S3C24 - Pharmacology of Vasopressor Agents

Question 1

Dobutamine

Answer 1

Actions: -sympathomimetic -potent inotropic, mild chronotropy -beta 1/2 and mild alpha -increased myocardial contractility and systemic vasodilation with minimal change in heart rate -doses 20mcg/kg/min increase HR and arrhythmias Pharmacokinetics: -onset 1-2min peak response 10min (IV) Indications: -short-term positive inotropic -preferred for septic shock with depressed CO despite adequate L ventricular filling pressures -cardiogenic shock -increases CO and renal blood flow w/o increasing HR and also decreases systemic vascular resistance Dosing: -2-20mcg/kg/min **may be given peripherally Adverse Effects: -modest increase HR, BP, ectopic arrhythmias, h/a, paresthesias, tremor, nausea, angina, dyspnea

Question 2

Dopamine

Answer 2

Actions: -endogenous catecholamine (precursor of norepi) -acts on dopaminergic, beta 1, and alpha receptors -low dose: dopaminergic - vasodilation -intermediate dose: beta 1 agonist - increased contractility, CO, but also stimulates alpha resulting in vasoconstriction and increased BP Pharmacokinetics: onset 5 mins, duration 10mins Indications: -reverses hypotension caused by MI, trauma, CHF, renal failure -first-line therapy for septic shock (so is norepi) -increases CO, BP Dosing: 3-20mcg/kg/min Adverse Effects: hypotension/HTN, ectopy, h/a, n/v, angina, palpitations, tachy, tissue necrosis

Question 3

Epinephrine

Answer 3

Actions: -catecholamine, non-selective alpha and beta agonist -used in: anaphylactic shock, bronchodilator for asthma, cardiac arrest -increases HR, contractility, PVR, bronchodilation and antagonizes histamine Pharmacokinetics: -onset 1-2mins, duration 2-10mins Indications: -anaphylaxis -acute asthma exac -cardiac arrest -vasopressor: increase BP, reverse bronchospasm -refractory brady Dosing: -asthma: 0.3-0.5mg of 1:1000 SC q20-30mins (NMT 3x) -brady or hypotension: 2-10mcg/min of 1:10,000 -cardiac arrest: 1mg IV/IO 1:10,000 q3-5min Adverse Effect: -HTN, tachy, palpitations, arrhythmias, necrosis with extravasation

Question 4

Milrinone / Inamrinone

Answer 4

Actions: -positive inotropy: inhibits phosphodiesterase which increases cAMP which increases ICF Ca+ -also vasodilatory -increase contractility and stroke volume with a reduction in preload and afterload Pharmacokinetics: -onset 2-5min, peak effect 10 min, duration .5-2h (IV) Indications: -short-term management of decompensated CHF Dosing: -loading dose milrinone is bolus infusion 50mcg/kg over 10 mins followed by infusion 0.5-0.75mcg/kg/min Adverse effect: -ventricular and SVT arrhythmias, hypotension, h/a, thrombocytopenia, hepatotoxicity (rare)

Question 5

Norepinephrine (levophed)

Answer 5

Actions: -stimulates alpha and beta 1 (no beta2) -increased arterial a nd venou vascular tone -increased inotropy and chronotropy in heart Pharmacokinetics: onset 1-2min, duration 5-10min Indications: -vasoconstriction and cardiac stimulation for shock that persists after adequate volume resusc -hypotension in polio, drug OD, spinal anesthesia, pheo Dosing: 2mcg/min, increase by 1mcg/min q3-5min, max dose is 30mcg/min Adverse Effects: -ventricular irritability, cardiac depression, decreased renal flow, reflex brday -if extravasation occurs give phentolamine

Question 6

Phenylephrine

Answer 6

Actions: -simimlar to epi however primarily targets alpha receptors with minimal beta1/2 -marked vasoconstriction -usually has a compensatory decrease in heart rate Pharmacokinetics: onset 5-10min, duration 15min Indications: hypotension and shock, however not preferred for severe hypotension Dosing: 100-200mcg/min, usually maintained on 40-60mcg/min Adverse Effect: -do not give if pt bradycardic -avoid if narrow-angle glaucoma

Question 7

Vasopressin

Answer 7

Actions: -vasoconstriction (from contraction of smooth muscles) Pharmacokinetics: onset immediate, duration 10-30min Indications: -prevention and treatment of diabetes insipidus -may be used for resusc of pulseless VT/VF (no benefit) -sometimes used in addition to norepi in septic shock but no mortality benefit Dosing: 40units IV push -can be used in place of the initial or 2nd epi in arrest -refractory hypotension: 0.01-0.04 unit/min Adverse effect: HTN, brady, arrhythmia, PAC, herat block, decreased CO, ischemia

Question 8

Adrenergic Receptors

Answer 8

Alpha - smooth muscle contraction NE > E Beta1 - Positive Chronotropic, Dromotropic and inotropic effects NE=E Beta2 - Smooth muscle relaxation (Ex. Bronchodilation) E>>NE

Question 9

Common Sympathomimetic Agents and their effects on Adrenergic Receptors

Answer 9