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ANALGESIA = a state of decreased
awareness of pain, sometimes with

characterized by unconsciousness,
analgesia, amnesia, skeletal muscle
relaxation and loss of reflexes.


 General anesthesia is a reversible state of
central nervous system (CNS) depression,
causing loss of response to and
perception of stimuli.

 In addition. amnesia. and skeletal muscle relaxation. GENERAL ANESTHESIA  The neurophysiologic state produced by general anesthetics is characterized by five primary effects: unconsciousness. smooth loss of consciousness. and possess a wide margin of safety .  None of the currently available anesthetic agents when used alone can achieve all five of these desired effects well. analgesia. an ideal anesthetic drug should induce rapid. be rapidly reversible upon discontinuation. inhibition of autonomic reflexes.

 Potent general anesthetics are delivered via inhalation and/or intravenous (IV) injection. . relieve pain. Balanced Anesthesia  Preanestheticshelp calm patients.  Neuromuscular blockers facilitate tracheal intubation and surgery. and prevent side effects of subsequently administered anesthetics or the procedure itself.

and recovery. maintenance.  Maintenance provides sustained anesthesia  Recovery is the time from discontinuation of anesthetic until consciousness and protective reflexes return.  Induction is the time from administration of a potent anesthetic to development of effective anesthesia. . STAGES AND DEPTH OF ANESTHESIA  General anesthesia has three stages: induction.

. Induction of anesthesia depends on how fast effective concentrations of anesthetic reach the brain  Recovery is essentially the reverse of induction and depends on how fast the anesthetic diffuses from the brain.  Depth of anesthesia is the degree to which the CNS is depressed.

A. or succinylcholine to facilitate tracheal intubation and muscle relaxation. . such as sevoflurane. are inhaled to induce general anesthesia.]  For children without IV access. Induction  General anesthesia in adults is normally induced with an IV agent like propofol. vecuronium.  Additional inhalation and/or IV drugs may be given to produce the desired depth of anesthesia. producing unconsciousness in 30 to 40 seconds. nonpungent agents. [Note: This often includes an IV neuromuscular blocker such as rocuronium.

 IV infusions of various drugs may be used during the maintenance phase.  Opioids such as fentanyl are used for analgesia along with inhalation agents. B. . which offer good control over the depth of anesthesia. because the latter are not good analgesics. MAINTENANCE OF ANESTHESIA  After administering the anesthetic. vital signs and response to stimuli are monitored continuously to balance the amount of drug inhaled and/or infused with the depth of anesthesia.  Maintenance is commonly provided with volatile anesthetics.

and the patient is monitored for return of consciousness.  For most anesthetic agents.  Redistribution from the site of action (rather than metabolism of the drug) underlies recovery .C. RECOVERY  Postoperatively. recovery is the reverse of induction. the anesthetic admixture is withdrawn.

C. acceptable blood pressure and heart rate. Recovery  Thepatient is monitored to assure full recovery. with normal physiologic functions (spontaneous respiration. . intact reflexes. and no delayed reactions such as respiratory depression).

DEPTH OF ANESTHESIA  Thedepth of anesthesia has four sequential stages characterized by increasing CNS depression as the anesthetic accumulates in the brain .D.

. STAGE I.  The patient progresses from conscious and conversational to drowsy.ANALGESIA  Loss of pain sensation results from interference with sensory transmission in the spinothalamic tract.  Amnesia and reduced awareness of pain occur as stage II is approached.

as well as a risk of laryngospasm. STAGE II. .EXCITEMENT  The patient displays delirium and possibly combative behavior.  A rise and irregularity in blood pressure and respiration occur.

 Regular respiration and relaxation of skeletal muscles with eventual loss of spontaneous movement occurs  This is the ideal stage for surgery. . STAGE III.SURGICAL ANESTHESIA  There is gradual loss of muscle tone and reflexes as the CNS is further depressed.  Careful monitoring is needed to prevent undesired progression to stage IV.

 Ventilation and/or circulation must be supported to prevent death. .MEDULLARY PARALYSIS  Severe depression of the respiratory and vasomotor centers occurs.STAGE IV.

17 .


