Anti-Anemic Drugs

Question 1

what are the classes of anti-anemic drugs?

Answer 1

• erythroid stimulating agents
• iron preparations
• vitamin B12 preparations
• folic acid preparations

Question 2

what will the reduction of RBCs cause in iron deficiency anemia?

Answer 2

• decrease blood viscosity and lower vascular resistance which will increase venous return and cardiac output
• low blood pressure
• increase in heart rate

Question 3

what are the 5 main causes of iron deficiency anemias?

Answer 3

1. bleeding
2. increased demand
3. malabsorption
4. diet
5. B12 or folate replacement therapy

Question 4

How is iron absorbed in the GI tract?

Answer 4

Ferric iron (Fe³⁺) must first be reduced to ferrous (Fe²⁺) before absorption in the gut lumen via the DMT-1 channel (for Fe²⁺) and heme carrier protein (HCP1) (for heme iron)

Question 5

What is the role of transferrin in iron metabolism?

Answer 5

Transferrin transports iron through the bloodstream and delivers it to places like the bone marrow for red blood cell (RBC) production

Question 6

How is iron stored and released in the body?

Answer 6

stored in the liver and released via a transporter called ferroportin (FP)

Question 7

What is the function of hepcidin?

Answer 7

Hepcidin blocks ferroportin, reducing both iron absorption and its release from the liver which prevents iron overload and low iron levels decrease hepcidin production

Question 8

Who is oral iron therapy recommended for?

Answer 8

patients with adequate GI absorption, no chronic kidney disease (CKD), not on dialysis, and who are receiving erythropoietin

Question 9

What types of iron are preferred for oral therapy and how long does it take to replenish iron stores?

Answer 9

• Ferrous salts like ferrous gluconate, ferrous sulfate, and ferrous fumarate
• 3-6 months

Question 10

What are common adverse effects of oral iron therapy?

Answer 10

• GI distress, nausea, vomiting (dose-related)
• Black stools (can mask GI bleeding)
• Hypersensitivity reactions

Question 11

Why must iron supplements be kept away from children?

Answer 11

Overdose can cause necrotizing gastroenteritis, shock, and metabolic acidosis.
**Activated charcoal is ineffective; use parenteral deferoxamine instead

Question 12

When is parenteral iron therapy used?

Answer 12

When oral iron is not tolerated and in severe anemia not managed by oral iron alone

Question 13

What form is iron in during IV/parenteral therapy?

Answer 13

ferric form (Fe³⁺), which limits how much can be given directly

Question 14

How is IV iron modified to be safe and effective?

Answer 14

It’s given as a colloid particle to increase the elemental iron content and allow safer dosing

Question 15

What are examples of parenteral iron formulations?

Answer 15

• Iron dextran
• Sodium ferric gluconate complex
• Iron sucrose

Question 16

What caution should be taken with iron in infections?

Answer 16

Iron promotes bacterial growth, so it must be used carefully in patients with existing infections

Question 17

what are the adverse effects of Iron Dextran (IV,IM)?

Answer 17

• Headache, fever, flushing, arthralgia
• Nausea, vomiting, skin staining (if given IM)
• Rare anaphylaxis → always give test dose before full administration

Question 18

what is a key feature of Ferumoxytol (IV) and what are its adverse effects?

Answer 18

• Coated in carbohydrate shell, processed by reticuloendothelial system → stored as ferritin or transferred to transferrin
  AE:
• Hypotension, nausea, vomiting, abdominal discomfort
• Interferes with MRI imaging
• Black-box warning: Risk of fatal allergic reactions

Question 19

what are the adverse effects of Iron Sucrose?

Answer 19

• Leg cramps, hypotension
• Nausea, vomiting, abdominal discomfort
• no test dose required

Question 20

what are the adverse effects of Ferric Gluconate and what are the dosing considerations?

Answer 20

• Transient hypertension, tachycardia
• GI symptoms, muscle cramps, local injection site reactions
• Test dose only needed if hypersensitivity is suspected

Question 21

what are the adverse effects of Ferric Carboxymaltose?

Answer 21

• Transient hypertension, nausea
• Flushing, dizziness, hypophosphatemia
• Skin discoloration at injection site
• no test dose required

Question 22

How does vitamin C help with iron absorption?

