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2374 Supplementary Drugs and Other Substances

5. Burdock GA. Review of the biological properties and toxicity of Pharmacokinetics reduced to the endoperoxide 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 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, , and prostaglandin F2 , to throm- violin maker. J Am Acad Dermatol 2002; 46 (suppl): S30–S31. damaged skin. boxane A2 (TXA2) via the 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 (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 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. 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 -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 it was realised that these primary prostaglandins OH The prostaglandins, along with and leukotrienes, belong to a large family of physiologically active . HO are all derived from 20-carbon polyunsaturated fatty acids and Thromboxane A2 induces 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 , 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 ) 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. After topical use, propylene glycol may produce some local irri- tation, particularly if applied under occlusive dressings or to mu- Cell-membrane Phospholipids cous membranes; toxicity may occur on application to burns. Hypersensitivity reactions have also been reported. Local sensi- tivity has been reported after use of ear drops with a propylene Phospholipase A2 glycol vehicle. Injections of preparations containing high con- centrations of propylene glycol may produce pain or irritation. Lipoxygenase Lactic acidosis. Lactic acidosis developed in a patient with nor- Arachidonic Acid Hydroperoxyeicosatetraenoic Acids Leukotrienes mal renal function given a high-dose continuous lorazepam infu- sion for which propylene glycol was the principal diluent.1 De- Cyclo-oxygenase spite temporary resolution of symptoms when the infusion was (COX-1 or COX-2) stopped and bicarbonate given, the patient eventually died. A prospective observational pilot study2 found propylene glycol to be a common cause of metabolic disturbances in intensive care (PGG2) patients receiving intravenous benzodiazepines, and the authors recommended close monitoring of all such patients. Thromboxane synthase Thromboxane A (TXA ) 1. Neale BW, et al. Propylene glycol-induced lactic acidosis in a 2 2 patient with normal renal function: a proposed mechanism and monitoring recommendations. Ann Pharmacother 2005; 39: 1732–6. Prostaglandin H (PGH ) 2. Wilson KC, et al. Propylene glycol toxicity: a severe iatrogenic 2 2 illness in ICU patients receiving IV benzodiazepines: a case se- ries and prospective, observational pilot study. Chest 2005; 128: 1674–81. Prostacyclin (PGI2) Interactions

Anticoagulants. Propylene glycol has been reported to de- (PGD2) crease the effect of heparin.1 Prostaglandin E2 (PGE2) 1. Col J, et al. Propylene glycol-induced heparin resistance during Prostaglandin F (PGF ) nitroglycerin infusion. Am Heart J 1985; 110: 171–3. 2a 2a Propylene Glycol/Pulmonary Surfactants 2375 ing compounds that are more stable, have a longer duration of Profile Goombas; Gus; Hombrecitos; Jesus; Lalkas; Las mujercitas; Lit- action, and a more specific effect. Applications include: Proxazole citrate has been used as an antispasmodic and in vas- tle smoke; Magic mushroom; Magic mushrooms; Marios; Mex- • softening and dilating the cervix and for uterine stimulation, cular disorders. ican mushroom; Mexican mushrooms; Mucks; Muggers; Mush; e.g. dinoprost (prostaglandin F ) (p.2006) and its analogue Mushies; Mushroom soup; Mushroom tea; Mushrooms; Musk; 2 Preparations Philosopher’s Stones; Pizza toppings; Rooms; Sacre mushroom; (p.2006); dinoprostone (prostaglandin E2) Proprietary Preparations (details are given in Part 3) Sacred mushroom; Sacred mushrooms; Shroomies; Shrooms; (p.2007) and