38. Vasopressors & Inotropes Flashcards
PHENYLEPHRINE
Synthetic a1 agonist
• Colourless solution:
10 mg/mL
DOSE
• Boluses of 50–100 μg repeated as necessary
• Infusion: 30–60 μg/min, titrate to response
MOA
• Potent a adrenoreceptor
agonist
• No effect on b receptors
METABOLISM AND EXCRETION
• Hepatic metabolism by monoamine oxidase
• Products and route of elimination have
not been identified
ABSORPTION/
DISTRIBUTION
• Rapid ↑ SVR lasting 5–10 min
USES
• ↑ SVR
• Nasal decongestant
EFFECTS
CVS
• ↑ SVR
- ↑ BP
- May cause reflex bradycardia
OTHER:
• ↓ Renal blood flow
METARAMINOL
Mainly a1 agonist some b activity
• Clear colourless solution:
10 mg/mL
DOSE
• Cautious boluses of 0.5 mg, titrate to effect
• Can be run as infusion, tritrate to effect
MOA
• Potent sympathomimetic amine
• Direct stimulation of a1 and
some b receptors –
a effects predominate
USES
- Hypotension
- In treatment of priapism (off licence use)
METARAMINOL
ADME
EFFECTS
METABOLISM
AND EXCRETION
• Hepatic metabolism
ABSORPTION/ DISTRIBUTION
- IV administration
- Dose effective within 1–2 min
- Lasts 20–60 min
EFFECTS CVS • ↑ SVR (this may CO) • ↑ BP • ↑ Coronary artery blood flow • ↑ Pulmonary artery pressure and vascular resistance
RS
• ↑ RR
• ↑ VT
OTHER
• ↓ Uterine blood flow
- Uterine contraction therefore, avoid in pregnancy
- ↓ CNS blood flow
• Inhibits insulin release and glycogenolysis
causes hyperglycaemia
- ↑ Lipolysis
- ↑ Basal metabolic rate and temperature
SIDE-EFFECTS
- Severe hypertension
- Nausea and vomiting
- Tissue necrosis with extravasation
NORADRENALINE
Naturally occurring catecholamine
a > b agonist
• Clear colourless solution:
2 mg/mL for dilution
DOSE
• Infusion via central vein:
from 0.01 μg/kg/min,
titrate to effect
USES
• By infusion to maintain BP and SVR
(especially in sepsis)
MOA
• Direct and indirect a1 agonist
• Some small action
at b receptors
Noradrenaline
effects
EFFECTS
CVS
• ↑ BP and SVR (CO may )
- Peripheral vasoconstriction
- ↑ Myocardial O2 consumption
- Coronary artery vasodilation
- ↑ Pulmonary vascular resistance
In excess:
• Hypertenison
- Bradycardia
- Headache
- Peripheral ischaemia
GI
• ↓ Renal blood flow
• ↓ Splanchnic blood flow
CAUTION!
• Contraindicated in patients on MAOIs
Noradrenaline
effects
EFFECTS
CVS
• ↑ BP and SVR (CO may )
- Peripheral vasoconstriction
- ↑ Myocardial O2 consumption
- Coronary artery vasodilation
- ↑ Pulmonary vascular resistance
In excess:
• Hypertenison
- Bradycardia
- Headache
- Peripheral ischaemia
GI
• ↓ Renal blood flow
• ↓ Splanchnic blood flow
CAUTION!
• Contraindicated in patients on MAOIs
ADRENALINE
Naturally occurring catecholamine
a and b agonist
• Clear colourless solution:
0.1–1 mg/mL for IV/IM injection/ nebulisation
• In combination with
local anaesthetic at
1:80 000 or 1:200 000
DOSE
- Infusion: 0.01–0.1 μg/kg/min
- 1 mg IV in ALS protocol
USES
• In cardiac arrest ALS algorhythm
- Anaphylaxis
- Inotrope
- Nebulised in upper airway obstruction
- Infiltration with local anaesthetic to decrease bleeding
ADRENALINE
METABOLISM AND EXCRETION
• By mitochondrial monoamine oxidase
(MAO)
and catechol-O-methyl transferase
(COMT) in liver, kidney and blood
• Inactive products 3-methoxy-4- hydroymandelic acid
(vanillylmandelic acid or VMA) and metadrenaline
• Excreted in urine
ABSORPTION/ DISTRIBUTION
- Inactivated if given orally
- t½ 2 min
MOA
• a and b adrenoreceptor agonist
ADRENALINE
EFFECTS
CVS
Low Dose – b effects
predominate
• ↑ CO
- ↑ Cardiac oxygen consumption
- Coronary artery vasodilation
- ↓ Diastolic BP
• ↓ Peripheral vascular
resistance
High Dose – a effects
predominate
• ↑ SVR
RS
- Potent bronchodilator
- Slight ↑ minute volume
- ↑ Pulmonary vascular resistance
CNS
• ↑ MAC
• ↑ Peripheral pain threshold
GI
• ↓ Splanchnic blood flow
GU
• ↓ Renal blood flow
• ↑ Bladder sphincter tone
METABOLIC
• ↑ BMR
• Glycogenolysis and
plasma glucose
• ↑ Initial insulin secretion
( b effect) followed by
reduction ( a effect)
- ↑ Glucagon secretion
- ↑ Lactate
- ↑ Lipase causing fatty acid oxidation and ketogenesis
• ↑ Renin and aldosterone
secretion
EPHEDRINE
a and b agonist
- Tablets: 15/30/60 mg
- Clear colourless solution: 30 mg/mL
- Elixir: 3 mg/mL
- Nasal drops: 0.5/1%
DOSE
- Oral: 30 mg t.d.s.
