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CVS 常用藥物概論. Yeh Yu Chang 94.06.04. 分類. Inotropes: 強心 Chronotropic: 增快心律 Pressors: 升壓 Vasodilator: 降壓 Antiarrhytmic agents: 抗心律不整. 常用藥物. Bosmine (Epinephrine) Levophed (Norepinephrine) Dopamine Dobutamine Primacor (Milrinone) Isuprel NTG Nitroglyceride Perdipine

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slide1

CVS 常用藥物概論

Yeh Yu Chang

94.06.04.

slide2
分類
  • Inotropes: 強心
  • Chronotropic: 增快心律
  • Pressors: 升壓
  • Vasodilator: 降壓
  • Antiarrhytmic agents:抗心律不整
slide3
常用藥物
  • Bosmine (Epinephrine)
  • Levophed (Norepinephrine)
  • Dopamine
  • Dobutamine
  • Primacor (Milrinone)
  • Isuprel
  • NTG
  • Nitroglyceride
  • Perdipine
  • Amiodarone
  • PGE1
  • DDAVP
slide5
HEARTRATE

Rhythm

CONTRACTILITY

CARDIAC

OUTPUT

(CI=CO/m²)

L/Min

AFTERLOAD

PRELOAD

catecholamines
Catecholamines
  • Natural
    • Norepinephrine: a, b1
    • Epinephrine: a, b
    • Dopamine: D, a1, b1 (also some NE release)
  • Synthetic
    • Isoproterenol: b
    • Dobutamine: b1 (and mix of b2 stimulation and a1 inhibition and stimulation)
g kg min
μg/kg/min
  • 160 mg in 100 ml, 50 kg (mg/ml)
  • 160*1000 : mg/ml → μg/ml
  • 160 * 1000/100 : 100ml → 1ml
  • 160 *1000/100/60 : μg/h → μg/min
  • 160/6/50 = 0.533 μg/kg/min
alpha adrenergic medications
ALPHA-ADRENERGIC MEDICATIONS
  • Can be divided into:
    • Alpha1-adrenergic effects:
      • Vascular smooth muscle contraction
    • Alpha2-adrenergic effects:
      • Vascular smooth muscle relaxation--this is a very mild effect only at low doses of an alpha-adrenergic agent like epinephrine.
beta adrenergic medications
BETA-ADRENERGIC MEDICATIONS
  • Can be divided into:
    • Beta1-adrenergic effects:
      • Direct cardiac effects
        • Inotropy (improved cardiac contractility)
        • Chronotropy (increased heart rate)
    • Beta2-adrenergic effects:
      • Vasodilation
      • Bronchodilation
epinephrine
Epinephrine
  • 1 –↑contractility and H.R → ↑C.O. and myocardial oxygen demand.
  • 1 –↓splanchnic and renal blood flow but↑coronary and cerebral perfusion pressure, SBP 
  • 2 – vasodilation in skeletal muscle may lower diastolic pressure also relaxes bronchial smooth muscle
slide31
Selecting inotropic and vasopressor agents for specific hemodynamic disturbances in children

Blood pressure or SVR

Hemodynamic pattern

Normal

Deceased

Elevated

Epinephrine or dopamine

(or dobutamine plus

norepinephrine)

Dobutamine or dopamine

or amrinone

Dobutamine

plus

nitroprusside

Myocardial dysfunction

Dobutamine

Primacor

Dobutamine

plus

nitroprusside

CHF

Dopamine

Bradycardia

Isoproterenol

None

None

dobutamine indications
Dobutamine Indications

Consider for pump problems (CHF) with systolic blood pressure of 70 to 100 mm Hg and no signs of shock

