1) The document provides information on inotropes and vasopressors including their classification, sites of action, clinical effects, indications, and doses. It discusses catecholamines like adrenaline, noradrenaline, dopamine, and dobutamine. It also covers phosphodiesterase inhibitors, vasopressin, ephedrine, metaraminol, phenylephrine, methoxamine, and digoxin. 2) The document concludes with recommendations on first and second line vasopressor/inotropic agents for different clinical situations like septic shock, heart failure, cardiogenic shock, anaphylactic shock, and anesthesia-induced hypotension.

1. Johnny Kenth – ST3 Anaesthesia,
Royal Blackburn Hospital

2. Inotropes
Definition:
An inotrope is an agent that alters force of contraction of cardiac muscle without
affecting the pre or after load. E.g. +ve inotropes  contractility
Classification
• Class 1  intracellular [ca], include:
• Ca ions
• Drugs  cAMP - adrenoagonists, PDIs, Glucagon
• Drugs affecting Na-K ATPase - digoxin
 Class 2  sensitivity actomyosin to Ca ions – Levosimendan
 Class 3 Metabolic / endocrinological – T3

3. Catecholamine Synthesis

5. Site of action
du Toit E et al. Heart 2001;86:81-87

6. Drug Alpha-1 Beta-1 Beta-2 Dopaminergic Predominant Clinical Effects
Phenylephrine *** 0 0 0 SVR ↑ ↑, CO ↔/↑
Noreadrenaline *** ** 0 0 SVR ↑ ↑, CO ↔/↑
Adrenaline *** *** ** 0
CO ↑ ↑, SVR ↓ (low dose)
SVR/↑ (higher dose)
Dopamine
(mcg/kg/min)
0.5 to 2 0 * 0 ** CO
5 to 10 * ** 0 ** CO ↑, SVR ↑
10 to 20 ** ** 0 ** SVR ↑ ↑
Dobutamine 0/* *** ** 0 CO ↑, SVR ↓
Isoproterenol 0 *** *** 0 CO ↑, SVR ↓
*** Very Strong Effect, ** Moderate effect, * Weak effect, 0 No effect.

7. Actions
Acts on 1, 2, + 1 receptors.
• CVS:  HR (chronotropic) + contractility (inotropic -force of contraction)
CO; also +ve dromotropic, bathmotropic & -ve lusitropic
SBP rises, but with low doses DBP may fall due to (2 vasodilation and
increased blood flow through skeletal muscle beds (2).
At higher doses = 1 mediated vasoconstrictor effects
• RS: Bronchial smooth muscle is relaxed 2 = bronchodilation
• Other: Adrenaline mobilises glucose from glycogen and raises blood
sugar. Pupillary dilation (mydriasis) occurs.
• Side effects Ventricular arrhythmias, hypertension. Care with halothane
anaesthesia as arrhythmias may occur
Adrenaline (Epinephrine)
Prepare the body for a "fight or flight" response.

8. Site of action
du Toit E et al. Heart 2001;86:81-87

9. • Noradrenaline
Acts mainly on 1 receptors with few effects on  receptors.
 BP by vasoconstriction. Less likely to cause tachycardia than
adrenaline.
Indications Septic shock where peripheral vasodilation may be causing
hypotension.
Cautions Acts by  afterload and therefore not appropriate for use in
patients in cardiogenic shock.  Blood supply to kidneys and peripheries
Dose - 0.01-1 mcg/kg/min
• Dopamine
Acts on D, 1, 2 and 1 receptors, depending on the dose administered.
Actions Dose dependent
1-2mcg/kg/min - acts on D receptors usually  UO
2-10mcg/kg/min - acts on  receptors   CO
>10mcg/kg/min - additional effects on 1 receptors  vasoconstrict.

10. • Dobutamine
Acts on 1 & 2, with minimal action on 1 receptors.
It  CO and  afterload (2 effects).
Indications Cardiogenic shock.
Dose 2-30mcg/kg/min
• Dopexamine
Acts on 2 and D receptors.
 CO and afterload.  blood supply to kidneys and ? + GI tract.
Dose 0.5-6mcg/kg/min
• Salbutamol
Acts on 2 receptors
Actions Relaxes bronchial smooth muscle i.e. bronchodilation;  HR
Indications Severe acute asthma.
Dose By infusion 5-20mcg/min. IV bolus 1- 5mcg/kg

11. Site of action
du Toit E et al. Heart 2001;86:81-87

12. • e.g. aminophylline, enoximone, milrinone
• Prevent breakdown of cAMP by enzyme phosphodiesterase: 
intracellular [Ca] in myocytes - augments catecholamines at 1 and 2
receptors.
• Actions: Inodilation, i.e.  rate and force of contraction, peripheral
vasodilation in skeletal muscle, bronchodilation.
Indications
• Aminophylline: asthma, cardiac failure.
• Enoximone: cardiac surgery - patients failing to respond to dobutamine
Phosphodiesterase inhibitors

