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Nadide/Nicaraven 2351
apy or when patients are unable to discontinue chronic concomitant corticosteroid use within 6 months of starting natalizumab.
Natalizumab has also been investigated for the treatment of ulcerative colitis.
Profile
Neroli oil is used as a flavour and in perfumery. It is also used in
aromatherapy. Photosensitivity reactions have been reported.
Preparations
◊ References.
Proprietary Preparations (details are given in Part 3)
1. Sweet BV. Natalizumab update. Am J Health-Syst Pharm 2007;
64: 705–16.
Multi-ingredient: Chile: Agua Melisa Carminativa; Cz.: Stopangin; Ital.:
Controller; Rus.: Stopangin (Стопангин); Switz.: Hygiodermil; Kemeol;
Oculosan.
Inflammatory bowel disease. The efficacy and safety of natalizumab in the treatment of Crohn’s disease have been reviewed, including proposed mechanisms for the role of α4 integrins in the immunopathogenesis of inflammatory bowel
disease (p.1697).1,2 A systematic review3 of controlled studies of
the use of natalizumab in the treatment of Crohn’s disease concluded that it is effective for induction of clinical response and
remission in some patients with moderately to severely active
Crohn’s disease, particularly those with active inflammation or
chronically active disease despite use of conventional treatment.
However, this benefit must be weighed against the risks of developing progressive multifocal leukoencephalopathy.
9. Anonymous. Prevention and treatment of injury from chemical
warfare agents. Med Lett Drugs Ther 2002; 44: 1–3.
10. Janowsky DS. Central anticholinergics to treat nerve-agent poisoning. Lancet 2002; 359: 265–6.
11. Anonymous. Nerve agents. J R Army Med Corps 2002; 148:
344–57.
12. Lee EC. Clinical manifestations of sarin nerve gas exposure.
JAMA 2003; 290: 659–62.
13. Rotenberg JS, Newmark J. Nerve agent attacks on children: diagnosis and management. Pediatrics 2003; 112: 648–58.
14. Newmark J. The birth of nerve agent warfare: lessons from Syed
Abbas Foroutan. Neurology 2004; 62: 1590–6.
Nerve Agents
Gases nerviosos.
Neutral Red
Sarin
CI Basic Red 5; Colour Index No. 50040; Neutral Red Chloride;
Nuclear Fast Red; Rojo neutro; Toluylene Red. 3-Amino-7dimethylamino-2-methylphenazine hydrochloride.
C 15 H 16 N 4 ,HCl = 288.8.
C AS — 553-24-2.
GB; Sarín. Isopropyl methylphosphonofluoridate.
C 4 H 10 FO 2 P = 140.1.
C AS — 107-44-8.
Natalizumab is also under investigation for ulcerative colitis.4
1. Keeley KA, et al. Natalizumab for the treatment of multiple sclerosis and Crohn’s disease. Ann Pharmacother 2005; 39:
1833–43.
2. Lanzarotto F, et al. Novel treatment options for inflammatory
bowel disease: targeting α 4 integrin. Drugs 2006; 66: 1179–89.
3. MacDonald JK, McDonald JWD. Natalizumab for induction of
remission in Crohn’s disease. Available in The Cochrane Database of Systematic Reviews; Issue 1. Chichester: John Wiley;
2007 (accessed 11/02/08).
4. Feagan BG, et al. Treatment of ulcerative colitis with a humanized antibody to the α4β7 integrin. N Engl J Med 2005; 352:
2499–2507.
Multiple sclerosis. The efficacy and safety of natalizumab in
the treatment of multiple sclerosis (p.892) have been reviewed,
including proposed mechanisms for the role of α4 integrins in its
immunopathogenesis.1-3 Randomised controlled studies4-7
showed beneficial results in suppressing inflammatory lesions
and reducing the frequency of relapse. Subsequent review8 of the
data from the AFFIRM trial5 and the SENTINEL study6 demonstrated reduction of visual loss. In the SENTINEL study,6 natalizumab was given with interferon beta, a combination that may
have contributed to the development of progressive multifocal
leukoencephalopathy in 2 of the study patients, one of whom
died (see Infections, above). As a consequence, natalizumab is
currently licensed only as monotherapy.
