Injection intravascular

An ester group can be introduced into a local anesthetic, such as tolycaine (3.26), to prevent the drug from reaching the CNS if it is injected intravascularly hy accident or abuse. The ester group is fairly stable in the tissues but is very rapidly hydrolyzed in the serum to the polar carboxylic acid, which cannot penetrate the blood-hrain barrier. 

The authors proposed that some or all of the local anesthetic had been inadvertently injected intravascularly, despite negative aspiration tests. There were no cardiovascular complications, underlining the proposed greater cardiovascular safety of levobupivacaine over bupivacaine. The authors accepted that if the patient had been awake during the procedure, earlier detection of neurological symptoms might have been possible. 

Local anesthetics have diverse effects on the neuromuscular junction. In very large doses they produce paralysis on their own. When the recommended doses are used for local anesthesia, systemic absorption is small and interaction with relaxants is not to be expected. However, large doses injected intravascularly (accidentally, or therapeutically for dysrhythmias) can potentiate relaxants of both types (67,68). 

Oleamide (cw-9-octadecenamide Scheme 2.2.1) is a brain constituent that accumulates under conditions of sleep deprivation and disappears upon sleep recovery. Nanomolar quantities induce physiological sleep when oleamide is injected intravascularly. An integral membrane oleamide hydrolase then catalyzes its degradation (Cravatt et al, 1996 Patterson et al, 1996). 

This chapter gives an overview of parenteral dosage forms and the rational for their use. Parenterals are sterile preparations that are injected intravascularly, administered into body tissues or into visceral cavities. The parenteral route of administration is often chosen for active substances that are poorly absorbed via the oral route or when rapid systemic availability and effects are required, or both. An introduction to the formulation and preparation of parenteral dosage forms is provided. Parenteral medicines can be formulated as solutions, emulsions or suspensions. Products, such as implants and microspheres are only briefly discussed. Knowledge about these types of products is a prerogative for the sound education of patients and caregivers in using the products. 

It should be noted that, in two of these studies, " the perfusion parameter used to define the mismatch was not CBF or MTT, but instead the time it took for contrast concentration to reach peak concentration in each image voxel after contrast injection ( time to peak or TTP). TTP measurements are often used as rough approximations of MTT measurements because calculation of CBF and MTT are somewhat complex, requiring a mathematical process called deconvolution. The details of deconvolution are beyond the scope of this chapter, and the reader is referred to other sources for further explanation. In many clinical settings, maps of parameters like TTP that do not require deconvolution may be available much more quickly than those that do require deconvolution. TTP is less specific than MTT in detecting underperfused tissue because it does not distinguish between delayed contrast arrival time (such as that related to perfusion via collateral vessels) and truly prolonged intravascular transit time. 

The presence of particles in the brains of experimental rats and humans exposed to asbestos has been reported (Pontefiart and Cunningham, 1973 Auerbach et al., 1980). In experimental studies, particles of Teflon, a reflux paste, enter the brain via intravascular transport when injected into the bladder (Aaronson et al., 1993). Encephalitic reactions to accumulated calcium oxalate crystals in the brain as a result of infusions of glucose surrogate polyol solutions have been described (PciflPcr etal., 1984). Such studies indicate the capacity of particulates to enter the brain and thus pose a potential pathological threat to the functioning of the central nervous system (CNS). 

Concerning applications where CNTs are injected into the human body, few investigators have explored the outcome of CNTs in contact with the intravascular environment and components of circulating blood (particularly platelets) [112-114],... 

IM 300 mg. The deltoid muscle is preferred. Avoid intravascular injection. Use only the 10% solution for IM injection. 

Transcoronary venous injection is performed with a catheter system threaded percutaneously into the coronary sinus. Initial studies in swine have confirmed the feasibility and safety of this approach [121]. This delivery method has also been used to deliver skeletal myoblasts to scarred myocardium in cardiomyopathy patients [120]. With intravascular ultrasound guidance, this approach allows the operator to extend a catheter and needle away from the pericardial space and coronary artery into the adjacent myocardium. To date, human feasibility studies have had a good safety profile. This technique is limited, however, by coronary venous tortuosity, lack of site specific targeting, and its own technically challenging nature. Unlike the transendocardial approach, in which cells are... 

