HIJ Drug Manufacturing FactoryKetamine 6S Chu Man Hin, Hinson (9) Chung Siu Wa, Jennifer (10) Lau Yuk Ping, Isa (14)

Lead Compound Discoveryphencyclidine (PCP)causehallucinations(), neurotoxicity() and seizures()Ketamine for replacementA kind of an anesthetic()

Laboratory Session

Molecular ModificationYear195819591962PCPCyclohexamineKetamine

Drug synthesisStep 12-chlorobenzonitrileCyclopentylmagnesium bromide

Drug synthesisStep 2Br21-(2-chlorobenzoyl) cyclopentane

Drug synthesisStep 3CH3NH2 + H2O

Drug synthesisStep 4Decalin(C10H18)Methylimino derivative

Drug synthesisKetamine made!!

Formulation Development

Injection10% ketoprofen5% Lidocaine10% ketamine

InjectioncyclobenzaprinetramadolclonidineThese are all longer-acting local anaesthetics()

Liquid Aerosol Formulationcarriersdiluentssolubilizing or emulsifying agentssurfactantsexcipients

Liquid Aerosol FormulationcarriersExamples :Soya lecithin ()oleic acid ()sorbitan trioleate ( )= Preferred

Liquid Aerosol FormulationdiluentsExamples :Sterile waterSaline()Buffered salineDextrose()solutionIn Specific embodiment:phosphate buffered salinebuffered saline solution generally between the pH 7.0-8.0 rangewater

Liquid Aerosol Formulationsolubilizing or emulsifying agentssurfactantsexcipientsThey are useful for1) pH maintenance2) solution stabilization3) regulating osmotic pressure

Liquid Aerosol Formulation Benzodiazepine() narcotic analgesic()

Aerosol Dry Powder Formulationketaminea bulking agent (eg. lactose, sucrose) a dispersing agent

Aerosol Dry Powder FormulationDispersing agent facilitates the dispersal of the powder from the device May include another therapeutically effective drug like benzodiazepine and narcotic analgesic

Safety TestsAccording to several research and studies:1) tolerance and/or dependence to the drug2) great deal in common with other drugs linked with dependence including stimulants, opiates, alcohol, and cannabis 3) indulges in excessive amounts over a short period of time

Human TrialsThedrugwasfirstgivento American soldiers during the Vietnam War.

A 2-year prospective audit of sedation practice was undertaken by the Department of Emergency Medicine.

TestTotal people involved : 210

Chart1

85

107

18

Types of drugs given

1

Ketamine85

Midazolam107

Propofol18

ResultsTime/ min

Chart1

25

30

10

Median time to full orientation

Median time to full orientation()

1

Median time to full orientation

Ketamine25

Midazolam30

Propofol10

44.5

ResultsPercentage/ %14.6 %22.2 %

Chart1

14.6

15.8

22.2

15.8 %

Percentage of people having complications()

Percentage of people having complications()

1

Percentage of people having complications() 2 3

Ketamine14.62.42

Midazolam15.84.42

Propofol22.21.83

44.52.85

ResultsApnoea() and hypoxia() most often occurred with midazolam and propofolhypertension() and hypertonicity()were encountered more frequently with ketamine19.5% of patients given ketamine suffered from the reemergence phenomenon.

Conclusion1) Ketamine is both safe and effective2) Ketamine compares favourably with midazolam as an agent for procedural sedation3) Ketamine may be particularly useful in groups of patients at high risk of adverse effects with midazolam

Market Approval1) In 1970, the FDA approved ketamine for human use 2) It was (and still is) legally sold as (i) Ketalar (Parke-Davis, for humans) (ii) Ketaset (For Dodge, for animals), (iii) other brands (like Ketamine Hydrochloride)

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