Remifentanil ) f. Droperidol ) 19 . Fentanyl. Alfentanil.e. Sufentanil. Dexmedetomidine. OPIOID ANALGESICS ( Morphine. MISCELLANEOUS SEDATIVE-HYPNOTICS ( Etomidate.

Sevoflurane ) . Methoxyflurane. INHALATION ANESTHETICS .VOLATILE LIQUIDS ( Halothane.GAS ( Nitrous oxide ) 20 . Isoflurane. Enflurane. Desflurane.

Check table 25 – 1 Pharmacokinetic characteristics of inhalation anesthetics  table 25 – 2 Pharmacokinetic characteristics of inhalation anesthetics 21 .


. INHALATION ANESTHETICS  Inhaled gases are used primarily for maintenance of anesthesia after administration of an IV agent  Depth of anesthesia can be rapidly altered by changing the inhaled concentration. so the difference in concentrations causing surgical anesthesia and severe cardiac and respiratory depression is small.  Inhalational agents have very steep dose–response curves and very narrow therapeutic indices.

INHALATION ANESTHETICS  No antagonists exist. . potent inhaled agents are delivered in a recirculation system containing absorbents that remove carbon dioxide and allow rebreathing of the agent.  To minimize waste.

 These agents decrease cerebrovascular resistance. . including nitrous oxide and volatile. halogenated hydrocarbons. Common features of inhalation anesthetics  Modern inhalation anesthetics are nonflammable. nonexplosive agents. A. resulting in increased brain perfusion.

Potency  Potency is defined quantitatively as the minimum alveolar concentration (MAC) the end-tidal concentration of inhaled anesthetic needed to eliminate movement in 50% of patients stimulated by a standardized incision  MAC is the median effective dose (ED50) of the anesthetic. expressed as the percentage of gas in a mixture required to achieve that effect. . B.

MAC  Numerically. thus. . the higher the potency. the lower the concentration needed to produce anesthesia and. MAC is small for potent anesthetics such as sevoflurane and large for less potent agents such as nitrous oxide.  The more lipid soluble an anesthetic.


C. Uptake and distribution of
inhalation anesthetics

 The principal objective of inhalation anesthesia
is a constant and optimal brain partial pressure
(Pbr) of inhaled anesthetic (partial pressure
equilibrium between alveoli [Palv] and brain

 The partial pressure of an
anesthetic gas at the origin
of the respiratory pathway
is the driving force moving
the anesthetic into the
alveolar space and,
hence, into the blood (Pa),
which delivers the drug to
the brain and other body

general anesthetics increase the sensitivity of the γ-aminobutyric acid (GABAA) receptors to the inhibitory neurotransmitter GABA.  This increases chloride ion influx and hyperpolarization of neurons  Postsynaptic neuronal excitability and. CNS activity are diminished . Mechanism of Action  It appears that a variety of molecular mechanisms may contribute to the activity of general anesthetics. thus. At clinically effective concentrations. D.

 Unlike other anesthetics, nitrous oxide and ketamine do
not have actions on GABAA receptors.

 Their effects are likely mediated via inhibition of the N-
methyl-d-aspartate (NMDA) receptors.

 Other receptors are also affected by volatile
anesthetics. For example, the activity of the
inhibitory glycine receptors in the spinal motor
neurons is increased.

 In addition, inhalation anesthetics block excitatory
postsynaptic currents of nicotinic receptors.

1. Halothane

 Halothane is the prototype to which newer inhalation
anesthetics are compared.
 When halothane [HAL-oh-thane] was introduced, its rapid
induction and quick recovery made it an anesthetic of
 Due to adverse effects and the availability of other
anesthetics with fewer complications, halothane has been
replaced in most countries.

 Thus. it is usually coadministered with nitrous oxide.  It is a potent bronchodilator. Therapeutic Uses:  Halothane is a potent anesthetic but a relatively weak analgesic. . or local anesthetics. opioids.

it is suitable in pediatrics for inhalation induction. .  Halothane is not hepatotoxic in children (unlike its potential effect on adults).  Combined with its pleasant odor. although sevoflurane is now the agent of choice. Therapeutic uses  Halothane relaxes both skeletal and uterine muscles and can be used in obstetrics when uterine relaxation is indicated.

