pharm ch 49 anemia

not enough healthy red blood cells (RBCs) or not enough hemoglobin, so the blood cannot carry enough oxygen

anemia

ramps up marrow production the moment hypoxia is detected

makes RBC

erythropoesis

what structure deploys erythropoesis

kidneys

happens first Oxygen Feedback Loop

Decreased arterial oxygen pressure in tissues.

tissue hypoxia

happens 2nd Oxygen Feedback Loop

The kidney detects low oxygen and releases erythropoietin (EPO).

renal trigger

Stem cells in the bone marrow are stimulated by erythropoietin.

happens third Oxygen Feedback Loop

marrow stimulation

Mature RBCs are formed, restoring O2 carrying capacity. (Increased O2 carrying capacity shuts the loop off.)

last step Oxygen Feedback Loop

correction

Building red blood cells in the

myeloid tissue of the bone marrow

Used in the formation of hemoglobin rings to bind and carry oxygen.

Iron

Form the vital stromal structure (the cell's frame), allowing the cell to survive 120 days of battering through blood vessels.

Vitamin B12 and folic acid

Complete the hemoglobin rings, the cell membrane, and the overall basic cellular structure.

Amino acids and carbohydrates

the oxygen-carrying protein inside red blood cell

iron sit at center and grab oxygen

hemoglobin

iron deficiency anemia underlying problem

Negative iron balance (losing/using more iron than you take in).

who gets iron deficiency anmeia

Menstruating individuals, pregnant/lactating individuals, growing adolescents, GI bleed patients.

First-line intervention iron deficieny anemia

iron preparations

Megaloblastic anemias underlying problem

Insufficient folic acid or vitamin B12.

red cells are abnormally huge

cell impact Megaloblastic anemias

Failure to create a strong stromal structure; cells become excessively large and fragile. (Includes pernicious anemia.)

first line intervention megaloblastic anemia

b12/folate replacemnt

underlying issue Hemolytic and aplastic anemias

Inherited disorders (sickle cell disease, thalassemia) causing abnormal hemoglobin, or severe bone marrow suppression.

first line intevrnetion Hemolytic and aplastic anemias

Hemoglobin modulators (hydroxyurea) or erythrop oiesis-stimulating agents

Erythropoiesis-Stimulating Agent (ESA) prototype drug

Epoetin alfa (Epogen, Procrit).

Epoetin alfa (Epogen, Procrit)- ESA mechanism

Acts exactly like the natural glycoprotein erythropoietin to stimulate RBC production in the bone marrow

Epoetin alfa (Epogen, Procrit)- ESA indications

Anemia associated with chronic renal failure/kidney disease, and to reduce the need for allogenic blood transfusions in surgical patients

Epoetin alfa (Epogen, Procrit)- ESA onset and how to give

subQ

onset 7-14 days

Epoetin alfa (Epogen, Procrit)- ESA where metabolized and excreted

serum

urine

Epoetin alfa (Epogen, Procrit)- ESA boxed warning

: increased risk of death, myocardial infarction, stroke, venous thromboembolism, thrombosis of vascular access, and tumor progression/recurrence

Epoetin alfa (Epogen, Procrit)- ESA do not use if hemoglobin is

> 11 g/dL

iron preparation drug prototype

Ferrous sulfate (Feosol).

Ferrous sulfate (Feosol). Class: Iron preparation what is mechanism

Elevates serum iron concentration, which is then converted into functional hemoglobin or stored.

Ferrous sulfate (Feosol). Class: Iron preparation

indication

Prevention and treatment of iron deficiency anemia; dietary supplement.

Ferrous sulfate (Feosol). Class: Iron preparation

pharmokinetics

Oral. Iron is recycled for use by the body; not excreted.

Ferrous sulfate (Feosol). Class: Iron preparation

adverse effect

GI upset, anorexia, nausea, constipation, dark stools.

Ferrous sulfate (Feosol). Class: Iron preparation

overdose symptoms

severe CNS toxicity progressing to coma and death.

Ferrous sulfate (Feosol). Class: Iron preparation

drug interaction DO NOT MIX

Antacids, calcium/magnesium, tetracyclines, cimetidine, levodopa

Ferrous sulfate (Feosol). Class: Iron preparation

food that block absorption

Eggs, milk, coffee, tea

Ferrous sulfate (Feosol). Class: Iron preparation

food that enhance absorption

vitamin c

: A 4-year-old child is brought to the ER in shock. The parent states they found the child eating iron-fortified vitamin pills 2.5 hours ago, consuming close to 200 tablets. Treatment:

Administer deferoxamine mesylate (Desferal).

how does deferoxamine mesylate (Desferal). work for iron overdose

Heavy metals deactivate cellular enzymes. Chelating agents ("chelate" is Greek for claw) grasp and hold the toxic metal, forming a nontoxic complex safely excreted by the kidneys

for acute iron toxicity

IV/IM

Deferoxamine

for chronic iron toxicity

oral

Deferasirox

for lead toxicity

Succimer and calcium disodium edetate

shared role of folic acid and vit b12

essential for cell growth and the creation of a strong stromal structure in RBCs

what happen wityhout b12 and folic acid

cells become large and fragile (megaloblastic anemia).

