|
Adrenaline |
Metaraminol |
Structure |
|
|
Structure-activity |
� Catecholamine: direct, potent, sensitive to COMT � OH on β-carbon: direct, alpha � No substitution on α-carbon: MAO sensitive � Larger amine: β>α |
� Non-catecholamine: resistant to COMT � OH on β-carbon: direct, alpha � CH3 substitution on α-carbon: indirect, MAO resistant � Smaller amine: α>β |
Presentation |
� 1mg in 1mL or 10mL (concentrated ++++) |
� 10mg in 1mL (concentrated++) |
Tissue necrosis |
� High risk � CVC only |
� Low risk � PIVC ok |
|
Adrenaline |
Metaraminol |
Administration |
� IV infusion: 1-30mcg/min � IV bolus: 1mg in cardiac arrest � IM bolus: 500mcg in anaphylaxis |
� IV bolus: 0.5-1mg (10-20mcg/kg) PRN � IV infusion: typically 0.5-5mg/h (20-200mcg/kg/h) � S/C or IM |
Time course |
� Onset < 1min � Duration 5 mins o Drug elimination rapid o Receptor effects prolonged |
� Onset 1-2 min � Duration: stated 20-60mins, likely shorter |
Absorption |
� Not orally bioavailable |
� Orally bioavailable, % unknown |
Distribution |
� VD 0.1-0.2L/kg � 12% protein bound � Should not cross blood-brain barrier |
� Poorly studied in humans � 45% protein bound � VD 4L/kg � Should not cross BBB |
Metabolism |
� By COMT and MAO -> VMA � By COMT only -> normetadrenaline � t1/2β 2 mins |
� Poorly studied in humans; likely slow � Not susceptible to MAO or COMT � t1/2β 6 hours |
Excretion |
� Metabolites -> urine |
� Unknown |
|
Adrenaline |
Metaraminol |
Receptor activity |
� β1 > β2 > α1 � Direct only (i.e. via adrenoceptors) |
� α1 >> β1 � Direct and indirect o Displaces noradrenaline from vesicles |
Use |
� Anaphylaxis (↑CO, ↑SVR, stabilize mast cells) � Cardiogenic shock (↑CO) � Cardiac arrest (↑SVR -> vital organ perfusion) � Additive with local anaesthetic (↑duration, ↓LAST) |
� Peri-operative hypotension � GA and neuraxial � Unclear if equivalent to phenylephrine in obstetrics |
Toxicity |
� Safer with noradrenaline reuptake inhibitors (NRI) � Tachyphylaxis slow: adrenoceptor downregulation |
� Dangerous with NRI e.g. MAOi (↑↑NAd release) � Tachyphylaxis rapid: catecholamine depletion |
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