Loading dose effect

Compared to streptokinase, urokinase has been less extensively studied because of its high cost, ie, about 10 times that of a comparable treatment with streptokinase. In addition to the indications described for streptokinase, urokinase is indicated for use in patients with prior streptokinase treatment, or prior Streptococcal infection. Urokinase is commonly used at a loading dose of 4400 units /kg, with a maintenance intravenous infusion dose of 4400 units/kg/h for thromboses other than acute myocardial infarction. In the latter case, a much larger dose, ie, 0.5—2.0 million units/h or a bolus dose of 1.0 million units followed by a 60-min infusion with 1.0 million units, has been found optimal (106). An intracoronary dose of 2000 units/min for two hours was used in one comparative study with intracoronary streptokinase (107). In this study, urokinase exhibited efficacy equivalent to streptokinase with fewer side effects. Other studies with intracoronary urokinase have adrninistered doses ranging from 2,000 to 24,000 units/min with a reperfusion efficacy of 60—89% (108—112). In another urokinase trial, 2.0 million units were adrninistered intravenously, resulting in a thrombolytic efficacy of 60% (113). Effectiveness in terms of reduction in mortaUty rate has not been deterrnined because of the small number of patients studied. 

If an immediate effect is needed, a loading dose (Dload) must be given to administer the therapeutic amount (Dload = Ao). To maintain the drug effect, the maintenance dose (D) must be administered repetitively with the administration interval (Tau). 

D = Dnorm Cl/Clnorm D = Dnorm Fl/2norm/Fl/2 The administration interval could be selected based on standard peak and trough concentrations or from effect duration time (TED50, TED90). If the dose is reduced, a loading dose (Dload = Cpeak Vd = Dnorm) must be administered to obtain an immediate effect. If Dnorm = const. 

Administration of a loading dose of 150-300 mg produces a more rapid inhibitory effect than seen with the 75 mg daily dose." ... 

Haloperidol 2 mg slow IVP, followed by doubling the dose every 15-20 min until desired effect. For maintenance regimen, add up total loading dose and administer 25% every 6 h for a few days. Then taper dose over several days... 

Dosing recommendations for milrinone include a loading dose of 50 mcg/kg, followed by an infusion beginning at 0.5 mcg/kg per minute (range 0.23 mcg/kg per minute for patients with renal failure up to 0.75 mcg/kg per minute). A loading dose is not necessary if immediate hemodynamic effects are not required or if patients have low systolic blood pressures (less than 90 mm Hg). Decreases in blood pressure during an infusion may necessitate dose reductions as well. 

Levetiracetam Unknown Loading dose Not recommended due to excessive adverse effects Maintenance dose 1 000-3000 mg/day. Start at 1 000 mg/day and titrate upward as indicated by response Half-life Not established 6-8 hours Apparent volume of distribution 0.5-0.7 L/kg Protein binding less than 10% Primary elimination route 70% renal 30% hepatic Somnolence, dizziness Depression... 

Once the loading dose of the AED is administered, it is important to remember to initiate maintenance doses to ensure that therapeutic levels are sustained. Chronic and idiosyncratic side effects as well as potential drug interactions should be considered if the patient will continue AED therapy indefinitely. All drug therapy should be adjusted for any hepatic or renal disease states. Table 28-1 summarizes the drug doses used in SE, and Table 28-2 provides an example of an algorithm for the treatment of patients in SE. Published studies comparing these treatment strategies are summarized in Table 28-3. 

Drug Name (Brand Name) Loading Dose Administration Rate Therapeutic Level Side Effects Comments... 

I with seizures and require anticonvulsant therapy. Phenytoin is the most frequently used agent, with a loading dose of 15 mg/kg followed by 300 mg by mouth daily (titrated to therapeutic levels between 10 and 20 mcg/mL). Diazepam 5 mg intravenously may be used for rapid control of persistent seizures. Prophylactic anticonvulsants have been used frequently, but a recent meta-analysis did not support their use.23 Thus, because adverse effects and drug interactions are common, the routine use of prophylactic anticonvulsants is not recommended. 

Equipotent doses of loop diuretics (furosemide, bumetanide, torsemide, ethacrynic acid) have similar efficacy. Ethacrynic acid is reserved for sulfa-allergic patients. Continuous infusions of loop diuretics appear to be more effective and to have fewer adverse effects than intermittent boluses. An initial IV loading dose (equivalent to furosemide 40 to 80 mg) should be administered before starting a continuous infusion (equivalent to furosemide 10 to 20 mg/hour). 

The toxic effects model uses concentration-time profiles from the respiratory and skin protection models as input to estimate casualty probabilities. Two approaches are available a simple linear dose-effect model as incorporated in RAP and a more elaborate non-linear response model, based on the Toxic Load approach. The latter provides a better description of toxic effects for agents that show significant deviations of simple Haber s law behaviour (i.e. toxic responses only depend on the concentration-time product and not on each quantity separately). 

Loading dose 15 mg/kg IV. then 30-120 mg PO/IV/IM bid. Reduces the effect of oral contraceptives. 

The units of volume of distribution are those of volume (i.e. litres) and can be adjusted for, say, body weight. The two main uses of volume of distribution are in the calculation of loading doses for rapid onset of drug effect, and in understanding changes in half-life (see below). 

Rapid digitalization with a loading dose Peak digoxin body stores of 8 to 12 mcg/kg should provide therapeutic effect with minimum risk of toxicity in most patients with heart failure and normal sinus rhythm. Because of altered digoxin distribution and elimination, projected peak body stores for patients with renal insufficiency should be conservative (ie, 6 to 10 mcg/kg see Precautions). 

Initial loading dose For rapid control of ventricular arrhythmia, give an initial loading dose of 300 mg immediate release (200 mg for patients less than 50 kg [110 lbs]). Therapeutic effects are attained in 30 minutes to 3 hours. If there is no response or no evidence of toxicity within 6 hours of the loading dose, 200 mg every 6 hours may be administered instead of the usual 150 mg. If there is no response within 48 hours, discontinue the drug or carefully monitor subsequent doses of 250 or 300 mg every 6 hours. 

Loading dose - Loading dose, 1 mg/kg/dose given IV or intratracheally every 5 to 10 min to desired effect, maximum total dose 5 mg/kg Maintenance 20 to 50 mcg/kg/min. 

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