Intravenous infusions additives

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. 

Another approaeh to the problem of providing an intravenous drug additive serviee is to add the drug to a small-volume (50-100 ml) infusion in a eollapsible plastie eontainer and store the preparation at -20°C in a freezer. The infusion ean be removed when required and thawed rapidly by microwave. Many antibiotics are stable for several months when stored in minibags at -20° C and are unaffected by the thawing process in a suitable microwave oven. Other antibiotics, e.g. ampieillin, are degraded when frozen. 

A sensitive method for detecting low levels of eontamination in intravenous infusion fluids involves the addition of a concentrated eulture medium to the fluid in its original container, such that the resultant mixture is equivalent to single strength culture medium. In this way, sampling of the entire volume is aehieved. 

Recombinant GM-CSF (produced in Escherichia coli, yeast or COS cells) has been tested for its ability to affect haematopoiesis in primates and humans. Because of its relatively short half-life in the circulation, daily administration (usually via intravenous infusion) is required. Administration results in a transient neutropenia, monocytopenia and eosinopenia within 30 min of administration, presumably because of the ability of GM-CSF to stimulate the expression of adhesins and hence increase the numbers of leukocytes adhered to the capillary endothelium in the marginated pool. Additionally, these leukocytes may accumulate in the lungs after GM-CSF administration, which may contribute to the decrease in the observed numbers... 

An intravenous infusion of PAF causes rapid (within 60 s) intravascular platelet aggregation, thrombocytopenia and platelet factor 4 release, as well as a profound and reversible neutropenia, due to enhanced aggregation and adherence of these cells. In vitro, PAF effects on neutrophils are dependent upon extracellular Ca2+ and Mg2+ and occur within 60 s of addition. The addition of inhibitors of 5-lipoxygenase activity (e.g. ETYA, 5,8,11,14-eicosatetraenoic acid and NDGA, nordihydroguaiaretic acid) - but not those... 

Even if a medication is available in multiple formulations and dosage forms, the prescriber must consider the absorption and distribution differences between adult and pediatric patients. Blood supply at injection or infusion site, available blood supply for unit muscle mass, and skeletal muscle mass relative to body mass vary with patient age and size, causing drug absorption to vary, as well. A rapid intravenous bolus in a pediatric patient might result in acute toxicity a slow intravenous infusion, often required in neonates, can cause erratic, unreliable drug delivery in an older child. In addition, the volume of fluid tolerated for intravenous delivery varies significantly with the age and size of the patient. The blood supply and blood flow to and from the injection site are of prime importance since a gradual decrease in blood supply per unit muscle mass is seen with maturation. In addition, the skeletal muscle mass relative to... 

Noradrenaline and adrenaline are the classic catecholamines and neurotransmitters in the sympathetic nervous system. Noradrenaline stimulates the following subtypes of adrenoceptors P, a, U2. It has positive inotropic and chronotropic activities as a result of /3i-receptor stimulation. In addition, it is a potent vasoconstrictor agent as a result of the stimulation of both subtypes (ai,a2) of a-adrenoceptors. After intravenous infusion, its effects develop within a few minutes, and these actions disappear within 1-2 minutes after stopping the infusion. It may be used in conditions of acute hypotension and shock, especially in patients with very low vascular resistance. It is also frequently used as a vasoconstrictor, added to local anaesthetics. Adrenaline stimulates the following subtypes of adrenoceptors /3i, P2, oil, 0L2. Its pharmacological profile greatly resembles that of noradrenaline (see above), as well as its potential applications in shock and hypotension. Like noradrenaline, its onset and duration of action are very short, as a result of rapid inactivation in vivo. Both noradrenaline and adrenaline may be used for cardiac stimulation. Their vasoconstrictor activity should be kept in mind. A problem associated with the use of /3-adrenoceptor stimulants is the tachyphylaxis of their effects, explained by the /3-adrenoceptor downregulation, which is characteristic for heart failure. 

The most common side effects, which are related to the intravenous infusion itself, include rash, low blood pressure, chills, and chest pain. These symptoms are generally temporary and often respond to a decrease in infusion rate. In addition, some patients develop antibodies, which have been associated in rare cases with symptoms similar to those of patients with systemic lupus erythematosus. These symptoms were also temporary. Another side effect is increased risk of infections. Fatal cases of tuberculosis have been reported following infliximab therapy. Another potential side effect is an increased risk of lymphoma. Its occurrence remains controversial. 

