ANESTHETICS DRUGS

Depart. of Pharmacology and Therapy Medical School -Padjadjaran University

HISTORY OF ANESTHESIA
Ancient Egypt China 1776 1795

: Narcotics : Canabis indica, traumatic : the first gas anesthetic (N2O) : Ether

TERMINOLOGY
ANESTHETICS : Drugs that caused anesthesia ANESTHESIA : No pain sensation
TWO GROUPS OF ANESTHESIA : 1. General Anesthetics 2. Local Anesthetic

THEORY OF ANESTHESIA
1. No stimuli from perifer 2. Stimuli + Block at Gg. cervicalis sup 3. Stimuli + No block at Gg. Cervicalis sup No interpretation 4. Stimuli + No block interpretation + No response

GENERAL ANESTHESIA
Analgesic, amnesic, unconscious state Muscle relaxation Suppresion of undesirable reflexes

BALANCED ANESTHESIA
PRE ANESTHETIC MEDICATION
SKELETAL MUSCLE RELAXANTS

PRE ANESTHETIC MEDICATION

SERVES TO :

Calm the patient Relieve pain Protect against undesirable effects of the subsequently administered anesthetic or the surgical procedures

INCLUDING : Hipnotic sedatives, anti histamines, anti emetics, opioids, anti cholinergics

STAGES OF ANESTHESIA
STAGE I STAGE II Analgesia Excitement violent combative behavior BP Respiratory rate Reflexes Hyper secretion

STAGES OF ANESTHESIA
STAGE III Surgical anesthesia Regular respiration Skeletal muscles relaxation Eye reflexes Eye movements Fixed pupil Medullary paralysis

STAGE IV

STAGES OF ANESTHESIA

PLANE I EYE

PLANE II

PLANE III

Roving midconstrictio middilatatio movment of n n eye ball. Myotic pupil

PLANE IV dilatation

REFLEXES Small MUSCLE muscles RELAXATION RESPIRATION Thoracal > Abdominal Large muscles Thoracal = Abdominal All muscles Abdominal > Thoracal All muscles

EVALUATION
Rhythm and automatization of respiration Conjunctival reflexes Gradually loss of Mm. Intercostales activity Fixated eye

DEEP ANESTHESIA

GENERAL ANESTHESIA

INHALATIONAL ANESTHETICS

INTRAVENOUS ANESTHETICS

INHALATIONAL ANESTHETICS
MECHANISM OF ACTION

Non selective action Their clinically important effect on the CNS also alter the function of various peripheral cell types Site of action :Reticular activating system and cortex cerebri (controlling the overall state consciousness and response to sensory stimuli)

INHALATIONAL ANESTHETICS
THE POTENCY

Defined quantitatively as the MINIMUM ALVEOLAR CONCENTRATION (MAC) MAC : The concentration of gas anesthetic needed to eliminate movement among 50% of patient challenged by a standardized skin incision MAC is small for potent anesthetics and large for the less one The more lipid soluble an anesthesia, the lower the concentration of anesthetics needed to produce anesthesia

THE PHARMACOKINETICS OF INHALATIONAL ANESTHETICS

Partial pressure of anesthetic gas driving force moves the anesthetics into the alveolar space blood brain and body compartment Steady state : The partial pressure in each of these compartments is equivalent to that in inspired mixtures

THE PHARMACOKINETICS OF INHALATIONAL ANESTHETICS

The steady state depends on : Alveolar wash-in Solubility in blood
Blood-gas

partition coefficient halothane > enflurane > isoflurane > N20 solubility faster achievement of steady state

Tissue uptake Wash-out

COMMON FEATURES OF INHALATIONAL ANESTHETICS

Decrease cerebrovascular resistance resulting in increased perfusion of the brain Bronchodilation and decrease minute ventilation Potency does correlate with their solubility in lipid Recovery is due to redistribution from the brain