dobutamine precautions
Dobutamine Precautions
  • Avoid with systolic blood pressure <100 mm Hg and signs of shock
  • May cause tachyarrhythmias, fluctuations in blood pressure, headache, and nausea
  • Contraindication: Suspected or known poison/drug-induced shock
  • Do not mix with sodium bicarbonate.
dobutamine iv infusion
Dobutamine IV Infusion
  • Usual infusion rate: 2 to 20 µg/kg /min
  • Titrate so heart rate does not increase by >10% of baseline
  • Hemodynamic monitoring is recommended for optimal use
dopamine indications
DopamineIndications
  • 2nd drug for symptomatic bradycardia after atropine
  • Use for hypotension (systolic blood pressure = 70 - 100 mm Hg) with signs and symptoms of shock
dopamine precautions
Dopamine Precautions
  • May use in patients with hypovolemia but only after volume replacement
  • Use with caution in cardiogenic shock with accompanying congestive heart failure
  • May cause tachyarrhythmias, excessive vasoconstriction
  • Taper slowly.
  • Do not mix with sodium bicarbonate
dopamine continuous infusions
Dopamine Continuous Infusions

Titrate to patient response:

  • Low Dose
    • 1 to 5 µg/kg per minute (“renal doses)
  • Moderate Dose
    • 5 to 10 µg/kg per minute (“cardiac doses”)
  • High Dose
    • 10 to 20 µg/kg per minute (“pressor doses”)
epinephrine indications
Epinephrine Indications
  • Cardiac arrest:
    • VF, pulseless VT, asystole, PEA
  • Symptomatic bradycardia:
    • After atropine, dopamine and TCP
  • Severe hypotension,Anaphylaxis:
    • Combine with large fluid volumes, corticosteroids, antihistamines
epinephrine precautions
EpinephrinePrecautions
  • Raising BP and increasing HR may cause myocardial ischemia, angina
  • High doses do not improve survival or neurologic outcome and may contribute to postresuscitation myocardial dysfunction
  • Higher doses may be required to treat poison/drug-induced shock
epinephrine in cardiac arrest
Epinephrine in Cardiac Arrest
  • IV Dose: 1 mg (10 mL of 1:10 000 solution) administered every 3 to 5 minutes during resuscitation
  • Follow each dose with 20 mL IV flush.
  • ETT: 2 to 2.5 mg (1:1000) diluted in 10 mL normal saline.
isoproterenol indications
Isoproterenol Indications
  • Use cautiously as temporizing measure if external pacer is not available for treatment of symptomatic bradycardia
  • Refractory torsades unresponsive to MgSO4
  • Temporary control of bradycardia in heart transplant patients
  • Poisoning from ß-adrenergic blockers
isoproterenol precautions
Isoproterenol Precautions
  • Do not use for treatment of cardiac arrest
  • Increases myocardial oxygen requirements
  • Do not give with epinephrine; can cause VF/VT
  • Do not administer with poison/drug induced shock (exception: ß-blocker poisoning)
  • Higher doses are Class III (harmful) except for ß-adrenergic blocker poisoning
isoproterenol iv infusion
Isoproterenol IV Infusion
  • Infuse at 2 to 10 µg/min
  • Titrate to adequate heart rate
  • In torsades, titrate to increase heart rate until VT is suppressed
lidocaine indications
Lidocaine Indications
  • Cardiac arrest from VF/VT
  • Stable VT, wide-complex tachycardias of uncertain type, wide-complex PSVT (Class Indeterminate)
lidocaine precautions
Lidocaine Precautions
  • Prophylactic use in AMI patients is not recommended
  • Reduce maintenance dose (not loading dose) in presence of impaired liver function or left ventricular dysfunction
  • Discontinue infusion immediately if signs of toxicity develop
lidocaine in cardiac arrest from vf vt
Lidocaine inCardiac Arrest From VF/VT
  • Initial dose: 1 to 1.5 mg/kg IV
  • For refractory VF may give additional 0.5 to 0.75 mg/kg IV push, repeat in 5 to 10 minutes; maximum total dose: 3 mg/kg.
  • ETT: 2 to 4 mg/kg.
lidocaine
Lidocaine

Perfusing Arrhythmia

  • For stable VT, wide-complex tachycardia of uncertain type, significant ectopy: 1 to 1.5 mg/kg IVP
  • Repeat 0.5 to 0.75 mg/kg every 5 to 10 minutes
  • Maximum total dose: 3 mg/kg.

