Pharmacology: hematinics viva questions with answers exam oriented Pharmacological basis commonly tested

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Hematinics - Viva Questions & Answers (Exam-Oriented)

Sources: Katzung's Basic & Clinical Pharmacology 16e, Lippincott Illustrated Reviews Pharmacology, Goodman & Gilman's Pharmacological Basis of Therapeutics

SECTION 1: IRON

Q1. What is the most common cause of chronic anemia? Iron deficiency. It produces a microcytic, hypochromic anemia due to insufficient hemoglobin synthesis.

Katzung 16e

Q2. What is the role of iron in the body? Iron forms the nucleus of the iron-porphyrin heme ring, which combines with globin chains to form hemoglobin. Hemoglobin reversibly binds oxygen for tissue delivery. Iron-containing heme is also essential in myoglobin, cytochromes, and other proteins.

Katzung 16e

Q3. What are the common causes of iron deficiency?

Acute or chronic blood loss (most common in adults - GI, menstrual)
Menstruation (most common in premenopausal women)
Pregnancy (increased demand)
Dietary deficiency (rare in developed world)
Malabsorption (celiac disease, post-gastrectomy)
Rapid growth in infants/children
Katzung 16e, Lippincott

Q4. What are the unique clinical features of iron deficiency anemia beyond typical anemia symptoms?

Pica - craving for ice (pagophagia), dirt, paper
Koilonychia (spoon-shaped nails)
Angular stomatitis / cheilosis (cracking at corners of mouth)
Glossitis (smooth sore tongue)
Plummer-Vinson syndrome (iron deficiency + dysphagia + esophageal web)
Lippincott Pharmacology

Q5. In what form is iron absorbed, and where?

Iron must be in the reduced ferrous (Fe²⁺) form for absorption
Gastric acid maintains iron in this reduced soluble form
Absorbed in the duodenum (proximal small intestine)
The amount absorbed is inversely proportional to body iron stores (regulated by hepcidin)
Lippincott Pharmacology

Q6. What is the role of hepcidin in iron regulation? Hepcidin is a peptide hormone produced by the liver. It inhibits ferroportin (the iron export protein on enterocytes and macrophages), thereby reducing iron absorption from the gut and iron release from stores. In iron deficiency, hepcidin levels fall, increasing iron absorption. In inflammation/iron overload, hepcidin rises, reducing iron release.

Katzung 16e

Q7. How is iron stored and transported in the body?

Stored as ferritin (iron-protein complex) in intestinal mucosal cells, liver, spleen, and bone marrow; also as hemosiderin
Transported in plasma bound to transferrin (a beta-globulin transport protein)
Transferrin delivers iron to bone marrow for hemoglobin synthesis
Lippincott Pharmacology, Katzung 16e

Q8. What are the lab findings in iron deficiency anemia?

Parameter	Finding
Serum iron	↓
Serum ferritin	↓ (earliest and most sensitive)
TIBC (Total Iron Binding Capacity)	↑
Transferrin saturation	↓ (<16%)
MCV	↓ (microcytic)
Peripheral smear	Hypochromic, microcytic RBCs, target cells
Reticulocyte count	Low (inadequate production)

Q9. Name the oral iron preparations with their elemental iron content.

Preparation	Elemental Iron Content
Ferrous sulfate	~20% (65 mg per 325 mg tablet)
Ferrous fumarate	~33% (highest per mg)
Ferrous gluconate	~12%
Carbonyl iron	~99% pure iron
Polysaccharide-iron complex	Variable

The recommended dose is 60-120 mg/day of elemental iron in divided doses.

Lippincott Pharmacology

Q10. Why is ferrous sulfate preferred over ferric iron salts orally? Ferrous (Fe²⁺) is the more soluble, better-absorbed form. Ferric (Fe³⁺) salts are poorly soluble at intestinal pH and have much lower bioavailability. Gastric acid converts ferric to ferrous form, aiding absorption.

Katzung 16e

Q11. What factors increase or decrease oral iron absorption?

Increases Absorption	Decreases Absorption
Ascorbic acid (Vitamin C) - reduces Fe³⁺ to Fe²⁺	Antacids, PPIs (raise gastric pH)
Acidic environment (HCl)	Tetracyclines, fluoroquinolones (chelation)
Empty stomach	Calcium, phosphates
Iron deficiency state	Tannins (tea), phytates (cereals)
	H. pylori infection

Q12. When should parenteral iron be used?

Malabsorption (celiac, inflammatory bowel disease, post-gastrectomy)
Intolerance to oral iron (severe GI side effects)
Non-compliance with oral therapy
Hemodialysis patients on erythropoietin (need for rapid iron delivery)
Inflammatory bowel disease where oral iron worsens mucosal inflammation
Katzung 16e, Lippincott

Q13. Name the parenteral iron preparations.

