Efficacy collateral

This term indicates a receptor ligand having different intrinsic activities at different transduction pathways coupled to a single receptor. To quote Urban et al. (2006 JPET, 104463 PiP) and Kenakin (2007 Trends Pharmacol Sci 28 359-361) the term biased agonism can be considered as a synonym of collateral efficacy, ... 

Drug Interactions Analysis and Management (quarterly). Wolters Kluwer Publications, 111 Westport Plaza, Suite 300, St Louis, MO 63146. Pharmacology Examination Board Review, 7th ed. McGraw-Hill Companies, Inc, 2 Penn Plaza 12th Floor, New York, NY 10121-2298. Symposium Allosterism and collateral efficacy. TIPS 2007 28(8) entire issue. 

Kenakin, T. P. (2006). Collateral efficacy as pharmacological problem applied to new drug discovery. Expert Opin. Drug Disc. 1 635-652. 

Kenakin, TP. (2005). New concepts in durg discovery Collateral efficacy and permissive antagonism. Nature Rev. Durg Disc. 4 919-927. 

Kenakin, T. P. (2007). Collateral efficacy in drug discovery Taking advantage of the good (allosteric) nature of 7TM receptors. Trends Pharmacol. Sci. 28 407 115. 

Kenakin T. New concepts in drug discover collateral efficacy and permissive antagonism. Nat Rev Drug Discov 2005 4(ll) 919-927. 

There will be an ethical advantage to this approach as well. Instead of using markers such as ApoE4 to predict safety and efficacy, which may carry significant collateral (and sensitive) information, the use of SNPs should minimize the risk of release of additional information. 

The safety of G-CSF stimulation in patients with CAD has been questioned in two recent studies. Hill et al. [138] report the results of administration of 10 mcg/kg/day of G-CSF for 5 days in patients with chronic CAD n = 16). There was no clinical benefit as assessed by exercise stress testing and dobuta-mine cardiac MRI. Additionally two patients in the G-CSF group developed serious adverse events related to the therapy (one non-ST elevation MI one MI causing death). Zbinden et al. [139] also tested the efficacy of the same G-CSF dose in patients with chronic CAD ( = 7). The invasive endpoint collateral flow index was significantly better in the G-CSF treated patients when compared to the placebo group. However, two patients in the G-CSF treated group developed acute coronary syndrome during treatment. 

Zbinden S, Zbinden R, Meier P, Windecker S, Seiler C. Safety and efficacy of subcutaneous-only granulocyte-macrophage colony-stimulating factor for collateral growth promotion in patients with coronary artery disease. J Am Coll Cardiol 2005 46 1636-1642. 

A small study of plasmid-derived VEGF showed collateral vessel growth and improved outcome in patients with critical limb ischemia (37), In the regional angiogenesis with VEGF (RAVE) study, AdVEGF-121 was injected into the skeletal muscle of the lower extremity and safety and efficacy were compared with placebo control in patients with unilateral, severe, disabling intermittent claudication. No symptomatic or objective evidence of clinical benefit were reported at 26-week follow-up (38). 

Endothelial progenitor cells can be sorted from the peripheral blood of patients with peripheral artery diseases and can be implanted into ischemic limbs in order to increase collateral vessel formation and to secrete various angiogenic factors or cytokines, Although this novel angiogenic cell therapy seems to be feasible, remote angiogenic actions should be considered as possible side effects, and the clinical efficacy should be tested by specific studies (79-81). 

The treatment with anthocyanosides for at least three months had therapeutic effects on fibrocystic mastopathy. There was a marked improvement in 75 patients, equivalent to 33.78%, their symptoms were reduced in 61 women (27.47%) and disappeared in 14 (6.30%), whereas the treatment had no effect in 72 cases (32.43%). An echopalpation (clinical examination + echography) was extremely valuable in the treatment of these patients, especially with ages below 40. Moreover, three months therapy for the patients with mastodynia, consequent to fibrous mastopathy, was efficacious in reducing the symptoms and mammary tension. At the same time, it is important to emphasize the virtual absence of any collateral effects [3]. 

These microspheres are precisely calibrated, spherical, hydrophilic, microporous beads made of tris-acryl co-polymer coated with gelatin. They come in defined range of sizes, ranging from 40 to 1200 pm in diameter. Their smooth hydrophilic surface, deformability and minimal aggregation tendency have been shown to result in a lower rate of catheter occlusion and more distal penetration into the small vessels [32]. Their efficacy has been evaluated in several conditions, and vdien compared to the standard polyvinyl alcohol particles (PVA) particles, a deeper penetration and embolization of smaller and more peripheral vessels may be achieved. This distal embolization may limit the development of any collateral blood supply. Also, in a study where PVA particles and tris-acryl microspheres of similar size were compared, the level of vascular occlusion with calibrated tris-acryl microspheres precisely correlated with particle size whereas the level of vascular occlusion with PVA particles did not. Another study has demonstrated that in embolized tumors. 

Renal scarring secondary to vesicoureteral reflux may be the cause of renovascular hypertension. Renal ablation is an alternative to nephrectomy to remove to involved kidney. The selective embolization should be performed with alcohol to prevent collateral revascularization. The efficacy is debated considering that embolization may delay the definitive treatment [26]. Gelfoam and coils are less valuable than alcohol because of collateral revascularization (Fig. 23.9a,b). 

The chemoprotective activity against carcinogens has been used as a preventative in chemotherapy treatments of tumor. Most dmgs used in tumor treatment can have side effects and induce genotoxic effects in healthy cells. Tests both in vitro [44] and in vivo with mice [45] have demonstrated the efficacy of chlorophyll derivatives in decreasing the collateral mutagenic activity of the dmg in all cases without modifying the antitumoral effect. 

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