Prostaglandins table

Many compounds contain more than one functional group Prostaglandin Ei a hormone that regulates the relaxation of smooth muscles con tains two different kinds of carbonyl groups Classify each one (aldehyde ketone carboxylic acid ester amide acyl chloride or acid anhydride) Identify the most acidic proton in prostaglandin Ei and use Table 1 7 to estimate its pK ... 

Prostaglandins arise from unsaturated C20 carboxylic acids such as arachidonic acid (see Table 26 1) Mammals cannot biosynthesize arachidonic acid directly They obtain Imoleic acid (Table 26 1) from vegetable oils m their diet and extend the car bon chain of Imoleic acid from 18 to 20 carbons while introducing two more double bonds Lmoleic acid is said to be an essential fatty acid, forming part of the dietary requirement of mammals Animals fed on diets that are deficient m Imoleic acid grow poorly and suffer a number of other disorders some of which are reversed on feed mg them vegetable oils rich m Imoleic acid and other polyunsaturated fatty acids One function of these substances is to provide the raw materials for prostaglandin biosynthesis... 

In the early work on the synthesis of prostaglandins, zinc borohydride was used for the reduction of the 15-ketone function and a 1 1 mixture of epimeric 15(S)- and 15(/ )-alcohols was generally obtained. Subsequent studies led to reaction conditions for highly selective reduction to the desired 15(S)-alcohol. Some of the results are summarized in the following table. The most practical method is E which utilizes borane as the stoichiometric reductant and a chiral, enzyme-like catalyst which is shown. 

Rats fed a purified nonlipid diet containing vitamins A and D exhibit a reduced growth rate and reproductive deficiency which may be cured by the addition of linoleic, a-linolenic, and arachidonic acids to the diet. These fatty acids are found in high concentrations in vegetable oils (Table 14-2) and in small amounts in animal carcasses. These essential fatty acids are required for prostaglandin, thromboxane, leukotriene, and lipoxin formation (see below), and they also have various other functions which are less well defined. Essential fatty acids are found in the stmctural lipids of the cell, often in the 2 position of phospholipids, and are concerned with the structural integrity of the mitochondrial membrane. 

Palytoxin is hemolytic (4) and is an extremely potent toxin (7). We have shown that in rat liver cells palytoxin stimulates de-esterification of cellular lipids to liberate arachidonic acid (5). These rat liver cells metabolize this increased arachidonic acid via the cyclooxygenase pathway to produce prostaglandin (PG) I2 and lesser amounts of PGE2 and PGp2. Palytoxin acts on many cells in culture to stimulate the production of cyclooxygenase metabolites (Table I). Clearly, the myriad pharmacological effects of the arachidonic acid metabolites must be considered in any explanation of the many clinical manifestations of palytoxin s toxicity. 

The second most widely used detector in HPLC is the differential refractometer (RI). Being a bulk property detector, the RI responds to all substances. As noted in Table 3 the detection limits are several orders of magnitude higher than obtained with the UV detector. Thus, one turns to the RI detector in those cases in which substances are non-UV active, e.g. lipids, prostaglandins. In addition, the RI detector finds use in preparative scale operation. Finally, relative to the UV detector, the RI is significantly more temperature and flow sensitive and cannot be used in gradient elution. 

Sleep-active neurons have been identified in the ventrolateral and medial preoptic areas. These neurons exhibit increased discharge during SWS and REMS rather than W. Sleep-active neurons colocalize GABA and are excited by adenosine and prostaglandin D2 (McGinty Szymusiak, 2001) (Table 9.3). 

TABLE 33-1 Characteristics of cyclooxygenases or prostaglandin synthetases (IUPAC IUB EC 1.14.99.1)... 

NSAIDs act primarily by inhibiting prostaglandin synthesis, which is only a small portion of the inflammatory cascade. They possess both analgesic and antiinflammatory properties and reduce stiffness but do not slow disease progression or prevent bony erosions or joint deformity. They should seldom be used as monotherapy for RA instead, they should be viewed as adjuncts to DMARD treatment. Common NSAID dosage regimens are shown in Table 4-4. 

Topical corticosteroids (Table 16-1) may halt synthesis and mitosis of DNA in epidermal cells and appear to inhibit phospholipase A, lowering the amounts of arachidonic acid, prostaglandins, and leukotrienes in the skin. These effects, coupled with local vasoconstriction, reduce erythema, pruritus, and scaling. As antipsoriatic agents, they are best used adjunc-tively with a product that specifically functions to normalize epidermal hyperproliferation. 

The nonopioids are preferred over the opioids for mild to moderate pain (see Table 54-1). The salicylates and nonsteroidal antiinflammatory drugs (NSAIDs) reduce prostaglandins produced by the arachidonic acid cascade, thereby decreasing the number of pain impulses received by the CNS. 

Table 7.8. The possible role of prostaglandins and cytokines in depression...

A wide range of pharmaceutical substances are derived from animal sources (Table 1.10). Many are protein-based and detailed description of products such as insulin and other polypeptide hormones, antibody preparations, vaccines, enzymes, etc., have been deferred to subsequent chapters. (Many of the therapeutic proteins are now also produced by recombinant DNA technology. Considerable overlap would have been generated had a product obtained by direct extraction from native sources been discussed here, with further discussion of a version of the same product produced by recombinant DNA technology at a later stage.) Non-proteinaceous pharmaceuticals originally derived from animal sources include steroid (sex) hormones, corticosteroids and prostaglandins. A limited discussion of these substances is presented below, as they will not be discussed in subsequent chapters. Most of these substances are now prepared synthetically. 

Apart from their anti-inflammatory activity the NSAIDs also show, dependent on the condition and the type of pain, considerable analgesic efficacy. In some forms of postoperative pain the NSAID s can be as efficacious as opioids, especially when prostaglandins, bradykinin and histamine, which are released by inflammation, have caused sensitization of pain receptors to normally painless stimuli. In Table 4 some advantages and disadvantages of NSAID s and opioids are compared. Although analgesic effects at peripheral or central neurons cannot be excluded completely, most studies indicate that... 

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