‫بسم الله الرحمن الرحيم‬

University of Gezira
Faculty of pharmacy
Department of clinical pharmacy
and pharmacy practice

Vasopressors and Inotropic

Agents

prepared by:
EJLAL and HIBA
supervised by:
D.Tawasul Mohammed
 Objectives
• Understand the vasopressor and inotropic
agent receptor physiology.
• Understand appropriate clinical
application of vasopressors and inotropic
agents.
 Definitions

• Pressor: Increases blood pressure by stimulating

constriction of blood vessels
– Increases vascular tone
 Definitions cont:

• Inotrope: Alters force or energy of muscular

contractions
– Positive: Increases myocardial
contractility
 Definitions cont:
Many drugs have both vasopressor and
inotropic effects.
Definitions cont:

Inodilator:
• inotropic and vasodilating effect
(dobutamine and milrinone)
Receptor Physiology
Receptor Location Effect

Alpha-1 Adrenergic Vascular wall Vasoconstriction

Heart Increase duration of

contraction without
increased chronotropy

Beta Adrenergic Beta-1 Heart Inotropy and chronotropy↑

Beta-2 Blood vessels Vasodilation

Dopamine Renal Vasodilation
Splanchnic
(mesenteric)
Coronary
Cerebral

Subtype Vasoconstriction
Vasoactive Medications
Catecholamine

Vasopressin

Phosphodiesterase
inhibitors

Calcium sensitizers
Catacholamines with
inotropic properties

• Epinephrine
• Norepinephrine
• Isoproterenol
• Dopamine
• Dobutamine
Catacholamines with
pressor properties

• Epinephrine
• Norepinephrine
• Dopamine
• Phenylephrine(nonCatachola
mine)
Other vasoactive Options

• Milrinone
– PDE inhibitor
• Vasopressin
– Vasoconstriction
– Improves sensitivity to
catachols
• Levosimendan
– Calcium sensitizing agent
 Drug Alpha-1 Beta-1 Beta-2 Dopaminergic Predominant Clinical Effects
)Neosynephrine(
Phenylephrine *** 0 0 0 ↑/↔ SVR ↑ ↑, CO
)Levophed(
Norepinephrine *** ** 0 0 ↑/↔ SVR ↑ ↑, CO
)Adrenalin( CO ↑ ↑, SVR ↓ (low dose) SVR/↑
Epinephrine *** *** ** 0 (higher dose)

)Intropin(
Dopamine
(mcg/kg/min)
to 2 0.5 0 * 0 ** CO
to 10 5 * ** 0 ** ↑ CO ↑, SVR
to 20 10 ** ** 0 ** ↑ ↑ SVR

Dobutamine */0 *** ** 0 ↓ CO ↑, SVR

Isoproterenol 0 *** *** 0 ↓ CO ↑, SVR

.Very Strong Effect, ** Moderate effect, * Weak effect, 0 No effect ***

Inotropes
DOBUTAMINE
 Dobutamine cont:
Cautions:
 Arrhythmias and tachycardia .
 Occlusive vascular disease.
 Ischemic heart disease.
 Acute heart failure.
 Severe hypotension.
 Correct hypovolaemia .
 Monitor serum-potassium concentration.
 Tolerance may develop with continuous infusions longer than 72
hours.
 Dobutamine cont:

Dose:
By intravenous infusion, usual dose 2.5–10
micrograms / kg/minute, adjusted according to
response; dose range 0.5–40micrograms/kg/minute
has been used.
 Dobutamine cont:

Contra-indications:
phaeochromocytoma

Pregnancy:
category B

Breast-feeding:
Avoid—no information available
 Dobutamine cont:
Side-effects:
 Nausea.
 Hypotension.
 hypertension (marked increase in systolic blood pressure
indicates overdose).
 Arrhythmias and tachycardia.
 chest pain, dyspnea and bronchospasm.
 Dopamine:
Indications:
 Cardiogenic shock .
Hypotension
 Cardiac surgery.
 To increase renal blood flow in patients with impaired
renal perfusion, usually in the setting of multi-organ
failure.
Dopamine cont:

Cautions:
correct hypovolaemia.
Use low dose in shock due to acute myocardial
infarction
hyperthyroidism.
 Dopamine cont:

Dose :
At low infusion rates(0.5-2mcg/ kg/min selectively
vasodilates the renal(and mesenteric) vascular beds,
increasing renal blood flow and GFR.
At rates higher(2-5 mcg/kg/ min) there is activation of β1
and it receptor and subsequent decrease of renal blood
flow
At rate >10mcg/kg/min act on α1
 Dopamine cont:
Contra-indications:
 tachyarrhythmia .
 phaeochromocytoma .

