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IRON PHARMACOLOGY - Complete 2nd MBBS Answer

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IRON ABSORPTION - Mechanism (Essential Background)

• Fe²+ (Ferrous) - absorbed form
• Fe³+ (Ferric) - storage/dietary form (must be reduced first)

DIETARY IRON (Fe³⁺ / Haem iron)
         ↓
Gastric acid + Vitamin C → reduces Fe³⁺ to Fe²⁺
         ↓
Ferrireductase (Dcytb) on brush border
         ↓
DMT-1 transporter → enters enterocyte
         ↓
    ┌────────────────────────────────┐
    │         ENTEROCYTE             │
    │  • Stored as FERRITIN         │
    │  • (mucosal block mechanism)  │
    │  • OR exported via FERROPORTIN│
    └────────────────────────────────┘
         ↓ (ferroportin)
Plasma → binds TRANSFERRIN (Fe³⁺)
         ↓
  BONE MARROW → Hb synthesis
  LIVER/SPLEEN/BM → stored as FERRITIN/HEMOSIDERIN

• Men: 1 mg/day
• Premenopausal women: 2 mg/day
• Pregnant women: 3-4 mg/day

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SECTION 1: ORAL IRON PREPARATIONS

Enumerate - Oral Iron Preparations

Key Point (KD Tripathi): Ferrous salts (Fe²⁺) are better absorbed than ferric salts (Fe³⁺). Ferrous sulfate is the cheapest and most widely used.

• Fumarate = 33% (highest)
• Sulfate = 20%
• Gluconate = 11% (lowest)

Indications for Oral Iron

1. Iron deficiency anemia (IDA) - most common indication
2. Prophylaxis during pregnancy (National Iron + Folic Acid supplementation program)
3. Premature infants and rapid growth periods in children
4. Menorrhagia / chronic blood loss - menstruating women
5. Post-gastrectomy (if absorption is adequate)
6. Nutritional deficiency states

Mechanism of Action

• Oral iron provides elemental iron for incorporation into hemoglobin in erythroid precursors in bone marrow
• ~50-100 mg of iron can be incorporated into Hb daily
• ~25% of ferrous iron from oral preparation is absorbed
• So 200-400 mg elemental iron/day needed for rapid correction

Uses / Dose

• Therapeutic dose: 200 mg elemental iron/day in 3 divided doses (equivalent to ~300 mg ferrous sulfate TDS)
• Prophylactic dose: 60 mg elemental iron + 500 mcg folic acid daily (in pregnancy)
• Continue treatment 3-6 months after Hb normalizes (to replenish stores)
• Expected Hb rise: ~1 g/dL/week after adequate treatment

Adverse Effects of Oral Iron

GI Side Effects (most common, dose-related):

How to minimize GI side effects:

• Take with food (reduces absorption ~30-50% but improves tolerance)
• Start with lower dose and titrate up
• Change to a different iron salt
• Use liquid formulation (children)
• Enteric-coated tablets (reduce GI side effects but also reduce absorption)

Other adverse effects:

• Tooth staining - liquid preparations (use straw)
• Metallic taste
• Darkening of teeth (in liquid forms)

Interactions:

• Tetracyclines, fluoroquinolones, antacids - chelate iron, reduce absorption
• Vitamin C (ascorbic acid) - ENHANCES iron absorption (reduces Fe³⁺ to Fe²⁺)
• Tea, coffee, phytates - reduce iron absorption
• Give iron 1 hour before or 2 hours after these drugs/foods

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SECTION 2: PARENTERAL IRON PREPARATIONS

Enumerate - Parenteral Iron Preparations

KD Tripathi Note: Iron dextran is a stable complex of ferric oxyhydroxide and dextran polymers containing 50 mg elemental iron/mL.

Indications for Parenteral Iron

1. Intolerance to oral iron (persistent GI side effects)
2. Malabsorption syndromes (celiac disease, Crohn's of proximal small bowel)
3. Post-gastrectomy / short bowel syndrome - inadequate intestinal surface
4. Inflammatory bowel disease (IBD) involving proximal small bowel
5. Chronic kidney disease (CKD) on hemodialysis + EPO therapy - PREFERRED route
6. Functional iron deficiency in cancer patients on erythropoiesis-stimulating agents
7. Non-compliance with oral iron
8. Rapid iron repletion required (pre-operative patients)
9. Severe IDA where oral route is too slow

Adverse Effects of Parenteral Iron

Iron Dextran - Specific Risks:

All Parenteral Iron - General Side Effects:

Iron Sucrose / Ferric Carboxymaltose (Safer profile):

