G7i / 20A10: Compare and contrast the pharmacology of noradrenaline and vasopressin
20A10: Exam Report
Compare and contrast the pharmacology of noradrenaline and vasopressin.
49% of candidates passed this question.
These are both level 1 drugs regularly used in intensive care. Significant depth and detail of each drug were expected. Overall knowledge was deemed to be superficial and lacked integration. Better answers identified key points of difference and overlap in areas such as structure, pharmaceutics, parmacokinetics, pharmacodynamics, mechanism of action, adverse effects and contraindications. A tabular list of individual drug pharmacological properties alongside each other did not score as well as answers which highlighted key areas of difference and similarities.
G7i / 20A10: Compare and contrast the pharmacology of noradrenaline and vasopressin
Noradrenaline
Vasopressin
Chemical
Noradrenaline
Endogenous catecholamine neurotransmitter released from postganglionic sympathetic n. endings
Also accounts for 20% adrenal medulla secretions
Vasopressin
Synthetic peptide hormone
Use
Noradrenaline
to ↑SVR
Vasopressin
- Cranial DI (ineffective for Renal DI)
- Platelet dysfunction (F VIII & vWF deficiency)
- Oesophageal variceal bleeding
- NA sparing in Septic Shock
Used synergistically in vasoplegia
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
Vasopressin
Clear colourless vial
20U/mL
Both need time to draw up as require reconstitution with crystalloid and infusion
Dose
Noradrenaline
Infusion 1 – 20mcg/min
Vasopressin
0.01 – 0.1 units/min
Route
Noradrenaline
central vein
Vasopressin
CVC
Both require CVC
Onset
Noradrenaline
immediate: tachyphylaxis with prolonged infusions
Vasopressin
Fast
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
Vasopressin
Vasopressin receptor agonist (all GPCR)
- V1 – vascular smooth m.
- Gq – intense VC
- V2 – BASOLATERAL MEMBRANE of distal tubules & collecting duct → ↑H2O reabsorption
V2 – endothelial cells → ↑vWF release
Noradrenaline being a catecholamine has theoretical inotropy
Noradrenaline has more metabolic effects
PD
Noradrenaline
CVS
Intense VC all vascular beds = ↑↑SVR
↑HR
↑FoC
Reflex ↓HR
Renal, hepatic, cerebral & skeletal
Resp
Small ↑MV
Metbolic
↑BSL
↑FFA
Renal
↑Renin
Vasopressin
CVS
- ↑SVR
- ↑Circulating vol
- ↑CO
- CA vc & ↑afterload = ↓Myocardial O2 delivery
GI
- Marked splanchnic VC
- ↑Glycogenolysis
Haem
- ↑platelet aggregation
- ↑vWF, ↑F VIII
Renal
↑H2O reabsorption
Comments
Both confer intense VC
Vasopressin associated with restricted myocardial BF and avoided in IHD
Vasopressin able to constrict splanchnic vessel preferentially
PK
Noradrenaline
A
IV administration
D
25% uptake via 1 lung passage
M
rapid metabolism t½ = 2 mins
E
metabolites conjugated to glucuronic
Vasopressin
A
0% OBA
D
30% PPB. VD 0.2L/kg
M
65% unchanged by kidneys
35% liver + kidney peptidases
E
Renally
t½ B 30 mins
Comments
Both rapidly metabolized with quick offset following cessation of infusion
Adverse Effects
Noradrenaline
Extravasation → necrosis
Headache
Anxiety
NB CAUTION: Patients taking MAO inhibitors
PREGNANCY = ↑contraction of pregnant uterus, foetal bradycardia & asphyxia
Vasopressin
- Hyponatraemia
- Hypertensive crisis
- Author: Krisoula Zahariou