its analogue (p.2018); and gemepro- Ital.: Toness†. Silly putty; Simple Simon; Smurfhats; Teonanactl; Toads; Truf- st (p.2010) and (p.2013), analogues of prostag- fles; Umbrellas; Yellow Bentines; Zoomers; Zoomies. landin E1 • vasodilators and inhibitors of platelet aggregation, e.g. alpros- Profile Prozapine Hydrochloride (rINNM) Psilocin and psilocybine are indole alkaloids obtained from the tadil ( ) (p.2183) and its analogue limaprost 1 sacred Mexican mushroom (teonanácatl), Psilocybe mexicana (p.1325); and epoprostenol (prostacyclin) (p.1279) and its an- Hexadiphane Hydrochloride; Hidrocloruro de prozapina; Proza- (Agaricaceae). alogue (p.1313) pine, Chlorhydrate de; Prozapini Hydrochloridum. 1-(3,3-Diphe- nylpropyl)cyclohexamethyleneimine hydrochloride. In the UK, psilocybine is present in the indigenous mushroom • inhibition of gastric acid secretion and protection of the gas- Psilocybe semilanceata (magic mushroom; liberty cap). Psilocy- Прозапина Гидрохлорид trointestinal mucosa, e.g. misoprostol (p.2013) bine is also present in other species of mushrooms including • glaucoma treatment, e.g. (p.1878), C21H27N,HCl = 329.9. Stropharia cubensis and Conocybe spp. (p.1882), (p.1886), and (p.1886) CAS — 3426-08-2 (prozapine); 13657-24-4 (prozapine hydrochloride). Psilocybine has hallucinogenic and sympathomimetic properties • as luteolytics (causing regression of the corpus luteum in the similar to those of lysergide (p.2335). It is less potent than ovary) in veterinary medicine, e.g. synthetic analogues of lysergide and its hallucinogenic effects last for up to 6 hours. prostaglandin F2 . There is evidence to suggest that psilocybine is converted to the active form psilocin in the body. It has no therapeutic use. ◊ References. 1. Moncada S, Vane JR. Arachidonic acid metabolites and the in- teractions between and blood-vessel walls. N Engl J Med 1979; 300: 1142–7. Pulegium Oil 2. Higgs GA, Vane JR. Inhibition of cyclo-oxygenase and lipoxy- genase. Br Med Bull 1983; 39: 265–70. Pennyroyal Oil; Poleo, aceite esencial de. 3. Halushka PV, et al. Thromboxane, prostaglandin and receptors. Annu Rev Pharmacol Toxicol 1989; 29: 213–39. N Profile 4. Smith WL, et al. Prostaglandin and thromboxane biosynthesis. Pulegium oil is a volatile oil distilled from pennyroyal herb, Pharmacol Ther 1991; 49: 153–79. Mentha pulegium (Labiatae), containing pulegone 5. O’Neill C. The of prostaglandins: a primer. Aust N (C10H16O = 152.2). It was formerly used as an emmenagogue. Z J Obstet Gynaecol 1994; 34: 332–7. Severe toxic effects have followed its use as an abortifacient with 6. Wu KK. Molecular regulation and augmentation of prostacyclin (prozapine) convulsions, hepatotoxicity, and death. It is reported to have in- biosynthesis. Agents Actions Suppl 1995; 45: 11–17. sect repellent activity. Profile Adverse effects. Severe hepatotoxicity accompanied by sei- Prozapine hydrochloride is an antispasmodic that has been given zures occurred in 2 infants each of whom had received herbal Protoporphyrin IX Disodium orally with sorbitol in biliary and gastrointestinal disorders. teas containing pulegium oil.1 In one of the infants multiple or- gan failure developed, and fulminant hepatic failure with hepato- Protoporfirina IX disódica; Protoporphyrin Disodium. Disodium cellular necrosis and cerebral oedema proved fatal. A further 4 7,12-diethenyl-3,8,13,17-tetramethyl-21H,23H-porphine-2,18-di- cases of toxicity associated with ingestion of pulegium oil have propanoate. Psilocin been reported;2 three of the cases were adult patients who had C34H32N4Na2O4 = 606.6. 4-Hydroxy-NN-dimethyltryptamine; Psilocina; Psilocyn. 3-(2- ingested either herbal teas to induce menses (2 cases) or a herbal CAS — 50865-01-5 (protoporphyrin IX disodium); 553- Dimethylaminoethyl)indol-4-ol. extract as an abortifacient (1 fatality), and the fourth was a 22- 12-8 (protoporphyrin IX). month old child who had ingested the oil. C12H16N2O = 204.3. CAS — 520-53-6. 