Pregnancy :
category C
 Dopamine cont:

Side-effects :
 Nausea and vomiting
 chest pain and dyspnoea
 tachycardia
 vasoconstriction
 hypotension
 headache
 Milrinone:
Indications:
 Short-term treatment of severe congestive heart failure
unresponsive to conventional maintenance therapy (not
immediately after myocardial infarction).
Acute heart failure.
Low output states following heart surgery.
 Milrinone cont:
Cautions:
 Correct hypokalaemia.
 Heart failure associated with hypertrophic
cardiomyopathy.
 Stenotic or obstructive valvular disease or other outlet
obstruction.
 Platelet count(thrompocytopenia).
 Milrinone cont:

Dose:
By intravenous injection over 10 minutes, either
undiluted or diluted before use, 50 micrograms/kg
followed by intravenous infusion at a rate of 375– 750
nanograms/kg/minute, usually for up to 12 hours
following surgery or for 48–72 hours in congestive
heart failure; max. daily dose 1.13 mg/kg
 Milrinone cont:

Contra-indications:
severe hypovolaemia.

Renal impairment:
reduce dose and monitor response if eGFR less than
50 mL/minute/1.73m2.
Milrinone cont:
Pregnancy :
category C

Breast-feeding :
Avoid—no information available
 Milrinone cont:
Side-effects :
 Ventricular tachycardia.
 Supraventricular arrhythmias (more likely in patients with
pre-existing arrhythmias).
 Hypotension.
 less commonly ventricular fibrillation, chest pain, tremor,
hypokalaemia, thrombocytopenia; very rarely
bronchospasm, anaphylaxis, and rash.
 Isoproterenol
Indication :
 Bradycardia with poor perfusion ( adrenaline
may be preferred as it is less likely to decrease
blood pressure).
 Short term emergency treatment of heart block
or severe bradycardia.
Isoproterenol cont:
Cautions:

 Not given in arrest.

 Iv use with asthmatic child.
 Arrhythmia .
 Hypotensive patient.
Isoproterenol cont:
Dose:
0.1-0.5mcg/kg/min may be up to 1mcg/kg /min
(but result in tachycardia)
Isoproterenol cont:
Side effects:

 Sweating
 Headache
 Hypotension
 Increase myocardial oxygen consumption
 Tachycardia
Isoproterenol cont:

Pregnancy:
category C
Vasoconstrictors
 Norepinephrine
Indications:
 Acute hypotensive state.
 Cardiac arrest.
 Pulmonary vascular disease.
 Sepsis with significant vasodilation.
Norepinephrine cont:

Cautions:
 Diabetes mellitus.
 Uncorrected hypovolaemia.
 Hypoxia.
 Elderly.
 Extravasation at injection site may cause necrosis.
 Norepinephrine cont:
Dose:
Acute hypotension, by intravenous infusion , via central
venous catheter, of a solution containing noradrenaline
40 micrograms (base)/mL at an initial rate of 0.16–0.33
mL/minute, adjusted according to response.

Note: 1mg of noradrenaline base is equivalent to 2mg of

noradrenaline acid tartrate .
Dose expressed as the base (For dilution before use).
Norepinephrine cont:

Side effects:
 Anorexia,nausea and vomiting.
 hypoxia.
 Arrhythmias.
 Hypertension.
 bradycardia, tachycardia, dyspnoea and headache.
 CNS :insomnia, confusion, anxiety and psychosis.
Norepinephrine cont:

Contra-indications:
 Severe hyperthyroidism.
 Hypertension.

