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SOE Pharmacology > 38. Vasopressors & Inotropes > Flashcards

38. Vasopressors & Inotropes Flashcards

1
Q

PHENYLEPHRINE

A

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

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2
Q

METARAMINOL

A

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)
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3
Q

METARAMINOL

ADME

EFFECTS

A

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
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4
Q

NORADRENALINE

A

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

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5
Q

Noradrenaline

effects

A

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

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6
Q

Noradrenaline

effects

A

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

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7
Q

ADRENALINE

A

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
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8
Q

ADRENALINE

A

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

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9
Q

ADRENALINE

EFFECTS

A

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

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10
Q

EPHEDRINE

A

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
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11
Q

EPHEDRINE

ADME

EFFECTS

A

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

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12
Q

DOBUTAMINE

A

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

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13
Q

Dobutamine ADME

A

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
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14
Q

Dobutamine EFFECTS

A

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

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15
Q

DOPAMINE

A

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
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16
Q

DOPAMINE

ADME

A

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
17
Q

DOPAMINE

A

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

18
Q

DOPEXAMINE

A

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

19
Q

DOPEXAMINE

adme

A

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

20
Q

DOPEXAMINE

A

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

21
Q

ISOPRENALINE

A

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

22
Q

ISOPRENALINE

Effects

A 
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

23
Q

MILRINONE

A

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

24
Q

MILRINONE

A

METABOLISM
AND EXCRETION

  • Hepatic metabolism
  • Excreted in urine, 85% unchanged

ABSORPTION/
DISTRIBUTION

  • Protein binding 70%
  • VD 0.45 L/kg
  • t½ 2.5 hours
25
Q

MILRINONE

A 
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.
26
Q

LEVOSIMENDAN

A

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

27
Q

LEVOSIMENDAN

A

ABSORPTION/
DISTRIBUTION
• Oral bioavailability 85%

  • Protein binding 98%
  • t½ 1 hour

METABOLISM
AND EXCRETION

  • Hepatic metabolism
  • Excreted in urine, 85% unchanged
28
Q

LEVOSIMENDAN

fx

A 
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

SOE Pharmacology (38 decks)

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