Drugs biological response

It is important to note that both the quality and quantity of biological response obtained with a given drug depends very much on the assay system used to make the measurement. If the assay does not have the means to detect a given efficacy, then none will be observed this should not be taken to mean that the drug does not have that particular efficacy. A common case in point... 

PTKs have been implicated in the regulation of a variety of biological responses such as cell proliferation, migration, differentiation, and survival. They have been demonstrated to play significant roles in the development of many disease states, including immunodeficiency, atherosclerosis, psoriasis, osteoporosis, diabetes, and cancer. In recent clinical trials impressive antitumor effects of PTK inhibitors have been observed. In future, PTK inhibitors may therefore become important drugs for the treatment of specific cancers. 

Bioavailahility studies are used to compare different formulations of the drug product, or different batches of the same formulation and, as discussed in Chapter 8, generic copies of a reference drug. Their comparative value is based on the premise that, if similar amounts of identical active substance are delivered to the site of action at similar rates, then a similar biological response can be expected, which leads to the conclusion that the two preparations are bioequivalent. 

This quadratic dependence has been observed in many systems, and the dominance of lipophilicity in controlling activity reflects its importance in transport [74]. Nevertheless, the biological response (BR) of a series of compounds (which is often expressed by the inverse of the drug concentration) may also involve an electronic ( ) and/or a steric (5) contribution. Hence, QSARs have been mostly constructed using the generalized Hansch equation [337] ... 

Once again we come upon a chemical classification that has no pharmacological significance. The three drugs in this small group cause widely different biological responses. 

Another major challenge for implantable pH sensors is the biological response of living systems toward sensors when making contact with blood or tissue [134], The experiments often showed a progressive loss of function and lack of reliability of the implanted sensors. This lack of reliability and progressive loss of function, common to all implantable sensors, is believed to be caused by tissue or blood reactions such as inflammatory response, fibrosis, and loss of vasculature and thrombus formation [135, 136], The delivery of anti-inflammatory drugs to the sensor site can minimize tissue reactions and extend the lifetime of the device [50, 137],... 

Although in most cases the use of trend tests is appropriate since most biological responses are dose related, there are exceptions to this rule. Certain drugs, especially those with hormonal activity, may not produce classical dose responses and may even induce inverse dose-response phenomena. In these cases, a pairwise comparison may be appropriate in the absence of a significant positive trend. 

Generally, to produce a biological response, a drug molecule must first cross at least one biological membrane. The biological membrane acts as a lipid barrier to most drugs and permits the absorption of lipid-soluble substances by passive diffusion while lipid-insoluble substances can diffuse if at all across the barrier only with considerable difficulty. The interrelationship of the dissociation constant, lipid solubility, and pH at the absorption site and absorption characteristics of various drugs are the basis of the pH-partition theory. 

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