Transcript Pharmacology2 017 - King Saud University Medical Student

Pharmacology of general
anesthetics
Dr. Ashraf Arafat, MD
Assistant Professor
Department of Anesthesia, King Saud University
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General anesthesia
Loss of consciousness
Amnesia
Analgesia
Muscle relaxation
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Intravenous Anesthetics
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Benzodiazepines (BZ)
Midazolam, lorazepam, and diazepam.
Primary uses: sedation, amnesia, anxiolysis for
premedication or as adjuncts to general anesthesia.
Mechanism. Enhance inhibitory neurotransmission by
increasing the affinity of GABAA receptors for GABA.
– Pharmacokinetics
Effects are terminated by redistribution.
All are metabolized in the liver.
Diazepam clearance is reduced in the elderly.
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Pharmacodynamics
CNS
–Amnestic, anticonvulsant, anxiolytic, musclerelaxant, and sedative-hypnotic (dosedependent manner).
–No analgesia.
Cardiovascular system
–Mild systemic vasodilation and ↓ in cardiac
output.
HR is usually unchanged.
Respiratory system
–Mild dose-dependent ↓ in RR and TV.
–Respiratory depression may be more if
administered with an opioid
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Adverse effects
Pregnancy and labor
–Risk of cleft lip and palate in the first
trimester.
–CNS depression in the neonate.
Superficial thrombophlebitis and
injection pain by diazepam and
lorazepam.
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Flumazenil
– A competitive antagonist at the benzodiazepine
binding site of GABAA receptors in the CNS.
Reversal of sedative effects occurs within 2
minutes; peak effects at 10 minutes.
Half-life is shorter than the benzodiazepine
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Barbiturates
 Such as thiopental and methohexital (highly
alkaline).
 Mechanism.
 Facilitate inhibitory neurotransmission by enhancing
GABAA receptor function.
 Primary Use: Induction of anesthesia
Advantages:
Rapid onset (30 - 45 sec)
Short duration (5 – 8 min) initial dose; redistributed from brain
to muscle;
Pharmacokinetics
Hepatic metabolism & elimination.
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Pharmacodynamics
CNS
–Dose-dependent CNS depression .
–↓ in (CMRO2) cause ↓ in ICP and (CBF).
–Potent anticonvulsant properties
Cardiovascular system
–Depress myocardial contractility, leading to
dose-dependent ↓ in BP and cardiac output,
–Baroreceptor reflexes remain largely intact;
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–Respiratory system
–Dose-dependent decreases in RR and TV.
–Apnea may result for 30 to 90 seconds after
an induction dose.
–Laryngeal reflexes are suppressed to a
lesser degree compared with propofol; …..
high incidence of cough and laryngospasm.
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Adverse effects
Allergy.
Absolutely contraindicated in Porphyria
Venous irritation and tissue damage
– Thiopental can cause severe pain and tissue necrosis if injected
extravascularly or intra-arterially. If intra-arterial administration
occurs, heparin, vasodilators, and regional sympathetic
blockade may be helpful in treatment.
Myoclonus and hiccups .
Less suitable for day case surgery OR
maintenance of anaesthesia
Multiple doses or prolonged infusions may produce
prolonged sedation or unconsciousness
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Ketamine
A sedative-hypnotic agent with potent analgesic
properties
‘Dissociative anaesthesia’ with loss of consciousness
and profound analgesia .
Primary uses:
Induction of GA.
Sedation and analgesia .
Mechanism: NMDA receptor antagonist
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Pharmacokinetics
Unconsciousness in 30 to 60 s after an IV.
Terminated by redistribution in 15 to 20
minutes.
Metabolized rapidly in the liver ;
Elimination half-life is 2 to 3 hours.
Repeated bolus doses or prolonged infusions
result in accumulation.
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Pharmacodynamics:
CNS
– Produces a “dissociative” state accompanied by
amnesia and profound analgesia.
– ↑ (CBF), ↑ (CMR), and ↑(ICP) pressure.
