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LECTURE 2 - Kuliah Local Anestetik 2017
LECTURE 2 - Kuliah Local Anestetik 2017
Outline
• History
• Mechanism of Action
• Clinical aspects
Pharmacology of Local Anesthetics - History
1860 Albert Niemann isolated crystals from the coca shrub – and called it
“cocaine” – he found that it reversibly numbed his tongue!
Sigmund Freud became aware of the mood altering properties
of cocaine, and thought it might be useful in curing morphine
addiction. Freud obtained a supply of cocaine (from Merck) and shared
it with his friend Carl Koller, a junior intern in ophthalmology at the
University of Vienna
1905 German chemist Alfred Einhorn produced the first synthetic ester-
type local anesthetic - novocaine (procaine) - retained the nerve
blocking properties, but lacked the powerful CNS actions of cocaine
1943 Swedish chemist Nils Löfgren synthesized the first amide-type local
anesthetic - marketed under the name of xylocaine (lidocaine)
Local anesthetics
Cocaine Niemann 1860 Ester
Benzocaine Salkowski 1895 Ester
Procaine Einhorn 1904 Ester
Tetracaine Eisler 1928 Ester
Lidocaine Lofgren 1943 Amide
Chloroprocaine Marks, Rubin 1949 Ester
Mepivacaine Ekenstam 1956 Amide
Bupivacaine Ekenstam 1957 Amide
Ropivacaine Sandberg 1989 Amide
Structure-Activity Relationships:
Structure-Activity Relationships:
procaine 1 1 6 60-90
lidocaine 4 2 65 90-200
tetracaine 80 8 80 180-600
Pharmacology of Local Anesthetics – Chemistry
Outline
• History
• Mechanism of Action
• Clinical aspects
Mechanism of Action
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E
ASPEK KLINIS ANESTETIK
LOKAL
TIMBUL ANALGESIA KOMPLIT REVERSIBEL
TERGANTUNG CARA PEMBERIAN
CARA TOPIKAL, INJEKSI,
EPIDURAL/SUBARACHNOID MEDULA
PEMILIHAN OBAT TERGANTUNG LAMA
OPRASI
DAPAT DIKOMBINASI VASOKONSTRIKTOR
BILA MASA KERJA PENDEK
PEMBERIAN BERULANG-ULANG EPIDURAL
TERJADI TACHIPHYLAXIS KARENA
KEMAMPUAN BUFFER CAIRAN
CEREBROSPINALIS MENURUN/HABIS
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E
EFEK TOKSIK ANESTETIK
LOKAL
OBAT YANG DISERAP
CNS: COCAIN EUPORIA. YANG LAIN
MENGANTUK, SAKIT KEPALA,GANGGUAN
PENGLIHATAN,KONVULSI, DEPRESI CNS
BILA KADAR TINGI
EFEK PADA SYARAF TEPI: DEPISIT
NEUROLOGIS BERKEPANJANGAN
KARDIOVASKULER. JANTUNG CELAH Na.
Cocain vasokonstriksi
DARAH PRILOCAINE METABOLIT
TOKSIK PADA HEMOGLOBIN
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E
BEBERAPA OBAT
ANESTETIK
PROCAINE HYDROCHLORIDE:
DIGUNAKAN SEJAK LAMA
TIDAK BAIK TOPIKAL
MULA KERJA LAMBAT DAN SINGKAT
KIRA-KIRA 1 JAM
DIPECAH DALAM PLASMA
DOSIS 500-600MG. Nerve blok dapat
dipakai procaine 2 % 25 ml. Infiltrasi
dipakai 0,25%-0,5%.
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E
Lidocaine hydrochloride( xylocaine )
golongan amide yang paling luas digunakan
dapat juga topikal
dosis 4,5 mg/Kg BB. Dengan adrenalin 7
mg
tidak boleh diulang sebelum 2 jam
BUPIVACAINE
MASA KERJA PANJANG
ETIDOCAINE
EFEK PADA MOTORIK MENONJOL
BAIK UNTUK OPRASI ABDOMEN
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E
Clinical aspects
Applications of local anesthesia:
nerve block: injected locally to produce regional
anesthesia (e.g., dental and other minor surgical procedures)
topical application: to skin for analgesia (e.g., benzocaine)
or mucous membranes (for diagnostic procedures)
spinal anesthesia: injection into CSF to produce anesthesia
for major surgery (e.g., abdomen) or childbirth
local injection: at end of surgery to produce long-lasting
post-surgical analgesia (reduces need for narcotics)
i.v. infusion: for control of cardiac arrhythmias (e.g.,
lidocaine for ventricular arrhythmias)
Clinical aspects
Nerve block by local anesthetics
most common use of local anesthetics (e.g., dental)
order of blockade: pain > temperature > touch and pressure
> motor function - recovery is reverse (i.e., sensation of
pain returns last)
recall: onset of anesthesia determined by pK, duration
increases with lipophilicity of the anesthetic molecule
recall: concommitant use of vasoconstrictor →
prolongation of anesthesia and reduction in toxicity
inflammation → reduced susceptibility to anesthesia
(lowered local pH increases proportion of anesthetic in
charged form that cannot permeate nerve membrane)
Clinical aspects
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E
ANESTETIK UMUM
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E
PENDAHULUAN
MENIMBULKAN ANESTESIA
DENGAN KEADAAN TIDAK
SADAR/TIDUR YANG DALAM.
BEDA DENGAN ANESTETIK LOKAL
MENEKAN CNS.
LEBIH KUAT DARI
TRANSQUILIZER,SEDATIVE
HIPNOTIC.
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E
CARA KERJA ANESTETIK
UMUM
Lipid teori : Obat bekerja tergantung
kelarutan dalam lemak pada sel.
Effects on ion channel: Obat berikatan
dengan protein terutama membran
protein fungsional seperti ion channel.
Beberapa obat anestetik dapat
menghambat reseptor excitatory atau
meningkatkan efek inhibisi
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E
CARA PEMBERIAN
INHALASI
INTRAVENA
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E
ANESTETIK INHALASI
1. Nitrous oksida
2. Siklopropan
3. Halotan
4. Metoksifluran
5. Enfluran
6. Isofluran
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E
ANESTETIK INTRAVENA
1. Pentotal
2. Droperidol
3. Etomidat
4. Ketamin hidroklorida
W A K E F O R E S T U N I V E R S I T Y S C H O O L O F M E D I C I N E