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Transcript
HIJ Drug Manufacturing Factory
Ketamine
H
N
Cl
O
6S
Chu Man Hin, Hinson (9)
Chung Siu Wa, Jennifer (10)
Lau Yuk Ping, Isa (14)
used in human and
veterinary medicine
(獸醫用藥)
used as a recreational
drug
Ketamine
induces a state referred to
as “dissociative anesthesia”
(分離性麻醉)
classified as an NMDA
receptor antagonist
Lead Compound Discovery
Ph
N
phencyclidine
(PCP)
A kind of an
anesthetic
(麻醉藥)
cause hallucinations(幻覺),
neurotoxicity(神經毒性)
and seizures(癲癇)
Ketamine for replacement
Laboratory Session
Molecular Modification
PCP
Cyclohexamine
Ketamine
Year
1958
1959
1962
Drug synthesis
Step 1
MgBr
Cl
CN
2-chlorobenzonitrile
Cyclopentylmagnesium
bromide
Drug synthesis
Step 2
Cl
O
1-(2-chlorobenzoyl)
cyclopentane
Br2
Drug synthesis
Step 3
CH3NH2
+ H2O
Cl
O
Br
Drug synthesis
Step 4
Cl
Decalin
(C10H18)
N
OH
Methylimino derivative
Drug synthesis
Ketamine
made!!
H
N
Cl
O
Formulation Development
Methods 1) Injection
of using
Ketamine 2) Liquid Aerosol
3) Nasal administration
Injection
10% ketoprofen
5% Lidocaine
10% ketamine
Injection
cyclobenzaprine
tramadol
clonidine
These are all longer-acting
local anaesthetics(麻醉藥)
Liquid Aerosol Formulation
carriers
diluents
solubilizing or
emulsifying
agents
surfactants
excipients
Liquid Aerosol Formulation
carriers
Examples :
1)Soya lecithin (大豆豆黃素)
2)oleic acid (油酸)
3)sorbitan trioleate (山梨糖醇酐三油酸
酯)
= Preferred
Liquid Aerosol Formulation
diluents
Examples
In
Specific:embodiment:
1)Sterile water
1)phosphate
buffered saline
2)buffered
saline solution generally
2)Saline(鹽水)
3)Buffered
saline
between
the
pH 7.0-8.0 range
3)water
4)Dextrose(葡萄糖)solution
Liquid Aerosol Formulation
They are useful for
1) pH maintenance
2) solution stabilization
3) regulating osmotic pressure
solubilizing or
emulsifying
agents
surfactants
excipients
Liquid Aerosol Formulation
Benzodiazepine
(苯二氮平類藥物)
narcotic
analgesic
(麻醉止痛劑)
Aerosol Dry Powder Formulation
a dispersing agent
ketamine
a bulking agent (eg. lactose, sucrose)
Aerosol Dry Powder Formulation
Dispersing agent
facilitates the
dispersal of the
powder from the
device
May include another
therapeutically
effective drug like
benzodiazepine and
narcotic analgesic
Safety Tests
According to several research and studies:
1) tolerance and/or dependence to the drug
2) 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 Trials
The drug was first given to American soldiers
during the Vietnam War.
A 2-year prospective audit of sedation practice
was undertaken by the Department of
Emergency Medicine.
Test
Types of drugs given
Propofol
18people
9%
Ketamine
85people
Midazolam 40%
107people
51%
Total people
involved : 210
Results
Time/ min
Median time to full orientation(康復)
35
30
25
20
15
10
5
0
Ketamine
Midazolam
Propofol
Results
Percentage/ %
Percentage of people having
complications
(併發症)
25
20
15
10
5
14.6 %
15.8 %
22.2 %
Ketamine
Midazolam
Propofol
0
Results
1) Apnoea(窒息) and hypoxia(缺氧) most often
occurred with midazolam and propofol
2) hypertension(過度緊張) and hypertonicity(張
力過高)were encountered more frequently
with ketamine
3) 19.5% of patients given ketamine suffered
from the reemergence phenomenon.
Conclusion
1) Ketamine is both safe and effective
2) Ketamine compares favourably with
midazolam as an agent for procedural
sedation
3) Ketamine may be particularly useful in groups
of patients at high risk of adverse effects with
midazolam
Market Approval
1) 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)