Vasoactive drugs

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Vasoactive drugs

• ???
  ???

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Drugs in improving cardiac contractility (1)

• Cardiac output (CO) Heart rate (HR) ? Stroke
  volume
• Pharmacologic support always ? in stroke
  volume, unless HR exceptionally low ( e.g., SSS)

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Drugs in improving cardiac contractility (2)

• Positive inotropic drugs ? O2 demand ?
  detrimental in CAD or other critical care
  situations
• Conversely, ? CO may improve hemodynamic situation

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Dobutamine (1)

• A synthetic catecholamine
• Devoid of potent vasoactive properties
• No important activity on dopamine receptor

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Dobutamine (2)

• ? ventricular filling pressure
• Mild vasodilatation
• ? coronary perfusion
• ? peripheral perfusion (skeletal gt renal
  mesenteric)
• Less tachycardia than other adrenergic drugs

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Dobutamine (3)

• Most useful low CO in normal BP with ? systemic
  vascular resistance (SVR)
• In AMI less likely to worsen ischemia than other
  agents

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Dobutamine (4)

• Septic shock ? CO is a hallmark
• Frequently combined with dopamine
• CO O2 delivery ? 1/3, while BP remain unchanged

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Dobutamine (5)

• Occasionally BP may fall
• Restoring adequate preload
• Judicious administration of fluid with or without
  dose reduction

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Dobutamine (6)

• Well-tolerated
• Dose-related problem ? tachycardia, arrhythmias,
  and gastrointestinal irritation

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Dopamine (1)

• Positive inotropic action starts at doses as low
  as 2 to 5 ?g/kg/min ??1-adrenergic action
• Higher dose (gt10 ?g/kg/min) causes
  vasoconstriction ? ?1-adrenergic receptors

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Dopamine (2)

• Very low dose (0.5-2 ?g/kg/min) causes ? BP ?
  activation of dopamine-1 (DA-1) receptors in
  renal splanchnic circulation
• Occasionally causing nausea vomiting ? central
  DA-2 receptors

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Dopamine (3)

• Catecholamine release from endogenous myocardial
  stores ? positive inotropic and vasoconstictor
  effects
• Dose-dependant tachycardia, arrhythmia, cardiac
  and other tissue ischemia

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Isoproterenol (1)

• Powerful inotropic agent
• Potent chronotropic agent
• ?1 ?2-adrenergic receptors
• ?1?inotropic, ?2?chronotropic, vasodilatation
  bronchodilatation

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Isoproterenol (2)

• ? HR and contractility ? ?O2 demand ?detrimental
  result
• A vasodilator, may ? BP
• Redistribute BF to skin muscle ? ? flow to
  cecebral, myocardial renal tissues

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Isoproterenol (3)

• Isoproterenol is best reserved for the treatment
  of hemodynamically significant bradycardia
  (although a pacemaker is preferable)

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Digoxin (1)

• Mostly used for chronic Tx of heart failure
• Inhibition of Na/K ATPase ? ? intracellular
  calcium
• Modest improvement in CO ? limited in therapy of
  shock

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Digoxin (2)

• Mostly used for the acute control of a rapid
  ventricular response in atrial tachyarrhythnias
• The onset of positive inotropic effect is delayed
  ? less used for shock in ICU

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Digoxin (3)

• Hypokalemia, hypomagnesemia, hypercalcemia ? ?
  propensity to cause arrhythmias
• Digoxin toxicity is a frequent occurrence ?
  digoxin-specific Ab (HD or HP ineffective)

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Vasoconstrictors (1)

• Used in severely hypotensive Pt to restore
  perfusion pressure
• Disadvantage ? ? peripheral BF worsen tissue
  ischemia
• ? afterload ? ? CO, especially in heart failure

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Vasoconstrictors (2)

• Before the drugs used, adequate intravascular
  volume is ensued
• Crystalloid VS colloid fluid no study show a
  significant difference in outcome
• 2-4 fold crystalloid 1 colloid