Iron dextran (IM or IV; risk of anaphylaxis - test dose required)
Sodium ferric gluconate (IV; safer, fewer reactions)
Iron sucrose (IV; used in CKD/dialysis patients)
Ferric carboxymaltose (IV; single large dose possible)
Ferumoxytol (IV; rapid infusion)
Katzung 16e, Lippincott

Q14. What is the major danger of parenteral iron dextran? Anaphylaxis/anaphylactoid reactions - a test dose of 0.5 mL (25 mg) must be given first, with resuscitation facilities available. Iron dextran carries the highest risk among parenteral iron preparations. Delayed reactions (arthralgias, myalgias, fever) also occur.

Katzung 16e

Q15. What are the side effects of oral iron?

GI disturbances - most common: nausea, vomiting, constipation, diarrhea, epigastric pain
Black discoloration of stools (harmless; important to distinguish from melena)
Liquid preparations can stain teeth temporarily
Higher doses paradoxically decrease absorption and worsen side effects
Every-other-day dosing emerging as effective with fewer side effects
Lippincott Pharmacology

Q16. How long does it take to correct iron deficiency anemia and when should treatment be stopped?

Hemoglobin rises by ~1-2 g/dL per week after therapy begins
Reticulocytosis appears at 3-5 days (first sign of response)
Continue iron for 3-6 months after Hb normalizes to replenish body stores
Katzung 16e

Q17. What is iron overload (hemosiderosis/hemochromatosis) and how is it treated? Excess iron deposits in liver, heart, pancreas, skin ("bronze diabetes"). Iron dextran overdose or repeated transfusions cause hemosiderosis. Treatment: Deferoxamine (IV/SC chelating agent), deferasirox (oral chelator), or phlebotomy.

Katzung 16e

SECTION 2: FOLIC ACID

Q18. What is the role of folic acid in erythropoiesis? Folic acid (as tetrahydrofolate, THF) is essential for one-carbon transfer reactions required for synthesis of:

Thymidylate (dTMP) - essential for DNA synthesis
Purines - for DNA and RNA synthesis Without folate, DNA synthesis is impaired in rapidly dividing cells (including erythroblasts), leading to megaloblastic anemia.
Katzung 16e

Q19. Describe the folate absorption pathway.

Dietary folate (as polyglutamates) is converted to monoglutamates by intestinal conjugases
Absorbed in the proximal jejunum
Converted to N5-methyltetrahydrofolate (the main plasma form)
Stored primarily in the liver (body stores last ~3-4 months only - much less than B12)
Daily requirement: 50-200 mcg (400 mcg in pregnancy)
Katzung 16e

Q20. What are common causes of folate deficiency?

Dietary deficiency (most common - alcoholics, elderly, poor diet)
Pregnancy/lactation (increased demand - commonest cause in pregnancy)
Malabsorption (celiac disease, tropical sprue)
Drugs - methotrexate (inhibits dihydrofolate reductase), trimethoprim, phenytoin, sulfonamides
Hemolytic anemia (increased cell turnover demands more folate)
Katzung 16e

Q21. What is the mechanism by which methotrexate causes folate deficiency? Methotrexate inhibits dihydrofolate reductase (DHFR), the enzyme that converts dihydrofolate (DHF) to tetrahydrofolate (THF). Without THF, one-carbon transfers for dTMP and purine synthesis are blocked, impairing DNA synthesis. Leucovorin (folinic acid/citrovorum factor) bypasses DHFR and is used as a "rescue" agent.

Katzung 16e

Q22. Why is folate supplementation important in pregnancy? Neural tube defects (spina bifida, anencephaly) are strongly linked to folate deficiency in early pregnancy. 400 mcg/day periconceptionally (1 mg/day if prior NTD history) prevents NTDs. Folate is needed for rapid cell division in early neurulation.

Q23. Blood smear in folate/B12 deficiency - what do you see?

Macrocytic, megaloblastic anemia
Hypersegmented neutrophils (>5 lobes in >5% neutrophils; or any cell with 6+ lobes) - pathognomonic
Macro-ovalocytes
Elevated MCV (>100 fL)
Pancytopenia in severe cases

SECTION 3: VITAMIN B12 (CYANOCOBALAMIN)

Q24. What is intrinsic factor and why is it important? Intrinsic factor (IF) is a glycoprotein secreted by gastric parietal cells. Dietary B12 (liberated in stomach/duodenum) binds to IF, and the IF-B12 complex is absorbed via specific receptors in the terminal ileum. Without IF (pernicious anemia, gastrectomy), B12 cannot be absorbed.

