Oxazepam/Penfluridol 1015

Oxypertine (BAN, USAN, rINN) However, US licensed product information recommends the fol- be given rectally in the presence of colitis. Old paraldehyde must lowing maximum doses: Oksipertiini; Oxipertin; Oxipertina; Oxypertinum; Win-18501- never be used. 2. 5,6-Dimethoxy-2-methyl-3-[2-(4-phenylpiperazin-1-yl)ethyl]- • CC 50 to 80 mL/minute: 6 mg once daily Paraldehyde must be well diluted before oral or rectal use; if it is deemed essential to give paraldehyde intravenously it must be indole. • CC 10 to 50 mL/minute: 3 mg once daily has not been studied in patients with a CC of less well diluted and given very slowly with extreme caution (see Оксипертин than 10 mL/minute; UK product information does not recom- also Adverse Effects, above and Uses, below). Intramuscular in- C23H29N3O2 = 379.5. mend its use in such patients. jections may be given undiluted but care should be taken to avoid CAS — 153-87-7 (); 40523-01-1 (oxypertine nerve damage. Plastic syringes should be avoided (see Incompat- hydrochloride). Preparations ibility, above). ATC — N05AE01. Proprietary Preparations (details are given in Part 3) ATC Vet — QN05AE01. Cz.: Invega; Fr.: Invega; Port.: Invega; UK: Invega; USA: Invega. Interactions The effects of paraldehyde are enhanced by CNS de- pressants such as , , and other . A H Paraldehyde few case reports suggest that disulfiram may enhance the toxicity H3CO of paraldehyde; use together is not recommended. N Paracetaldehyde; Paraldehid; Paraldehidas; Paraldehído; Paralde- Pharmacokinetics CH3 hit; Paraldehyd; Paraldéhyde; Paraldehydi; Paraldehydum. The Paraldehyde is generally absorbed readily, although absorption is H CO trimer of acetaldehyde; 2,4,6-Trimethyl-1,3,5-trioxane. reported to be slower after rectal than after oral or intramuscular 3 N (C2H4O)3 = 132.2. doses. It is widely distributed and has a reported half-life of 4 to CAS — 123-63-7. N 10 hours. About 80% of a dose is metabolised in the liver proba- ATC — N05CC05. bly to acetaldehyde, which is oxidised by aldehyde dehydroge- ATC Vet — QN05CC05. nase to acetic acid. Unmetabolised drug is largely excreted un- changed through the lungs; only small amounts appear in the urine. It crosses the placental barrier and is distributed into breast H3C O CH3 Profile milk. Oxypertine is an indole derivative with general properties similar Uses and Administration to those of the , (p.969). It has OO Paraldehyde is a hypnotic and sedative with antiepileptic effects. been given orally in the treatment of psychoses including schiz- However, because of the hazards associated with its use, its ten- ophrenia, mania, and disturbed behaviour, and in severe anxiety. CH3 dency to react with plastic, and the risks associated with its dete- rioration, it has largely been superseded by other drugs. It is still Pharmacopoeias. In Eur. (see p.vii) and US. occasionally used to control status epilepticus (p.469) resistant to Ph. Eur. 6.2 (Paraldehyde). A colourless or slightly yellow, conventional treatment. Given rectally or intramuscularly it Paliperidone (USAN, rINN) transparent liquid. It solidifies on cooling to form a crystalline causes little respiratory depression and is therefore useful where 9-Hydroxyrisperidone; Paliperidona; Palipéridone; Paliperidon- mass. It may contain a suitable amount of an antoxidant. Relative facilities for resuscitation are poor. um; RO-76477. (±)-3-{2-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)pip- density 0.991 to 0.996. F.p. is 10° to 13°; not more than 10% dis- At low temperature it solidifies to form a crystalline mass. If it eridino]ethyl}-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyri- tils below 123° and not less than 95% below 126°. Soluble in wa- solidifies, the whole should be liquefied before use. do[1,2-a]pyrimidin-4-one. ter but less soluble in boiling water; miscible with alcohol and A usual dose for adults is 10 to 20 mL given rectally as a 10% Палиперидон with volatile oils. Store in small well-filled airtight containers. solution in sodium chloride 0.9% solution or diluted with 1 or 2 Protect from