Pharmacokinetics  Halothane is oxidatively metabolized in the body to tissue-toxic hydrocarbons (for example.  This begins as a fever. nausea.  These substances may be responsible for toxic reactions that some adults (especially females) develop after halothane anesthesia. . and vomiting. followed by anorexia. trifluoroethanol) and bromide ion. and possibly signs of hepatitis.

but at a much lower incidence than with halothane. To avoid this condition. halothane is not administered at intervals of less than 2 to 3 weeks.  All halogenated inhalation anesthetics have been associated with hepatitis. .

Adverse effects A. halothane has the undesirable property of causing cardiac arrhythmias. . Cardiac effects:  Halogenated hydrocarbons causes bradycardia  In addition.  Halogenated anesthetics produce concentration- dependent hypotension.

B. Malignant hyperthermia  exposureto halogenated hydrocarbon anesthetics or the neuromuscular blocker succinylcholine may induce malignant hyperthermia (MH) .

 MH causes a drastic and uncontrolled increase in skeletal muscle oxidative metabolism. and regulate temperature. overwhelming the body’s capacity to supply oxygen. Malignant Hyperthermia  a rare life-threatening condition. remove carbon dioxide. eventually leading to circulatory collapse and death if not treated immediately .

circulatory. the patient must be monitored and supported for respiratory. . reducing heat production and relaxing muscle tone.  In addition. and measures are taken to rapidly cool the patient  Dantrolene blocks release of Ca2+ from the sarcoplasmic reticulum of muscle cells. and renal problems. dantrolene is given as the anesthetic mixture is withdrawn. Malignant Hyperthermia  Should a patient exhibit symptoms of MH.

it produces dose- dependent hypotension. not toxic to the liver or kidney.  However. therefore. . Isoflurane  This agent undergoes little metabolism and is. 2.  Isoflurane does not induce cardiac arrhythmias or sensitize the heart to catecholamines. like other halogenated gases.

 It has a pungent odor and stimulates respiratory reflexes (for example. .  With higher blood solubility than desflurane and sevoflurane. coughing. breath holding. isoflurane is typically used only when cost is a factor. salivation. laryngospasm) and is therefore not used for inhalation induction.

it has a low volatility. it decreases vascular resistance and perfuses all major tissues very well.  This makes it a popular anesthetic for outpatient procedures.  Like isoflurane. . requiring administration via a special heated vaporizer. Desflurane  Desflurane [DES-floor-ane] provides very rapid onset and recovery due to low blood solubility.  However. 3.

 It has a rapid onset and recovery due to low blood solubility. Sevoflurane  Sevoflurane has low pungency. and compounds formed in the anesthesia circuit may be nephrotoxic if fresh gas flow is too low. .  Sevoflurane is metabolized by the liver. allowing rapid induction without irritating the airways  This makes it suitable for inhalation induction in pediatric patients. 4.

5.  It is frequently used at concentrations of 30 to 50% in combination with oxygen for analgesia. but it is commonly combined with other more potent agents.  Nitrous oxide alone cannot produce surgical anesthesia. particularly in dentistry. Nitrous Oxide  Nitrous oxide is a nonirritating potent analgesic but a weak general anesthetic. .

it has moderate to no effect on the cardiovascular system or on increasing cerebral blood flow.  When coadministered with other anesthetics. Nitrous oxide does not depress respiration and does not produce muscle relaxation. . and it is the least hepatotoxic of the inhalation agents.


INTRAVENOUS ANESTHETICS  IV anesthetics cause rapid induction  Anesthesia may then be maintained with an inhalation agent. .

. IV anesthetics may be used as sole agents for short procedures or administered as infusions to help maintain anesthesia during longer cases  In lower doses. they may be used for sedation.