Cardiovascular system
– ↑ HR, and BP whilst COP is maintained.
– Direct myocardial stimulation & a central sympathetic
effect
– Used in hemodynamically compromised patients.
Respiratory system
– Minimal respiratory depression
– Potent bronchodilator .
– laryngeal/pharyngeal reflexes are preserved
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Adverse effects
Oral secretions (increased salivation) .
Emotional disturbance. agitation &
hallucinations
↑ Muscle tone: increased uterine tone
↑ ICP : contraindicated in patients with
head trauma or intracranial hypertension.
Ocular effects. mydriasis, nystagmus,
diplopia, and ↑ intraocular pressure.
PONV
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Propofol (Diprivan)
1%(10 mg/mL) isotonic oil-in-water emulsion, which contains egg
lecithin, glycerol, and soybean oil.
Highly lipid soluble
Primary uses:
A sedative/hypnotic (ICU)
Induction or maintenance of anesthesia
Mechanism: Facilitates inhibitory neurotransmission by
enhancing the function (GABAA) receptors in CNS .
Pharmacokinetics:
Hepatic and extrahepatic metabolism to inactive
metabolites which are renally excreted.
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Pharmacodynamics:
– CNS
Induction : rapid onset of unconsciousness (30
to 45 seconds), followed by a rapid termination
of effect by redistribution
Emergence is rapid (short distribution half-life
(1–2 min).
Weak analgesic effects .
↓ (CBF) ↓ (ICP), ↓ (CMRO2). and ↓ (CPP) due
to markedly ↓ (MAP).
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Anticonvulsant .
Less (PONV) occurs.
– Cardiovascular system
Direct myocardial depression with ↓ SVR
Dose-dependent ↓ in preload, afterload, and
contractility lead to ↓ in (BP) and COP.
Hypotension may be marked in hypovolemic,
elderly, or hemodynamically compromised
patients.
Heart rate (HR) is minimally affected, and
baroreceptor reflex is blunted.
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– Respiratory system
Dose-dependent decreases in (RR) and (TV).
↓Ventilatory responses to hypoxia and
hypercarbia.
Apnoea is common.
Laryngeal and pharyngeal muscle relaxation
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Advantages
Safe in porphyria;
Antiemetic properties
Use in day case surgery .
Total intravenous anaesthesia (TIVA)
Situations where volatile anaesthetics cannot be
used (e.g.
 Malignant hyperthermia (MH) patients,
 Transfer of sedated patients,
 Airway surgery when periods of apnoeic
oxygenation are employed).
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Adverse effects
Venous irritation.
Bacterial growth
Lipid disorders. used cautiously in disorders of
lipid metabolism (e.g., hyperlipidemia and
pancreatitis).
Myoclonus and hiccups
Propofol infusion syndrome : a rare fatal
disorder that occurs in critically ill patients (usually
children) subjected to prolonged, high-dose
propofol infusions.
(Rhabdomyolysis, metabolic acidosis, cardiac failure,
and renal failure).
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Etomidate
Primary use:
Induction in patients w/ cardiovascular problems
Mechanism: Facilitates inhibitory neurotransmission
by enhancing
GABAA receptor function.
–Pharmacokinetics
Effects of a single bolus dose are terminated by
redistribution.
Very high clearance in the liver and by
circulating esterases to inactive metabolites.
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Pharmacodynamics
CNS
–No analgesic properties.
– ↓ (CBF), cerebral metabolic rate, (CMR),
and (ICP), .
Cardiovascular system
–Minimal changes in HR, BP, and COP.
Respiratory system
–Dose-dependent ↓ in ( RR) & (TV).
– Transient apnea may occur.
N.B Useful in elderly and shocked patients
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Adverse effects
Myoclonus .
Excitatory phenomena (e.g. involuntary limb
twitches);
PONV;
Venous irritation and superficial
thrombophlebitis may be caused by the propylene
glycol vehicle. Minimized by administration into a freeflowing IV carrier infusion.
