The pdf file includes chemical structures.
Feel free to download! :)
What are General Anesthetics?
•
A
drug that brings about a reversible loss of consciousness.
•
Not
for therapeutic or diagnostic procedures
•
These
drugs are generally administered by an anesthesiologist in order to induce or
maintain general anesthesia to facilitate surgery.
FUNCTIONS OF GENERAL ANESTHETICS:
Analgesia
(pain relief)
Amnesia
Loss
of consciousness
Impairment
of all skeletal muscle (motionlessness)
Weakened
autonomic responses
Reversible
*Not all anesthetics bring about all these.
SHORT HISTORICAL BACKGROUND
Dr. Crawford W. Long -a surgeon and pharmacist
-diethyl ether used as anesthetic
in 1842
Dr. William Morton -diethyl ether publicized as anesthetic
in 1846
CLASSIFICATION OF GENERAL
ANESTHETICS:
•
INHALATIONAL
-liquid
inhalation
-gaseous
inhalation
•
INTRAVENOUS
STRUCTURE-ACTIVITY
RELATIONSHIP
•
Although halogenations of hydrocarbons and ethers
increase anesthetic potency, it also increase the potential for inducing
cardiac arrhythmias in the following order F<Cl<Br.1
•
Ethers that have an asymmetric halogenated carbon tend
to be good anesthetics (such as Enflurane).
Halogenated methyl ethyl ethers (Enflurane and Isoflurane)
are more stable, are more potent, and have better clinical profile than
halogenated diethyl ethers.
• Fluorination decrease flammability and increase stability of adjacent
halogenated carbons.
• Complete halogenations of alkane and ethers or full halogenations of end
methyl groups decrease potency and enhances convulsant activity. Flurorthyl
(CF3CH2OCH2CF3) is a potent convulsant, with a median effective dose (ED50) for
convulsions in mice of 0.00122 atm.
• The presence of double bonds tends to increase chemical reactivity and
toxicity.
LIQUID
INHALATION ANESTHETICS
- Diethyl ether
- Halothane
- Methoxyflurane
- Enflurane
- Isoflurane
- Desflurane
- Sevoflurane
Diethyl ether
•
a volatile liquid
•
first
anesthetic used
•
causes a
slow induction of and slow emergence from narcosis
•
irritating and explosive (flammable)
•
post-op
nausea & vomiting
•
no longer used in modern
anesthesiology
•
IUPAC
name: ethoxyethane or diethyl ether
Halothane
•
an alkyl halide
•
common in
pedia due to lack of airway irritation
•
rapid
induction & emergence
•
non-flammable
•
may cause
liver damage
•
IUPAC
name: 2-bromo-2-chloro-1,1,1-trifluoroethane
Methoxyflurane
•
halogenated ether
•
non-flammable
•
skeletal muscle relaxant
•
no bronchial irritation
•
slow induction and recovery
•
Nephrotoxic due to fluoride ion and oxalate
metabolites
• 70% metabolized due to lesser number of fluorine
•
IUPAC
name: 2,2-dichloro-1,1-difluoroethyl methyl ether
Enflurane
•
halogenated ether
•
retained the ether structure, but substituted
hydrogen by halogen atoms
•
non-flammable
•
less potential liver damage
•
low frequency of adverse CV effects
•
relatively easy induction
•
CI to epileptic patients
•
IUPAC
name: 2-chloro-1,1,2,-trifluoroethyl difluoromethyl ether
Isoflurane
•
structural isomer of enflurane
•
retained the ether structure, but substituted
hydrogen by halogen atoms
•
non-flammable
•
lesser potential liver damage as compared to
enflurane
•
IUPAC
name: 1-chloro-2,2,2-trifluoroethyl difluoromethyl ether
Desflurane
•
modern liquid inhalational anesthetic
•
not metabolized because it is highly-fluorinated
methyl ethyl ether
•
non-flammable
•
it is a greenhouse gas
•
IUPAC
name: 2-(difluoromethoxy)-1,1,1,2-tetrafluoro-ethane
Sevoflurane
•
modern liquid inhalational anesthetic
•
not metabolized because it is highly-fluorinated
methyl ethyl ether
•
non-flammable
•
IUPAC
name: 1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane
GASEOUS
INHALATION ANESTHETICS
- Cyclopropane
- Nitrous oxide
- Ethylene
Cyclopropane
•
obsolete and rarely used
•
highly explosive when mixed with oxygen
•
stored in orange colored cylinders at 75 psi
•
fast onset of action
•
IUPAC
name: cyclopropane
Nitrous oxide
•
“laughing gas”
•