 After entering the blood.”  The drug is carried by venous blood to the right side of the heart. through the pulmonary circulation. and via the left heart into the systemic circulation. and the rest remains unbound or “free. . a percentage of drug binds to plasma proteins.

liver. The majority of CO flows to the brain. and kidney (“vessel-rich organs”).  Thus. . a high proportion of initial drug bolus is delivered to the cerebral circulation and then passes along a concentration gradient from blood into the brain.

and the degree of ionization.  Once the drug has penetrated the CNS. the exact mode of action of IV anesthetics is unknown. nonionized molecules cross into the brain most quickly. .  Like inhalation anesthetics. The rate of this transfer is dependent on the arterial concentration of the unbound free drug. it exerts its effects. the lipid solubility of the drug. lipid-soluble.  Unbound.

 Recovery from IV anesthetics is due to redistribution from sites in the CNS  Following initial flooding of the CNS and other vessel-rich tissues with nonionized molecules. plasma concentration of the drug falls . the drug diffuses into other tissues with less blood supply. predominantly by skeletal muscle.  With secondary tissue uptake.

 This initial redistribution of drug into other tissues leads to the rapid recovery seen after a single IV dose of induction agent. This allows the drug. to diffuse out of the CNS. down the resulting reverse concentration gradient. .

 A greater proportion of the IV anesthetic enters the cerebral Circulation under these circumstances. .  Therefore. Effect of reduced cardiac output on IV anesthetics  When CO is reduced (for example. the body compensates by diverting more CO to the cerebral circulation. the dose of the drug must be reduced. in shock. the elderly. cardiac disease).

1. Propofol  Propofol is an IV sedative/hypnotic used for induction and/or maintenance of anesthesia.  It is widely used and has replaced thiopental as the first choice for induction of general anesthesia and sedation. .

 Because propofol is poorly water soluble. . giving it a milk-like appearance. it is supplied as an emulsion containing soybean oil and egg phospholipid.

Following an IV bolus.ONSET Induction is smooth and occurs 30 to 40 seconds after administration. there is rapid equilibration between the plasma and the highly perfused tissue of the brain. .

. followed by a more prolonged period of hepatic metabolism and renal clearance. Plasma levels decline rapidly as a result of redistribution.

Actions  Although propofol depresses the CNS. spontaneous movement. and hiccups. yawning.  Transient pain at the injection site is common  Propofol decreases blood pressure without depressing the myocardium.  It also reduces intracranial pressure. it is occasionally accompanied by excitatory phenomena. such as muscle twitching. . mainly due to systemic vasodilation.

 Propofol is commonly infused in lower doses to provide sedation.  The incidence of postoperative nausea and vomiting is very low. . It does not provide analgesia. so supplementation with narcotics is required. as this agent has some antiemetic effects.

 It is a potent anesthetic but a weak analgesic. 2. Barbiturates  Thiopental is an ultra–short-acting barbiturate with high lipid solubility. .  Barbiturates require supplementary analgesic administration during anesthesia.

 However. When given IV. diffusion out of the brain can also occur very rapidly because of redistribution to other tissues . agents such as thiopental and methohexital quickly enter the CNS and depress function. often in less than 1 minute.

metabolism of thiopental is much slower than its redistribution .  Thus. These drugs may remain in the body for relatively long periods. because only about 15% of a dose entering the circulation is metabolized by the liver per hour.

chest wall spasm. coughing. All barbiturates can cause apnea. laryngospasm.  These agents have largely been replaced with newer agents that are better tolerated. . and bronchospasm (of particular concern for asthmatics).

particularly GABA. Benzodiazepines  The benzodiazepines are used in conjunction with anesthetics for sedation. . 3.  All three facilitate amnesia while causing sedation.  The most commonly used is midazolam. enhancing the inhibitory effects of various neurotransmitters. Diazepam and lorazepam are alternatives.

.  They are metabolized by the liver with variable elimination half-lives. Minimal cardiovascular depressant effects are seen. and erythromycin may prolong their effects. but all are potential respiratory depressants (especially when administered IV).

 Benzodiazepines can induce a temporary form of anterograde amnesia in which the patient retains memory of past events. important treatment information should be repeated to the patient after the effects of the drug have worn off. but new information is not transferred into long-term memory. .  Therefore.

 The choice of opioid is based primarily on the duration of action needed  The most commonly used opioids are fentanyl and its congeners. Opioids  Because of their analgesic property. sufentanil and remifentanil because they induce analgesia more rapidly than morphine. opioids are commonly combined with other anesthetics. . 4.

