Adrenaline and nor Adrenaline atropine Classification Receptors Dosage
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Adrenaline (Epinephrine), Noradrenaline (Norepinephrine), and Atropine
1. ADRENALINE (Epinephrine)
Classification
- Chemical class: Catecholamine (endogenous)
- Source: Secreted primarily by the adrenal medulla (~80%); also synthesized in neurons
- Drug class: Sympathomimetic, direct-acting adrenergic agonist
- Synthesis: Derived from tyrosine → DOPA → dopamine → norepinephrine → epinephrine (via PNMT enzyme in adrenal medulla)
Receptors Acted On
| Receptor | Effect |
|---|---|
| α1 (at higher doses) | Vasoconstriction (skin, mucosa, viscera) |
| α2 | Presynaptic feedback inhibition |
| β1 | ↑ Heart rate, ↑ force of contraction, ↑ excitability |
| β2 (at low doses) | Vasodilation in skeletal muscle/liver; bronchodilation |
| β3 | Lipolysis in adipose tissue |
- At low doses, β2 effects predominate (vasodilation, bronchodilation)
- At high doses (>0.3 mcg/kg/min), α1 effects dominate (vasoconstriction, ↑ BP)
- Net cardiovascular effect: ↑ HR, ↑ cardiac output, widened pulse pressure, ↓ total peripheral resistance (contrast with noradrenaline)
Key Physiological Effects
- Glycogenolysis in liver and skeletal muscle (via β and α receptors)
- ↑ Blood glucose; ↑ free fatty acids; ↑ blood lactate
- Bronchodilation (β2)
- ↑ CNS alertness, anxiety, fear
- ↑ Metabolic rate
Dosage
| Indication | Route | Dose |
|---|---|---|
| Anaphylaxis (first line) | IM (vastus lateralis) | 0.01 mg/kg up to 0.5 mg; may repeat |
| Anaphylaxis IV | IV bolus | 0.001 mg/kg, then 0.1–1 mcg/kg/min infusion |
| Cardiac arrest / ACLS | IV | 1 mg every 3–5 min |
| Septic shock (inotrope/vasopressor) | IV infusion | Start 0.05–0.2 mcg/kg/min; titrate up to 2 mcg/kg/min |
| Pediatric shock | IV infusion | 0.05–2 mcg/kg/min |
| Adult shock | IV infusion | 0.05–2 mcg/kg/min |
Source: Harriet Lane Handbook 23e; Rosen's Emergency Medicine; Tintinalli's Emergency Medicine
2. NORADRENALINE (Norepinephrine)
Classification
- Chemical class: Catecholamine (endogenous)
- Source: Released from sympathetic postganglionic nerve endings (main neurotransmitter); also from adrenal medulla (~20%)
- Drug class: Sympathomimetic, direct-acting adrenergic agonist
- Difference from adrenaline: Lacks the N-methyl group; cannot be converted further (no PNMT in sympathetic neurons)
Receptors Acted On
| Receptor | Effect |
|---|---|
| α1 (dominant) | Vasoconstriction in virtually all vascular beds |
| α2 | Presynaptic feedback inhibition |
| β1 | ↑ Force and rate of cardiac contraction |
| β2 | Minimal (unlike epinephrine) |
- Key difference from adrenaline: Noradrenaline produces vasoconstriction in virtually all organs via α1; it does NOT dilate skeletal muscle or liver vessels
- Net cardiovascular effect: ↑ systolic AND diastolic BP → baroreceptor-mediated reflex bradycardia → ↓ cardiac output (this is the key contrast with adrenaline)
Key Physiological Effects
- ↑ Total peripheral resistance (dominant effect)
- Reflex bradycardia (baroreceptor stimulation overrides direct β1 effect)
- Glycogenolysis (via β and α)
- ↑ Metabolic rate
- ↑ Alertness (similar to adrenaline)
Dosage
| Population | Route | Dose |
|---|---|---|
| Adult (vasopressor) | IV continuous infusion | Start 8–12 mcg/min; usual maintenance 2–4 mcg/min |
