Drugs, therapeutic doses

I suppose that some ingenious minds will be able to find a way of accommodating the chemical-balance hypothesis to these data, but I suspect that the accommodation will require convoluted circumventions, like those used by the Flat Earth Society in their efforts to maintain their defunct theory in the face of photographic evidence from space. If depression can be equally affected by drugs that increase serotonin, drugs that decrease it and drugs that do not affect it at all, then the benefits of these drugs cannot be due to their specific chemical activity. And if the therapeutic benefits of antidepressants are not due to their chemical composition, then the widely proffered chemical-imbalance theory of depression is without foundation. It is an accident of history produced serendipitously by the placebo effect. 

The answer is a. (Hardman, p 436J The most common side effects associated with tricyclic antidepressants are their anti muscarinic effects, which may be evident in over 50% of patients. Clinically, the anti muscarinic effects may manifest as dry mouth, blurred vision, constipation, tachycardia, dizziness, and urinary retention. At therapeutic plasma concentrations, these drugs usually do not cause changes in the EKG Direct cardiac effects of the tricyclic antidepressants are important in over dosage. 

Although PK data in children and adolescents are limited, clinical observations suggest that children and adolescents require larger, weight-adjusted doses of most drugs than do adults to achieve comparable blood levels and therapeutic effects (Soldin and Steele, 2000). This appears to be mostly the result of increased rate of metabolism and elimination. 

The nitrofurans are synthetic antibacterial compounds, all containing in their molecule a characteristic 5-nitrofuran ring (Fig. 3.5). Furazolidone, nitrofurazone, furaltadone, and nitrofurantoin are all nitrofiirans that have been widely used in the prophylactic and therapeutic treatment of infections caused by bacteria and protozoa in swine, cattle, poultry, rabbits, and fish. They have been also used as feed additives in animal husbandry. They are very effective drugs and do not appreciably contribute to the development of resistance (120). 

The newer atypical psychotropics vary widely in their receptor binding profiles. Olanzapine and quetiapine bear resemblance to the profile of clozapine in that their therapeutic effects appear to derive from action on different receptors and transmitter systems. All atypicals (except amisulpride) exhibit greater antagonism of SHT -receptors than Baroceptors compared with the classical agents. Atypical drugs that do antagonise dopamine D -receptors appear to have affinity for those in the... 

Biological and clinical studies have underlined the fundamental importance of the polymer-drug linker. When a conjugate is administered parenterally its stability in the circulation and ability to release drug at an appropriate rate on arrival in the target tissue is a principal determinant of therapeutic index. A variety of chemistries can be used to create pendant linkers (Fig. 5) (10). Lysosomally degradable peptides ensure site-specific intracellular activation, but many drug candidates do not have a convenient aliphatic -NH2 for this purpose. 

A major consideration in screening is the detection capability of the screen for both false negatives (lack of detection of an active drug) and propensity to find false positives (detection of a response to the compound not due to therapeutic activity of interest). Ostensibly, false positives might not be considered a serious problem in that secondary testing will detect these and they do not normally interfere with the drug discovery process. 

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