The safety and efficacy of Remicade when given in conjunction with methotrexate (MTX) were assessed in a multicenter, randomized, double-blind, placebo-controlled study of 428 patients with active rheumatoid arthritis despite treatment with MTX. All patients were to have received MTX for >6 months and be on a stable dose >12.5mg/week for 4 weeks prior to study. All Remicade and placebo groups continued their stable dose of MTX and folic acid. In addition to MTX, patients received placebo or Remicade by intravenous infusion at weeks 0, 2, and 6 followed by additional infusions every 4 or 8 weeks thereafter. The primary end point was the proportion of patients at week 30 who attained an improvement in signs and symptoms as measured by the American College of Rheumatology criteria (ACR 20). An ACR 20 response is defined as at least a 20% improvement in both tender and swollen joint counts and in 3 of 5 clinical criteria. At week 30, 43/86 (50%) of patients treated every 8 weeks with 3 mg/kg of Remicade plus MTX attained an ACR 20 compared with 18/88 (20%) of patients treated with placebo plus MTX ip < 0.001). 

The primary cardiovascular effects of muscarinic agonists are reduction in peripheral vascular resistance and changes in heart rate. The direct effects listed in Table 7-3 are modified by important homeostatic reflexes, as described in Chapter 6 and depicted in Figure 6-7. Intravenous infusions of minimally effective doses of acetylcholine in humans (eg, 20-50 mcg/min) cause vasodilation, resulting in a reduction in blood pressure, often accompanied by a reflex increase in heart rate. Larger doses of acetylcholine produce bradycardia and decrease atrioventricular node conduction velocity in addition to hypotension. 

Most clinical experience with iloprost has been gained in patients with critical leg ischemia. An intermittent intravenous infusion of up to 2 nanograms/kg/minute for 2-4 weeks reduced rest pain and improved ulcer healing in roughly half of the patients with critical leg ischemia, including diabetics. Compared with placebo, the improvement obtained with iloprost was significant in most but not all individual clinical trials. In addition, a meta-analy-sis showed a 15% reduction in major amputation rate compared with placebo (2). 

Infliximab Remicade Slow intravenous infusion 3 mg/ kg body weight. Additional doses at 2 and 6 weeks after first infusion, then every 8 weeks thereafter. Should be administered in combination with methotrexate. 

The stability of procainamide in glucose infusions may be improved by the addition of sodium bicarbonate. Patients receiving sodium chloride infusions of procainamide are prone to the risk of heart failure due to sodium load.121122 Quinidine gluconate is incompatible with intravenous infusion sets made of PVC due to drug loss by adsorption.123... 

Side effects, such as headache and jaw pain, are observed, but the major drawbacks with epoprostenol therapy relate to its delivery. Epoprostenol has an extremely short half-life in the blood (2-3 min) and therefore must be administered by continuous intravenous infusion via a surgically implanted central vein catheter. This can lead to complications such as local infections, sepsis, or catheter-associated thrombosis. In addition, interruption of therapy due, for example, to pump failure can lead to a life-threatening rebound of symptoms. The compound itself is unstable at room temperature and must be stored in the refrigerator. Despite these severe drawbacks, i.v. epoprosenol remains a useful treatment for patients presenting with WHO class IV PAH. The problems with epoprostenol have led to the development of alternative agents. 

A 34-year-old alcoholic man with acute pancreatitis was given continuous intravenous infusion of haloperidol (2 mg/hour) for agitation after 7 hours he received a bolus dose of haloperidol 10 mg for worsening agitation and 20 minutes later, QT interval was 560 ms (420 ms before treatment) (131). He developed torsade de pointes and ventricular fibrillation, which resolved with electric defibrillation. He was a smoker and was also taking tiapride and alprazolam for depression, in addition to pantoprazole, piperazilline + tazobactam, paracetamol, and vitamins Bi, B6, and B 12-... 

In addition, because one of the effects of ethylene glycol is to cause the blood and tissues to become more acidic, treatment also involves giving the patient an intravenous infusion of bicarbonate of soda (sodium... 

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