 Opioids are not good amnesics.  Opioid effects can be antagonized by naloxone. . and they can all cause hypotension. as well as postanesthetic nausea and vomiting. respiratory depression. and muscle rigidity.

and the drug is short-acting. . 5.  Its water solubility is poor. but it lacks analgesic activity. Etomidate  Etomidate is a hypnotic agent used to induce anesthesia. so it is formulated in a propylene glycol solution  Induction is rapid.

 Etomidate is usually only used for patients with coronary artery disease or cardiovascular dysfunction.  Its adverse effects include decreased plasma cortisol and aldosterone levels. Among its benefits are little to no effect on the heart and circulation. which can persist up to 8 hours .

 Injection site reaction and involuntary skeletal muscle movements are not uncommon. .  The latter are managed by administration of benzodiazepines and opioids. because prolonged suppression of these hormones is hazardous. Etomidate should not be infused for an extended time.

nonbarbiturate anesthetic.  This dissociative anesthesia provides sedation. . induces a dissociated state in which the patient is unconscious (but may appear to be awake) and does not feel pain. Ketamine  Ketamine a short-acting. amnesia.6. and immobility.

 The drug is lipophilic and enters the brain very quickly.  Like the barbiturates. it redistributes to other organs and tissues.  Ketamine is used mainly in children and elderly adults for short procedures .

 Ketamine may be used illicitly. because it increases cerebral blood flow and may induce hallucinations. particularly in young adults. It is not widely used. since it causes a dream-like state and hallucinations similar to phencyclidine .

7. sympatholytic.  Dexmedetomidine has sedative. analgesic. and anxiolytic effects that blunt many cardiovascular responses.  It is relatively unique in its ability to provide sedation without respiratory depression. it is an α2 receptor agonist in certain parts of the brain. Dexmedetomidine  Dexmedetomidine is a sedative used in intensive care settings and surgery. .  Like clonidine.

which reflects depression of myocardial function.  Nitrous oxide found to depress the myocardium in a concentration-dependent manner. (administration of nitrous oxide in combination with the more potent inhaled (volatile) anesthetics can minimize cardiac depressant effects owing to its anesthetic-sparing effect)  Sevoflurane and desflurane are less likely to produce 81arrhythmias. All inhaled anesthetics tend to increase right atrial pressure in a dose-related fashion. less soluble halogenated anesthetics.  Enflurane and halothane have greater myocardial depressant effects than isoflurane and the newer. .

82 .

 Isoflurane and enflurane being the most depressant.  The respiratory depressant effects of anesthetics are overcome by assisting (or controlling) ventilation mechanically. With the exception of nitrous oxide.  All volatile anesthetics increase the resting level of PaCO2 (the partial pressure of carbon dioxide in arterial blood). 83 .  Volatile anesthetics increase the apneic threshold and decrease the ventilatory response to hypoxia. all inhaled anesthetics in current use cause a dose-dependent decrease in tidal volume and an increase in respiratory rate.  All volatile anesthetics are respiratory depressants.

prolonged anesthesia may lead to pooling of mucus and then result in atelectasis and postoperative respiratory infections. asthma.the ventilatory depressant effects of inhaled anesthetics are counteracted by surgical stimulation. Furthermore. chronic obstructive pulmonary disease). bronchitis. Thus. 84 .  Thebronchodilating action of halothane and sevoflurane makes them the induction agents of choice in patients with underlying airway problems (eg.  Volatile anesthetics possess varying degrees of bronchodilating properties.  Inhaledanesthetics also depress mucociliary function in the airway.

85 .

and increase the filtration fraction. EFFECTS:  On the KIDNEY depending on the concentration. 86 . volatile anesthetics decrease the glomerular filtration rate and renal blood flow.

 However. it can also lead to increased uterine bleeding.  The halogenated anesthetics are potent uterine muscle relaxants.  This pharmacologic effect can be used to advantage when profound uterine relaxation is required for an intrauterine fetal manipulation or manual extraction of a retained placenta during delivery. 87 .Effects on Uterine Smooth muscle  Nitrous oxide have little effect on uterine musculature.

88 .

