Catecholamine Biosynthetic Pathway
Alpha Adrenergic Receptors
Alpha-1: peripheral vasoconstriction
Alpha-2: presynaptic inhibition (inhibit NA release) in the vasomotor centre decreasing sympathetic output
Beta-1: increase function of JG cells, SA node, AV node, and the myocardium
Beta-2 : not directly innervated, activated by adrenaline in circulation causing bronchodilation, central vasodilation (heart & skeletal muscle), decreased bronchial secretion and increases glucose production
Classification of sympathomimetics
Catcholamines
- Natural
- Adrenaline
- Noradrenaline
- Dopamine
- Unnatural
- Dobutamine
- Isoprenaline
Non-Catecholamines
- Ephedrine
- Phenylephrine
Mechanism of action
- Adrenaline - agonist across alpha receptors
- Noradrenaline - alpha-1 agonist (some beta-1 agonism)
- Dopamine - progressively larger doses causes stimulation of the following receptors: dopamine-1, (causing vasoconstriction), beta-1, and alpha-1
- Dobutamine - beta-1 and beta-2 agonist
- Isoprenaline - beta-1 and beta-2 agonist
- Ephedrine - agonist at alpha-1, beta-1, and beta-2 receptors (indirectly via NA release)
- Phenylephrine - alpha-1 agonist
Indications
- Cardiac arrest
- Anaphylaxis (0.3 saves all!)
- Inotropic support in sepsis, hypovolemia and cardiac surgery
- Myocardial infarct (dopamine)
- Neuraxial anesthesia (ephedrine and phenylephrine)
Contraindications
- Ischemic heart disease
- Occlusive vascular disease
- Diabetes mellitus
- Arrhythmia
- Hypertension
- Hyperthyroidism
- Phaeochromocytoma
- Cardiac outflow obstruction
Drug interactions
- Halothane (predisposition to arrhythmia)
- Alpha and beta blockers (negate effect)
- MAOI (hypertensive crisis and arrhythmia within 2 weeks of each other)
Side effects
- Increased cardiac oxygen demand (angina, MI)
- Palpitations
- Hypertension
- Arrhythmia
- Cerebrovascular accident
- Local necrosis and gangrene (central line for the big boys)
- Reflex bradycardia
- Glucose intolerance
- Pulmonary edema
Adrenaline - Dosage
Cardiac arrest: 1mg (1 amp) stat
Bolus:
- Preparation: 1mg in 200ml NS (5μg/ml)
- Dose: 10-20μg
Infusion:
- Preparation: 5mg in 200ml NS (25μg/ml)
- Dose: titrate at intervals of 0.1μg/kg/min
- Tachyphylaxis at 1.5-2μg/kg/min
**1 amp = 1ml = 1mg **
Dopamine - Dosage
Preparation: 200mg (1 amp) in 200ml NS (1mg/ml)
Dose: Titrated to effect; ~5μg/kg/min
Dobutamine - Dosage
Preparation: 250mg (1 amp) in 200ml NS (1.25mg/ml)
Dose: titrated to effect; ~5μg/kg/min
Ephedrine - Dosage
Preparation: 50mg (1 amp; 1ml) in 9ml water (5mg/ml)
Dose: 10-20mg boluses (beware tachyphylaxis)
Phenylephrine - Dosage
Preparation: 10mg (1 amp) in 200ml NS (50μg/ml)
Bolus: 100-200μg
Infusion: 0.5-2μg/kg/hour