light. C H FN O = 426.5. parts of oil. Doses of 5 to 10 mL are also occasionally given in- 23 27 4 3 USP 31 (Paraldehyde). A colourless transparent liquid with a CAS — 144598-75-4. tramuscularly up to a maximum of 20 mL daily with not more strong characteristic, but not unpleasant or pungent, odour. It is ATC — N05AX13. than 5 mL being given at any one site. In the UK it is licensed for subject to oxidation to form acetic acid. It may contain a suitable intramuscular use in children; however, the BNFC advocates use ATC Vet — QN05AX13. stabiliser. Specific gravity is about 0.99. It has a congealing tem- of the rectal route instead, diluted as above. Recommended sin- perature of not lower than 11° and distils completely between gle daily doses by either route are: 120° and 126°. Soluble 1 in 10 of water v/v, but only 1 in 17 of • up to 3 months, 0.5 mL (the BNFC suggests a single rectal H OH and enantiomer boiling water v/v; miscible with alcohol, with chloroform, with dose of 0.4 mL/kg (maximum of 0.5 mL) in those under 1 N CH3 ether, and with volatile oils. Store in well-filled airtight contain- month) ers of not more than 30 mL at a temperature not exceeding 25°. • 3 to 6 months, 1 mL Protect from light. It must not be used more than 24 hours after • 6 to 12 months, 1.5 mL N opening the container. N • 1 to 2 years, 2 mL F Incompatibility. Paraldehyde exerts a solvent action upon rub- O • 3 to 5 years, 3 to 4 mL ber, polystyrene, and styrene-acrylonitrile copolymer and should • 6 to 12 years, 5 to 6 mL not be given in plastic syringes made with these materials. N Paraldehyde has been given by slow intravenous infusion in spe- O An evaluation of the compatibility of paraldehyde with plastic cialist centres with intensive care facilities but this route is not syringes and needle hubs concluded that, if possible, all-glass sy- usually recommended; it must be diluted in sodium chloride ringes should be used with paraldehyde.1 Needles with plastic 0.9% before use. Paliperidone Palmitate (USAN, rINNM) hubs could be used. Polypropylene syringes with rubber-tipped plastic plungers (Plastipak), or glass syringes with natural rub- Paraldehyde has been given orally; it should always be well di- Palipéridone, Palmitate de; Paliperidoni Palmitas; Palmitato de ber-tipped plastic plungers (Glaspak) were acceptable only for luted to avoid gastric irritation. paliperidona; RO-92670. (9RS)-3-{2-[4-(6-Fluoro-1,2-benzisoxa- the immediate administration or measurement of paraldehyde Preparations zol-3-yl)piperidin-1-yl]ethyl}-2-methyl-4-oxo-6,7,8,9-tetrahydro- doses. BP 2008: Paraldehyde Injection. 4H-pyrido[1,2-a]pyrimidin-9-yl hexadecanoate. 1. Johnson CE, Vigoreaux JA. Compatibility of paraldehyde with Proprietary Preparations (details are given in Part 3) Палиперидона Палмитат plastic syringes and needle hubs. Am J Hosp Pharm 1984; 41: USA: Paral. 306–8. C39H57FN4O4 = 664.9. CAS — 199739-10-1. Stability. Paraldehyde decomposes on storage, particularly after the container has been opened. Partly decomposed paraldehyde Profile is dangerous if given. It must not be used if it has a brownish Penfluridol (BAN, USAN, rINN) Paliperidone is a derivative and is the major active colour or a sharp penetrating odour of acetic acid. McN-JR-16341; Penfluridoli; Penfluridolum; R-16341. 4-(4-Chlo- metabolite of the atypical (p.1024). It Dependence and Withdrawal ro-3-trifluoromethylphenyl)-1-[3-(p,p′-difluorobenzhydryl)pro- is reported to be an antagonist at D2, serotonin (5- Prolonged use of paraldehyde may lead to dependence, especial- pyl]piperidin-4-ol. HT2), adrenergic (α1 and α2), and (H1) receptors. It is used in the treatment of . ly in alcoholics. Features of dependence and withdrawal are sim- Пенфлуридол The recommended oral dose of paliperidone is 6 mg once daily ilar to those of barbiturates (see Amobarbital, p.962). C28H27ClF5NO = 524.0. as a modified-release preparation; doses may range from 3 to Adverse Effects and Treatment CAS — 26864-56-2. 