TOXICITY  Hepatotoxicity ( Halothane )  Nephrotoxicity  Malignant hyperthermia 89 .

CHRONIC TOXICITY  MUTAGENICITY under normal conditions. inhaled anesthetics are neither mutagens nor carcinogens in patients. 90 .  CARCINOGENICITY increase in the cancer rate in OR personnel who were exposed to trace concentrations of anesthetic agents.

91 . abortions  HEMATOTOXICITY .higher incidence of miscarriages. EFFECTS ON REPRODUCTIVE ORGANS .prolonged exposure to nitrous oxide decreases methionine synthase activity and theoretically can cause megaloblastic anemia.

fentanyl. 92 . enhanced sedation. and perioperative analgesia.  Recovery is sufficiently rapid with most intravenous drugs to permit their use for short ambulatory (outpatient) surgical procedures. or both.  Most IV anesthetics lack antinociceptive (analgesic) properties  Their potency is adequate for short superficial surgical procedures when combined with nitrous oxide or local anesthetics.IV anesthetics  Intravenous agents are commonly used for induction of general anesthesia.  Adjunctive use of potent opioids (eg. sufentanil or remifentanil) contributes to improved CV stability.

93 .  Thiamylal is structurally almost identical to thiopental and has the same pharmacokinetic and pharmacodynamic profile.  Thiopental rapidly diffuses out of the brain and other highly vascular tissues and is redistributed to muscle and fat.  After an IV bolus injection. if given in sufficient dosage. produces loss of consciousness in one circulation time. thiopental rapidly crosses the B-B-B and.  Similar effects occur with methohexital.BARBITURATES  Thiopental is a barbiturate commonly used for induction of anesthesia.

 Methohexital is also preferred over thiopental for short ambulatory procedures. myoclonus. stroke volume.  Thiopental is also a potent respiratory depressant. 94 . and cardiac output.  Because intracranial pressure and blood volume are not increased. produces dose-dependent decreases in arterial blood pressure.  Methohexital can cause central excitatory activity eg. head trauma. Thiopental with large doses (or a continuous infusion). brain tumors). thiopental is a desirable drug for patients with cerebral swelling (eg.

which cause pain and local irritation. 95 . anxiolytic. lorazepam.  Midazolam is water-soluble and is the benzodiazepine of choice for parenteral administration.BENZODIAZEPINES  Diazepam. and midazolam are used for preanesthetic medication and as adjuvants during surgical procedures performed under local anesthesia. and their ability to control acute agitation. these compounds are considered to be the drugs of choice for premedication.  Diazepam and lorazepam are not water-soluble.  As a result of their sedative. and amnestic properties. and their intravenous use necessitates nonaqueous vehicles.

 Because it possesses sedative-anxiolytic properties and causes a high incidence of amnesia (> 50%). 96 . Usinglarge doses of benzodiazepines to achieve deep sedation prolongs the postanesthetic recovery period and can produce a high incidence of anterograde amnesia. midazolam is frequently administered intravenously before patients enter the operating room.

particularly in patients undergoing cardiac surgery or other major surgery when patient`s circulatory reserve is limited.OPIOID ANALGESICS Large doses of opioid analgesics have been used in combination with large doses of BZ to achieve a general anesthetic state. 97 .

a potent and extremely short- acting opioid has been used to minimize residual ventilatory depression. 98 . Remifentanil.  Lower doses of Fentanyl and Sufentanil have been used as premedication and as an adjunct to both intravenous and inhaled anesthetics to provide perioperative analgesia.

 Fentanyland Droperidol administered together produce analgesia and amnesia and combined with nitrous oxide provide a state referred to as neuroleptanesthesia 99 .  Opioidanalgesics can also be administered in very low doses by the epidural and subarachnoid (spinal) routes of administration to produce excellent postoperative analgesia. Remifentanilis rapidly metabolized by esterases in the blood (not plasma cholinesterase) and muscle tissues. contributing to an extremely rapid recovery from its opioid effects.

PROPOFOL  2.  Agent of choice for ambulatory surgery. (out-patient surgery) 100 .6-DIISOPROPYLPHENOL  Has become the most popular IV anesthetic  Is used for both induction and maintenance of anesthesia as part of total IV or balanced anesthesia techniques.