Adrenal suppression: Inhibits 11β-hydroxylase;
- A single induction dose suppresses adrenal steroid
synthesis for up to 24 hours.
- Repeated doses or infusions is associated with increased
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mortality in ICU patients.
Opioids
 Opioids produce moderate sedation and profound
analgesia.
 They exert their effects by binding with opioid
receptors in CNS ( 3 major opioid receptors μ (mu), κ
(kappa), and δ (delta).
Meperidine, Morphine, Alfentanil, Fentanyl,
Sufentanil, Remifentanil
Advantages:
Minimal cardiac effects
No myocardial depression
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Fentanyl
A potent synthetic opioid agonist with between 100
times the analgesic potency of morphine.
Used in
 Induction
 Maintenance of GA
 Supplement regional and spinal anesthesia.
 Ability to maintain cardiac stability.
Sufentanil citrate (Sufenta)
 10 times as potent as fentanyl
 Rapid elimination ,
 Relatively more rapid recovery as compared with
fentanyl.
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Alfentanil
 Shorter duration of action compared to fentanyl and
sufentanil,
Remifentanil (Ultiva)
 Ultra short acting and rapidly cleared
 widespread extrahepatic metabolism by blood and
tissue nonspecific esterases,
Morphine
 May produce hypotension and bronchoconstriction as
a consequence of its histamine-releasing action.
 Morphine may be a poor choice for a patient with
renal failure.
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Side effects
Nausea & vomiting
Drowsiness or sedation,
Respiratory depression,
Miosis,
Chest wall rigidity,
Bradycardia in large doses
Some peripheral vasodilation and histamine release -hypotension
Constipation,
Urinary retention & biliary colic,
Slow gastric emptying
Tolerance & Dependence
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Naloxone
A specific opiate receptor antagonist, binding the
receptor
The effective dose is 1 to 4 μg/kg IV, and the duration
of action is 30 to 45 minutes.
Dose may need to be repeated or an infusion
Side effects
- Reversal of analgesia, nausea, vomiting,
- Increased sympathetic nervous system activity,
( tachycardia, hypertension, pulmonary edema, and
cardiac dysrhythmias).
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Dexmedetomidine
 Highly selective α2-adrenergic receptor agonist.
 A sedative agent with analgesic properties.
 A sedated but arousable state similar to natural
sleep.
 Weak amnestic; no anticonvulsant properties.
 Airway reflexes remain intact.
 Minimal respiratory depression,
 Metabolized extensively in the liver.
 Decreases HR and BP, although transient
hypertension may occur after an IV bolus.
 Side effects : Antimuscarinic effects (e.g., dry mouth
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and blurred vision)
Inhalational Anesthetics
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History of Anesthesia
 Joseph Priestly – discovers N2O in 1773
 William Morton, dentist – first demonstration of
successful surgical anesthesia with ether 1846
 Dr. John Snow administers chloroform to Queen
Victoria (1853)– popularizes anesthesia for childbirth
in UK
He becomes the first anesthesia specialist.
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Characteristics of the ideal inhaled
anesthetic agent
Non-toxic.
Non-allergenic.
Not a malignant hyperthermia (MH) trigger.
Stable in storage, non-flammable.
No extra specialist equipment needed.
Low solubility in blood and tissues,
Analgesic
Lack of injury to vital tissues.
The lack of seizures, respiratory irritation, and circulatory
stimulation;
Resistance to physical and metabolic degradation
No reaction with soda lime/breathing circuit
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Factors affecting minimum alveolar
concentration (MAC)
Decreased MAC
Increased MAC
 Age (peak at 6 months)
 Premedication (e.g.
benzodiazepines)
 Opioids
 Pregnancy
 Acute alcohol intoxication
 Other volatiles (MACs are
additive. 0.6 of one agent +
0.4 of another = 1 MAC)
 Nitrous oxide
 Hypothermia
 Chronic alcohol consumption
(liver enzyme induction)
 Increased sympathetic
activity (e.g. amphetamine,
cocaine)
 Hypermetabolic states (e.g.
thyrotoxicosis, pyrexia)
Anxiety
 Some antidepressants
(tricyclics, monoamine
oxidase inhibitors)
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 The minimum alveolar concentration
(MAC) : the amount of vapour (%) needed
to render 50% of spontaneously breathing
patients unresponsive to a standard
painful surgical stimulus.
