Pharmacological differences between Pharmacology

The receptor compartment is defined as the aqueous volume containing the receptor and cellular system. It is assumed that free diffusion leads to ready access to this compartment (i.e., that the concentration within this compartment is the free concentration of drug at the receptor). However, there are factors that can cause differences between the experimentally accessible liquid compartment and the actual receptor compartment. One obvious potential problem is limited solubility of the drug being added to the medium. The assumption is made tacitly that the dissolved drug in the stock solution, when added to the medium bathing the pharmacological preparation, will stay in solution. There are cases where this may not be a valid assumption. 

Dtug interactions can cause serious problems in clinical practice especially when the affected dmg has the potential to be highly toxic. Furthermore, pharmacokinetic interactions are clinically important if the affected dmg has a narrow therapeutic range (i.e. small difference between the minimum effective concentration and the toxic concentration Fig. 1) and a steep concentration-response curve (i.e. significant alterations in pharmacological and/or adverse effects caused by small changes in blood concentration). 

Apart from possible clinical differences between the P-block-ers approved for HF, selection of a p-blocker may also be affected by pharmacologic differences. Carvedilol exhibits a more pronounced blood pressure lowering effect and thus causes more frequent dizziness and hypotension as a consequence of its ar receptor blocking activity. Therefore, in patients predisposed to symptomatic hypotension, such as those with advanced LV dysfunction (LVEF less than 20%) who normally exhibit low systolic blood pressures, metoprolol succinate may be the most desirable first-line P-blocker. In patients with uncontrolled hypertension, carvedilol may provide additional antihypertensive efficacy. 

Several pharmacologic classes are available for the treatment and maintenance of IBD. Because there may be differences in the underlying disease process, distribution, and severity between CD and UC, response rates to drugs in the same pharmacologic class may differ between these two diseases. Therefore, initial selection of an appropriate agent for patients with active IBD should be designed to deliver maximum efficacy while minimizing toxicity. Response rates to individual classes of medications for both UC and CD will be discussed within the specific treatment section for each disease. 

These population changes have important implications for pharmacotherapy. It is now widely accepted that genetic differences between the various ethnic groups are quite small and probably less than individual differences. The recent experience with the newly approved congestive heart failure medication, BiDil, suggests that even minor differences can have significant pharmacological consequences. 

The biochemical and pharmacological properties of the kappa receptor and the differences between the kappa, mu and delta receptors have been reviewed elsewhere. The reader is directed to the opioid review articles by Rees and Hunter (1990) [4], Casy (1989) [3] and Leslie (1987) [10] and also to two shorter reviews which deal specifically with kappa agonists the review by Horwell published in 1988 entitled Kappa Opioid Analgesics [8] and the review by Millan in 1990 on kappa opioid receptors and analgesia [9]. An account of the medicinal chemistry of selective opioid agonists and antagonists was published in 1990 by Zimmerman and Leander [5]. 

Bromocriptine (11), pergolide (12), cabergoline (13) and lisuride (14) are examples of compounds which have been developed in this way and are now used clinically. The pharmacological differences between the compounds is not very great. All are D2-dopamine receptor agonists, although... 

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