| Pediatric | IV continuous infusion | Start 0.05–0.1 mcg/kg/min; max 2 mcg/kg/min |
| First-line in septic shock | IV infusion | 0.05–0.5 mcg/kg/min; titrate to MAP ≥60 mmHg |
| Anesthesia | IV infusion | 0.05–2 mcg/kg/min |
Source: Harriet Lane Handbook 23e; Morgan & Mikhail's Clinical Anesthesiology 7e; Rosen's Emergency Medicine
3. ATROPINE
Classification
- Chemical class: Tertiary amine (belladonna alkaloid)
- Source: Naturally occurring in Atropa belladonna and related plants; commercial preparation is a racemic mixture (levorotatory form is active)
- Drug class: Antimuscarinic (parasympatholytic, anticholinergic)
- Precise terminology: "anticholinergic" is commonly used, but antimuscarinic is more accurate since it blocks muscarinic (not nicotinic) receptors
Receptors Acted On
| Receptor Subtype | Location | Atropine Effect |
|---|---|---|
| M1 | CNS, autonomic ganglia, gastric parietal cells | Blocked |
| M2 | Cardiac tissue (SA/AV node) | Blocked → tachycardia |
| M3 | Smooth muscle, glands | Blocked → relaxation, ↓ secretions |
- Mechanism: Competitive antagonist at muscarinic ACh receptors; blocks all parasympathetic effects
- At normal doses: acts peripherally; crosses the blood-brain barrier (tertiary amine) but CNS effects minimal at therapeutic doses
Key Effects by System
| System | Effect |
|---|---|
| Heart (M2 block) | ↑ HR, ↑ AV conduction |
| Respiratory | Bronchodilation, ↓ secretions |
| GI | ↓ Motility, ↓ salivation |
| Eye | Mydriasis, cycloplegia |
| CNS | Mild excitation at toxic doses |
Comparison: Atropine vs Scopolamine vs Glycopyrrolate
| Effect | Atropine | Scopolamine | Glycopyrrolate |
|---|---|---|---|
| Tachycardia | +++ | + | ++ |
| Bronchodilation | ++ | + | ++ |
| Sedation | + | +++ | 0 |
| Antisialagogue | ++ | +++ | +++ |
Glycopyrrolate is a quaternary amine - does NOT cross the blood-brain barrier.
Dosage
| Indication | Route | Dose |
|---|---|---|
| Symptomatic bradycardia (first-line) | IV | 0.5 mg every 3–5 min; max 3 mg (0.04 mg/kg) |
| Premedication | IM or IV | 0.01–0.02 mg/kg; usual adult dose 0.4–0.6 mg |
| Severe bradycardia (vagal block) | IV | Up to 2 mg |
| Antisialagogue | IM | 0.01–0.02 mg/kg |
| Organophosphate poisoning | IV | 2–4 mg (repeat every 5–10 min until secretions dry) |
Important: IV doses < 0.5 mg and slow injection are associated with paradoxical bradycardia. Atropine is no longer recommended for asystole or pulseless electrical activity.
Source: Morgan & Mikhail's Clinical Anesthesiology 7e; Tintinalli's Emergency Medicine; Rosen's Emergency Medicine
Summary Comparison Table
| Feature | Adrenaline | Noradrenaline | Atropine |
|---|---|---|---|
| Class | Catecholamine | Catecholamine | Belladonna alkaloid |
| Receptor | α1, α2, β1, β2, β3 | α1, α2, β1 (minimal β2) | M1, M2, M3 (antagonist) |
| HR effect | ↑↑ (direct β1) | ↓ (reflex bradycardia) | ↑↑↑ (vagal block) |
| BP effect | ↑ systolic, ↓ diastolic (low dose) | ↑↑ systolic + diastolic | Variable (primarily ↑ HR) |
| Cardiac output | ↑↑ | ↓ | ↑ (rate-dependent) |
| Bronchial effect | Bronchodilation (β2) | Minimal | Bronchodilation (M3 block) |
| Primary use | Anaphylaxis, cardiac arrest, shock | Septic/vasodilatory shock | Bradycardia, organophosphate poisoning, premedication |
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