 MAC is inversely proportional to potency.
Halothane, isoflurane, sevoflurane, and
desflurane are 0.75%, 1.15%, 1.85%, and
6.0% at one atmosphere
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Volatile anesthetics
– Present as liquids at
room temperature and
pressure
– Vaporized into gases
for administration
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General pharmacokinetics
The higher the vapor pressure, the more volatile
the anesthetic.
Blood solubility determines the speed of build-up /
elimination from blood / brain
Lower blood solubility means (faster
induction/recovery)
Inspired air → Alveolar air → Blood → Brain
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Volatile anesthetics
Mechanism: Various ion channels in the CNS involved in
synaptic transmission (including GABAA, glycine, and glutamate
receptors) may play a role.
Metabolism: hepatic .
Exhalation:This is the predominant route of elimination:
CNS
–Unconsciousness and amnesia .
–↑ cerebral blood flow (CBF).
–↑ intracranial pressure
BMR: reduced; a MAC of 2 reduces oxygen
consumption by 30%.
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Cardiovascular system
– Myocardial depression and systemic vasodilation,
reduce SVR .
– Hypotensive effect,
– Change in HR, (desflurane)
– Sensitize the myocardium to the arrhythmogenic
effects of catecholamines.
Neuromuscular system
- Dose-dependent ↓ in skeletal muscle tone.
-Potentiation of muscle relaxants.
All volatile anaesthetics may
precipitate malignant hyperthermia (MH) .
A dramatic increase in body temperature, acidosis,
electrolyte imbalance and shock
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Hepatic system: ↓ hepatic perfusion. Rarely,
(“halothane hepatitis”).
Renal system. ↓ renal blood flow .
Respiratory system
– Dose-dependent respiratory depression
– ↓ TV↑RR
– Airway irritation and, during light levels of
anesthesia, may precipitate coughing, laryngospasm,
or bronchospasm
(sevoflurane makes it more suitable )
– Bronchodilator,
(with the exception of desflurane).
- Respiratory response to hypoxia and hypercarbia is
reduced.
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Isoflurane:
Advantages:
It causes peripheral vasodilation
A drop in blood pressure, systemic vascular
resistance (SVR)
Tachycardia (sympathetic stimulation)
Increased coronary blood flow .
Disadvantages:
Moderate solubility, so recovery from anesthesia
may be delayed
Isoflurane can make the heart “more sensitive” to
circulating catecholamines (like epinephrine).
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sevoflurane
Advantages:
Low solubility in blood-- produces rapid induction and
emergence
Non-irritant with Pleasant smelling (suitable for children)
Has good bronchodilating properties
Agent of choice in asthma, bronchitis, and COPD.
It causes bradycardia, blood pressure and SVR
Mild respiratory and cardiac suppression (cardiac output is
maintained)
Disadvantages:
Carbon dioxide absorbents in anesthesia machines
degrade sevoflurane to Compound A
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Desflurane
Advantages:
Rapid onset and recovery of anesthesia due to a low
blood/gas solubility coefficient (0.42).
(outpatient procedures)
One of least metabolized to toxic byproducts
Disadvantages:
Requires a special vaporizer
Pungent and irritating to the airway (leading to more
coughing, laryngospasm) cannot be used for induction
It increases salivary and respiratory secretions
High inspired gas concentrations lead to a significant ↑ in the
patient’s BP & HR.
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Halothane
Used for induction in children (sweet pleasant odor);
Side effects:
Sensitize the myocardium to the arrhythmogenic
effects of catecholamines,
Myocardial depression,
“Halothane hepatitis” (rare) related to repeated
exposure,
Blood pressure usually falls, .
