Pharmacology and Drug Treatment of Anemia and Bronchial Asthma

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PART I — ANEMIA

Overview

1. Iron preparations (for iron deficiency anemia)
2. Vitamin B₁₂ (for megaloblastic/pernicious anemia)
3. Folic acid (for folate-deficiency anemia)
4. Erythropoiesis-stimulating agents (for anemia of chronic disease/renal failure)
5. Myeloid growth factors (G-CSF, GM-CSF) for neutropenia/aplasia

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1. Iron Deficiency Anemia

Pathophysiology

A. Oral Iron Therapy

• Dosing: Adults typically receive 150–200 mg of elemental iron per day in divided doses
• Duration: Treatment must continue for 3–6 months after the cause of iron loss is corrected, to replenish iron stores fully
• Absorption enhancement: Vitamin C (ascorbic acid) maintains iron in the ferrous (Fe²⁺) form, significantly improving absorption
• Absorption inhibitors: Antacids, milk, tetracyclines, and proton pump inhibitors reduce absorption; doses should be spaced accordingly
• Side effects: Nausea, vomiting, epigastric pain, constipation, diarrhea. Dark stools are expected. Taking with food reduces GI side effects but also reduces absorption by ~40%

B. Parenteral Iron Therapy

C. Acute Iron Toxicity

• Deferoxamine (desferrioxamine) — a chelating agent administered parenterally that binds free iron and allows renal excretion (ferrioxamine complex turns urine red-brown = "vin rosé" urine)

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2. Megaloblastic Anemias

Vitamin B₁₂ (Cobalamin) Deficiency

• Megaloblastic, macrocytic anemia with hypersegmented neutrophils
• Neurological syndrome: paresthesias → spasticity → ataxia → subacute combined degeneration of the spinal cord
• Elevated serum homocysteine AND methylmalonic acid (both are useful diagnostic markers)

1. Conversion of homocysteine → methionine (via methionine synthase) — disruption impairs DNA synthesis, causing megaloblastic changes
2. Isomerization of methylmalonyl-CoA → succinyl-CoA — disruption causes methylmalonic acid accumulation

• Cyanocobalamin or hydroxocobalamin given IM (1000 µg/day × 7 days, then weekly × 4 weeks, then monthly for life in pernicious anemia)
• Oral high-dose B₁₂ (1000–2000 µg/day) can be used when intrinsic factor is not the problem
• Critical warning: Folic acid alone will correct the anemia but will NOT prevent or reverse the neurological damage of B₁₂ deficiency — B₁₂ must be given

Folic Acid Deficiency

• Folic acid 1 mg/day orally
• Leucovorin (folinic acid, 5-formyl-THF) — the active reduced form, used when dihydrofolate reductase is blocked (e.g., methotrexate toxicity rescue)
• Prevention: All women of childbearing age should receive 0.4 mg/day to prevent neural tube defects; 4 mg/day if prior neural tube defect pregnancy

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3. Anemia of Chronic Renal Failure — Erythropoietin

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4. Myeloid Growth Factors (Neutropenia/Aplasia)

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PART II — BRONCHIAL ASTHMA

Overview

• Relievers (quick-relief/rescue): used acutely for bronchoconstriction
• Controllers (long-term maintenance): used daily to prevent inflammation and attacks

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Drug Classes for Asthma

1. Short-Acting β₂ Agonists (SABAs) — First-Line Rescue

• Inhaled onset: 5–15 minutes, duration 4–6 hours
• Oral bioavailability poor; inhaled route preferred to minimize systemic effects

• First-line rescue bronchodilator for acute attacks
• Pre-treatment before exercise (exercise-induced bronchospasm)
• All asthma severity levels

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2. Long-Acting β₂ Agonists (LABAs)

• Add-on therapy to inhaled corticosteroids (ICS) in moderate-to-severe persistent asthma
• Never use as monotherapy in asthma — FDA black-box warning for increased risk of asthma-related death when used without ICS
• Combination inhalers (ICS + LABA) are preferred: salmeterol/fluticasone (Advair), formoterol/budesonide (Symbicort)

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3. Inhaled Corticosteroids (ICS) — Cornerstone of Controller Therapy

• Bind glucocorticoid receptors → inhibit transcription of pro-inflammatory genes (IL-4, IL-5, TNF-α, eotaxin)
• Decrease eosinophil and mast cell activity
• Reduce vascular permeability, airway edema, and mucus secretion
• Reduce airway hyperresponsiveness over weeks of use