13. • Action : directly on 1 + 2 receptors,
indirectly on 1 receptors via NA release.
• Side effects May cause tachycardia and hypertension. Possible
arrhythmias if used with halothane. C/I MAOs, SNRI
• Indications Low blood pressure due to vasodilation e.g. following
spinal or epidural anaesthesia and drug overdoses. Better
vasopressor to use in pregnancy as it does not reduce placental blood
flow.
• Dose 3-10 mg boluses iv, repeat until effective. Maximum dose is
60mg.
• Length of action 5-15 minutes, repeated doses less effective (i.e. it
demonstrates tachyphylaxis)
EPHEDRINE

14. • Metaraminol
Acts directly on 1 receptors
also causes some noradrenaline and adrenaline release.
Actions  MAP and  CO.
Less likely to cause a reflex bradycardia than methoxamine or
phenylephrine.
Dose - 0.5 1mg boluses iv, 2-10mg s/c or im, by infusion at 1-20mg/hr.
• Phenylephrine
Acts directly on 1 receptors.
Action Hypertension and a reflex  HR.
Dose, 0.1-0.5mg iv, by infusion 0.1 – 1 mcg/kg/min
• Methoxamine
acts on 1 receptors.
Actions.  MAP + reflex  HR, and therefore it is good for hypotension
with tachycardia. Useful during spinal anaesthesia.
Side effects May produce bradycardia
Dose 2-4mg boluses IV.
Other pressors:

15.  Naturally occurring nonapetide hormone, produced in post
hypothamalamus by PVN SON, stored + released post pituitary.
 Acts on V1, V2, V3 and OTR - GPCR
 V1: receptors are found on vascular smooth muscle of the systemic,
splanchnic, renal, and coronary circulations  vasoconstriction (Gq)
 V2: predominantly located in the distal tubule and collecting ducts of
the kidney  aquaporin chn   water re-absorption
 Uses:
• Sepsis:  NA usage, VASST, as safe as NA, VANISH -
• Cardiac Arrest: ?  survival ( Krismer et al)
Asystole: ? survival to ED adm, + discharge. (Wenzel et), no
affect mortality.
VASOPRESSIN

16.  Direct: Inhibits cardiac Na-K ATPase:
•  Intracellular Na
•  Na / Ca exchange   intracellular Ca
•  Ca release from SR   actin-myosin cross linkage
•   contractile force
 Inirect: inhibits neuronal Na-K ATPase
•  Vagal activity
 PK
• Long T1/2 needs LD
• Renal clearence
Large VD
Digoxin

17. Clinical
Application
1st Line Agent 2nd Line Agent
Septic Shock Noradrenaline Adrenaline
Dopamine Vasopressin
Heart Failure Dopamine PDIs (Milrinone)
Dobutamine + Norad
Cardiogenic
Shock
Dobutamine
Levosimendan
+/- Norad SBP<80 PDIs
Anaphylactic
Shock Adrenaline Vasopressin
Neurogenic Shock Norad
Hypotension
Anesthesia-
induced
Ephedrine / Metaraminol /
Phenylephrine **Adrenaline
Following
CABG Epinephrine (Adrenalin)

18.  72 year-old woman with DM Type II, hypertension and Stage II
CKD, recurrent UTIs, is transferred from a MAU. Her vitals upon
arrival are as follows: Temp 39C, BP 70/45, Hr 140, RR 20, O2 Sat
95% 4L02 Lab findings: WCC 24, Cr 3.5, Lac 3.4, Positive Ur Dp,
CRP 241
 After adequate IVF resuscitation, pt continues to remain
hypotensive MAP 40-50s + tachycardic HR 110-130s. What is the
most appropriate 1st line vasopressor/inotropic agent?
A. Adrenaline
B. Dobutamine
C. Noreadrenaline
D. Dopamine

19.  64 year-old man with PMHx IHD; prev. MI and PCI (2004; drug-
eluting stents), ischemic cardiomyopathy (EF 30-35%) with ICD
(2007). ED 1/52 Hx progressively worsening SOB at rest,
orthopnea and bilateral lower extremity oedema, after running out of
all medications about 10 days ago.
 In ED, vitals: Temp 36.6 C, BP 88/48, Hr 75, RR 25, O2 Sat 91%
on RA. CXR reveals vascular congestion and bilateral pleural
effusion. Bedside ultrasound reveals significantly diminished EF.
 What is the most appropriate 1st line vasoactive agent?
A. Adrenaline
B. Dobutamine
C. Noreadrenaline
D. Dopamine

20.  76 year-old cachexic female with PMHx: COPD, HTN and
Osteoporosis was initially admitted under medics for acute exac
COPD. Had fall on ward # L-NOF.
 Underwent CNB-spinal anaesthesia. 15 mins post induction her
BP was 64/44, P108, RR18, SpO2 99% RA.
 What is the most appropriate 1st line vasopressor/inotropic
agent?
A. Adrenaline
B. Dobutamine
C. Dopexamine
D. Dopamine
E. Metaradine