ANESTHETIC DRUGS

ARMAYA ARIYOGA
Depart. Of Pharmacology & Theraphy
Faculty of Medicine Padjadjaran University
 ANESTHETIC DRUGS

DRUGS THAT CAUSED ANESTESIA

NO PAIN
SENSATION

1. GENERAL ANESTHETICS
2. LOCAL ANESTHETICS
ANESTHETICS
ESSENTIAL TO SURGICAL PRACTICE
- Analgesic
- Amnesic
- Unconsciouc
- Muscle Relaxation
- Suppresion Reflexes

HISTORY

THEORY
ADJUNCTS TO ANESTHETICS

PREANESTHETICS MEDICATION
- ANTICHOLINERGICS
- ANTIEMETICS
- ANTIHISTAMINES
- BARBITURATES
- BENZODIAZEPINES
- OPIOIDS
MUSCLE RELAXANTS

- ATRACURIUM
- SUCCINYL KHOLINE
- VECURONIUM
GENERAL ANESTHETICS
INHALED
- ENFLURANE
- HALOTHANE
- ISOFLURANE
- METHOXYFLURANE
- N2O
- SEFOFLURANE
INTRAVENOUS
- METHOHEXITAL
- THIAMYLAL BARBITURATES
- THIOPENTAL
- DIAZEPAM
- LOKAZEPAM BENZODIAZEPIN
- MIDAZOLAM
- FENTANYL OPIOIDS
- MORPHINE
- DROPERIPIL + FENTANYL NEUROLEPTIC
- ETOMIDATE
- KETAMINE
- PROPOFOL
LOCAL ANESTHETICS
COCAINE NATURAL

PROCAINE
SINTHETIC
LIDOCAINE
TETRACAINE
BUPIVACAINE
 ANESTESI LOKAL
DEFINISI
AN. LOKAL : OBAT YG MENGHAMBAT HANTARAN
SARAF BILA DIKENAKAN SECARA
LOKAL PADA JARINGAN SARAF
DENGAN KADAR CUKUP

OBAT-OBAT AN. LOKAL :

KOKAIN (E. COCA) ALAM
PROKAIN LIDOKAIN LAIN-LAIN SINTETIK
IDEALLY LOCAL ANASTETIC DRUGS

1. No iritating tissues
2. No damaging nervous tissues permanently
3. Margin of safety Wide
4. Onset of action short and Duration of
action long
5. Soluble in water stable as solute can be
sterilized without change
EFEK SAMPING : TERUTAMA ALERGI
AN. LOKAL - DERMATITIS ALERGIK
- SERANGAN ASMA
- ANAFIKLAKTIK FATAL
KOKAIN ADDIKSI
KELAINAN HATI HATI-HATI AN. LOKAL
PENGGOLONGAN ANESTETIK LOKAL
1. ALAM : KOKAIN
2. SINTETIK :
- PROKAIN
- LIDOKAIN
YANG LAIN :
- A.L SUNTIKAN
- A.L UNTUK MATA
- A.L UNTUK SELP. LENDIR & KULIT
- A.L DAYA LARUT RENDAH
- ALKOHOL AROMATIK
- GARAM KINA
 KOKAIN :
- S/ ESTER AS. BENZOAT
- P. ORAL TIDAK EFEKTIF (DIHIDROLISIS)
- SSP : MERANGSANG DARI ATAS KE BAWAH
MULAI DI KORTEKS
BANYAK BICARA-GELISAH-GEMBIRA
KEKUATAN MENTAL - KAPASITAS
KERJA OTOT ME
DOSIS TREMOR.KEJANG
FREKUENSI RESP
MUNTAH
TERUSAN KOKAIN
- KARDIOVASKULER :
DOSIS KECIL : DJ (PERANGSANG VAGUS)
DOSIS SEDANG : DJ (PERANGSANG SIMPATIK)
DOSIS .I.V : PAYAH JANTUNG +
SISTEMIK : T.D - TAKIKARDIA
- OTOT SKELET : PENGARUH (-) KEKUATAN. KONTR.
- SUHU BADAN : PIROGEN KUAT T
PIREKSIA PADA KERACUNAN
- SISTEM S.SIMPATIK : KOKAIN POTENSIASI
RESPON THD
EP._NOREP_PERANGS.SIMP.
- EFEK LOKAL :
- MATA : - ANESTESI PD 0.25 0.5 %
- KONJUNGTIVASKLERA PUCAT
- MIDRIASIS
- KERUSAKAN KORNEA
Muscle Relaxants
Muscle Relaxants
What are they used for?
Facilitate intubation of the
trachea
Facilitate mechanical

ventilation
Optimized surgical working
conditions
Muscle Relaxants
How skeletal muscle relaxation can be
achieved?
High doses of volatile anesthetics
Regional anesthesia
Administration of neuromuscular
blocking agents
Proper patient positioning on the
operating table
Muscle Relaxants

Muscle relaxants must not be given

without adequate dosage of
analgesic and hypnotic drugs

Inappropriately given : a patient is

paralyzed but not anesthetized
Muscle Relaxants
How do they work?
Neuromuscular junction
Nerve terminal
Motor endplate of a muscle
Synaptic cleft
Nerve stimulation
Release of Acetylcholine (Ach)
Postsynaptic events
Neuromuscular Junction
(NMJ)
Binding of Ach to receptors on muscle end-plate
Muscle Relaxants
Depolarizing muscle relaxant
Succinylcholine
Nondepolarizing muscle relaxants
Short acting
Intermediate acting
Long acting
 Depolarizing Muscle
Relaxant
Succinylcholine
What is the mechanism of action?
Physically resemble Ach
Act as acetylcholine receptor agonist
Not metabolized locally at NMJ
Metabolized by pseudocholinesterase in plasma
Depolarizing action persists > Ach
Continuous end-plate depolarization causes
muscle relaxation
Depolarizing Muscle
Relaxant
Succinylcholine
What is the clinical use of succinylcholine?
Most often used to facilitate
intubation

What is intubating dose of succinylcholine?

