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2374 Supplementary Drugs and Other Substances 2374 Supplementary Drugs and Other Substances 5. Burdock GA. Review of the biological properties and toxicity of Pharmacokinetics reduced to the endoperoxide prostaglandin H2 (PGH2). Prostag- bee propolis (propolis). Food Chem Toxicol 1998; 36: 347–63. Propylene glycol is rapidly absorbed from the gastrointestinal landin H2 is then converted to the primary prostaglandins pros- 6. Lieberman HD, et al. Allergic contact dermatitis to propolis in a tract. There is evidence of topical absorption when applied to taglandin D2, prostaglandin E2, and prostaglandin F2 , to throm- violin maker. J Am Acad Dermatol 2002; 46 (suppl): S30–S31. damaged skin. boxane A2 (TXA2) via the enzyme thromboxane synthetase, or 7. Giusti F, et al. Sensitization to propolis in 1255 children under- It is extensively metabolised in the liver primarily by oxidation to prostacyclin (PGI2) via the enzyme prostacyclin synthetase. going patch testing. Contact Dermatitis 2004; 51: 255–8. to lactic and pyruvic acid and is also excreted in the urine These products are further metabolised and rapidly inactivated in 8. Walgrave SE, et al. Allergic contact dermatitis from propolis. unchanged. the body. Dermatitis 2005; 16: 209–15. The secondary prostaglandins, prostaglandin A (PGA ), pros- 9. Majiene D, et al. Antifungal and antibacterial activity of propo- ◊ References. 2 2 lis. Curr Nutr Food Sci 2007; 3: 304–8. 1. Yu DK, et al. Pharmacokinetics of propylene glycol in humans taglandin B2 (PGB2), and prostaglandin C2 (PGC2) are derived during multiple dosing regimens. J Pharm Sci 1985; 74: 876–9. from prostaglandin E2, but are formed during extraction and Preparations 2. Speth PAJ, et al. Propylene glycol pharmacokinetics and effects probably do not occur biologically. after intravenous infusion in humans. Ther Drug Monit 1987; 9: Proprietary Preparations (details are given in Part 3) 255–8. The prostaglandins are all derivatives of the carbon skeleton 7- Arg.: Propoleos; Austral.: Helastop†; Chile: Propolkit; Ger.: Propolisept- (2-octilcyclopentyl)heptanoic acid (also known as prostanoic ac- Salbe; Ital.: Golapiol; Oral Spray; Pro-30C†; Pro-Gola; Propociclina; Uses and Administration id). All natural prostaglandins have a double bond at position 1,2 Propolcream; Pol.: Apizel; Propolan; Propolisan; Propolisol; USA: Probax. Propylene glycol is widely used in pharmaceutical manufactur- and a hydroxyl group at position 3 of the octil side-chain. De- ing as a solvent and vehicle, especially for drugs unstable or Multi-ingredient: Braz.: Calmatoss†; Infantoss†; Malvatricin Natural Or- pending on the substitutions on the cyclopentane ring, the main ganic; Proplax†; Fr.: Pollen Royal†; Propargile; Ital.: Actires; Altuss; Apist- insoluble in water. It may also be used as a stabiliser in vitamin series of prostaglandins are distinguished by the letters A, B, C, ress; Biogreen; Bodyguard; Fosfarsile Forte; Golapiol C; Immumil Plus; Im- preparations, as a plasticiser, and as a preservative. Propylene D, E, and F; the members of each series are further subdivided by mumil†; Keratolip; Neo-Stomygen; Nepiros; Otosan Natural Ear Drops†; glycol is used extensively in foods and cosmetics. subscript numbers which indicate the degree of unsaturation in Probigol; Promix 3†; Promix†; Propast; Propomill†; Valda Propoli; Switz.: Propylene glycol has humectant properties and is used similarly Osa gel dentaire aux plantes; UK: Sinose. the side-chains—hence, those derived from eicosatrienoic acid to glycerol in topical moisturising preparations. (dihomo-γ-linolenic acid) have the subscript 1, those derived Propylene glycol is used in veterinary medicine as a glucose pre- from arachidonic acid have the subscript 2, and those derived cursor. from eicosapentaenoic acid have the subscript 3. In man, only Propylene Glycol Preparations prostaglandins of the ‘2’ series appear to be of physiological im- portance. Thromboxane A2 has an oxane rather than a cyclopen- E1520; Glicol Propilênico; Glikol propylenowy; Propilenglicol; Proprietary Preparations (details are given in Part 3) USA: Advanced Eye Relief. tane ring; it is chemically unstable and breaks down to throm- Propilénglikol; Propilenglikolis; Propilenoglicol; Propyleeniglykoli; boxane B . Prostacyclin has a double-ring structure and breaks Multi-ingredient: Arg.: Systane; Austral.: Dermatech Liquid; Austria: 2 Propylèneglycol; Propylenglycolum; Propylenglykol. (±)-Propane- Acerbine; Canad.: Episec; Gyne-Moistrin†; Rhinaris; Rhinedrine Moisturiz- down to 6-keto-prostaglandin F1 . 