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Dopamine

• Dose above 10 ?g/kg/min, its ?1-adrenergic
  vasoconstrictor properties become increasing
  evident

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Epinephrine (1)

• Combined ? ? adrenergic agent
• Drug of choice CPR anaphalactic shock
• If IV access not available ? administered
  endotracheally ? well absorbed through mucosa

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Epinephrine (2)

• Powerful adrenergic vasoconstrictor ? potent
  action on ?1 receptors lack of effect on
  vasodilatory ?2 receptors
• CO may ?, dose-dependant

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Norepinephrine

• Used in severely hypotensive Pt when other
  agents failed
• May cause vagally mediated bradycardia
• High dose ? ischemia seen in kidneys, spleen,
  skin, muscle

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Drugs in lowering SVR

• Two groups
• Smaller number available for IV administration
• Larger number first delivered into GI tract

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Nitroprusside (1)

• Drug of choice acutely lowering BP
• Very short time of onset (1-2 min)
• Short elimination half-life (2-3 min in normal
  renal liver function)
• Relative ease of administration

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Nitroprusside (2)

• In higher dose (gt5 ?g/kg/min) ? flushing,
  headache, tingling of the scalp
• Over a prolonged period (e.g. gt24hr) ?
  troublesome toxicity

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Nitroprusside (3)

• Nitroprusside RBC cyanide liver
  thiocyanate (cleared by kidneys)
• S/S of cyanide/thiocyanate toxicity ?
  restlessness, mental confusion, hyperreflexia,
  metabolic acidosis, ?lactate

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Nitroprusside (4)

• Stopping nitroprusside
• Hydroxocobalamine ?complex circulating cyanide to
  form Vit B12
• Methylene blue, sodium nitrite, sodium
  thiosulfate ? side effect methomoglobinemia

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Nitroprusside (5)

• The most important thing how and when the
  medication can be stopped

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? blockers

• Should not used in reactive airway disease,
  cardiac conduction disease, severe ventricular
  dysfunction, or CHF

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Labetalol (1)

• Most common use labetalol
• Four compounds
• IV ? vs ? ?13
• Oral ? vs ? ?17 (first pass effect)
• IV more potent in lowering BP than oral form

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Labetalol (2)

• Minibolus IV injection 10 mg, then 25mg in 10
  min
• Once the BP is under control, q4-6 hour or
  constant dose infusion

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Esmolol

• Esmolol IV to reduce HR BP
• Hydrolyzed by serum esterase
• Short elimination half-life 9 min
• Short duration of action 20-30 min
• Often used during anesthesia

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Verapamil

• Calcium channel blocker
• IV for interruption of supraventricular
  arrhythmias
• IV not for BP control when no supraventricular
  arrhythmias

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Direct-acting Vasodilators

• IV form available hydralazine, diazoxide and
  nitroglycerine

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Hydralazine

• Disadvantage reflex tachycardia? impair coronary
  circulation
• Best used in toxemia
• 5-20 mg q4-6 hour

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Nitroglycerin

• Very prompt onset of action
• Side effect headache, flushing, tachycardia
  vomiting metheglobinemia

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Drugs in Lowering HR

• ? blockers, calcium channel blocker, adenosine
  and digoxin

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? blockers

• In a ICU patient, esmolol is preferred
• Shortest elimination half-life of all ? blockers

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Verapamil Adenosine

• Often useful in lowering HR, especially PSVT

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Verapamil

• Verapamil terminatint PSVT over 90
• Side effect hypotension
• Relatively hypotensive only for short period
• Antidote calcium cation

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Adenosine

• In PSVT, equal or better efficacy than verapamil
• Lower incidence of hypotension
• In WPW syndrome, first choice (verapamil may
  precipitate ventriculat fibrillation)

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Digoxin

• Atrial fibrillation with a rapid ventricular
  response
• 0.5 mg (in two divided dose over 30 min),
  followed by two further 0.25-mg boluses over the
  next 2 hr
• Dependant on ventricular rate