16B15: Exam Report
Compare and contrast the pharmacology of noradrenaline and dobutamine
84% of candidates passed this question.
The best answers used tables and key pharmacological headings for comparisons, and avoided long sentences/ paragraphs.
An answer that correctly considered the following sections would be awarded a very good pass: Presentation, pharmacodynamics, mechanism of action, organ effects, side effects and pharmacokinetics.
Many candidates failed to identify agents as natural / synthetic catecholamines.
Few answers correctly mentioned the available preparations of these drugs or considered the structure activity relationships. Only 3 candidates commented that dobutamine is a racemic mixture.
Intracellular second messenger pathways were often incorrectly recounted or not mentioned at all. Pharmacodynamic effects on all organ systems, and all CVS parameters (HR, inotropy, PVR, SVR, SBP/DBP/MAP, regional circulations) should be considered. Metabolic fate and clinical dosage ranges were frequently incorrectly quoted.
G7i / 16B15: Compare and contrast the pharmacology of noradrenaline and dobutamine
Noradrenaline
Dobutamine
Comparison
Chemical
Noradrenaline
Endogenous catecholamine neurotransmitter released from postganglionic sympathetic n. endings
Also accounts for 20% adrenal medulla secretions
Dobutamine
Synthetic catecholamine with predominate β1 activity
Comparison
One is natural and the other synthetic
Use
Noradrenaline
to ↑SVR
Dobutamine
Inotrope in low cardiac output states
Comparison
NA used as a vasopressor, dobutamine as an inotrope
Presentation
Noradrenaline
Clear, colourless solution 1mg/mL
Brown ampoule → prevent light oxidation
Must be diluted in D5W to provide sufficient acidity to prevent oxidation
1 pH D5W = 4, pH 0.9% NaCl = 6
Dobutamine
250mg / 20mL Clear, colourless solution
Racemixture of 2 isomers
- Dextro (+) = potent β1 agonist & α1 antagonist
- Levo (–) = potent α1 agonist ∴α1 effects neutralised
Comparison
Both require reconstitution
Dose
Noradrenaline
Infusion 1 – 20mcg/min
Dobutamine
1 – 20mcg/kg/min
Comparison
Similar dose ranges
Route
Noradrenaline
central vein
Dobutamine
IV
Comparison
Dobutamine can be given peripherally at low dose
Onset
Noradrenaline
immediate: tachyphylaxis with prolonged infusions
Dobutamine
Immediate
Comparison
MoA
Noradrenaline
α1 = α2 > β1 > β2
Potent α agonist
Equal β1 cf. adrenaline
Little β2 activity
α1 → Gq → stimulates Phospholipase C → ↑IP3 & DAG → ↑Ca2+
Smooth m. vasoconstriction
Cardiac: weak +ve inotropy
Metabolic: ↑BSL
α2 → Gi → inhibits AC → ↓cAMP → ↓Ca2+
CNS: ↓symp. outflow
Peripheries: inhibits NA release from nerve terminals
Platelets: ↓plat. aggregation
β1 → GS → ↑AC →↑cAMP → ↑Ca2+
Heart: +ve inotropy, +ve chronotropy, +ve dromotropy
Renal: ↑renin, ↑AII
Metabolic: ↑lipolysis, ↑FFAs
Dobutamine
- β agonist → selective β1 agonist
- β1 → G5 → Activates AC → ↑cAMP → ↑Ca2+
- Effects of ↑Ca2+
- Heart: +ve ino, chrono, dromotropy
- Metabolism: ↑lipolysis, ↑FFAs
- Renal: ↑renin, ↑AII, VC
- Small effect @ β2 receptors ∴may VD vessels
Comparison
Both act via adrenoreceptors
PD
Noradrenaline
CVS
Intense VC all vascular
beds = ↑↑SVR
↑HR
↑FoC
Reflex ↓HR
Renal, hepatic, cerebral & skeletal m. BF all ↓
RESP Small ↑MV
METABOLIC↑BSL, ↑FFA
RENAL ↑Renin
Dobutamine
CVS
- ↑FoC
- ↑HR
- ↑Myocardial O2 consumption
- BP usually ↑ despite ↓SVR from β2 effects
Comparison
Dobutamine has a cardiac profile but increases myocardial O2 consumption
PK
Noradrenaline
A
IV administration
D
25% uptake via 1 lung passage
M
rapid metabolismby COMT
t½ = 2 mins
E
metabolites conjugated to glucuronic acid for renal excretion
Dobutamine
A
N/A
D
0.2L/kg
M
Rapidly by COMT
E
t½ B = 2 mins. Metabolites
conjugated & excreted in urine
Comparison
Both given IV and metabolized by COMT
Adverse Effects
Noradrenaline
Extravasation → necrosis
Headache
Anxiety
NB CAUTION: Patients taking MAO inhibitors
PREGNANCY = ↑contraction of pregnant uterus, foetal bradycardia & asphyxia
Dobutamine
Arrhythmias
↑ventricular response due to ↑ AV conduction
Avoid with outflow obstruction → AoS/Tamponade
Tachyphylaxis
Comparison
Both have unfavourable side effects