• Much lower risk of anaphylaxis compared to iron dextran
• No test dose required for iron sucrose and ferric carboxymaltose
• Ferric carboxymaltose: most common side effect is transient hypophosphatemia

Calculation of parenteral iron dose (Iron Dextran):

Total iron (mg) = Weight (kg) × 2.3 × (Target Hb - Actual Hb) + 500
                                              (g/dL)
OR
= 0.3 × Body weight (lbs) × (100 - [Hb × 100/14.8])

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SECTION 3: IRON DEFICIENCY ANEMIA - DRUG TREATMENT

Enumerate: Drug Treatment of IDA

                    DIAGNOSIS OF IDA
          ┌──────────────────────────────┐
          │ • Low Hb (microcytic,        │
          │   hypochromic)               │
          │ • Low MCV (<80 fL)           │
          │ • Low serum ferritin (<20)   │
          │ • Low serum iron (<30 mcg/dL)│
          │ • High TIBC                  │
          │ • Transferrin sat <10%       │
          └──────────────┬───────────────┘
                         ↓
              TREAT UNDERLYING CAUSE
                         +
                IRON SUPPLEMENTATION
                         ↓
            ┌────────────────────────────┐
            │     FIRST LINE:            │
            │   ORAL IRON THERAPY        │
            │                            │
            │ • Ferrous Sulfate 200mg    │
            │   elemental iron/day       │
            │   (in 3 divided doses)     │
            │ • Continue 3-6 months      │
            │   after Hb normalizes      │
            └──────────┬─────────────────┘
                       │
          ┌────────────┴──────────────┐
          │ Indications for IV/IM     │
          │ (Parenteral Iron):        │
          │ • Intolerance to oral     │
          │ • Malabsorption           │
          │ • CKD + dialysis + EPO    │
          │ • IBD (proximal bowel)    │
          │ • Post-gastrectomy        │
          │ • Non-compliance          │
          └────────────┬──────────────┘
                       ↓
            PARENTERAL IRON THERAPY
            (Iron sucrose preferred)

Drug Treatment - Enumerated List:

1. Ferrous Sulfate - 325 mg TDS (standard first choice)
2. Ferrous Gluconate - 325 mg TDS/QID
3. Ferrous Fumarate - 325 mg BD/TDS
4. Carbonyl iron (slow release, better GI tolerance)
5. Ferric polymaltose complex (IPC) - better GI tolerance, less interaction with food

1. Iron Sucrose (Venofer) - 200 mg IV in 100 mL NS over 15 min
2. Ferric Carboxymaltose (Ferinject) - up to 1000 mg single dose
3. Sodium Ferric Gluconate - 125 mg IV per session
4. Iron Dextran - IM or IV (test dose required)
5. Ferumoxytol - 510 mg IV; two doses over 3-8 days

• Folic acid (if co-deficiency, common in pregnancy)
• Vitamin C (500 mg) with iron - enhances absorption
• Erythropoietin in CKD patients (given WITH parenteral iron)
• Blood transfusion - reserved for Hb <7 g/dL with severe symptoms

Monitoring Response to Iron Therapy:

Exam Point: If no response to oral iron after 4 weeks, check: compliance, ongoing blood loss, malabsorption, wrong diagnosis.

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SECTION 4: IRON POISONING - ANTIDOTES AND TREATMENT

Iron Poisoning - Overview

• Most common in children who accidentally ingest parents' iron tablets or prenatal vitamins
• Toxic dose: >20 mg/kg elemental iron = toxic; >60 mg/kg = potentially lethal
• Fatal dose in children: as low as 200-250 mg elemental iron/kg

Stages of Iron Toxicity (KD Tripathi / Rosen's Emergency Medicine)

Mnemonic for stages: "GI Lies Sick Having Stenosis" (GI, Latent, Systemic, Hepatic, Strictures)

Mechanism of Iron Toxicity

Free Iron (Fe²⁺/Fe³⁺) in excess
         ↓
Fenton Reaction:
Fe²⁺ + H₂O₂ → Fe³⁺ + OH⁻ + OH• (hydroxyl radical)
         ↓
Lipid peroxidation of cell membranes
         ↓
Mitochondrial dysfunction
         ↓
↓ ATP production
         ↓
Cell death in: Liver, Heart, CNS, GI mucosa
         ↓
Metabolic acidosis (lactic acidosis) + Multi-organ failure

Iron Poisoning - Antidotes

PRIMARY ANTIDOTE: DEFEROXAMINE (Desferrioxamine)

Deferoxamine + Fe³⁺ → FERRIOXAMINE (water-soluble chelate)
                              ↓
                    Renally excreted
                    ("Vin rose" / pink-orange colored urine)