Answer 22

keeps iron in its ferrous (Fe²⁺, reduced) state, which is the form most easily absorbed in the GI tract which is especially important for oral iron therapy, as Fe²⁺ is better absorbed than Fe³⁺

Question 23

what are the drugs that decrease iron absorption?

Answer 23

• Aluminum, magnesium, and
  calcium-containing antacids
• Tetracycline and doxycycline
• Histamine 2 antagonists
• Proton-pump inhibitors
• Cholestyramine

Question 24

what are the drugs that are affected by iron?

Answer 24

• Levodopa (chelates with iron)
• Levothyroxine (decreases efficacy)
• Penicillamine (chelates with iron)
• Fluroquinolones (forms ferric ion
  quinolone complex)
• Tetracyclines (chelates with iron)

Question 25

What causes acute iron toxicity, and what are the symptoms and treatment?

Answer 25

Often from accidental ingestion of iron tablets, especially in children - Symptoms: GI damage (abdominal pain, vomiting), Hematochezia (blood in stool), Shock or cardiovascular collapse, Liver failure, Neurotoxicity -Treatment: whole bowel irrigation

Question 26

What causes chronic iron toxicity, and how is it treated?

Answer 26

iron overload from genetic causes Hemochromatosis or repeated blood transfusions in diseases like thalassemia or sickle cell disease - treated with phlebotomy (hemochromatosis) or iron chelation therapy with (Oral deferasirox, Parenteral deferoxamine)

Question 27

what is Deferasirox and how does it work?

Answer 27

- oral, iron chelator that has a selective affinity for ferric iron in a 2:1 iron to drug ratio

Question 28

what are the pharmacokinetics of Deferasirox?

Answer 28

- peak concentration in 0.5-1 hour with a half life of 8-16 hours - excreted in the urine as a iron-deferasirox complex

Question 29

what are the adverse effects of Deferasirox?

Answer 29

mild GI issues and skin rash

Question 30

what is Deferoxamine and how does it work?

Answer 30

parental iron chelator that has a selective affinity for ferric iron in a 1:1 iron to drug ratio

Question 31

what are the pharmacokinetics of Deferoxamine?

Answer 31

- half life is biphasic - excreted in the urine as a iron-deferoxamine complex

Question 32

what are the adverse effects of Deferoxamine?

Answer 32

- GI issues - Rash - Imparts orange/red color to urine - Hypotension with rapid infusion - Renal, oto-, pulmonary toxicity with long term therapy

Question 33

what is Vitamin B₁₂ (cobalamin) and what is its role in?

Answer 33

vitamin made by microbes containing a central cobalt atom that activates folate for DNA synthesis and converts methylmalonyl-CoA into succinyl-CoA, which is essential for energy (ATP) production ** must be obtained from animal-based foods like liver, eggs, and dairy (RDA ≥ 2.4 mcg)

Question 34

What is folate's structure and main function in the body?

Answer 34

made of a pteridine ring, PABA, and a glutamate residue and is converted to tetrahydrofolate (THF), which is crucial for 1-carbon transfers involved in DNA synthesis and amino acid metabolism (e.g., converting formiminoglutamate to glutamate, glycine to serine). **RDA ≥ 400 mcg, higher in pregnancy

Question 35

What commonly causes vitamin B₁₂ deficiency and how is B₁₂ stored and transported?

Answer 35

- most common cause, especially in the elderly, is inadequate absorption of dietary vitamin B₁₂ - B₁₂ is stored in the liver (3–5 mg total body pool) and transported in the blood by transcobalamin I, II, and III, which carry B₁₂ to cells throughout the body

Question 36

What are the two key reactions that require vitamin B₁₂?

Answer 36

1. Methylation Reaction (Reaction A): - B₁₂ (as methylcobalamin) converts homocysteine to methionine, allowing regeneration of tetrahydrofolate (THF) for DNA synthesis. 2. Isomerization Reaction (Reaction B): - B₁₂ (as deoxyadenosylcobalamin) converts methylmalonyl-CoA to succinyl-CoA, important for ATP production and detecting deficiency via elevated methylmalonic acid (MMA)

Question 37

What neurologic symptoms occur with B₁₂ deficiency, and are they reversible?

