Subject side-effects

A9. Asberg, M. B., Cronholm, F., and Sjoqvist, F., The correlation of subjective side-effects with plasma concentrations of nortriptyline. Brit. Med. J. Iv, 18-21... 

Improvement can be determined by regular clinical assessment, patient self-report, and weekly use of subjective and objective symptom measures. It can commence very early in the ECT course. ECT should be continued until the patient no longer seems to be improving. The usual number of treatments required by young persons is similar to that required by adults (a mean of 6-12). Assessment of unwanted events should be made following each ECT administration by systematic inquiry of the common side effects or by use of specially developed scales such as the Columbia ECT Subjective Side Effects Schedule (Sackeim et al., 1987). Where possible, neuropsychological assessment should be per-... 

Sackeim, H.A., Ross, F.R., Hopkins, N., Calev, L., and Devanand, D.P. (1987) Subjective side effects acutely following ECT associations with treatment modality and clinical response. Convulsive Ther 3 100—110. 

An important group of antihistamines, the pheniramines (92), use 2-chloropyridine as a basic feedstock. The activity of chlorpheniramine (92 X = Cl) as an H receptor blocker has recently been reported (79MI20906). Zimelidine (93), a relatively new compound of related structure, exhibits antidepressant activity with reduced subjective side-effects found with other antidepressants (79MI20907). 2-Halopyridines also function as precursors to another group of antihistamines exemplified by p-bromotripelennamine (94) (51USP2572569). 

Ziegler VE, Taylor JR, Wetzel RD, Biggs JT. Nortriptyline plasma levels and subjective side effects. Br J Psychiatry 1978 132 55. 

The absorption of tricyclics varies considerably in patients. Significant differences were observed in the plasma levels of nortriptyline (7) in individuals receiving the seune amount of drug however, there was a positive correlation between the plasma levels and the subjective side effects. The monitoring of plasma levels of a drug might be rewarding in terms of improved patient care. ... 

Phase I. This involves general testing for human pharmacology in healthy volunteers, ie, safe-dose adjustment deterrnination of absorption, metabohsm, and excretion patterns and monitoring for side effects. Usually fewer than 10 test subjects ate involved. 

P-Adrenoceptors have been subdivided into P - and P2-adrenoceptors. A third subset called nontypical P-adrenoceptors or P -adrenoceptors have been described but are stiU the subject of debate. In terms of the interactions with various subsets of P-adrenoceptors, some antagonists are nonselective in that they antagonize the effects of activation of both P - and P2-adrenoceptors, whereas others are selective for either P - or P2-adrenoceptors. P - and P2-adrenoceptors coexist in almost all organs but generally, one type predominates. The focus herein is on the clinically relevant P -adrenoceptor-mediated effects on heart and on P2-adrenoceptor-mediated effects on smooth muscles of blood vessels and bronchioles, the insulin-secreting tissue of the pancreas, and skeletal muscle glycogenolysis for side effects profile (36). 

The first two selective COX-2 inhibitors to be marketed and subjected to in depth clinical trials were celecoxib and rofecoxib. Both compounds are as effective as standard NSAIDs in rheumatoid arthritis, osteoarthritis and for pain following orthopaedic or dental surgery. Gastrointestinal side effects were far fewer than with comparator diugs and in fact were no... 

The study will commence with the administration of low doses, as judged from the non-clinical data. As the study progresses - and provided that there are no indications that it is unsafe to do so - the dosage levels may be increased past the anticipated therapeutic range. Subjects are closely monitored for changes in vital signs (blood pressure, heart rate, body temperature, etc.) and the emergence of any adverse side effects (nausea, drowsiness, pain, headache, irritability, hair loss, etc.). 

Purpose Safety Pharmacology (pharmacokinetics, side effects tolerance assessment, evidence of toxicity, pharmacodynamics) Subjects 10-100 usually healthy males Duration <1 year... 

Kleimnan et al. 2008). In addition, synthetic siRNAs are also subject to degradation in vivo by nuclease activity. Besides side effects and instability, the efficient and specific delivery of the RNAi indncers to the target cell still requires optimization. Here we snmmarize the cnrrent statns of nncleic acid-based antiviral therapentics. The focns will be on antiviral strategies nsing antisense and RNAi technology. Additionally, antiviral ribozymes and aptamers will be discussed briefly, with a focus on recent studies. Gene therapy approaches and delivery systems are the subject of Chapter 11 of this book. 

In pharmaceutical and medical device development, clinical trials are classified into four main phases designated with Roman numerals 1,11, III and lY The various phases of development trials differ in purpose, length and number of subjects involved. Phase I trials are conducted to determine safe dose levels of a medication, treatment or product (National Institutes of Health, 2002). The main purpose is often to determine an acceptable single dosage - how much can be given without causing serious side-effects. Phase I trials will also involve studies of metabolism and bioavailabity (Pocock, 1983). The sample size of a Phase 1 clinical trial is usually small, ranging from 10-80 subjects (National Institutes of Health, 2002 Pocock, 1983). 

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