12 mg daily. US licensed product information recommends that Paraldehyde decomposes on storage and deaths from corrosive ATC — N05AG03. dose increases are made in small steps of 3 mg at intervals of poisoning have followed the use of such material. Paraldehyde ATC Vet — QN05AG03. more than 5 days. has an unpleasant taste and imparts a smell to the breath; it may cause skin rashes. For details of dose reductions in patients with renal impairment, F see below. Oral or rectal use of paraldehyde may cause gastric or rectal irri- Paliperidone palmitate is being developed as a long-acting intra- tation. Intramuscular injection is painful and associated with tis- muscular formulation. sue necrosis, sterile abscesses, and nerve damage. Intravenous use is extremely hazardous since it may cause pulmonary oede- N Administration in renal impairment. The plasma concen- OH ma and haemorrhage, hypotension and cardiac dilatation, and CF3 trations of paliperidone are increased in patients with renal im- circulatory collapse; thrombophlebitis is also associated with in- pairment. The usual oral daily dosage (see above) should there- travenous use. fore be adjusted according to creatinine clearance (CC). Overdosage results in rapid laboured breathing owing to damage Cl In the UK, licensed product information recommends the follow- to the lungs and to acidosis. Nausea and vomiting may follow an ing doses: overdose by mouth. Respiratory depression and coma as well as F • CC 50 to 80 mL/minute: initially 3 mg once daily, may be in- hepatic and renal damage may occur. Treatment is as for barbit- creased thereafter according to response and tolerance urate overdose (see Amobarbital, p.962). Pharmacopoeias. In Chin. • CC 30 to 50 mL/minute: 3 mg once daily Precautions Profile • CC 10 to 30 mL/minute: initially 3 mg on alternate days Paraldehyde should not be given to patients with gastric disor- Penfluridol is a antipsychotic and shares which may be increased thereafter to 3 mg once daily after ders and it should be used with caution, if at all, in patients with the general properties of the phenothiazine, chlorpromazine clinical reassessment bronchopulmonary disease or hepatic impairment. It should not (p.969). After oral doses it has a prolonged duration of action that 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) 1016 Anxiolytic Sedatives Hypnotics and lasts for about a week. It is used in the treatment of psychoses Pharmacopoeias. In Eur. (see p.vii) and US. Pharmacopoeias. Pol. includes only an injection of the di- including schizophrenia (p.955). Ph. Eur. 6.2 ( Sodium). A white or almost white, malonate. It also includes a monograph for Dimaleate. The usual oral dose of penfluridol for the treatment of chronic hygroscopic, crystalline powder. Very soluble in water. A 10% solution in water has a pH of 9.6 to 11.0 when freshly prepared. Profile psychoses is 20 to 60 mg once a week. Doses of up to 250 mg Perazine dimalonate is a phenothiazine with general properties once a week may be required in severe or resistant conditions. Store in airtight containers. USP 31 (Pentobarbital Sodium). White, crystalline granules or similar to those of chlorpromazine (p.969) and is used for the Schizophrenia. A systematic review1 concluded that penflu- white powder. Is odourless or has a slight characteristic odour. treatment of psychotic conditions. It has a side-chain. ridol appears to have a similar efficacy and adverse effects pro- Very soluble in water; freely soluble in alcohol; practically insol- It is given orally as the dimalonate although doses are expressed file to other classical antipsychotics used in the treatment of uble in ether. pH of a 10% solution in water is between 9.8 and in terms of the base; perazine dimalonate 40.3 mg is equivalent schizophrenia (p.955). The authors also suggested that penflu- 11.0. Solutions decompose on standing, the decomposition being to about 25 mg of perazine. Usual doses are the equivalent of 50 ridol, in a weekly oral dose of 40 to 80 mg, is a suitable alterna- accelerated at higher temperatures. Store in airtight containers. to 600 mg of the base daily; up to 1000 mg daily has been given tive, particularly for patients who do not respond to daily oral in resistant cases. It has also been given intramuscularly. medication or adapt well to depot drugs. Incompatibility. Pentobarbital may be precipitated from prep- arations containing pentobarbital sodium, depending on the con- Perazine dimaleate given orally has been used similarly. 