• Deferoxamine chelates free iron (Fe³⁺) specifically
• Does NOT chelate iron from hemoglobin, transferrin, or ferritin (selective - only free ionic iron)
• Forms ferrioxamine - excreted in urine (pink/orange = sign of effective chelation)

1. Serum iron >500 mcg/dL
2. Serum iron >300 mcg/dL with symptoms
3. Metabolic acidosis
4. Lethargy, hypotension, signs of shock
5. Severe GI symptoms (regardless of measured level)

• Hypotension (rapid infusion)
• ARDS (with prolonged infusion >24 hours)
• Yersinia sepsis (deferoxamine is a siderophore for Yersinia)
• Tachycardia, urticaria, flushing
• Cataracts with prolonged use (chronic use in thalassemia)

Full Treatment of Iron Poisoning - Enumerate

IRON POISONING MANAGEMENT
         │
         ├─── 1. STABILIZE (ABC)
         │         Airway, Breathing, Circulation
         │         IV access, O₂, fluids for shock
         │
         ├─── 2. DECONTAMINATION
         │         • Gastric lavage (if within 1-2 hr of ingestion)
         │         • Activated charcoal - NOT effective for iron
         │           (iron does not adsorb to AC)
         │         • Whole Bowel Irrigation (WBI) with
         │           polyethylene glycol (PEG) solution
         │           - if radiopaque tablets visible on X-ray
         │           - Rate: 250-500 mL/hr (child) or
         │             1.5-2 L/hr (adult) until effluent clear
         │
         ├─── 3. ANTIDOTE - DEFEROXAMINE
         │         • IV: 15 mg/kg/hr continuous infusion
         │         • Indication: serum Fe >500 mcg/dL
         │           OR severe symptoms
         │         • Monitor: vin rose urine
         │         • Duration: max 24 hours continuous
         │
         ├─── 4. SUPPORTIVE CARE
         │         • Correct metabolic acidosis (sodium bicarbonate)
         │         • Fluid resuscitation for hemorrhagic shock
         │         • Vasopressors if refractory hypotension
         │         • Correct coagulopathy
         │         • Monitor liver function tests
         │
         ├─── 5. DIALYSIS / EXCHANGE TRANSFUSION
         │         • Hemodialysis - NOT effective
         │           (iron has large Vd)
         │         • Exchange transfusion - only if not
         │           responding to chelation (rare)
         │
         └─── 6. MONITORING
                   • Serum iron (3-5 hr post ingestion,
                     repeat at 6-8 hr)
                   • LFTs, PT/INR, electrolytes, ABG
                   • Abdominal X-ray (radiopaque tablets)

Summary Table: Iron Poisoning Treatment

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QUICK REVISION TABLES

Oral vs Parenteral Iron - Comparison

Mnemonic - Indications for Parenteral Iron: "MAGIC"

• M - Malabsorption
• A - Advanced CKD / hemodialysis
• G - GI intolerance to oral iron
• I - IBD (proximal bowel)
• C - Compliance failure / post-gastrectomy

Mnemonic for Iron Deficiency Lab Findings: "Low SFTM, High T"

• Low Serum iron
• Low Ferritin
• Low Transferrin saturation (<10%)
• Low MCV, MCH, MCHC
• High TIBC (Total Iron Binding Capacity)

Key Drug Interactions

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SOURCES

• Katzung's Basic & Clinical Pharmacology, 16e - Chapter 33 (Agents Used in Anemias)
• Lippincott Illustrated Reviews: Pharmacology - Chapter 44 (Iron) & Chapter 46 (Toxicology)
• Rosen's Emergency Medicine - Chapter 146 (Iron Toxicity)
• KD Tripathi Essentials of Medical Pharmacology - Chapter on Haematinics

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HIGH-YIELD EXAM POINTS (2nd MBBS)

1. Iron sucrose is the safest parenteral iron (preferred in pregnancy and CKD)
2. Activated charcoal does NOT adsorb iron - a common MCQ trap
3. Vin rose (pink-orange) urine = sign that deferoxamine is working
4. Deferoxamine chelates ONLY free iron, not iron in Hb/transferrin/ferritin
5. Deferoxamine >24 hours continuous infusion → risk of ARDS and Yersinia sepsis
6. Ferrous fumarate has highest elemental iron content (33%)
7. Black stools with oral iron = normal, clinically insignificant (but may mask GI bleeding)
8. Reticulocytosis peaks at 5-10 days = earliest sign of response to iron therapy
9. Stage II (latent phase) of iron poisoning = dangerous - patient seems to recover but systemic toxicity is developing
10. Iron dextran requires test dose - other parenteral irons (sucrose, carboxymaltose) do not