Katzung 16e

Q25. What are the two active coenzyme forms of vitamin B12 and their functions?

Coenzyme	Reaction
Methylcobalamin	Transfers methyl group from N5-methylTHF to homocysteine → methionine (links B12 & folate metabolism)
Deoxyadenosylcobalamin	Converts methylmalonyl-CoA → succinyl-CoA (via methylmalonyl-CoA mutase)

Deficiency of deoxyadenosylcobalamin → methylmalonic acid accumulates → demyelination of posterior and lateral columns of spinal cord (subacute combined degeneration of spinal cord - SACD).

Katzung 16e

Q26. Explain the "methylfolate trap" concept. In B12 deficiency, the conversion of N5-methylTHF to THF is blocked (because methylcobalamin, the required co-factor, is absent). Folate becomes "trapped" as N5-methylTHF, which cannot be used for DNA synthesis. This is why:

B12 deficiency causes megaloblastic anemia (via functional folate deficiency)
Large doses of folic acid can partially correct the anemia of B12 deficiency (folic acid can be reduced directly to THF by DHFR)
BUT folic acid does NOT correct the neurological damage of B12 deficiency - masking B12 deficiency with folate is dangerous

Katzung 16e

Q27. What are the neurological features of B12 deficiency (SACD)? Subacute Combined Degeneration of the Spinal Cord (SACD):

Posterior column involvement: loss of vibration sense, proprioception, sensory ataxia
Lateral column (corticospinal) involvement: UMN signs - spasticity, hyperreflexia, extensor plantar
Peripheral neuropathy (also common)
Neuropsychiatric features: megaloblastic madness, dementia The mechanism is failure of myelin synthesis due to methylmalonyl-CoA accumulation and impaired methionine synthesis.
Katzung 16e

Q28. What investigations help differentiate B12 deficiency from folate deficiency?

Feature	B12 Deficiency	Folate Deficiency
Serum B12	↓	Normal
Serum folate	Normal (may be high)	↓
RBC folate	↓ (functional)	↓
Methylmalonic acid	↑ (specific for B12)	Normal
Homocysteine	↑	↑
Neurological features	Present (SACD)	Absent
Schilling test	Abnormal	Normal

Q29. What is pernicious anemia? An autoimmune condition in which antibodies destroy:

Anti-parietal cell antibodies (against H+/K+ ATPase)
Anti-intrinsic factor antibodies (most specific)

This leads to gastric atrophy, loss of parietal cells, absent IF → B12 malabsorption → megaloblastic anemia + SACD. Associated with other autoimmune diseases (thyroid, type 1 DM, vitiligo).

Q30. How is B12 deficiency treated?

Pernicious anemia / malabsorption: IM cyanocobalamin 1000 mcg daily for 7 days, then weekly for 4 weeks, then monthly for life
Dietary deficiency (vegans): oral B12 1000 mcg/day (high-dose oral is sufficient as some absorption occurs by passive diffusion even without IF)
Hydroxocobalamin (preferred in UK): longer half-life, retained better in body
Katzung 16e

Q31. Why should folic acid NOT be given alone in B12 deficiency? Folic acid corrects the hematological findings (anemia) but does NOT correct the neurological damage (SACD). Giving folate alone masks the B12 deficiency and allows neurological deterioration to continue - this is a classic exam trap. Always diagnose and treat B12 deficiency specifically.

Katzung 16e

SECTION 4: ERYTHROPOIETIN (EPO)

Q32. What is erythropoietin and where is it produced? Erythropoietin (EPO) is a glycoprotein hormone produced mainly by peritubular cells of the kidney (85%) and liver (15%) in response to tissue hypoxia. It stimulates erythroid progenitor cell differentiation and proliferation in bone marrow.

Q33. Name the recombinant EPO preparations and their uses.

Epoetin alfa (Epogen, Procrit): given SC or IV
Darbepoetin alfa (Aranesp): longer half-life (hyperglycosylated form), less frequent dosing
Epoetin beta: similar to epoetin alfa
Methoxy polyethylene glycol-epoetin beta (Mircera): continuous erythropoietin receptor activator, monthly dosing

Indications:

Anemia of chronic kidney disease (CKD) - most common indication
Cancer chemotherapy-induced anemia
HIV patients on zidovudine (AZT)
Pre-surgical autologous blood collection
Lippincott Pharmacology

Q34. What is the major adverse effect of erythropoietin therapy?