1,2-diol. ing†; Salinol†; Secaris; Systane; Chile: Systane; Fr.: Intrasite; Propy-Lacticare; Endogenous prostaglandins are autacoids; they can be formed by Systane; Ger.: Sekudrill†; Hong Kong: Moisture Eyes; Systane; Israel: Ped- C3H8O2 = 76.09. isol†; Taro Gel; Ital.: Dopo Pik; Sekudrill; Systane; Malaysia: Systane; virtually all tissues and cells in response to a variety of stimuli, CAS — 57-55-6 ((±)-propylene glycol); 4254-16-4 ((±)- Mex.: Moisture Eyes; Systane; Philipp.: Moisture Eyes; Systane; S.Afr.: have a wide range of actions, and are involved in the regulation propylene glycol); 4254-14-2 ((−)-propylene glycol); 4254- Aserbine; Singapore: Systane; Spain: Acerbiol; Switz.: Acerbine†; Thai.: of virtually all biological functions. Prostaglandins appear to act 15-3 ((+)-propylene glycol). Systane; UK: Aserbine†; USA: Astroglide; Biotene with Calcium; Surgel; through various receptor-mediated mechanisms. Some of their Zonite; Venez.: Systane. effects are mediated within cells by activation or inhibition of ATC Vet — QA16QA01. adenylate cyclase and the regulation of cyclic adenosine mono- phosphate production. At one time prostaglandin E2 and prosta- Prostaglandins glandin F2 were thought to be of paramount importance, but CH3 with the discovery of thromboxane A2, prostacyclin, and the Profile leukotrienes it was realised that these primary prostaglandins OH The prostaglandins, along with thromboxanes and leukotrienes, belong to a large family of physiologically active eicosanoids. HO are all derived from 20-carbon polyunsaturated fatty acids and Thromboxane A2 induces platelet aggregation and constricts ar- are collectively termed eicosanoids. In man, the most common terial smooth muscle whereas prostacyclin causes vasodilatation Pharmacopoeias. In Chin., Eur. (see p.vii), Int., Jpn, and US. precursor is arachidonic acid (eicosatetraenoic acid) whereas ei- and prevents platelet aggregation; the balance between these op- Ph. Eur. 6.2 (Propylene Glycol). A clear, colourless, viscous, hy- cosapentaenoic acid is a predominant precursor in fish and ma- posing actions has an important role in the regulation of intravas- groscopic liquid. Miscible with water and with alcohol. Store in rine animals. cular platelet aggregation and thrombus formation. The leuko- airtight containers. Arachidonic acid is released from cell-membrane phospholipids trienes are important mediators of inflammation. USP 31 (Propylene Glycol). A clear, colourless, practically by the enzyme phospholipase A and is then rapidly metabolised 2 The pharmacological properties of prostaglandins are wide- odourless, viscous liquid. It absorbs moisture when exposed to by several enzymes, the major ones being cyclo-oxygenase ranging and include contraction or relaxation of smooth muscle moist air. Miscible with water, with acetone, and with chloro- (prostaglandin synthetase) and lipoxygenase (see Figure 1, in the blood vessels, bronchi, uterus, and gastrointestinal tract; form; soluble in ether; will dissolve in many essential oils but is below). The prostaglandins, thromboxanes, and prostacyclin inhibition of gastric acid secretion; and effects on platelet aggre- immiscible with fixed oils. Store in airtight containers. (sometimes collectively termed prostanoids) all contain ring structures and are products of arachidonic acid oxidation by gation, the endocrine system, and metabolic processes. Adverse Effects and Precautions cyclo-oxygenase, an enzyme with 2 isoforms (COX-1 or COX- Individual prostaglandins vary greatly in their activities and po- Systemic toxicity of propylene glycol is considered to be low af- 2) widely distributed in cell membranes. tencies; their actions also depend on the animal species, on the ter oral doses unless large quantities have been ingested, or when The leukotrienes are products of the lipoxygenase pathway; ara- tissues in which they are acting, and on the concentration present, preparations containing propylene glycol are given to neonates chidonic acid is metabolised by lipoxygenases to hydroperoxyei- and entirely opposite actions may be elicited with very small or to patients in renal failure. Systemic toxicity is manifested cosatetraenoic acids, which are then further metabolised to leu- structural changes in the molecule. most commonly by CNS depression, especially in neonates and kotrienes. The diverse clinical applications of prostaglandins reflect their children. Other reported adverse effects include hepatic or renal The initial step in the cyclo-oxygenase pathway is the formation wide-ranging physiological and pharmacological properties. impairment, intravascular haemolysis, seizures, coma, arrhyth- of cyclic endoperoxide prostaglandin G (PGG ) which is then Synthetic analogues have been developed with the aim of obtain- mias, and cardiorespiratory arrest. Hyperosmolality has oc- 2 2 curred, particularly in small infants and in patients with renal im- pairment; lactic acidosis may also be a greater problem in the latter group. Figure 1. Prostaglandin biosynthesis.
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