Pregnancy:
Category C
 Epinephrine
Indication:
 Cardiac arrest.
 Anaphylactic reaction.
 Acute asthmatic attack.
 Hypotension with good CVP and stable rhythm.
Epinephrine cont:

Cautions:
 Metabolic acidosis(decrease effect).
 Diabetes mellitus.
 Narrow angel glaucoma.
 Thyrotoxicosis.
 Correct hypovolemia.
Epinephrine cont:

Dose:
 Cardiac arrest:
1mg repeat every 3-5 min MAX 0.2mg/kg.
 Hypotension:
2-10mcg /min.
 Anaphylaxis
0.1-0.5mg every 5-15 min.
Epinephrine cont:

Side effects:
 Anorexia, nausea and vomiting.
 Hypoxia.
 Tachyarrhythmias .
 Hypertension.
 Dyspnoea and headache .
 CNS :insomnia, confusion, anxiety and psychosis .
Epinephrine CONT:

Pregnancy :
Category C
 Phenylephrine:
Indications:
 Acute hypotension .
 Shock .
Phenylephrine CONT:

Cautions:
 Hypertensive response (Phenylephrine
has a longer duration of action than
noradrenaline, and an excessive
vasopressor response may cause a
prolonged rise in blood pressure).
 Phenylephrine cont:
Dose:
By subcutaneous or intramuscular injection 2–5 mg,
followed if necessary after at least 15 minutes by further
doses of 1–10mg

By slow intravenous injection of a 1mg/mL solution 100–

500 mcg repeated as necessary after at least 15 minutes

By intravenous infusion initial rate up to 180 mcg/min

reduced to 30–60 mcg/min according to response
 Phenylephrine cont:
Contra-indications:
VT,severe hypertension and severe hyperthyroidism.

Side-effects:
AS Noradrenaline; also tachycardia or reflex
bradycardia.
Phenylephrine cont:

Pregnancy:
Category C
lactation:
Safe.
Bohn (2006). Inotropic Agents in Heart Failure. Heart Failure in
Children and Young Adults. Chang & Towbin.
Bohn (2006). Inotropic Agents in Heart Failure. Heart Failure in
Children and Young Adults. Chang & Towbin.
Bohn (2006). Inotropic Agents in Heart Failure. Heart Failure in
Children and Young Adults. Chang & Towbin.
Bohn (2006). Inotropic Agents in Heart Failure. Heart Failure in
Children and Young Adults. Chang & Towbin.
Bohn (2006). Inotropic Agents in Heart Failure. Heart Failure in
Children and Young Adults. Chang & Towbin.
Vasoactive Medication Receptor Activity
and Clinical Effects
Clinical Application

1st Line Agent 2nd Line Agent

Septic Shock Norepinephrine (Levophed) Vasopressin
Epinephrine
Phenylephrine (Neosynephrine) (Adrenalin)
Heart Failure Dopamine Milrinone
Dobutamine
Dobutamine
Cardiogenic Shock

Anaphylactic
Shock Epinephrine (Adrenalin) Vasopressin

Neurogenic Shock Phenylephrine (Neosynephrine)

Anesthesia
Hypotension -induced Phenylephrine (Neosynephrine)
Following
CABG Epinephrine (Adrenalin)
Dosing calculation in critical
care setting
CONCLUSION
CONCLUSION:

 Vasopressor agents are indicated if hypotension is

refractory to fluid administration or in the setting
of severe hypotension while fluids are being
administered.
 The treating clinician will often need to make a
patient-specific assessment to define severe
hypotension or hypotension refractory to fluid
administration.
 CONCLUSION cont:

 Vasopressor agents primarily exert pharmacologic

benefit by augmenting SVR. Some vasopressors may
have an augmented benefit of increasing CO.

 Selection of a specific vasopressor agent is largely

guided by expert opinion and clinician preference.
 Agent chosen depends on clinical
situation:
•Cold shock: Dopamine, epinephrine if resistant.
• Warm shock: Norepinephrine.
• Low cardiac output and low systemic vascular .
resistance (SVR): Epinephrine .
• Low cardiac output and high SVR: Milrinone .
• High cardiac output and low SVR: Norepinephrine .
CONCLUSION CONT:

 Vasopressor agents should be administered through

central venous access to minimize the risk of
extravasation and tissue necrosis.

 Phentolamine (α-receptor antagonist) can be

administered subcutaneously directly to the
extravasation site to prevent tissue damage.
 CONCLUSION CONT:

 Inotropes exert a pharmacodynamic effect that

increases CO after adequate fluid administration.