Maintenance Infusion

  • 2 to 4 mg/min
magnesium sulfate indications
Magnesium Sulfate Indications
  • Cardiac arrest only if torsades de pointes or suspected hypomagnesemia is present
  • Refractory VF (after lidocaine)
  • Torsades de pointes with a pulse
  • Life-threatening ventricular arrhythmias due to digitalis toxicity
magnesium sulfate precautions
Magnesium Sulfate Precautions
  • Occasional fall in blood pressure with rapid administration.
  • Use with caution if renal failure is present.
magnesium sulfate administration
Magnesium Sulfate Administration

Cardiac Arrest (for hypomagnesemia or TdP)

  • 1 to 2 g (2 to 4 mL of a 50% solution) diluted in 10 mL of D5W IVP
  • Torsades de Pointes (not in cardiac arrest)
  • Loading dose of 1 to 2 g mixed in 50 to 100 mL of D5W, over 5 to 60 minutes IV
  • Follow with 0.5 to 1 g/h IV (titrate dose to control the torsades)
nitroglycerin indications
Nitroglycerin Indications
  • Initial antianginal for suspected ischemic pain
  • For initial 24 to 48 hours in patients with AMI and CHF, large anterior wall infarction, persistent or recurrent ischemia, or hypertension
  • Continued use (beyond 48 hours) for patients with recurrent angina or persistent pulmonary congestion
  • Hypertensive urgency with ACS
nitroglycerin precautions contraindications
NitroglycerinPrecautions/Contraindications
  • Limit normotensive BP drop to 10%
  • Limit hypertensive BP drop to 30%
  • Avoid BP drop below 90 mm Hg
  • Do not mix with other drugs
  • Sit or lie pt down when receiving med
  • Do not shake aerosol spray (affects metered dose)

Contraindications

  • Hypotension
  • Severe bradycardia or severe tachycardia
  • RV infarction
  • Viagra within 24 hours
nitroglycerin administration
Nitroglycerin Administration

IV Bolus/Infusion

  • IV bolus: 12.5 to 25 µg
  • Infuse at 10 to 20 µg/min
  • Route of choice for emergencies
  • Titrate to effect

Sublingual Route

  • 1 tablet (0.3 to 0.4 mg); repeat every 5 minutes.

