Intra-arterial administration

Starch (Spherex) 40 Intra-arterial administration of cytostatics 5-Fluorouracil, hepatic BCNU, renal actinomycin D... 

GaUo et al. [65] applied a physiologically-based pharmacokinetic model to the targeting of anti-cancer drugs to the brain following intra-arterial administration in gUoma-2 bearing rats. 

Children 6 to 11 years of age 30 mg once daily as a starting dose. HYDROXYZINE Administer by deep IM only may be given without further dilution. Avoid IV, subcutaneous, or intra-arterial administration. Do not administer IM injections into the lower and mid-third of the upper arm. 

Barbiturate sensitivity manifest or latent porphyria marked impairment of liver function severe respiratory disease when dyspnea or obstruction is evident nephritic patients patients with respiratory disease where dyspnea or obstruction is present intra-arterial administration subcutaneous administration previous addiction to the sedative/hypnotic group. 

IV Inject slowly, taking at least 1 minute for each 5 mg (1 mL). Do not use small veins (ie, dorsum of hand or wrist). Avoid intra-arterial administration or extravasation. Do not mix or dilute with other solutions or drugs. 

Reid, T., E. Galanis, J. Abbruzzese, D. Sze, J. Andrews, L. Romel, M. Hatfield, J. Rnbin, and D. Kirn, Intra-arterial administration of a replication-selective adenovirus (dll520) in patients with colorectal carcinoma metastatic to the liver a phase I trial. Gene Ther, 2001. 8(21) 1618-26. 

Intra-arterial injection of thiopentone is a serious complication as crystals of the thiobarbiturate can form in the arterioles and capillaries, causing intense pain, vasoconstriction, thrombosis, and even tissue necrosis. Accidental intra-arterial injections should be treated promptly with intra-arterial administration of a vasodilator (papaverine 20 mg) and lignocaine (lidocaine) Note leave the needle/cannula in the artery), as well as a regional anaesthesia-induced sympathectomy (stellate ganglion block, brachial plexus block) and anticoagulation with intravenous heparin. The risk of ischaemic damage is much higher with a 5% solution and the use of this concentration is not recommended. 

Systemic administration of endothelin receptor antagonists or endothelin-converting enzyme inhibitors causes vasodilation and decreases arterial pressure in humans and experimental animals. Intra-arterial administration of the drugs also causes slow-onset forearm vasodilation in humans. These observations provide evidence that the endothelin system participates in the regulation of vascular tone, even under resting conditions. The activity of the system is higher in males than in females. It increases with age, an effect that can be counteracted by regular aerobic exercise. 

In patients with ischemic syndromes, intra-arterial administration of rhVEGF significantly increases the development of collateral vessels (Isner and Asahara 1999), indicating its applicability in therapeutic angiogenesis. In patients who are not suitable for PTCA or CABG, administration of VEGF can be a novel treatment option. 

SMANCS has been shown to retain nearly all the in vitro activity of NCS, with much improved pharmacokinetic properties. Tumor uptake has been shown to increase in animal models, presumably by the EPR effect. Clinical successes have been reported with SMANCS in Lipiodol (a lymphographic vehicle) after intra-arterial administration in patients with unresectable hepatocellular carcinomas. 

In vivo, intravenous administration of ET-1 to conscious [20], anaesthetized [21] or pithed [22] rats produces a biphasic blood pressure response a small, transient depressor response followed by a prolonged pressor response. The systemic blood pressure changes induced by ET-1 are reflected in changes in regional haemodynamics, although the dilator response is not seen in all vascular beds [23-25], Big ET-1, when administered intravenously, is almost as potent as ET-1 in producing a pressor response which suggests effective in vivo conversion to ET-1 [22]. The haemodynamic effects of ET-1 have also been studied in man and pressor responses are seen after intravenous or intra-arterial administration [26-28]. 

Toxic (especially sclerosing) cholangitis (5,8,17-19,24,38, 39, 44-46) has been attributed to the effects of aromatic amines. Likewise, this condition can be caused by lithocholic acid. It may also be triggered by various medicaments acting as facultative toxins, e. g. allopurinol, antibiotics, carbamazepine, phenylbutazone, tolbutamide, (s. tab. 29.6) Such a type sometimes occurs after intra-arterial administration of cytostatics (18, 19, 24, 38) and as a result of burn injuries. (44) (s. p. 651) (s. tab. 32.4)... 

Intra-arterial administration in one case caused generalized arterial and venous thrombosis (19). 

Nicolau syndrome (embolia cutis medicamentosa) is a very rare complication of intramuscular injections, in which there is extensive necrosis of the injected skin area, perhaps due to accidental intra-arterial and/or para-arterial injection (233). It usually occurs in children in a review of 102 patients, 80 were under 12 years of age (234). Complications can include everything from an ischemic syndrome with local necrosis of the skin, subcutaneous tissue, and muscle, often combined with vascular and nervous system involvement, intestinal and renal hemorrhage, necrosis of the entire leg, and even paraplegia from spinal cord damage (235-241). Necrosis of the forearm has been described in two patients after inadvertent intra-arterial administration of dicloxacillin (242). 