1. Bakerink JA, et al. Multiple organ failure after ingestion of pen- nyroyal oil from herbal tea in two infants. Pediatrics 1996; 98: 944–7. H3C CH3 O- 2. Anderson IB, et al. Pennyroyal toxicity: measurement of toxic Na+ H metabolite levels in two cases and review of the literature. Ann N H2C Intern Med 1996; 124: 726–34. O NH N CH3 N Pulmonary Surfactants OH N HN - Tensioactivos pulmonares. O CH + 3 H3C Na Description. Pulmonary surfactants are mixtures consisting O NOTE. The following terms have been used as ‘street names’ (see mainly of phospholipids and surfactant proteins that are used to replace deficient endogenous lung surfactants. A number of CH3 p.vi) or slang names for various forms of psilocin or mushrooms containing psilocin: preparations have been studied including: H2C 1UP’s; Abhort; Aborts; Alice; Benzies; Blue Rimmers; Boom- • natural human surfactant obtained from amniotic fluid or bio- Dads; Boomers; Caps; Crumb Tarts; Cubes; FireWorks; Fun synthetic material Gus; Fun Guys; Fungus; God’s flesh; Goombas; Gus; Jesus; La- Profile lkas; Liberty caps; Little smoke; Magic mushroom; Magic • natural animal-derived surfactants, which are bovine or por- Protoporphyrin IX disodium has been given by mouth for the Mushrooms; Marios; Mexican mushroom; Mexican mush- cine lung extracts that may be modified by the addition of syn- treatment of impaired hepatic function associated with gallstones rooms; Mucks; Muggers; Mush; Mushies; Mushrooms; Musk; thetic surfactants, as in the case of beractant, or unmodified, as and cholecystitis. Pizza Toppings; Shroomies; Shrooms; Silly putty; Simple Si- in the case of bovactant and calfactant mon; Smurfhats; Toads; Umbrellas; Yellow Bentines; Zoomers; • synthetic or semisynthetic preparations, which may contain Zoomies. the phospholipid colfosceril palmitate, a major constituent of natural lung surfactants, in combination with other substances (USAN, rINNM) Proxazole Citrate Psilocybine (BAN, rINN) that aid spreading and absorption such as the synthetic peptide AF-634; Citrato de proxazol; Propaxoline Citrate; Proxazole, Ci- CY-39; 4-Phosphoryloxy-NN-dimethyltryptamine; Psilocibina; sinapultide. trate de; Proxazoli Citras; PZ-17105. NN-Diethyl-3-(1-phenyl- Psilocybin; Psilocybinum; Psilosybiini. 3-(2-Dimethylaminoe- propyl)-1,2,4-oxadiazole-5-ethanamine citrate. thyl)indol-4-yl dihydrogen phosphate. Beractant (BAN, USAN) Проксазола Цитрат Псилоцибин A-60386X. CAS — 108778-82-1. C17H25N3O,C6H8O7 = 479.5. C12H17N2O4P = 284.2. CAS — 5696-09-3 (proxazole); 132-35-4 (proxazole cit- CAS — 520-52-5. Description. Beractant is a modified bovine lung extract con- rate). taining mostly phospholipids, modified by the addition of colfo- ATC — A03AX07. sceril palmitate, palmitic acid, and tripalmitin. ATC Vet — QA03AX07. H The term Surfactant TA has been applied to a modified bovine N lung surfactant.

(BAN) H3C CH3 Bovactant HO N SF-R11. O HO O N CH Description. Bovactant is an extract of bovine lung containing N 3 P CH3 about 92% of phospholipids, 3.2% of cholesterol, 0.6% of sur- N factant-associated hydrophobic proteins, and 0.4% of free fatty O acid.

NOTE. The following terms have been used as ‘street names’ (see Calfactant (BAN, USAN) p.vi) or slang names for various forms of psilocybine or mush- CAS — 183325-78-2. H3C rooms containing psilocybine: 1 UP’s; Alice; Benzies; Blue caps; Blue Rimmers; Boom-Dads; Description. Calfactant is an unmodified calf lung extract that (proxazole) Boomers; Booms; Buttons; Caps; Champ; Crumb Tarts; Cubes; includes mostly phospholipids and hydrophobic surfactant- FireWorks; Fun Gus; Fun Guys; Fungus; Funguys; God’s flesh; specific proteins (SP-B and SP-C). The symbol † denotes a preparation no longer actively marketed The symbol ⊗ denotes a substance whose use may be restricted in certain sports (see p.vii)