Aerosol Spray

  • Spray for 0.5 to 1 second at 5-minute intervals (provides 0.4 mg per dose).
nitroprusside indications
Nitroprusside Indications
  • Hypertensive crisis.
  • To reduce afterload in heart failure and acute pulmonary edema
  • To reduce afterload in acute mitral or aortic valve regurgitation
nitroprusside precautions
Nitroprusside Precautions
  • Light-sensitive; therefore, wrap drug reservoir in aluminum foil
  • May cause hypotension, thiocyanate toxicity, and CO2 retention.
  • May reverse hypoxic pulmonary vasoconstriction in patients with pulmonary disease, exacerbating intrapulmonary shunting, resulting in hypoxemia
  • Other side effects include headaches, nausea, vomiting, and abdominal cramps
nitroprusside iv infusion
Nitroprusside IV Infusion
  • Begin at 0.1 µg/kg per minute and titrate upward every 3 to 5 minutes to desired effect (up to 5 µg/kg per minute).
  • Use with an infusion pump
  • Action occurs within 1 to 2 minutes
norepinephrine indications
Norepinephrine Indications
  • For severe cardiogenic shock and hemodynamically significant hypotension (BP<70 mm Hg) with low total peripheral resistance
  • This is an agent of last resort for management of ischemic heart disease and shock
norepinephrine precautions
Norepinephrine Precautions
  • Increases myocardial oxygen requirements because it raises blood pressure and heart rate
  • May induce arrhythmias. Use with caution in patients with acute ischemia; monitor cardiac output
  • Extravasation causes tissue necrosis
    • If extravasation occurs, administer phentolamine 5 to 10 mg in 10 to 15 mL NS, infiltrated into area
norepinephrine iv infusion
Norepinephrine IV Infusion
  • 0.5 to 1 µg/min titrated to improve BP (up to 30 µg/min)
  • Do not administer in same IV line as alkaline solutions
  • Poison/drug-induced hypotension may require higher doses to achieve adequate perfusion
cardiac physiology
Cardiac Physiology
  • Nervous Control of the Heart
    • Sympathetic
    • Parasympathetic
    • Autonomic Control of the Heart
      • Chronotropy
      • Inotropy
      • Dromotropy
    • Role of Electrolytes
catecholamines1
Catecholamines
  • Natural
    • Norepinephrine: a, b1
    • Epinephrine: a, b
    • Dopamine: D, a1, b1 (also some NE release)
  • Synthetic
    • Isoproterenol: b
    • Dobutamine: b1 (and mix of b2 stimulation and a1 inhibition and stimulation)
noncatecholamines
Noncatecholamines
  • Direct-acting
    • Albuterol: b2
    • Clonidine: a2
    • Phenylephrine: a1
  • Mixed-acting
    • Ephedrine: a (CNS), b, and NE release
  • Indirect-acting (effects from NE release)
    • Tyramine: a, b1
    • Amphetamine: a (CNS), b1 (also DA and 5-HT release centrally)
therapeutic uses 2
Therapeutic uses (2)
  • Cardiac stimulation (b1, b2)
    • In bradycardia: dopamine, epinephrine
    • In hypotension: dopamine,norepinephrine
    • In normotension: dobutamine
  • Bronchial dilation (b2)
    • In bronchial asthma: albuterol
    • In anaphylaxis: epinephrine
  • Ocular effects
    • Pupillary dilation (a1): phenylephrine
    • Glaucoma (a2): epinephrine
cardiovascular medications
CARDIOVASCULAR MEDICATIONS
  • Main actions of most of the following cardiovascular medications will be determined by the adrenergic effects of the medications.
  • Can either be:
    • alpha-adrenergic
    • beta-adrenergic
    • dopaminergic
cardiac meds via continuous infusion
CARDIAC MEDS VIA CONTINUOUS INFUSION
  • Epinephrine
  • Norepinephrine
  • Dopamine
  • Dobutamine
  • Milrinone/Amrinone
  • Sodium Nitroprusside
  • Nitroglycerin
  • Isoproterenol
epinephrine1
EPINEPHRINE
  • Both an alpha- and beta-adrenergic agent
  • Therefore, indications for its use as a continuous infusion are:
    • low cardiac output state
      • beta effects will improve cardiac function
      • alpha effects may increase afterload and decrease cardiac output
    • septic shock
      • useful for both inotropy and vasoconstriction
epinephrine2
EPINEPHRINE
  • Actions are dose dependent (mcg/kg/min):
    • 0.02-0.08 = mostly beta1 and beta2 stimulation.
      • increased cardiac output
      • mild vasodilation
    • 0.1-2.0 = mix of beta1 andalpha1
      • increase cardiac output
      • increase SVR = vasoconstriction
    • > 2.0 = mostly alpha1
      • increase SVR, and may decrease CO by increasing afterload
epinephrine3
EPINEPHRINE
  • Side effects include:
  • Anxiety, tremors,palpitations
  • Tachycardia and tachyarrhythmias
  • Increased myocardial oxygen requirements and potential to cause ischemia
  • Decreased splanchnic and hepatic circulation (elevation of AST and ALT)
  • Anti-Insulin effects: lactic acidosis, hyperglycemia
norepinephrine
NOREPINEPHRINE
  • Employed primarily for its alpha agonist effect - increases SVR (and B.P.) without significantly increasing C.O.
  • Used in cases of low SVR and hypotension such as profound “warm shock” with a normal or high C.O. state
  • Infusion rates titrated between 0.05 to 1 mcg/kg/min
norepinephrine1
NOREPINEPHRINE
  • In general, norepinephrine differs from epinephrine in that at doses used in clinical practice, the vasoconstriction outweighs any increase in cardiac output.
    • i.e. norepinephrine usually increases blood pressure and SVR, often without increasing cardiac output.
norepinephrine2
NOREPINEPHRINE
  • Side Effects:
  • Similar to those of Epinephrine
  • Can compromise perfusion in extremities and may need to be combined with a vasodilator e.g. Dobutamine or Nipride
  • More profound effect on sphlancnic circulation and myocardial oxygen consumption
dopamine
DOPAMINE