1. Soares BGO, Lima MS. Penfluridol for schizophrenia. Available centration and pH. Pentobarbital sodium has, therefore, been re- Adverse effects. A report of 5 patients receiving perazine di- in The Cochrane Database of Systematic Reviews; Issue 2. ported to be incompatible with many other drugs particularly Chichester: John Wiley; 2006 (accessed 19/03/08). malonate who developed acute axonal neuropathies of superfi- acids and acidic salts. cial nerve fibres after exposure to sunlight.1 Preparations Dependence and Withdrawal 1. Roelcke U, et al. Acute neuropathy in perazine-treated patients Proprietary Preparations (details are given in Part 3) As for Amobarbital, p.962. after sun exposure. Lancet 1992; 340: 729–30. Austria: Semap; Belg.: Semap; Braz.: Semap; Cz.: Semap†; Denm.: Sem- ap; Fr.: Semap†; Gr.: Flupidol; Israel: Semap; Mex.: Semap; Neth.: Semap; Adverse Effects, Treatment, and Precautions Preparations As for Amobarbital, p.962. Switz.: Semap. Proprietary Preparations (details are given in Part 3) Interactions Ger.: Taxilan; Pol.: Perazin; Perazyna; Pernazinum. As for Amobarbital, p.962. Pentobarbital (BAN, rINN) Pharmacokinetics Pentobarbital is well absorbed from the gastrointestinal tract af- Aethaminalum; Mebubarbital; Mebumal; Pentobarbitaali; Pento- ter oral or rectal doses, and is reported to be about 60 to 70% Pericyazine (BAN) barbitál; Pentobarbitalis; Pentobarbitalum; Pentobarbitone. 5- bound to plasma proteins. The elimination half-life appears to be (pINN); Periciazin; Periciazina; Périciazine; Periciazinum; Ethyl-5-(1-methylbutyl)barbituric acid. dose-dependent and reported values have ranged from 15 to 50 Perisiatsiini; Propericiazine; RP-8909; SKF-20716. 10-[3-(4-Hy- Пентобарбитал hours. Pentobarbital is metabolised in the liver, mainly by hy- droxylation, and excreted in the urine mainly as metabolites. droxypiperidino)propyl]phenothiazine-2-carbonitrile; 1-[3-(2- C11H18N2O3 = 226.3. Cyanophenothiazin-10-yl)propyl]piperidin-4-ol. CAS — 76-74-4. Uses and Administration Pentobarbital is a that has been used as a hypnotic and Перициазин ATC — N05C A01. sedative. It has general properties and uses similar to those of C21H23N3OS = 365.5. ATC Vet — QN05CA01; QN51AA01. amobarbital (p.962). It has been used as a sedative and in the CAS — 2622-26-6. short-term management of insomnia (p.957) but barbiturates are not considered appropriate for such purposes. Pentobarbital sodi- ATC — N05AC01. um has also been used for premedication in anaesthetic proce- ATC Vet — QN05AC01. H dures (p.1780), but barbiturates for pre-operative sedation have O N O been replaced by other drugs. Pentobarbital is usually given as the sodium salt, although pentobarbital itself and its calcium salt OH have both been used. H3C NH H3C A usual oral dose of pentobarbital sodium for insomnia was 100 to 200 mg, given at bedtime. Usual parenteral doses for other in- N O CH3 dications were 150 to 200 mg as a single intramuscular dose or 100 mg by slow intravenous injection. N CN

NOTE. The following terms have been used as ‘street names’ (see Cerebrovascular disorders. For reference to the use of bar- p.vi) or slang names for various forms of pentobarbital: biturate-induced coma in the management of patients with cere- Blockbuster; Menish; Nebbies; Nembies; Nemish; Nemmies; bral ischaemia, see under Thiopental, p.1796. See also p.1181 for S Nimbies; Nimby; Yellow; Yellow bullets; Yellow dolls; Yellow reference to the use of barbiturates in the management of raised jackets; Yellow submarines; Yellows. intracranial pressure. Adverse Effects, Treatment, and Precautions Pharmacopoeias. In Eur. (see p.vii) and US. Status epilepticus. General anaesthesia may be used to control As for Chlorpromazine, p.969. Sedation and orthostatic hypoten- Ph. Eur. 6.2 (Pentobarbital). Colourless