As outlined in Table 13.1, three Phase I trials for intramuscular and intra-arterial administration of naked plasmid VEGEigs in human lower-extremity ischemia and BuergeTs disease have been completed, having achieved their end-points within one year. Three Phase II clinical trials are currently recruiting patients to investigate the role of intramuscular VEGE plasmid delivery in lower-extremity ischemia. A Phase I trial for intra-arterial administration of recombinant PGE-2 has been completed (Table 13.1), and the Phase II TRAFFIC trial further evaluating the effect... 

Isner 1996 Critical lower extremity ischemia Critical ischemia, resistant to maximal medical therapy, not surgical candidates Naked plasmid VEGF 165 Intra-arterial administration Phase 1 12 weeks Improved angiographic and Doppler evaluations hemangiomas from and regress... 

Ledermann/Traffic 2001 Critical lower extremity ischemia Recruiting FGF-2 protein Intra-arterial administration Phase 1/11 Recmiting ... 

Fig. 7.13 y -Galactosidase staining in CC531 liver tumors to evaluate the gene transfection efficiency. (A-C) Beta-galactosidase activity after intra-arterial administration and (D) after i.v. substance administration. As indicated by the arrows, poor activity was seen with naked pUT651 and no ultrasound treatment (A), moderate activity was... 

Although interest in inhibition of glycolytic enzymes as anticancer treatment had waned somewhat in the late 1990s, the description of the promising in vivo activity of 3-bromopyruvate (2), an inhibitor of hexokinase II, has prompted a renewed interest in this field. Efficacy of 3-bromopyruvate was reported against various cancer cell lines in animal studies at Johns Hopkins.11 Further investigation has revealed that direct intra-arterial administration to the site of the primary tumor may be especially effective.12,13 Despite the promising pre-clinical activity of 3-bromopyruvate, no human clinical trials have been reported. 

For intra-arterial administration, dilute 10 mL of 10% calcium gluconate with 50 mL of D5W and infuse over 4 hours either through the brachial or radial artery catheter. The patient should be monitored closely over the next 4-6 hours and if pain recurs a second infusion should be given. Some authors have reported 48-72 hours of continuous infusion. 

No effect on ventricular pressure, diastolic pressure, or cardiac output and no changes in lead II EKG were observed after intra-arterial administration of 0.075 mg/kg of the compound sanguinarine to beagle dogs (Frankos et al. 1990 Schwartz 1986). In monkeys orally administered 0,10, 30, and 60 mg/kg daily for 90 days, no electrocardiographic evidence of a drug effect was noted at any of the dose levels (Frankos et al. 1990). 

Yanagie, H., H. Kumada, T. Nakamura, S. Higashi, I. Ikushima, Y. Morishita, A. Shinohara, M. Eijihara, M. Suzuki, Y. Sakurai, H. Sugiyama, T. Kajiyama, R. Nishimura, K. Ono, J. Nakajima, M. Ono, M. Eriguchi, and H. Takahashi. 2011a. Feasibility evaluation of neutron capture therapy for hepatocellular carcinoma using selective enhancement of boron accumulation in tumor with intra-arterial administration of boron-entrapped water-in-oil-in-water emulsion. A /. Radial hot. 69 1854-1857. 

Ariel IM (1965) Treatment of inoperable primary pancreatic and liver cancer by the intra-arterial administration of radioactive isotopes (Y90 radiating microspheres). Ann Surg 162 267-278... 

Ariel IM, Padula G (1973) Irradiation of the spleen by the intra-arterial administration of 90 yttrium microspheres... 

Abuse of buprenorphine was associated with livedoid and necrotic skin lesions after intra-arterial administration of buprenorphine in two women with a history of drug abuse [201Histology showed Maltese-cross-shaped bodies due to amidon, one of the excipients of buprenorphine. 

Drug administration route Tissue necrosis has been described in three cases of intravenous administration of promethazine, which is not recommended in two cases the complications were extensive—one patient needed an amputation of a thumb and index finger because of gangrene and the other developed chronic pain and hypersensitivity [17 ]. Other cases have been reported [18, 19 ], as have cases of accidental intra-arterial administration [20, 21, 22" ]. 

Perivascular and intra-arterial administration of neutral sphingomyelinase or exogenous short-chain ceramide resulted in a potent concentration-dependent constriction of cortical venules, followed by increased venular waU permeability, post-capillary venule rupture and micro-hemorrhaging (Altura et al, 2002). Treatment with antioxidants, calcium channel blockers and inhibitors of nuclear factor-KB activation could attenuate the effects of neutral sphingomyelinase and ceramide. These results suggest that ceramide can play a role in vasoconstriction and may be involved in the mechanisms resulting in brain injury and stroke. 

Platz J, Barath K, Keller E, Valavanis A. Disruption of the blood-brain barrier by intra-arterial administration of papaverine a technical note. Neuroradiology 2008 50 (12) 1035-9. 

The authors pointed out that inadvertent intra-arterial administration of promethazine leads to ischemia and tissue necrosis. They further suggested that hand surgeons must be aware of this compUcation and consider the diagnosis of intra-arterial promethazine administration when evaluating patients with digital and hand ischemia who have recently had intravenous injection of medications. 

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