Inotropes dosing

Cardiac inotropic dose 5-10 mcg/kg/min (beta-adrenergic) Vasoconstricting dose >10 mcg/kg/min (alpha-adrenergic)... 

Dopamine (Intropin) [Vasopressor/Adrenergic] Uses Short-tOTn use in cardiac decompensation secondary to X contractility when no hypovolemia is present T organ p fusion (at low dose) Action Renal dose 2-5 mcg/kg/min Inotropic dose 5-10 mcg/kg/min Pressor dose >10 mcg/kg/min Dose Adults Feds. 5-20 mcg/kg/min by cont inf, start at 5 and t by 5 mcg/kg/min to 20 mcg/kg/min max to effect (mix 400 mg in 250 mL DjW to make 1600 mcg/mL) (see Table 1-3) Caution [C, ] Contra Pheochromocytoma (adrenal gland tumor), VF, sulfite sensitivity Disp Inj 40, 80, 160 mg/mL, premixed 0.8, 1.6, 3.2 mg/mL SE Tach, vasoconstriction, 4- BP, HA, N/V, dyspnea Notes >10 mcg/kg/min X renal p fiision Interactions t Effects W/ a-blockers, diuretics, ergot alkaloids, MAOIs, BBs, anesthetics, phenytoin X effects W/ guanethidine EMS Correct hypovolemia before use use microdrip set or inf pump check soln- discolored... 

The cardiovascular effects of racemic dobutamine are a composite of the pharmacological properties of the (—) and (-V) stereoisomers. Dobutamine has relatively more prominent inotropic than chronotropic effects, compared to isoproterenol. This useful selectivity may arise because peripheral resistance is relatively unchanged due to a counterbalancing ofa receptor-mediated vasoconstriction and receptor-mediated vasodilation. Alternatively, cardiac receptors may contribute to the inotropic effect. At equivalent inotropic doses, dobutamine enfumces automatic-ity of the sinus node to a lesser extent than does isoproterenol however, enhancement of AV and intraventricular conduction is similar for both drugs. 

FIGURE 2.18 Inotropic and lusitropic responses of guinea pig left atria to (3-adrenoceptor stimulation. Panels A to C isometric tension waveforms of cardiac contraction (ordinates are mg tension abscissae are msec), (a) Effect of 0.3 nM isoproterenol on the waveform. The wave is shortened due to an increase in the rate of diastolic relaxation, whereas no inotropic response (change in peak tension) is observed at this concentration, (b) A further shortening of waveform duration (lusitropic response) is observed with 3 nM isoproterenol. This is concomitant with positive inotropic response (increase maximal tension), (c) This trend continues with 100 nM isoproterenol, (d) Dose-response curves for ino tropy (filled circles) and lusitropy (open circles) in guinea pig atria for isoproterenol, (e) Dose-response curves for inotropy (filled circles) and lusitropy (open circles) in guinea pig atria for the P-adrenoceptor partial agonist prenalterol. Data redrawn from [6]. 

Palytoxin (PTX) is one of the most potent marine toxins known and the lethal dose (LD q) of the toxin in mice is 0.5 Mg/kg when injected i.v. The molecular structure of the toxin has been determined fully (1,2). PTX causes contractions in smooth muscle (i) and has a positive inotropic action in cardiac muscle (4-6). PTX also induces membrane depolarization in intestinal smooth (i), skeletal (4), and heart muscles (5-7), myelinated fibers (8), spinal cord (9), and squid axons (10). PTX has been demonstrated to cause NE release from adrenergic neurons (11,12). Biochemical studies have indicated that PTX causes a release of K from erythrocytes, which is followed by hemolysis (13-15). The PTX-induced release of K from erythrocytes is depress by ouabain and that the binding of ouabain to the membrane fragments is inhibited by PTX (15). 

Dobutamine is a P-adrenergic inotropic agent that can be utilized for improvement of cardiac output and oxygen delivery. Doses of 2 to 20 mcg/kg per minute increase cardiac index however, heart rate increases significantly. Dobutamine should be considered in septic patients with adequate filling... 

Vasopressin levels are increased during hypotension to maintain blood pressure by vasoconstriction. However, there is a vasopressin deficiency in septic shock. Low doses of vasopressin increase MAP, leading to the discontinuation of vasopressors. However, routine use of vasopressin is not recommended because of lack of evidence of efficacy. Vasopressin is a direct vasoconstrictor without inotropic or chronotropic effects and may result in decreased cardiac output and hepatosplanchnic flow. Vasopressin use may be considered in patients with refractory shock despite adequate fluid resuscitation and high-dose vasopressors.24,27-28... 

Bradycardia, decreased conduction (atrioventricular block at high doses), small negative inotropic action... 

Because of their negative inotropic effects, /J-blockers should be started in very low doses with slow upward dose titration to avoid symptomatic worsening or acute decompensation. Patients should be titrated to target doses when possible to provide maximal survival benefits. However, even lower doses have benefits over placebo, so any dose is likely to provide some benefit. 

Dobutamine is a /Jj- and / -receptor agonist with some oq-agonist effects. The net vascular effect is usually vasodilation. It has a potent inotropic effect without producing a significant change in heart rate. Initial doses of 2.5 to 5 mcg/kg/min can be increased progressively to 20 mcg/kg/min on the basis of clinical and hemodynamic responses. 

Dopamine produces dose-dependent hemodynamic effects because of its relative affinity for cq-, /Jr, /J2-, and Dr (vascular dopaminergic) receptors. Positive inotropic effects mediated primarily by / -receptors become more prominent with doses of 2 to 5 mcg/kg/min. At doses between 5 to 10 mcg/kg/min, chronotropic and -mediated vasoconstricting effects become more prominent. Especially at higher doses, dopamine alters several parameters that increase myocardial oxygen demand and potentially decrease myocardial blood flow, worsening ischemia in some patients with coronary artery disease. 

There is no support of low doses of dopamine to maintain or improve renal function B Inotropic therapy... 

The data indicated that cochlearenine (11) exhibited dose dependent bradycardiac effect along with mild positive inotropic effect followed by cardiac suppression at higher dose, which is an interesting observation, as the dmgs with bradycardiac effect without accompanying negative effect is considered relatively safe for its use in cardioactive disorders like hypertension, palpitations and ischemic heart disease. 

A dose of 7.0 /ig/kg of indolidan (i.v. administration) resulted in a 50% increase in contractility in anaesthetized dogs. A selective inotropic response has been observed with conscious dogs upon oral administration of 25 ngj kg of (23). The haemodynamic profile of (23) has been evaluated in anaesthetized dogs [78]. The acute and subchronic toxicology of indolidan has been studied (rats, dogs) [79]. 

From this series, compound MCI-154 (CAS 98326-33-1) (30) has been investigated in detail [95,96]. In vivo studies (anaesthetized dogs) revealed that doses of 0.3-100 tg/kg (i.v. administration) of MCI-154 produce dose-dependent increases in dF/dtmax and cardiac output, and decreases in arterial blood pressure and total peripheral resistance. The positive inotropic effect of (30) has been found to be superior to that exhibited by amrinone and milrinone [97,98]. It has been stated that MCI-154 exerts its activity probably by increasing the calcium-ion sensitivity of the contractile protein system of the cardiac skinned fibres [99,100]. A recent investigation suggests that inhibition of phosphodiesterase III is an important component of its cardiotonic activity [101]. 

Q69 At therapeutic doses the occurrence of o negative inotropic effect v/ith omlodipine is rarely seen. Amlodipine has greater selectivity for vascular smooth muscle than for myocardium. 

---