- IV: given as boluses of 3 mg, titrate to effect
MOA
• Indirect sypathomimetic,
i.e. causes release of
noradrenaline from nerve terminals
- Direct stimulation of a and b receptors
- Inhibits monoamine oxidase
USES
• Hypotension
- Nasal decongestant
- Nocturnal enuresis
EPHEDRINE
ADME
EFFECTS
METABOLISM AND EXCRETION
- Minimal hepatic metabolism
- 65% excreted unchanged in urine
ABSORPTION/ DISTRIBUTION
- Well absorbed PO/IM/SC
- t½ 4 hours
EFFECTS CVS • ↑ HR ↑ CO • ↑ BP • ↑ Coronary artery blood ow ↑ Myocardial O2 consumption
RS
• Bronchodilation
• ↑ RR
GI
• ↓ Renal blood flow
• ↓ GFR
OTHER
• Caution with MAOIs can precipitate
hypertensive crisis
NB Tachyphylaxis occurs as noradrenaline
stores are depleted.
Usually seen after ~ 30 mg given
DOBUTAMINE
Synthetic b agonist
b1 > b2
• Clear colourless solution: 12.5/50 mg/mL
DOSE
• 0.5–40 μg/kg/min. Titrate to effect
MOA
• Direct stimulation B receptors
USES
• Inotrope in low cardiac output states,
e.g. sepsis, post MI
• Cardiac stress testing
Dobutamine ADME
METABOLISM
AND EXCRETION
- Hepatic metabolism via COMT
- Inactive metabolites excreted in urine
ABSORPTION/
DISTRIBUTION
- Dose effective within 1–2 min
- VD 0.2 L/kg
Dobutamine EFFECTS
EFFECTS
CVS
B1 EFFECTS
•↑ HR
(SA and AV conduction enhanced)
- ↑ Contractility
- ↑ CO
- ↑ Myocardial O2 demand
• SVR can fall because of dilating effects
of b2 stimulation.
May be desirable effect to offload
failing heart, or co-administration of
noradrenaline may be necessary
maintain SVR
• May precipitate arrhythmias
GI
- Urine output may ↑ with ↑CO
- No effect on splanchnic vessels
OTHER
• Hypoglycaemia
DOPAMINE
Naturally occurring catecholamine
and neurotransmitter D1 and D2
• Clear colourless solution:
200/800 mg in 5 mL
DOSE
• 1–20 μg/kg/min
MOA
• Low (‘renal’) dose (1–5 μg/kg/min
stimulates D1 and D2 receptors
- Higher doses stimulate a and b also
- 5–10 μg/kg/min mainly b effects
- 10–20 μg/kg/min mainly a effects
USES
- Inotrope
- Diuretic
DOPAMINE
ADME
METABOLISMAND EXCRETION
• Metabolism via COMT in liver,
kidney, plasma.
75% converted to inactive metabolites
which are excreted in urine
• 25% converted to noradrenaline in nerves
ABSORPTION/
DISTRIBUTION
- Works in 5 min
- Effects last 10 min
DOPAMINE
EFFECTS
CVS
< 5 μg/min – D1 receptors
• ↓ Renal vessel resistance ↑ renal blood flow
< 10 μg/min – b1 receptors
- ↑ HR
- ↑ Contractility
- ↑ CO
- ↑ Coronary artery blood flow
> 10 μg/min – a effects
• ↑ SVR
RS
• ↓ Response to hypoxia
AS
• Splanchnic dilation
CNS
• Modulates extrapyramidal movement
• Nausea and vomiting from stimulation of
chemoreceptor trigger zone
EXTRA
• Diuretic effect thought to be
due to ↑ CO and by inhibition
of Na+/K+ ATPase
DOPEXAMINE
DOPEXAMINE
Synthetic b2, D1 and D2 agonist
• Clear colourless solution:
10 mg/mL
DOSE
• 0.5–6 μg/kg/min. Titrate to fx
MOA
- Direct stimulation of dopaminergic receptors
- Direct stimulation of b2 receptors
- Inhibits uptake-1 of noradrenaline
USES
• Inotrope
• To ↑ splanchnic and renal perfusion
DOPEXAMINE
adme
ABSORPTION/
DISTRIBUTION
- 40% bound to red blood cells
- VD 0.3–0.45 L/kg
METABOLISM
AND EXCRETION
• Hepatic metabolism
• Metabolites excreted
in urine and faeces
DOPEXAMINE
EFFECTS
CVS
- ↑ HR
- ↑ Contractility
- ↑ CO (helped by ↓ afterload)
• Improved coronary artery perfusion with no increase in myocardial O2 demand • Rarely precipitates arrhythmias
GI
• ↑ Renal blood flow causes diuresis
• ↑ Splanchnic blood flow
RS
• Bronchodilation (b2)
OTHER
• Hyperglycaemia (b2)
• Hypokalaemia (b2)
• Nausea and vomiting from D2 effect
CTZ
NB Avoid in fixed cardiac output states or
phaeochromocytoma
ISOPRENALINE
Synthetic b1 and b2 agonist
- Tablets: 30 mg
- Colourless solution: 0.02 or 1 mg/mL
- Metered dose aerosol: 80/400 μg
DOSE
• Oral: 30 mg t.d.s.