  • Intermediate product in the enzymatic pathway leading to the production of norepinephrine; thus, it indirectly acts by releasing norepinephrine.
  • Directly has alpha, beta and dopaminergic actions which are dose-dependent.
  • Indications are based on the adrenergic actions desired.
dopamine1
DOPAMINE
  • Improve renal perfusion 2-5 mcg/kg/min
  • Improve C.O. in mild to moderate Cardiogenic or Distributive Shock 5-10mcg/kg/min
  • Post-resuscitation stabilization in patients with hypotension (in conjuction with fluid therapy) 10-20mcg/kg/min
dobutamine
DOBUTAMINE
  • Synthetic catecholamine with inotropic effect (increases stroke volume) and peripheral vasodilation (decreases afterload)
  • Positive chronotropic effect (increases HR)
  • Some lusotropic effect
  • Overall, improves Cardiac Output by above beta-agonist acitivity
dobutamine1
DOBUTAMINE
  • Major metabolite is 3-O-methyldobutamine, a potent inhibitor of alpha-adrenoceptors.
    • Therefore, vasodilation is possible secondary to this metabolite.
  • Usual starting infusion rate is 5 mcg/kg/min, with the dose being titrated to effect up to 20 mcg/kg/min.
dobutamine2
DOBUTAMINE
  • Used in low C.O. states and CHF e.g. myocarditis, cardiomyopathy, myocardial infarction
  • If BP adequate, can be combined with afterload reducer (Nipride or ACE inhibitor)
  • In combination with Epi/Norepi in profound shock states to improve Cardiac Output and provide some peripheral vasodilatation
milrinone amrinone
MILRINONE/AMRINONE
  • Belong to new class of agents “Bipyridines”
  • Non-receptor mediated activity based on selective inhibition of Phosphodiesterase Type III enzyme resulting in cAMP accumulation in myocardium
  • cAMP increases force of contraction and rate and extent of relaxation of myocardium
  • Inotropic, vasodilator and lusotropic effect
amrinone
AMRINONE
  • First generation agent - limited use now
  • Long half-life (4.4 hours) with potential for prolonged hypotension after loading dose
  • Associated with thrombocytopenia
  • Dosage: Load with 0.75 mg/kg with infusion rate of 5-10 mcg/kg/min
  • Milrinone is preferred drug from this group
milrinone
MILRINONE
  • Increases CO by improving contractility, decreased SVR, PVR (?), lusotropic effect; decreased preload due to vasodilatation
  • Unique in beneficial effects on RV function
  • Half-life is 1-2 hours
  • Load with 50 mcg/kg over 30 mins followed by 0.3 to 0.75 mcg/kg/min
  • No increase in myocardial O2 requirement
vasodilators
VASODILATORS
  • Classified by site of action
  • Venodilators: reduce preload - Nitroglycerin
  • Arteriolar dilators: reduce afterload Minoxidil and Hydralazine
  • Combined: act on both arterial and venous beds and reduce both pre- and afterload Sodium Nitroprusside (Nipride)
nitroprusside
NITROPRUSSIDE
  • Vasodilator that acts directly on arterial and venous vascular smooth muscle.
  • Indicated in hypertension and low cardiac output states with increased SVR.
  • Also used in post-operative cardiac surgery to decrease afterload on an injured heart.
  • Action is immediate; half-life is short; titratable action.
nitroprusside1
NITROPRUSSIDE
  • Toxicity is with cyanide, one of the metabolites of the breakdown of nipride.
  • Severe, unexplained metabolic acidosis might suggest cyanide toxicity.
  • Dose starts at 0.5 mcg/kg/min and titrate to 5 mcg/kg/min to desired effect. May go higher (up to 10 mcg/kg/min) for short periods of time.
nitroglycerin
NITROGLYCERIN
  • Direct vasodilator as well, but the major effect is as a venodilator with lesser effect on arterioles.
  • Not as effective as nitroprusside in lowering blood pressure.
  • Another potential benefit is relaxation of the coronary arteries, thus improving myocardial regional blood flow and myocardial oxygen demand.
nitroglycerin1
NITROGLYCERIN
  • Used to improve myocardial perfusion following cardiac surgery
  • Dose ranges from 0.5 to 8 mcg/kg/min. Typical dose is 2 mcg/kg/min for 24 to 48 hours post-operatively
  • Methemoglobinemia is potential side effect
isoproterenol
ISOPROTERENOL
  • Synthetic catecholamine
  • Non-specific beta agonist with minimal alpha-adrenergic effects.
  • Causes inotropy, chronotropy, and systemic and pulmonary vasodilatation.
  • Indications: bradycardia, decreased cardiac output, bronchospasm (bronchodilator).
  • No longer available in some markets
isoproterenol1
ISOPROTERENOL
  • Occasionally used to maintain heart rate following heart transplantation.
  • Dose starts at 0.01 mcg/kg/min and is increased to 1.0 mcg/kg/min for desired effect.
inhaled nitric oxide
INHALED NITRIC OXIDE
  • Selective Pulmonary vasodilator
  • Dilates only pulmonary capillaries to alveoli participating in gas exchange
  • Decreases intrapulmonary shunt and improves V/Q matching
  • Rapidly inactivated by Hgb in pulm. cap. so no systemic side effects (eg hypotension)
inhaled nitric oxide1
INHALED NITRIC OXIDE
  • Potential for use in ARDS and Pulmonary Hypertension
  • Currently only approved for use in neonatal Pulmonary Hypertension
  • Expensive
  • Special monitoring equipment required
  • Dose: Concentration of 0.5-60 ppm in inhaled gas
additional considerations
Additional considerations
  • Mechanical ventilation and oxygen therapy (to conserve CO)
  • Analgesia, anxiolysis and sedation
  • Electrolyte homeostasis esp Ca and Mg
  • Nutrition - avoid hypoglycemia
  • Anemia is an “unconstitutional surcharge”
  • Last but not the least: Maintain appropriate intravascular volume
slide90
Selecting inotropic and vasopressor agents for specific hemodynamic disturbances in children

