Salbutamol
Salbutamol
Generic Name
Salbutamol
Mechanism
- Selective β2‑adrenergic receptor agonist → ↑ cyclic‑AMP in airway smooth muscle
- Phosphodiesterase inhibition → prolongs cAMP signal
- Relaxation of bronchial smooth muscle → bronchodilation
- ↓ NF‑κB activation → modest anti‑inflammatory effect (secondary)
Pharmacokinetics
| Parameter | Summary |
| Absorption |
• Inhaled: ≥ 80 % deposited in lower airways; minimal systemic uptake. • Oral/IV: Rapid absorption; peak plasma 2–5 min (IV) or 40–60 min (oral). |
| Distribution |
• Protein binding ~ 15 % (low). • Volume of distribution: ~ 17 L/kg (IV). |
| Metabolism | Predominantly via hepatic glucuronidation (UGT1A1) → inactive glucuronide. Minor CYP2D6 oxidation. |
| Elimination | Renal excretion ~ 45 % unchanged; rest as metabolites. Half‑life: 4–5 h (IV/PO), ~ 10 min (inhaled first pass). |
| Drug‑Drug Interaction | CYP2D6 inhibitors (fluoxetine, paroxetine) ↑ plasma levels; β‑blockers antagonize effect. |
| Special Populations | Renal/hepatic impairment → cautious use; pregnancy category B. |
Indications
- Acute asthma exacerbation (rescue inhaler or nebulizer)
- Exercise‑induced bronchoconstriction
- COPD acute attacks (as rescue)
- Intra‑operative bronchospasm prevention (nebulized)
- Pre‑operative bronchodilatation in bronchial hyper‑reactive patients
Contraindications
- Contraindications: Severe, uncontrolled tachyarrhythmias; hypersensitivity to salbutamol or excipients.
- Warnings:
- Cardiovascular: tachycardia, arrhythmias, hypertension, hypokalemia.
- Neurologic: tremor, jitteriness, anxiety.
- Metabolic: hyperglycemia, especially with frequent high‑dose inhalation.
- Drug interactions: β‑blockers → blunted bronchodilation; i.e., caution in patients on propranolol, carvedilol.
- Special Note: Use with caution in patients with uncontrolled hypertension or ischemic heart disease.
Dosing
| Form | Typical Adult Dose | Notes |
| Metered‑Dose Inhaler (MDI) | 2–4 puffs (100–200 µg) every 4–6 h as needed; max 12–16 puffs/24 h. | Use spacer if coordination poor. |
| Nebulizer | 2.5 mg every 5–30 min until symptom control; then 2.5 mg every 4–6 h. | Residual dose can be calculated; avoid over‑aggressive dosing. |
| Oral | 4–8 mg PO q6‑8 h; max 32 mg/day. | Less effective for acute relief; used in moderate chronic asthma. |
| IV | 0.25 mg/kg over 5 min; repeat every 2 h as needed. | Monitor heart rate; reserved for severe attacks or intubated patients. |
Pediatric: 0.15–0.30 mg/kg/dose (max 2 mg/dose) by inhalation or nebulization; follow weight‑based guidelines.
Adverse Effects
| Class | Adverse Effect |
| Cardiovascular | tachycardia, palpitations, hypertension, arrhythmia, hypokalemia |
| Neurologic | tremor, headache, agitation, anxiety, muscle cramps |
| Respiratory | paradoxical bronchospasm (rare) |
| Metabolic | transient hyperglycemia, weight gain (with chronic high‑dose use) |
| Dermatologic | skin rash (rare) |
| Serious (rare) | severe systemic toxicity when IV dose exceeds guidelines; bronchospasm reversal failure → consider corticosteroids |
Monitoring
- Vital signs: HR, BP, SpO₂ (baseline, 15 min post‑dose, 1 h)
- Serum potassium if recurrent high‑dose use or with diuretics
- Glucoses in diabetic patients on high‑dose inhalation
- First‑dose response in new users – assess for paradoxical bronchospasm
- Adherence: inhaler technique review; spacer usage
- Long‑term: lung function (FEV₁, PEF) for chronic therapy
Clinical Pearls
- Inhaler technique matters: correct exhalation before inhalation and deep, slow inhalation substantially improves efficacy.
- Spacers reduce deposition in the oral cavity → lower tremor incidence and prevent local irritation.
- Nebulizer vs. MDI: Nebulizers deliver higher systemic bioavailability; use cautiously in patients on β‑blockers or with cardiac disease.
- "Rescue dose" vs. "maintenance dose": 100–200 µg (MDI) for rescue; 400–800 µg daily (MDI) for maintenance, often combined with a controller.
- Drug interactions: Clinical trial data show that calcium channel blockers (verapamil) modestly reduce salbutamol efficacy – consider monitoring pulmonary response.
- Banked inhaler safety: Sterile, properly stored glycerin‑laden inhalers can be kept 24 h in a sealed container if a fresh dose is needed during travel; saliva contamination is minimal.
- Endogenous bradykinin: Over‑use (>10 puffs/24 h) may precipitate bronchospasm via bradykinin accumulation; observed in patients with low serum albumin.
- Data‑driven titration: In stepwise asthma plans, increasing salbutamol dose from 2 to 4 puffs can double peak bronchodilation time but increases risk of systemic adverse effects – follow GINA step‑wise adjustments.
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• Sources (select references for quick lookup)
1. “American Thoracic Society/European Respiratory Society Standards for the Management of Asthma” (2022).
2. “Recent updates on β2‑agonist pharmacology”, *European Respiratory Journal*, 2020.
3. “Pharmacokinetics & Drug Interactions of Salbutamol”, *Clinical Pharmacokinetics*, 2018.
4. “ADA Guideline on Asthma in Children”, 2021.