• IV: 0.5–8 μg/min, titrate to
effect. Takes ~ 20 min to take effect
MOA
• Potent b1 and b2 adrenoreceptor agonist
• No a effects
METABOLISM AND EXCRETION
• Hepatic metabolism by catechol-Omethlytransferase
• Metabolites and large amount
of unchanged drug excreted in urine
ABSORPTION/
DISTRIBUTION
- Well absorbed orally
- Extensive first-pass metabolism
- Low bioavailability
USES
• Holding measure in complete heart block
while awaiting pacing (temporary or permanent)
Inotrope
ISOPRENALINE
Effects
EFFECTS CVS b1 • ↑ HR • ↑ Contractility • ↑ CO
b2
• Can ↓ SVR negating any rise in BP
caused by ↑CO
• Can ↑ coronary artery perfusion as
diastolic filling time reduced
RS
• Potent bronchodilator (but not used
in asthma as there is an associated rise
in mortality)
CNS
• Stimulant
GI
• ↑ Mesenteric and renal blood flow
Metabolic
• ↑Blood glucose and free fatty acids
MILRINONE
Selective phosphodiesterase III Inhibitor
• Yellow solution: 1 mg/mL
DOSE
• Loading: 50 μg/kg over 10 min
.• Maintenance: 0.375–0.75 μg/kg/min
MOA
• Inhibits PDE III and therefore reduces
degradation of cAMP in cardiac and smooth
muscle
• ↑ cAMP increases intracellular
release of Ca2+, therefore increasing
biventricular contractility
• Alters Ca2+ flux into smooth muscles
causing relaxation of vessels,
including pulmonary vasodilatation
USES
• Inotrope
• Low cardiac output states
espec following cardiac surgery
MILRINONE
METABOLISM
AND EXCRETION
- Hepatic metabolism
- Excreted in urine, 85% unchanged
ABSORPTION/
DISTRIBUTION
- Protein binding 70%
- VD 0.45 L/kg
- t½ 2.5 hours
MILRINONE
EFFECTS CVS • ↑ Stroke volume • ↑ Contractility • ↑ Cardiac index
• No increase in cardiac
oxygen consumption
- ↓ SVR
- ↑ Pulmonary vasodilatation
- Can cause hypotension
• Less tachycardia than with b-agonists
(e.g. dobutamine)
• Ventricular ectopics,
VT and VF reported (rarely)
• Angina
CNS
• Headache
CAUTION! Slightly increases AV nodal conduction use with care in patients with AF/flutter. Consider co-administration of digoxin if necessary.
LEVOSIMENDAN
LEVOSIMENDAN
Ca sensitiser
• Clear colourless solution:
2.5 mg/mL
DOSE
• Loading: 6–12 μg/kg over 10 min
• Maintenance: 0.05–0.2 μg/ kg/min.
Single infusion given for 24 hours
and then discontinued.
Continuing drug does not improve outcomes
MOA
• Binds to troponin C and
stabilises troponin C and actin-myosin cross-bridges
• Therefore, increases contractility
and vasodilatation without increasing Ca2+ concentration by sensitising cardiac muscle
filaments to Ca2+
• Does not increase oxygen or ATP consumption
USES
• Acute decompensated severe
congestive cardiac failure
LEVOSIMENDAN
ABSORPTION/
DISTRIBUTION
• Oral bioavailability 85%
- Protein binding 98%
- t½ 1 hour
METABOLISM
AND EXCRETION
- Hepatic metabolism
- Excreted in urine, 85% unchanged
LEVOSIMENDAN
fx
EFFECTS CVS • ↑ Stroke volume • ↑ Contractility • ↑ Cardiac index
• No increase in cardiac
oxygen consumption
• ↓ SVR, PVR and PCWP
• Arrhythmias: AF, atrial and
ventricular tachycardias
CNS
• Headache
CAUTION!
Use CI’d in:
• Severe hepatic/renal failure
- Ventricular outflow obstruction
- Severe hypotension/ tachycardia
- History of torsades de pointes
