cell proliferation, reticulocyte maturation, and release of erythrocytes

Building blocks for healthy RBCs

iron

b12 folic acid essential amnio acid carb

why is iron needed for rbc

Core element to build heme rings that bind oxygen

why is Vitamin B12 and folic acid needed for rbc

Essential coenzymes for DNA synthesis and structural stroma assembly, letting RBCs survive 120 days of vascular turbulence

why is Essential amino acids and carbohydrates needed for RBC

Make membrane lipids and globin protein chains

cause of iron deficiency anemia

Iron loss exceeds intake. RBCs are microcytic (small) and hypochromic (pale). Common in menstruating individuals, pregnant/lactating people, growing children, and chronic GI blood loss.

cause of Megaloblastic anemia

Too little folic acid or B12 impairs DNA synthesis, producing large, fragile, immature RBCs (megaloblasts).

cause of penicious anemia

A specific megaloblastic anemia from loss of gastric parietal cells or intrinsic factor, so B12 cannot be absorbed in the intestine.

cause of sickle cell disease

Inherited hemoglobinopathy with abnormal Hemoglobin S (HbS) that polymerizes under low oxygen, making RBCs rigid and sickle-shaped; they block capillaries and rapidly hemolyze

Pediatric iron safety:

give liquid oral iron through a straw to prevent permanent tooth enamel staining. Store iron supplements in child-proof containers, out of reach.

Acute pediatric iron ingestion causes

necrotizing gastroenteritis, CNS depression, shock, hepatic necrosis, and death

Myeloid stem cells / hemocytoblasts: targeted by

erythropoiesis-stimulating agents (epoetin alfa).

• Stromal and hemoglobin assembly: targeted by

iron, folic acid, and vitamin B12.

Iron replacement: prototype

FERROUS SULFATE

FERROUS SULFATE mechanism

Raises serum iron; incorporated into hemoglobin rings or stored as ferritin in the reticuloendothelial system.

FERROUS SULFATE PK

oral

iron is consevred and recycled, not excreted

FERROUS SULFATE onset peak duration half life

Onset 4 days. Peak 7-10 days. Duration 2-4 months. Half-life not applicable

FERROUS SULFATE adverse effect

GI irritation, severe constipation, black or tarry stools, nausea, vomiting, dark mucosal staining.

FERROUS SULFATE overdose effect

CNS toxicity and circulatory shock

FERROUS SULFATE food interaction decrease absorption

antacids, milk, eggs, coffee, tea, calcium.

FERROUS SULFATE food interaction increase absorption

vitamin C (ascorbic acid)

what does chelating agent do

act like claws that grab a toxic metal and carry it out in the urine as a harmless package

IM, SubQ, or IV. chelating agent for iron

Deferoxamine mesylate

used for Acute iron intoxication (e.g., pediatric overdose) and chronic transfusional iron overload.

Deferoxamine mesylate

oral chelating agent for chronic transfusional iron overload in patients over 2 years

Deferasirox

oral chelating agent transfusional iron overload in thalassemia and sickle cell disease

Deferiprone

is an oral pediatric lead chelator.]

Succimer

\ is IM/IV lead chelator and needs strict renal and hepatic monitoring.

Calcium disodium edetate

Erythropoiesis-stimulating agent: prototype

EPOETIN ALFA

EPOETIN ALFA mechanism

Recombinant human glycoprotein that binds erythropoietin receptors on bone marrow progenitor cells, stimulating RBC division and differentiation.

EPOETIN ALFA PK

subq

Metabolized in serum; excreted in urine.

EPOETIN ALFA onset peak duration half life

Onset 7-14 days. Peak 5-24 h. Duration 24 h. Half-life 4-13 h.

EPOETIN ALFA indication

Anemia of chronic renal failure, HIV therapy, or cancer chemotherapy; reduces allogeneic transfusions in surgical patients.

BOXED WARNING (ESAs)

target hemoglobin must NOT exceed 11 g/dL.

raises risk of severe cardiovascular events, DVT, stroke, MI, vascular access thrombosis, and death.

Essential for nucleoprotein synthesis and normal erythropoiesis.

folic acid

folic acid indication

megaloblastic anemia from folate deficiency and pre-conception prevention of fetal neural tube defects.

folic acid PK

Routes: oral, IM, SubQ, IV. excreted in urine. Indicated for

folic acid onset and peak

Onset varies; peak 30-60 min;

Essential for nucleic acid synthesis, hematopoiesis, and maintaining the myelin sheath of central and peripheral nerves.

Vitamin B12 (hydroxocobalamin)

Vitamin B12 (hydroxocobalamin) onset peak half life

Onset intermediate; peak 60 min; half-life 24-36 h; e

Vitamin B12 (hydroxocobalamin) PK

IM

excreted in urine

Intranasal cyanocobalamin is strictly contraindicated in patients with

nasal erosion, ulcers, or severe mucosal inflammation because absorption becomes erratic

Oral antineoplastic. Raises fetal hemoglobin (HbF); HbF dilutes abnormal HbS, inhibiting sickling, reducing painful vaso-occlusive crises and transfusion needs

Hydroxyurea

hydroxyurea adverse effect

. bone marrow suppression, nausea, vomiting, stomatitis, rash, hyperpigmentation

hydroxyurea PK

. Oral; ; liver metabolism; urine excretion

hydroxyurea peak duration half life

peak 1-4 h; duration 18-20 h; half-life 3-4 h

Inhibits P-selectin-mediated vascular adhesion

Crizanlizumab-tmca

Inhibits HbS polymerization

Voxelotor

Enhances erythroid maturation to decrease transfusion dependence in beta thalassemia

Luspatercept-aamt

Oral thrombopoietin (TPO) receptor agonist; interacts with the transmembrane domain of the TPO receptor to stimulate megakaryocyte proliferation and bone marrow cell production in severe aplastic anemia

Eltrombopag