Answer 37

Deficiency can cause paresthesias (tingling) in peripheral nerves, muscle weakness, and ataxia (impaired coordination) that reflect CNS and PNS dysfunction. ** If the deficiency is severe or prolonged, neurologic damage may be irreversible, even with vitamin B₁₂ therapy

Question 38

What is the “methyl-folate trap” and how does it relate to vitamin B₁₂ deficiency?

Answer 38

Vitamin B₁₂ is needed to convert methyl-THF (N⁵-methyltetrahydrofolate) back to active THF, which is essential for DNA synthesis but without B₁₂, folate becomes trapped in the methylated form, leading to the "methyl-folate trap" and buildup of homocysteine

Question 39

How could you restore THF to improve macrocytic anemia?

Answer 39

High folic acid intake but it does not reverse nerve damage (peripheral neuropathy) caused by B₁₂ deficiency

Question 40

What does Vitamin B₁₂ absorption depend on, and where is it stored?

Answer 40

Absorption requires intrinsic factor (IF), made by parietal cells, which binds B₁₂ in the ileum via a receptor called cubilin then its transported in the blood by transcobalamins and stored in the liver

Question 41

What are the main causes of Vitamin B₁₂ deficiency?

Answer 41

- Pernicious anemia (autoimmune destruction of parietal cells or intrinsic factor antibodies) - GI issues: chronic PPI use, gastrectomy, IBD, or ileal resection - Surgical removal of stomach or ileum - Poor diet (less common)

Question 42

What’s the best treatment for B₁₂ deficiency from absorption problems?

Answer 42

treatment should be with parenteral (injection) Vitamin B₁₂, bypassing the gut entirely

Question 43

Which forms of vitamin B₁₂ are used in therapy, and which is preferred?

Answer 43

- Hydroxocobalamin (preferred) - Cyanocobalamin **Hydroxocobalamin is better because it binds more tightly to proteins and stays in the blood longer (longer half-life).

Question 44

What is the typical parenteral (injection) dosing schedule for B₁₂ deficiency?

Answer 44

- Initial therapy (IM): 100–1000 mcg daily or every other day for 1–2 weeks - Maintenance therapy: 100–1000 mcg once per month

Question 45

When is oral or nasal vitamin B₁₂ therapy used?

Answer 45

- Oral B₁₂ is only used if injections aren't tolerated (high doses: ~1000 mcg/day) - After pernicious anemia is controlled, B₁₂ can be continued as a nasal spray or gel

Question 46

How is folic acid absorbed and stored in the body?

Answer 46

- Absorbed in the proximal jejunum via PCFT and RFC transporters - Total body stores: 10–30 mg, with 200 mcg/day recycled via enterohepatic circulation *** Deficiency develops faster than B₁₂ due to lower stores and less conservation

Question 47

What are common causes of folate deficiency?

Answer 47

- Poor diet (esp. in alcohol use disorder) - Malabsorption or renal dialysis - Increased demand (pregnancy, hemolysis) - Vitamin B₁₂ deficiency - Antifolate drugs like methotrexate, trimethoprim, or pyrimethamine

Question 48

How is folate deficiency diagnosed?

Answer 48

measuring either serum folate or red blood cell folate levels

Question 49

How is folate deficiency treated?

Answer 49

- Folic acid 1 mg/day orally — no need for injection, even in elderly - Leucovorin (folinic acid) is used for methotrexate toxicity

Question 50

When and how is epoetin alpha (rHuEPO) used?

Answer 50

- given IV 3 times per week because it's a glycoprotein (Darbepoetin alpha: longer half-life → once per week) - Used in: Anemia of CKD or critical illness, Chemotherapy-induced anemia, HIV treatment-related anemia

Question 51

How does epoetin alpha (Epogen®, Procrit®) work?

Answer 51

Binds to EPO receptors on erythroid progenitor cells to stimulate RBC production, division, and differentiation to increase reticulocytes (immature RBCs) in the blood

Question 52

What are the main adverse effects of epoetin alpha?

Answer 52

- Hypertension and thrombosis (especially if Hgb > 11 g/dL) - Hypersensitivity reactions (it's a recombinant protein) - Can be abused in sports for “blood doping”