1-1.5 mg/kg

Onset 30-60 seconds, duration 5-10

minutes
 Depolarizing Muscle
Relaxant
Succinylcholine
What is phase I neuromuscular blockade?
Phase 1 blocking has the principal paralytic effect. Binding of
suxamethonium to the nicotinic acetylcholine receptor results in
opening of the receptor's monovalent cation channel; a
disorganized depolarization of the motor end-plate occurs and
calcium is released from the sarcoplasmic reticulum.
What is phase II neuromuscular blockade?
Resemble blockade produced by nondepolarizing
muscle relaxant
Succinylcholine infusion or dose > 3-5 mg/kg
Depolarizing Muscle
Relaxant
Succinylcholine
Does it has side effects?
Cardiovascular
Fasciculation
Muscle pain
Increase intraocular pressure
Increase intragastric pressure
Increase intracranial pressure
Hyperkalemia
Malignant hyperthermia
Nondepolarizing Muscle
Relaxants
What is the mechanism of action?
Compete with Ach at the binding sites
Do not depolarized the motor endplate
Act as competitive antagonist
Excessive concentration causing channel
blockade
Act at presynaptic sites, prevent movement
of Ach to release sites
Nondepolarizing Muscle
Relaxants
Long acting
Pancuronium
Intermediate acting
Atracurium
Vecuronium
Rocuronium
Cisatracurium
Short acting
Mivacurium
Nondepolarizing Muscle
Relaxants
Pancuronium
Aminosteroid compound
Onset 3-5 minutes, duration 60-90 minutes
Intubating dose 0.08-0.12 mg/kg
Elimination mainly by kidney (85%),
liver (15%)
Side effects : hypertension, tachycrdia,
dysrhythmia,
Nondepolarizing Muscle
Relaxants
Vecuronium
Analogue of pancuronium
much less vagolytic effect and shorter
duration than pancuronium
Onset 3-5 minutes duration 20-35 minutes
Intubating dose 0.08-0.12 mg/kg
Elimination 40% by kidney, 60% by liver
Nondepolarizing Muscle
Relaxants
Atracurium
Metabolized by
Ester hydrolysis
Hofmann elimination
Onset 3-5 minutes, duration 25-35 minutes
Intubating dose 0.5 mg/kg
Side effects :
histamine release causing hypotension,
tachycardia, bronchospasm
Laudanosine toxicity
Nondepolarizing Muscle
Relaxants
Cisatracurium
Isomer of atracurium
Metabolized by Hofmann elimination
Onset 3-5 minutes, duration 20-35 minutes
Intubating dose 0.1-0.2 mg/kg
Minimal cardiovascular side effects
Much less laudanosine produced
Nondepolarizing Muscle
Relaxants
Rocuronium
Analogue of vecuronium
Rapid onset 1-2 minutes, duration 20-35
minutes
Onset of action similar to that of
succinylcholine
Intubating dose 0.6 mg/kg
Elimination primarily by liver, slightly by
kidney
Alteration of responses
Temperature
Acid-base balance
Electrolyte abnormality
Age
Concurrent diseases
Drug interactions
Alteration of responses
Concurrent diseases
Neurologic diseases
Muscular diseases
Myasthenia gravis
Myasthenic syndrome (Eaton-Lambert
synrome)
Liver diseases
Kidney diseases
Alteration of responses
Drug interactions
Inhalation agents
Intravenous anesthetics
Local anesthetics
Neuromuscular locking drugs
Antibiotics
Anticonvulsants
Magnesium
Monitoring Neuromuscular
Function

What are the purposes of monitoring?

Administer additional relaxant as
indicated
Demonstrate recovery
Monitoring Neuromuscular
Function

How to monitor?
Clinical signs
Use of nerve stimulator
Monitoring Neuromuscular
Function
Clinical signs
Signs of adequate recovery
Sustained head lift for 5 seconds
Lift the leg (child)
Ability to generate negative inspiratory
pressure at least 25 cmH2O, able to swallow
and maintain a patent airway
Other crude tests : tongue protrusion, arm lift,
hand grip strength
Monitoring Neuromuscular
Function
Use of nerve stimulator
Single twitch : single pulse 0.2 msec
Tetanic stimulation
Train-of-four : series of 4 twitch, 0.2 msec
long, 2 Hz frequency, administer every 10-
15 seconds
Double burst stimulation
Post tetanic count
Antagonism of
Neuromuscular Blockade
Effectiveness of anticholinesterases depends on
the degree of recovery present when they are
administered
Anticholinesterases
Neostigmine
Onset 3-5 minutes, elimination halflife 77
minutes
Dose 0.04-0.07 mg/kg

Pyridostigmine
Edrophonium
Antagonism of
Neuromuscular Blockade
What is the mechanism of action?
Inhibiting activity of acetylcholineesterase
More Ach available at NMJ, compete for
sites on nicotinic cholinergic receptors
Action at muscarinic cholinergic receptor
Bradycardia
Hypersecretion
Increased intestinal tone
Antagonism of
Neuromuscular Blockade
Muscarinic side effects are minimized by
anticholinergic agents
Atropine
Dose 0.01-0.02 mg/kg
Scopolamine
glycopyrrolate
Reversal of Neuromuscular
Blockade

Goal : re-establishment of
spontaneous respiration and the
ability to protect airway from
aspiration