 Propofol is excreted in the urine as glucoronide and sulfate conjugates. 101 .  Has greater direct negative inotropic effects.  Itcauses a marked decrease in blood pressure during induction of anesthesia through decreased peripheral arterial resistance and venodilation.

hypotonus. tremors  Fospropofol. 102 . has recently been approved. a water-soluble prodrug of propofol. Pain at the site of injection is the most common side effect of bolus administration.  Muscle movements.

 For induction of anesthesia in patients with limited cardiovascular reserve. 103 .  Its major advantage is that it causes minimal cardiovascular and respiratory depression.ETOMIDATE  A carboxylated imidazole.

 The drug has no analgesic effects and coadministration of opioids may be required to decrease cardiac responses during tracheal intubation. myoclonic activity.  A/E: pain on injection. postoperative nausea and vomiting 104 . It produces a rapid loss of consciousness with minimal hypotension.

105 . analgesia. with or without loss of consciousness (hypnosis)  The only IV anesthetic that possesses both analgesic properties and the ability to produce dose-related CV stimulation. amnesia.KETAMINE  Itproduces a dissociative anesthetic state characterized by catatonia.

 Is a potentially dangerous drug when intracranial pressure is elevated. reduce the incidence of these adverse effects) 106 . Mechanism of action may involve blockade of the membrane effects of the excitatory neurotransmitter glutamic acid at the NMDA receptor subtype. (C/I!)  A/E:postoperative disorientation. sensory and perceptual illusions and vivid dreams ( DIAZEPAM given before the admn.


is joined to a hydrophilic group . in turn. local anesthetics all include a lipophilic group joined by an amide or ester linkage to a carbon chain. which. Structurally.

= can be administered locally by topical application or by injection in the target area.LOCAL ANESTHESIA = is the condition that results when sensory transmission from a local area of the body to the CNS is blocked. these drugs have effects on other tissues. = when given IV. 109 . the anesthetic effect can be restricted to a localized area.

sensation cannot be transmitted from the source of stimulation to the brain.Mechanism of action  Na+ ion channels are blocked to prevent the transient increase in permeability of the nerve membrane to Na+ that is required for an action potential  When propagation of action potentials is prevented. .

lidocaine mepivacaine. procaine ropivacaine and tetracaine . Commonly used local anesthetics are bupivacaine.

 Prilocaine a dental anesthetic. is also metabolized in the plasma and kidney . Biotransformation of amides occurs primarily in the liver.

 Patients with pseudocholinesterase deficiency may metabolize ester local anesthetics more slowly . Esters are biotransformed by plasma cholinesterase (pseudocholinesterase).

.  This minimizes systemic toxicity and increases the duration of action. Local anesthetics cause vasodilation. the rate of local anesthetic absorption and diffusion is decreased.  By adding the vasoconstrictor epinephrine. leading to rapid diffusion away from the site of action and shorter duration when these drugs are administered alone.

 Hepatic function does not affect the duration of action of local anesthesia.  Some local anesthetics have other therapeutic uses (for example. which is determined by redistribution and not biotransformation. lidocaine is an IV antiarrhythmic) .

produced by all esters . because the allergenic component is the metabolite para-aminobenzoic acid. whereas the ester procaine is somewhat more allergenic. allergy to an amide local anesthetic is exceedingly rare.  Allergy to one ester rules out use of another ester.

 In contrast. allergy to one amide does not rule out the use of another amide.  A patient may be allergic to other compounds in the local anesthetic. such as preservatives in multidose vials. .

LOCAL ANESTHETICS ESTERS AMIDES LONG SHORT SURFACE LONG MEDIUM ACTION ACTION ACTION ACTION ACTION Bupivacaine Tetracaine Ropivacaine Levobupivacai Benzocaine Lidocaine Procaine ne Mepivacaine Cocaine Prilocaine Note: (medium) Articaine check table 26-1 118 .

they exist either as the uncharged base or as a cation.  In the body.  Local anesthetics are weak bases and are usually made available clinically as salts to increase solubility and stability. Most local anesthetic agents consist of a lipophilic group (eg. a tertiary amine).  Because ester links are more prone to hydrolysis than amide links. an aromatic ring) connected by an intermediate chain via an ester or amide to an ionizable group (eg. esters usually have a shorter duration of action. 119 .

