Loading doses

S-aminocaproic acid, 6-aminohexanoic acid (10) Amicar, Ledede [60-32-2] 4—6 g loading dose followed by 1 g/2—4 h iv or oral... 

Indications for treatment with streptokinase include acute occlusion of arteries, deep vein thrombosis, and pulmonary embolism. Streptokinase therapy in coronary thrombosis, which is the usual cause of myocardial infarction (54,71,72), has proved to be valuable. In this frequently fatal condition, the enzyme is adrninistered intravenously at a dose of 1.5 million units over 60 min, or given by intracoronary infusion at a 20,000- to 50,000-unit bolus dose followed by 2000 to 4000 units/min for 60 min therapy must be instituted as soon as practicable after the diagnosis of heart attack is made. For deep vein thrombosis, pulmonary embolism, or arterial occlusion, streptokinase is infused at a loading dose of 250,000 units given over 30 min, followed by a maintenance dose of 100,000 units over a 60-min period. 

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). 

Thus, for drug dosing, one only needs to know the loading dose or the standard dose and the elimination half-life. 

The calculated peak concentration is not always the measured concentration. For bi-exponential kinetics the calculated peak concentration is less, but after oral dosing, the calculated peak concentration is higher than the highest measurable plasma concentration. The peak concentration provides a target for the loading dose to start with (Dload). 

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. 

During the time on dialysis (/HD) a fraction (FR) of the amount in the body is eliminated. The required amount in the body often corresponds to the loading dose (Dload) otto (Dload - Dfail). This fraction must be rqftaced by a supplementary dose (Dsuppl) to maintain therapeutic dtug levels for the time interval between two dialysis sessions. 

Rapid digitalization (accomplished by administering a loading dose) or... 

The use of divalproex in benzodiazepine withdrawal has also become a common clinical strategy. It is usually started in doses of 500—1,000 mg in two or three divided doses daily and increased to achieve serum levels of 50—120 pg/mL. Some protocols recommend a loading dose of 20 mg/kg. 

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

Decrease loading dose in end stage renal disease uncontrolled hypothyroidism, or patients on quinidine by 30-50%... 

Loading dose of 50 mcg/kg over 10 min may be utilized Avoid or administer 50% if tenuous hemodynamics... 

Administer heparin without a loading dose when aPTT <2 x control after fibrinolysis... 

Utilize a central line +/- pulmonary artery catheter ° 10 mg/kg IV over 30 min followed by 5 mg/kg/h continuous IV infusion for 3 h (total loading dose is 25 mg/kg)... 

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... 

Must evaluate volume of medication administered to determine total propylene glycol exposure. High-dose lorazepam (i.e., >8-10 mg/h), phenytoin loading doses, and phenobarbital are the most likely offenders. 

Measure level 2 h after the initial loading dose... 

Begin phenytoin maintenance dose 12 h after the loading dose if indicated... 

Many experts would mechanically intubate the patient if a loading dose of phenobarbital is required... 

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