Only anesthetic agent that is inorganic
•
used only for short operations and in dentistry
•
weak anesthetic
•
good analgesic
•
IUPAC
name: nitrous oxide or dinitrogen monoxide
•
unsaturated hydrocarbon
•
obsolete
•
highly explosive and flammable when mixed with
oxygen
•
IUPAC
name: ethylene or ethene
INTRAVENOUS
ANESTHETICS
- Thiamylal
- Thiopental
- Methohexital
- Etomidate
- Propofol
Ketamine
•
Structural relative of medically dicontinued agent phencyclidine
(PCP)
•
for dissociative anesthesia (esp. children)
•
CV stimulation, advantage to elderly and those
in shock
•
bronchodilator
•
post-op hallucinations and delirium
•
popular veterinary anesthetic
•
IUPAC
name: (RS)-2-(2-Chlorophenyl)-2-(methylamino)cyclohexanone
•
most widely used ultra-short acting anesthetic
barbiturate
•
consciousness regained w/in 30mins
•
CV depression
•
used for short operations
•
2 alkyl side chains impart lipophilicity
•
IUPAC
name: (RS)-[5-ethyl-4,6-dioxo-5-(pentan-2-yl)-1,4,5,6-tetrahydropyrimidin-2-yl]sulfanide
•
highly hydrophobic
•
induction in surgical anesthesia
•
ultra-short acting anesthetic barbiturate
•
unconsciousness w/in secs, consciousness
regained w/in 30mins
•
IUPAC
name: 5-allyl-5-(1-methylbutyl)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione
•
N-methyl barbiturate that increases
lipophilicity of
the compound
•
rapid onset of narcosis
•
unsaturated bonds in the side chains
increase rate of
drug degradation
•
IUPAC
name: 5-hex-3-yn-2-yl-1- methyl-5-prop-2-enyl-1, 3-diazinane-2,4,6-trione
Etomidate
•
Short-acting IV anesthetic used for general
anesthesia and sedation
•
Contains a 4-carboxylic acid ester-substituted
imidazole moiety
•
IUPAC
name: ethyl 3-[(1R)-1-phenylethyl]imidazole-4-carboxylate
Propofol
•
Short-acting IV anesthetic used for induction
and maintenance of general anesthesia and sedation
•
unrelated to barbiturates
•
more rapid and clear recovery
•
not an analgesic, so combined w/ opioids
•
“milk of amnesia”
•
IUPAC
name: 2,6-diisopropylphenol
LIST OF DRUGS AVAILABLE IN THE MARKET
INHALATION ANESTHETICS
GENERIC
|
BRAND
|
MANUFACTURER
|
Enflurane
|
Enthrane
|
Abbott
|
Enflurane
|
Endurane
|
Singapore Pharmawealth Lifesciences
|
Enflurane
|
Phil Pharmawealth/Minrad Enflurane
|
Minrad
|
Isoflurane
|
Aerrane
|
Baxter Healthcare
|
Isoflurane
|
Florane
|
Singapore Pharmawealth Lifesciences
|
Isoflurane
|
Forane
|
Abbott
|
Isoflurane
|
Pascual Isoflurane
|
Rhodia
|
Isoflurane
|
Phil Pharmawealth/Minrad Isoflurane
|
Minrad
|
Desflurane
|
Suprane
|
Baxter Healthcare
|
Sevoflurane
|
Sevo
|
Singapore Pharmawealth Lifesciences
|
Sevoflurane
|
Sevorane Pen
|
Abbott
|
*Methoxyflurane
|
Penthrane
|
Abbott
|
*Halothane
|
Fluothane
|
---
|
*Not available in the
Philippines.
INTRAVENOUS ANESTHETICS
|
||
GENERIC
|
BRAND
|
MANUFACTURER
|
Ketamine HCl
|
Ketacor
|
Duopharma (M) Sdn Bhd
|
Ketamine HCl
|
Ketamax
|
Rotexmedica
|
Ketamine HCl
|
Ketazol
|
Korea United Pharma
|
Thiopental Sodium
|
Pentazol
|
Swiss Parenterals
|
Thiopental Sodium
|
Penthal
|
Oboi
|
Thiopental Sodium
|
Pentobrim
|
Rotexmedica
|
Thiopental Sodium
|
Pentothal
|
Hospira
|
Propofol
|
Diprifol
|
Dong Kook Pharm
|
Propofol
|
Diprivan
|
AstraZeneca
|
Propofol
|
Fresofol
|
Fresenius Kabi
|
Propofol
|
Hospira Propofol
|
Hospira
|
Propofol
|
IV-Pro
|
Claris Lifesciences
|
Propofol
|
Lipuro
|
B Braun
|
*Thiamylal Na
|
Surital Sodium
|
---
|
*Etomidate
|
Amidate
|
Hospira
|
*Methohexital Sodium
|
Brevital Sodium
|
JHP Pharmaceuticals
|
*Not available in the Philippines.
REFERENCES
Block,
J., Beale, J. (2004). Wilson and Gisvold’s Textbook of Organic Medicinals and Pharmaceutical Chemistry.11th ed, pp. 485-488. Lippincott Williams
and Wilkins.
Gringauz,
A. (1997). Introduction to Medicinal Chemistry: How Drugs Act and Why. pp.
564-571. Canada: Wiley-Veh.
Nogrady,
T. (1988). Medicinal Chemistry: A Biochemical Approach. 2nd ed, pp. 11-16. New
York: Oxford University Press, Inc.
MIMS Philippines. (2009). CMPMedica Asia Pte Ltd.
No comments:
Post a Comment