Infiltration anaesthesia is applied fan-shaped, with as few needle punctures as possible, in close proximity of the wound or the skin area to be treated. An aspiration should always take place to avoid intravascular injection. Suitable alternatives are lidocaine (lignocaine) or prilocaine for injection 5-10 mg/ml, with or without adrenaline. When making an incision of an abscess it is sometimes difficult to use a local anaesthetic if there is a pronounced inflammatory reaction, since the effect of the anaesthetic is reduced due to an increased acidity level. While adrenaline reduces bleeding and delays dispersion of the anaesthetic, local anaesthetic/adrenaline combinations are contraindicated for local anaesthesia of digits, on the face or where the skin survival is at risk. 

The existence of a barrier between the blood and testes is indicated by the absence of staining in testicular tissue after the intravascular injection of dyes. Morphological studies indicate that the barrier lies beyond the capillary endothelial cells and is most likely to be found at the specialized Sertoli-Sertoli cell junction. It appears that Pgp, the efflux transporter protein, also plays a role in forming this blood-testis barrier. This protein probably plays a role in preventing certain chemotherapeutic agents from reaching specific areas of the testis and thus hinders treatment of the neoplasm. 

The rate of absorption of a local anesthetic into the bloodstream is affected by the dose administered, the vascularity at the site of injection, and the specific physicochemical properties of the drug itself. Local anesthetics gain entrance into the bloodstream by absorption from the injection site, direct intravenous injection, or absorption across the mucous membranes after topical application. Direct intravascular injection occurs accidentally when the needle used for infiltration of the local anesthetic lies within a blood vessel, or it occurs intentionally when Udocaine is used for the control of cardiac arrhythmias. 

The xanthines are readily absorbed by the oral and rectal routes. Although these agents can be administered by injection (aminophylline is a soluble salt of theophylline), intravascular administration is indicated only in status asthmaticus and apnea in premature infants. Intramuscular injection generally produces considerable pain at the injection site. 

This may be the result of systemic toxicity, hypersensitivity, drug interactions and agent-specific effects. Serious toxicity is almost always the result of overdosage or inadvertent intravascular injection. The maximum recommended doses are shown in Table 5.2. 

The rate of progression of the symptoms and signs of local anaesthetic toxicity may be shortened or absent. The time course may be accelerated by intravascular injection or when large doses are inadvertently injected into the subdural space. 

Local anaesthetics directly depress myocardial conduction and contractility in a dose-dependent manner. They bind to and inactivate myocardial sodium channels, reducing the velocity of the cardiac action potential and prolonging the QRS interval. As plasma concentrations approach toxic values sodium channels become progressively inactivated until there is a generalised reduction in automaticity (cardiac slowing) with negative inotropy. Slow increases to near- or above-toxic levels are better tolerated than rapid rises seen following intravascular injection. 

In the intact organism, intravascular injection of muscarinic agonists produces marked vasodilation. However, earlier studies of isolated blood vessels often showed a contractile response to these agents. It is now known that acetylcholine-induced vasodilation arises from activation of M3 receptors and requires the presence of intact endothelium (Figure 7-5). 

The simplest nonviral gene transfer system in use for gene therapy is the injection of naked plasmid DNA (pDNA) into local tissues or the systemic circulation (88, 100). Naked DNA systems are composed of a bacterial plasmid that contains the cDNA of a reporter or therapeutic gene under the transcriptional control of various regulatory elements (101, 102). In recent years, work in several laboratories has shown that naked plasmid DNA (pDNA) can be delivered efficiently to cells in vivo either via electroporation, or by intravascular delivery, and has great prospects for basic research and gene therapy (101). Efficient transfection levels have also been obtained on direct application of naked DNA to the liver (103, 104), solid tumours (105), the epidermis (106), and hair follicles (106). 

Several phase I trials have been performed with LPS from Salmonella abortus equi administered i.v. in patients who suffered from disseminated cancer. White blood cell number decreased after each injection and returned to basal level by 24 hours. There were no changes in coagulation parameters, and no disseminated intravascular coagulation was observed. After the first injection of LPS, increases in TNF-a concentration and IL-6 activity in serum were detected. However LPS tolerance which is accompanied by a decrease in TNF-a and IL-6 production depended on the intervals between repeated injections, but it was not determined whether it was a benefit or a draw-back. Injections of IFN-y prevented this decrease in TNF-a and IL-6, and ibuprofen attenuated LPS toxicity [183,186],... 

This section will review how physiological factors at the site of injection impact the design of dosage forms and affect choice of excipients. First, pharmacokinetic factors affecting rates of delivery of drug to the blood will be considered. Then, biocompatibility or safety issues will be addressed. This analysis focuses on the intravascular (IV), IM, and SC routes of administration. 

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