 Vasoconstrictor substances such as epinephrine reduce systemic absorption of local anesthetics from the injection site by decreasing blood flow in these areas. which inhibit release of substance P (neurokinin-1) and reduce sensory neuron firing.  This is important for drugs with intermediate or short durations of action such as procaine.  When used in spinal anesthesia. 120 . epinephrine acts directly on the cord to both enhance and prolong local anesthetic- induced spinal anesthesia by acting on α2 adrenoceptors. lidocaine. and mepivacaine (but not prilocaine).

 Theamide local anesthetics are widely distributed
after IV bolus administration.

 Sequestration can occur in lipophilic storage sites
(eg, fat).

 After an initial rapid distribution phase, which
consists of uptake into highly perfused organs such
as the brain, liver, kidney, and heart, a slower
distribution phase occurs with uptake into
moderately well-perfused tissues, such as muscle
and the GIT.


 The local anesthetics are converted in the liver (amide type)
or in plasma (ester type) to more water-soluble metabolites,
which are excreted in the urine.

 Acidification
of urine promotes ionization of the tertiary amine
base to the more water-soluble charged form, leading to
more rapid elimination.

 Ester-type
local anesthetics are hydrolyzed very rapidly in the
blood by circulating butyrylcholinesterase
(pseudocholinesterase) to inactive metabolites. 122

 The amide linkage of amide local anesthetics is hydrolyzed by liver
microsomal cytochrome P450 isozymes.

 Variations in the rate of liver metabolism of individual amide
compounds: prilocaine (fastest) > lidocaine > mepivacaine >
ropivacaine ≈ bupivacaine and levobupivacaine (slowest).

 As a result, toxicity from amide-type local anesthetics is more likely
to occur in patients with hepatic disease.

 Decreased hepatic elimination of local anesthetics would also be
anticipated in patients with reduced hepatic blood flow.

In an attempt to improve the clinical properties of cocaine 124 .  Isolated by Niemann in 1860 and introduced into practice by Koller in 1884 as a topical ophthalmic anesthetic. which became the dominant local anesthetic for the next 50 years. cocaine was used clinically because it was the only local anesthetic drug available for 30 years.  Despite the fact that its chronic use was associated with psychological dependence (addiction).COCAINE  The first local anesthetic introduced into medical practice.  Einhorn in 1905 synthesized procaine.

 Lidocaine was synthesized in 1943 by Löfgren.  Theonset of local anesthesia can be accelerated by the addition of sodium bicarbonate to the local anesthetic solution. 125 .  Cocaine has intrinsic sympathomimetic action due to its inhibition of NE reuptake into nerve terminals and possesses high surface (topical) activity.

 Systemic LA drugs are commonly used as adjuvants to the combination of a tricyclic antidepressant (eg.e. tachyphylaxis) due to extracellular acidosis. Carbamazepine) in patients who fail to respond to the combination of antidepressant and anticonvulsant 126 . Amitriptyline) and an anticonvulsant (eg. Repeated injections of LA can result in loss of effectiveness (i.

circumoral & tongue numbness .tonic-clonic convulsions 127 .nystagmus & muscular twitching .metallic taste . TOXICITY  CNS .restlessness .visual and auditory disturbances .light-headedness or sedation .sleepiness .

128 . excitability. patients with preexisting CV disease may develop heart block. if given intravenously. CVS .BUPIVACAINE may produce severe CV toxicity. .all LA are vasodilators except cocaine.local anesthetics block cardiac sodium channels and thus depress abnormal cardiac pacemaker activity. and conduction. including arrhythmias and hypotension. .

cardiac arrhythmias and MI.** COCAINE`s cardiovascular toxicity includes severe hypertension with cerebral hemorrhage.  PRILOCAINE is metabolized to products that include an agent capable of causing methemoglobinemia (patient may appear cyanotic and the blood ʺchocolate- coloredʺ  Allergic reactions specially with ester-type of LA 129 .