• Inhaled: ~80–90% deposited in the oropharynx → swallowed → undergoes extensive first-pass hepatic metabolism (high safety profile)
• Only 10–20% reaches airways — the therapeutically active fraction
• Ciclesonide is a prodrug activated in the lung (further reduces systemic effects)

• First-line long-term controller therapy in persistent asthma (mild, moderate, severe)
• Reduce frequency of exacerbations, emergency visits, and oral corticosteroid use

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4. Systemic Corticosteroids

• Short courses (3–5 days) for acute asthma exacerbations and status asthmaticus
• Chronic oral dosing only in severe, refractory asthma due to extensive systemic side effects

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5. Short-Acting Muscarinic Antagonists (SAMAs)

• Acute severe asthma (emergency): combined with albuterol provides additional bronchodilation compared to either drug alone
• Maintenance therapy in COPD (preferred over β₂ agonists)

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6. Long-Acting Muscarinic Antagonists (LAMAs)

• Add-on therapy in severe asthma inadequately controlled on ICS + LABA
• Primary maintenance in COPD

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7. Methylxanthines (Theophylline)

• Inhibits phosphodiesterase (PDE) → increased cAMP → bronchial smooth muscle relaxation
• Adenosine receptor antagonism — contributes to bronchodilation and stimulates respiratory center
• Anti-inflammatory effects at low doses
• Stimulates diaphragmatic contractility

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8. Leukotriene Modifiers

a. Leukotriene Receptor Antagonists (LTRAs)

• Mild persistent asthma (alternative to low-dose ICS)
• Add-on therapy to ICS in moderate persistent asthma
• Aspirin-exacerbated respiratory disease (ASA triad)
• Allergic rhinitis

b. 5-Lipoxygenase Inhibitor

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9. Mast Cell Stabilizers

• Prophylaxis only — NOT for acute attacks
• Exercise-induced asthma (use 10–15 minutes before exercise)
• Mild persistent asthma (especially in children)
• Currently rarely used due to superior efficacy of ICS

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10. Biologic Agents (Targeted/Monoclonal Antibody Therapy)

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11. Step-Up Treatment Strategy (GINA Stepwise Approach)

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Status Asthmaticus Management

1. Inhaled SABAs (albuterol) — continuous nebulization
2. Ipratropium — add to albuterol nebulization in severe cases
3. IV/oral systemic corticosteroids — methylprednisolone 1–2 mg/kg IV or oral prednisolone
4. Oxygen — maintain SpO₂ > 94%
5. IV magnesium sulfate — smooth muscle relaxant; used for life-threatening cases unresponsive to above measures
6. Heliox (helium-oxygen mixture) — reduces turbulent airflow in severe obstruction
7. IV aminophylline — third-line due to toxicity; rarely used

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Summary Table: Asthma Drugs at a Glance

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Quick Navigation

Anemia — Key Takeaways

• Iron deficiency → Oral ferrous sulfate (cheapest, first-line); add vitamin C to enhance absorption; treat 3–6 months after correction of cause. Use parenteral iron (iron dextran/sucrose/ferric carboxymaltose) only when oral fails.
• B₁₂ deficiency / Pernicious anemia → IM cyanocobalamin or hydroxocobalamin, lifelong in pernicious anemia. Never give folic acid alone — it will not fix the neurological damage.
• Folate deficiency → Oral folic acid 1 mg/day. Use leucovorin for methotrexate rescue.
• Renal anemia → Erythropoiesis-stimulating agents (epoetin alfa, darbepoetin); keep Hb 10–11 g/dL; ensure iron stores are adequate.
• Iron overdose antidote → Deferoxamine (chelation therapy).

Asthma — Key Takeaways

• Rescue → Albuterol (SABA) is always first-line for acute bronchoconstriction.
• Controller → Inhaled corticosteroids (ICS) are the cornerstone of persistent asthma management. Always rinse mouth after use.
• Step 3+ → Add a LABA to ICS; never use LABA alone in asthma (FDA warning).
• Theophylline → Narrow therapeutic index; third-line only; monitor serum levels.
• Leukotriene modifiers → Montelukast, zafirlukast useful for mild persistent asthma and aspirin-sensitive asthma; boxed warning for neuropsychiatric events.
• Biologics → Reserve for severe uncontrolled disease; select by phenotype (IgE, eosinophil count).
• Status asthmaticus → SABA + ipratropium nebulization + systemic steroids + O₂; add IV magnesium if life-threatening.