1. Keeley KA, et al. Natalizumab for the treatment of multiple sclerosis and Crohn’s disease. Ann Pharmacother 2005; 39:
1833–43.
2. Rice GPA, et al. Anti-α4 integrin therapy for multiple sclerosis:
mechanisms and rationale. Neurology 2005; 64: 1336–42.
3. Ransohoff RM. Natalizumab for multiple sclerosis. N Engl J
Med 2007; 356: 2622–9.
4. Miller DH, et al. A controlled trial of natalizumab for relapsing
multiple sclerosis. N Engl J Med 2003; 348: 15–23.
5. Polman CH, et al. AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006; 354: 899–910.
6. Rudick RA, et al. SENTINEL investigators. Natalizumab plus
interferon beta-1a for relapsing multiple sclerosis. N Engl J Med
2006; 354: 911–23.
7. Miller DH, et al. AFFIRM Investigators. MRI outcomes in a placebo-controlled trial of natalizumab in relapsing MS. Neurology
2007; 68: 1390–1401.
8. Balcer LJ, et al. AFFIRM and SENTINEL investigators. Natalizumab reduces visual loss in patients with relapsing multiple
sclerosis. Neurology 2007; 68: 1299–1304.
Preparations
Proprietary Preparations (details are given in Part 3)
Austral.: Tysabri; Cz.: Tysabri; Gr.: Tysabri; Port.: Tysabri; UK: Tysabri;
USA: Tysabri.
Neroli Oil
Aurantii amari floris aetheroleum; Aurantii Amari Floris Aetheroleum (bitter-orange flower oil); Aurantii Amari Floris Etheroleum;
Azahar, aceite esencial de; Bitter-Orange Flower Oil; Esencia de
Azahar; Essência de Flor de Laranjeira; Karčiavaisiu˛ citrinmedžiu˛ žiedu˛ eterinis aliejus (bitter-orange flower oil); Keseru˝ narancs virág olaj (bitter-orange flower oil); Neroli aetheroleum; Néroli, huile essentielle de; Neroliolja; Neroliöljy; Olejek z
kwiatu pomarańczy gorzkiej; Oleum Neroli; Orange Flower Oil;
Orange-flower Oil; Silice květů hořkého pomeranče.
Pharmacopoeias. In Eur. (see p.vii).
Ph. Eur. 6.2 (Neroli Oil). A clear, pale yellow or dark yellow liquid with a characteristic odour obtained by steam distillation
from the fresh flowers of Citrus aurantium subsp. aurantium (C.
aurantium subsp. amara). Relative density 0.863 to 0.880. Store
in well-filled airtight containers at a temperature below 25°. Protect from light.
CH3 O
H3C
O
F
P
H3C
CH3
N
N
CH2
N
NH2
HCl
CH3
Soman
GD; Somán. Pinacolyl methylphosphonofluoridate.
C 7 H 16 FO 2 P = 182.2.
C AS — 96-64-0.
H3C
CH3
Neutral red is used as an indicator for alkalinity and for preparing
neutral-red paper. It is also used as a stain in microscopy.
It is a photoactive dye that has been tried in photodynamic therapy of recurrent herpes simplex infections, but with limited success.
CH3
O
H 3C
Profile
P
CH3 F
O
Niaouli Oil
Essence de Niaouli; Gomenol.
Pharmacopoeias. In It.
Tabun
GA; Tabún. Ethyl N-dimethylphosphoramidocyanidate.
C 5 H 11 N 2 O 2 P = 162.1.
C AS — 77-81-6.
VX
Methylphosphonothioic
acid
no]ethyl} O-ethyl ester.
C 11 H 26 NO 2 PS = 267.4.
C AS — 50782-69-9.
S-{2-[bis(1-methylethyl)ami-
H 3C
O
P
O
Niaouli oil is a volatile oil, obtained by distillation from the fresh
leaves of Melaleuca viridiflora or Melaleuca quinquenervia
(Myrtaceae). It contains cineole and has similar actions to eucalyptus oil (p.2301). It is an ingredient of many preparations. Typical indications include respiratory tract congestion. Cajuput oil
(p.2271) and melaleuca oil (p.2338) are also prepared from
Melaleuca spp.