unique role folic acid

Necessary for the production of DNA, RNA, and the division of RBCs, WBCs, and platelets

folic acid deficiency can happen bc of

Alcoholism, malnutrition, malabsorption (e.g., celiac disease), repeated pregnancies.

vit b12 unique role

maintenance of the myelin sheath in nerve tissues.

vit b12 deficiency can happen bc of

Strict vegetarian diets; inability of the GI tract to absorb the vitamin (pernicious anemia).

used fro Megaloblastic anemia due to folate/nutritional deficiency; rescue drug for toxic chemotherapy.

folic acid

folic acid routes

oral im subq iv

Hydroxocobalamin (vitamin B12) route

IM (intramuscular). Note: nasal forms exist but require nasal mucosa evaluation.

used for Vitamin B12 deficiency / megaloblastic anemia.

Hydroxocobalamin (vitamin B12)

adverse effect Hydroxocobalamin (vitamin B12)

Itching, transitory exanthema (temporary rash), mild diarrhea, pain at the injection site.

should folic acid and b12 be used in pregancy

yes

Folate is specifically vital to prevent neural tube defects.

an inherited disorder causing abnormal hemoglobin (hemoglobin S, or HbS), which makes red cells bend into a sickle shape and clog vessels.

sickle cell disease

what does Hydroxyurea do for sickle cell

does not cure but directly stimulates the bone marrow to ramp up production of fetal hemoglobin (HbF).

what does influx of HbF do for sickle cell do

dilutes the formation of abnormal hemoglobin S, reducing the frequency of painful crises and the need for blood transfusion

used to treat anemia fro adult with beta thalassemia who get reuglar rbc transfusion

Luspatercept-aamtia a thrombopoietin receptor agonists

is a thrombopoietin receptor agonists

used to raise platelet count

eltrombopag

sickel cell agent prototype

Hydroxyurea- droxia , hydrea

Hydroxyurea- droxia , hydrea - sickle cell agent mechaism

Increases fetal hemoglobin production in bone marrow, diluting abnormal hemoglobin S.

Hydroxyurea- droxia , hydrea - sickle cell agent indications

Reduction of the frequency of painful crises and need for blood transfusions in adult patients with sickle cell anemia.

Hydroxyurea- droxia , hydrea - sickle cell agent PK

Oral. Metabolized in the liver, excreted in urine.

Hydroxyurea- droxia , hydrea - sickle cell agent

half life

3-4 hr

Hydroxyurea- droxia , hydrea - sickle cell agent

adverse effect

Severe bone marrow depression, anorexia, nausea, stomatitis (mouth sores), rash, erythema, dizziness, and risk of cancer.

Hydroxyurea- droxia , hydrea - sickle cell agent

contraindication

Severe anemia, leukopenia (low white cells), impaired renal/liver function.

what to know about iron for kids

hgihly toxic - keep out

what to know about liquid iron

stain teeth

use straw

what to know about nasal b12 fro kids

OT approved for pediatric pernicious anemia (requires monthly injection)

what to know about iron for adult

frequently causes constipation (institute bowel regimens).

what to know about ESA for adult

requires close monitoring for pure red cell aplasia. (marrow stops making red blood cells entirely)

what to knwo about epoetin alfa or darbepoetin alfa

for pregancny

do not use

adverse fetal effect

what to knwo about iron older adult

Decreased natural absorption of iron. • High risk of severe constipation with iron replacement therapy.

(replace the erythropoietin signal) from kidney

Epoetin alfa / darbepoetin alfa

Bone marrow (hemocytoblasts) → reticulocytes → mature erythrocytes (120 days)

what the problem

Macrocytic (large-cell) anemia and megaloblastic anemia

used fro Macrocytic (large-cell) anemia and megaloblastic anemia

Hydroxocobalamin, cyanocobalamin (vitamin B12 injection); folic acid, leucovorin (folic acid injection)

waht the porblem

Circulation → hemolysis (old cells broken down in liver, spleen, bone marrow)

Iron deficiency anemia

what to use iron deficiency anemia

ferrous sulfate, iron sucrose (iron).

Broken-down RBC make bilirubin → bile and recycled iron, which feeds back into new cells (as does recycled B12).

• Lifespan of Red Blood Cells (RBCs): Red blood cells live for about 120 days before they wear out.

• Cell Breakdown: Special immune cells (macrophages in the spleen and liver) break down old red blood cells.

• Making Bilirubin & Bile: The leftover heme part of hemoglobin turns into bilirubin, which the liver processes and turns into bile (released into the digestive tract).

• Recycling Iron and B12: The iron stripped from the old heme and nutrients like Vitamin B12 are saved and sent back to the bone marrow to build new red blood cells.