HALOTHANE

Weak analgesic effect Vagomimetic, atropine-sensitive bradycardi Cardiac output , hipotension Cardiac arrhytmia, esp. to whom with hipercapnia and high concentration of blood catecholamine Toxic metabolites (trifluoroethanol + bromide ion) No hepatotoxic effect for children DOC for pediatric patient

ENFLURANE

Less potent than halothane Rapid induction and recovery The metabolite (fluoride ion) excreted by kidney, so its contra indicated in patient with renal failure Some differences from halothane: Fewer arrhytmia less heart sensitization to catecholamines greater potentiation of muscle relaxants Intra ocular pressure Disadvantage : CNS excitation

ISOFLURANE
Low biotransformation and low organ toxicity Doesnt induce cardiac arrhytmia No heart sensitization to catecholamine Less fluoride ion is produced

METHOXYFLURANE
High solubility in lipid Not for prolonged adminiostration (toxic effect to the kidney) Indication : obstetrical practice (does not relax the uterus)

NITROUS OXIDE
Potent analgesic, weak general anesthetic No respiration depression Less effect on CVS Increasing cerebral blood flow Less hepatotoxic effect

INTRAVENOUS ANESTHETIC
BARBITURATES
Quickly enter the CNS depress function diffusion out of the brain redistribution to other body tissue Not significant analgesic ADR : apnea, coughing, chest wall spasm, laryngospasm, bronchospasm

BENZODIAZEPINES
Lorazepam and Midazolam are more potent than diazepam Facilitate amnesia while causing sedation Etomidate : No analgesic effect uncontrolled skeletal muscle activity

OPIOIDS
Analgesic effect Amnesic effect < BP decreased, respioratory depression, muscle rigidity, post anestetic nausea and vomiting. Fentanyl, morphine Antagonis: Naloxone

NEUROLEPTANESTHESIA
Neuroleptic : adrenergik blocking as well as sedative, antiemetic and anticonvulsant properties Contraindicated in Parkinsons patient INNOVAR : Fentanyl + droperidol

LOCAL ANESTHETICS
IDEAL LOCAL ANESTHETIC: No tissue irritation No permanently nerve fiber damage Wide margin of safety Long duration of action Water soluble Stable Sterilable without agent changing

MECHANISM OF ACTION
Inhibition of impuls production and conduction DOA depends on:

contact

period with nerve fiber the act that localized drug

Site of action : cell membrane Small fibers and unmyelinated are more sensitive to the stimuli

Loss of sensation: pain cold hot tactile deep pressure Anesthesia due to nerve fiber pressure : tactile hot cold pain The conduction of local anesthetic could be inhibite by changing the pH to 7 or 9,5 (most of local anestheticin the form of cation )

EFFECT OF VASOCONSTRICTOR
Early OOA and longer DOA Epinefrin (1 : 200,000) and Nor epinefrin (1: 100,000) ADR : takikardi, palpitation, chest pain, delayed wound healing, udem or necrosis

CLASSIFICATION
AMIDE

LINKAGE : LIDOCAINE DIBUCAINE MEPIVACAINE PRILOCAINE

ESTER LINKAGE : PROCAINE COCAINE TETRACAINE BENZOCAINE

COCAINE

Source : Erythroxylon coca Very strong stimulation on cortex cerebri and medullary Bradicardia (low dose), tachycardia (high dose). Systemic administration will cause hipotension after hypertension strong pyrogenous effect Pharmacokinetics: absorpsi: from almost tissue detoxication : liver

SYNTHETIC LOCAL ANESTHETIC

PROCAINE

PHARMACODYNAMIC
Systemic

analgesia Procaine-sulfonamide antagonism PHARMACOKINETIC: fast absorption from site of injection

LIDOCAINE
Strong

local anesthetic Widely use as topical and injection agents faster, stronger, longer, and more extensive effect than procaine indication: anesthetic antiarrhytmia