Hypertension - most common; requires BP monitoring
Thrombosis / thromboembolic events (increased blood viscosity from rising Hct)
Pure red cell aplasia - rare but serious; anti-EPO antibodies develop; treat by stopping EPO and immunosuppression
Tumor progression risk (EPO receptors may be expressed on some tumor cells)
Iron deficiency (functional, from increased utilization) - must ensure adequate iron stores

Important: Target Hb should not exceed 11-12 g/dL in CKD to avoid cardiovascular risks.

Lippincott Pharmacology, Katzung 16e

SECTION 5: HYDROXYUREA & SICKLE CELL

Q35. How does hydroxyurea help in sickle cell disease? Hydroxyurea acts through poorly defined pathways (involving nitric oxide) to increase fetal hemoglobin (HbF) production. HbF does not participate in sickling and inhibits polymerization of HbS, thereby:

Reducing vaso-occlusive crises
Decreasing acute chest syndrome episodes
Reducing frequency of painful crises and transfusion requirements

Mechanism as a chemotherapy drug: inhibits ribonucleotide reductase, depleting deoxyribonucleotides and arresting cells in S-phase.

Katzung 16e

Q36. What are the adverse effects of hydroxyurea?

Myelosuppression (hematopoietic depression) - dose-limiting
GI disturbances
Teratogenicity - contraindicated in pregnancy
Skin changes (leg ulcers with long-term use)
Katzung 16e

SECTION 6: HIGH-YIELD RAPID-FIRE SUMMARY

Q37. Key "Why" questions:

Question	Answer
Why is vitamin C given with iron?	Ascorbic acid reduces Fe³⁺ → Fe²⁺ and maintains acidic pH, increasing absorption
Why is ferritin the earliest lab indicator of iron deficiency?	It reflects body stores before transport iron (serum iron/transferrin) changes
Why is B12 deficiency dangerous even when anemia is corrected by folate?	SACD (neurological damage) continues because it depends on deoxyadenosylcobalamin, not folate
Why does B12 deficiency cause folate-responsive anemia?	Methylfolate trap - THF cannot be regenerated; large exogenous folate bypasses this via DHFR
Why take iron on an empty stomach?	Maximum absorption; food, especially calcium and tannins, chelates iron and reduces uptake
Why are TIBC and transferrin elevated in iron deficiency?	Compensatory upregulation of transferrin synthesis by liver to capture available iron
Why is parenteral iron dangerous?	Risk of anaphylaxis (especially iron dextran), iron overload, hemosiderosis
Why is folate deficiency more rapidly symptomatic than B12 deficiency?	Body folate stores last only 3-4 months vs. B12 stores lasting 3-5 years

Q38. Drug interactions to know:

Drug	Interaction with Iron
Tetracyclines	Form insoluble chelate; iron reduces absorption of tetracyclines AND vice versa
Fluoroquinolones (ciprofloxacin)	Same chelation mechanism
Levodopa	Iron chelates levodopa, reducing its absorption
Levothyroxine	Iron impairs absorption; separate by 4 hours
Antacids/PPIs	Raise pH → reduce Fe²⁺ formation → less absorption

Q39. Differentiate the three nutritional anemias:

Feature	Iron Deficiency	Folate Deficiency	B12 Deficiency
MCV	↓ (microcytic)	↑ (macrocytic)	↑ (macrocytic)
Peripheral smear	Hypochromic, microcytic	Megaloblastic, hyperseg. neutrophils	Megaloblastic, hyperseg. neutrophils
Neurological signs	None	None	SACD (posterior/lateral columns)
Serum ferritin	↓	Normal	Normal
Methylmalonic acid	Normal	Normal	↑
Homocysteine	Normal	↑	↑
Schilling test	Normal	Normal	Abnormal
Common cause	Blood loss	Dietary/pregnancy/drugs	Pernicious anemia/gastrectomy
Treatment	Ferrous sulfate	Folic acid 5 mg/day	IM B12 (cyanocobalamin)

Q40. Classic exam viva traps:

"Can you correct B12 deficiency anemia with folic acid?" - Yes hematologically, but neurological damage (SACD) progresses. Never do this - always treat B12 deficiency with B12.
"Best indicator of iron stores" - Serum ferritin (not serum iron).
"Best form of iron for oral use" - Ferrous sulfate (cheap, effective, high elemental iron content).
"Why does iron therapy cause black stools?" - Unabsorbed iron reacts with intestinal sulfides to form iron sulfide (harmless, but must distinguish from melena).
"First sign of response to iron therapy" - Reticulocytosis at 3-5 days.
"Megaloblastic anemia with no neurological signs" - Think folate deficiency (not B12).
"Darbepoetin vs epoetin alfa" - Darbepoetin has a longer half-life due to additional carbohydrate chains (hyperglycosylation), allowing less frequent dosing.

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