crystals or a white or al- refractory tonic-clonic status epilepticus (p.469). A short-acting sion may be marked. most white, crystalline powder. Very slightly soluble in water; barbiturate such as thiopental is usually used, but pentobarbital freely soluble in dehydrated alcohol. It forms water-soluble com- has been used similarly. Interactions pounds with alkali hydroxides and carbonates, and with ammo- As for Chlorpromazine, p.973. Preparations nia. Uses and Administration USP 31 (Pentobarbital). A white or practically white, practically BP 2008: Pentobarbital Tablets; Pericyazine is a phenothiazine with general properties similar to odourless, fine powder. Very slightly soluble in water and in car- USP 31: Pentobarbital Elixir; Pentobarbital Sodium Capsules; Pentobarbital those of chlorpromazine (p.975). It has a piperidine side-chain. It bon tetrachloride; soluble 1 in 4.5 of alcohol, 1 in 4 of chloro- Sodium Injection. is used in the treatment of psychoses including schizophrenia form, and 1 in 10 of ether; very soluble in acetone and in methyl Proprietary Preparations (details are given in Part 3) (p.955) and disturbed behaviour (p.954), and in the short-term alcohol; soluble in benzene. Store in airtight containers. Canad.: Nembutal†; Denm.: Mebumal; Hong Kong: Nembutal†; S.Afr.: Sopental; Thai.: Nembutal†; USA: Nembutal. management of severe anxiety (p.952). Multi-ingredient: Arg.: Dimaval; Canad.: Cafergot-PB†; USA: Cafatine- Pericyazine is usually given as the base but the mesilate and tar- Pentobarbital Calcium (BANM, rINNM) PB. trate have also been used. Calcii Pentobarbitalum; Pentobarbital cálcico; Pentobarbital Cal- The usual oral dose for the treatment of severe anxiety, agitation, cique; Pentobarbitone Calcium. Calcium 5-ethyl-5-(1-methyl- aggression, or impulsive behaviour is 15 to 30 mg daily given in butyl)barbiturate. Perazine Dimalonate 2 divided doses, the larger amount in the evening. In schizophre- Кальций Пентобарбитал nia and severe psychoses initial doses of 75 mg daily may be giv- P-725 (perazine); Pemazine Dimalonate; Perazina, dimalonato en in divided doses, increased if necessary, at weekly intervals by (C11H17N2O3)2Ca = 490.6. de. 10-[3-(4-Methylpiperazin-1-yl)propyl]phenothiazine di- increments of 25 mg, to a maximum of 300 mg daily. malonate. ATC — N05C A01. A recommended initial oral dose in children aged over 1 year is ATC Vet — QN05CA01. C20H25N3S,2C3H4O4 = 547.6. 500 micrograms daily for a child weighing 10 kg; for heavier CAS — 84-97-9 (perazine); 14777-25-4 (perazine di- Pharmacopoeias. In Jpn. children this initial dose may be increased by 1 mg for each ad- malonate). ditional 5 kg, to a maximum total of 10 mg daily. Thereafter the ATC — N05AB10. dose may be gradually increased according to response but the Pentobarbital Sodium (BANM, rINNM) ATC Vet — QN05AB10. daily maintenance dose should not exceed twice the initial dose. Aethaminalum-Natrium; Ethaminal Sodium; Mebumalnatrium; Elderly patients should be given reduced doses: a recommended initial dose is 5 to 10 mg daily for anxiety or disturbed behaviour Natrii Pentobarbitalum; Pentobarbitaalinatrium; Pentobarbital CH sódico; Pentobarbital sodique; Pentobarbital sodná sůl; Pentobar- 3 and 15 to 30 mg daily for schizophrenia or , both in N bitalio natrio druska; Pentobarbitalnatrium; Pentobarbitál-nátri- divided doses. um; Pentobarbitalum natricum; Pentobarbitone Sodium; Sodium N Preparations Pentobarbital; Soluble Pentobarbitone. Sodium 5-ethyl-5-(1- Proprietary Preparations (details are given in Part 3) methylbutyl)barbiturate. N Arg.: Neuleptil; Austral.: Neulactil; Austria: Neuleptil; Braz.: Neuleptil; Натрий Пентобарбитал Canad.: Neuleptil; Chile: Neuleptil; Cz.: Neuleptil†; Denm.: Neulactil; C H N NaO = 248.3. Fin.: Neulactil; Fr.: Neuleptil; Gr.: Neuleptil; Hong Kong: Neulactil; Irl.: 11 17 2 3 Neulactil†; Israel: Neuleptil; Ital.: Neuleptil; Neth.: Neuleptil; NZ: Neu- CAS — 57-33-0. S lactil; Rus.: Neuleptil (Неулептил); S.Afr.: Neulactil†; Spain: Nemactil; UK: Neulactil; Venez.: Neuleptil. ATC — N05C A01. (perazine) ATC Vet — QN05CA01.