Preparations
Proprietary Preparations (details are given in Part 3)
Fr.: Gomenol; Gomenoleo; Huile Gomenolee.
H3C
H 3C
Profile
CH3
N
S
CH3
H3C
Multi-ingredient: Arg.: Aseptobron; Aseptobron Ampicilina†; Di-Neumobron; Medex Rub; No-Tos Adultos; Otorinazol†; Refenax Caramelos
Expectorantes; Braz.: Algice; Baldin-CE†; Canfomenol†; Gripanil†; Griponia†; Gripsay; Killgrip†; Mentalol†; Ozonyl; Ozonyl Aquoso; Ozonyl Expectorante; Tetrapulmo; Canad.: Balminil Suppositories; Fr.: Balsolene; Biogaze†; Dinacode†; Hexaquine; Terpone; Vaseline Gomenolee; Ger.:
Palatol†; Ital.: Paidorinovit; Rinantipiol†; Rinobalsamiche†; Rinofomentil†;
Rinopaidolo; Rinovit; Pol.: Argol Grip; Port.: Rectopulmo Adultos†; Rectopulmo Infantil†; Spain: Broncovital†; Brota Rectal Balsamico; Pastillas Pectoral Kely; Rinobanedif; Vapores Pyt; Vitavox Pastillas†; Switz.: Liberol
Bain†; Pulmex; Resorbane; Turk.: Buguseptil; Rinolar.
Profile
The nerve agents, sarin, soman, tabun, and VX (also referred to
as ‘nerve gases’) used in chemical warfare are extremely potent
inhibitors of cholinesterase. The effects of poisoning due to these
agents, and their treatment, are similar to those for organophosphorus insecticides (p.2047) but as the nerve agents have a much
greater intrinsic toxicity the symptoms of poisoning are more severe. Pyridostigmine has been given prophylactically to personnel at risk from exposure to nerve agents (see p.634).
Nicaraven (rINN)
Nicaravén; Nicaravenum. (±)-N,N′-Propylenebis[nicotinamide].
Никаравен
C 15 H 16 N 4 O 2 = 284.3.
C AS — 79455-30-4.
◊ References.
1. Ministry of Defence. Medical manual of defence against chemical agents. London: HMSO, 1987. (JSP312)
2. World MJ. Toxic gas trauma. Lancet 1995; 346: 260–1.
3. Nozaki H, et al. A case of VX poisoning and the difference from
sarin. Lancet 1995; 346: 698–9.
4. Okumura T, et al. Report on 640 victims of the Tokyo subway
sarin attack. Ann Emerg Med 1996; 28: 129–35.
5. Suzuki J, et al. Eighteen cases exposed to sarin in Matsumoto,
Japan. Intern Med 1997; 36: 466–70.
6. Holstege CP, et al. Chemical warfare: nerve agent poisoning.
Crit Care Clin 1997; 13: 923–42.
7. United States Army. Medical Management of Chemical Casualties
Handbook, 3rd ed. Aberdeen, Maryland: Medical Research Instit ute of Chem i cal De fense; 1999. Also available at:
http://www.brooksidepress.org/Products/OperationalMedicine/
DATA/operationalmed/Manuals/RedHandbook/001TitlePage.htm
(accessed 24/07/08)
8. Weinbroum AA, et al. Anaesthesia and critical care considerations in nerve agent warfare trauma casualties. Resuscitation
2000; 47: 113–23.
The symbol † denotes a preparation no longer actively marketed
N
N
H
N
O
N
H
O
CH3
Profile
Nicaraven is under investigation as a cerebral vasodilator.
◊ References.
1. Jain KK. Nicaraven for the treatment of cerebral vasospasm in
subarachnoid haemorrhage. Expert Opin Invest Drugs 2000; 9:
859–70.
The symbol ⊗ denotes a substance whose use may be restricted in certain sports (see p.vii)
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