Blood pressure or SVR

Hemodynamic pattern

Normal

Deceased

Elevated

Norepinephrine

Dopamine or epinephrine

(or dobutamine plus

norephinephrine)

Septic Shock

Stroke index High

Stroke Index low to N

None

Dobutamine

plus

nitroprusside

None or dopamine

Dobutamine or dopamine

Cardiogenic shock

Epinephrine or dopamine

Dobutamine or amrinone

or dopamine

--

Myocardial dysfunction

Epinephrine or dopamine

(or dobutamine plus

norepinephrine)

Dobutamine

plus

nitroprusside

Dobutamine or dopamine

or amrinone

Dobutamine or dopamine

or amrinone

Dobutamine

plus

nitroprusside

CHF

--

Bradycardia

None

Isoproterenol

None

slide91
DRIP FORMULA:

6 X WT. IN KG X MCG/KG/MIN = mg in 100 ml of D5W/NS

ML/HR

Also another way to calculate is:

}

ISOPROTERENOL

EPINEPHRINE

NOREPRINEPHRINE

0.6 X BODY WT. IN KG = ____ MG IN 100ML

1 ML/HR WILL DELIVER 0.1 MCG/KG/MIN

}

DOPAMINE

DOBUTAMINE

AMRINONE

NITROPRUSSIDE

6 X BODY WT. IN KG = _____ MG IN 100ML

1 ML/HR WILL DELIVER 1 MCG/KG/MIN

slide95
分類
  • Inotropes: agents that improve myocardial contractility and enhance stroke volume
  • Pressors: agents that increase systemic vascular resistance and increase blood pressure
  • Chronotropic: Increase heart rate
  • improve relaxation during diastole and decrease EDP in the ventricles
slide96
分類
  • 強心(升壓)
    • Bosmine
    • Levophed
    • Dopamine
    • Dobutamine
    • Primacor
  • 降壓
    • NTG
    • Nitroglyceride
    • Perdipine
  • 控制心率
    • Amirodarone
    • Isuprel
ad