Very soluble in blood and adipose
Prolonged emergence
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Nitrous Oxide
MAC is 104% at one atmosphere
CNS
Mechanism: antagonism of NMDA receptors in CNS.
- Weak anesthetic, produce analgesia
- Usually combined with other anesthetics.
- Used alone e.g. dental procedures);
 Cardiovascular system
- Mild myocardial depressant & a mild sympathetic
stimulant.
- HR and BP are usually unchanged.
- ↑ pulmonary vascular resistance.
Respiratory system. Little effect on respiration
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Nausea/vomiting;
Risk of bone marrow depression
Inhibits vitamin B-12 metabolism
Second Gas Effect: Increased uptake of volatile
agent when given together with N2O
 Expansion of closed gas spaces. nitrous oxide is
35 times more soluble in blood than nitrogen,
Contraindicated in (e.g. air embolus, pneumothorax,
Middle Ear Surgery etc)
Diffuse into the cuff of ETT.
 Diffusion hypoxia. After discontinuation, its rapid
elimination from the blood into the lung may lead to a
low partial pressure of oxygen in the alveoli.
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Xenon
A gas and exhibits many properties of an ideal
anaesthetic agent :
Colourless,
Odourless,
Non-flammable,
Stable in storage,
Low oil/gas and blood/gas coefficients,
Cardiovascularly stable,
Excreted unmetabolized,
Non-toxic,
MH safe
Disadvantage : very expensive .
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Neuromuscular blocking
drugs
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D. Neuromuscular blocking drugs
Used to
Perform tracheal intubation,
Facilitate ventilation,
Provide optimal surgical operating conditions.
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Neuromuscular blockers
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Depolarizing(Succinycholine)
Structurally similar to acetylcholine … activate the
acetylcholine receptors (Ach)
depolarization of
postjunctional membrane.
Fastest onset (60 s)
Very short duration of action
A short time intubation (Rapid sequence induction)
Metabolized very quickly by plasma cholinesterase.
Characterized by
Transient muscle fasciculations followed by relaxation.
Acetylcholine esterase (AChE) inhibitors potentiate
rather than reverse the block.
Side effects of Succinycholine:
Myalgia : abdomen, back, and neck
Cardiac dysrhythmias. sinus bradycardia,
junctional rhythm, and even asystole after the
first dose in children and following repeated
dose within a short time interval in adults
Hyperkalemia
-Major burns, renal failure
-Massive tissue injuries, muscular dystrophies
- Extensive denervation of skeletal muscle,
- upper motor neuron diseases.
A transient increase in intraocular pressure
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Increased intragastric pressure
Increase in intracranial pressure.
Succinycholine apnea (Prolonged blockade) :
-Low levels of plasma cholinesterase as in
severe liver or kidney disease,
- A drug-induced inhibition of its activity,
- A genetically atypical enzyme.
Anaphylaxis. over 50% of anaphylactic
reactions to NMBDs.
Malignant hyperthermia (MH).
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Nondepolarizing blockers
They act by competitively blocking the binding of
ACh to its receptors and inhibit muscular
contraction.
– It is characterized by :
Absence of fasciculations.
a slower onset than suxamethonium
Highly ionized, poorly lipid soluble and protein bound
at physiological pH
Potentiation by other nondepolarizing NMBDs and
volatile anesthetic agents.
Reversal by AChE inhibitors.
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2 types
Benzylisoquinoliniums, e.g. atracurium,
cisatracurium, mivacurium
Aminosteroids, e.g. pancuronium,
vecuronium, rocuronium
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Mivacurium
Short-acting.
Rapidly hydrolyzed by plasma cholinesterase.
Used with caution in patients with known
atypical plasma cholinesterase activity or
using cholinesterase inhibitors.
Histamine release causing a transient
hypotension and tachycardia.
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Atracurium besylate (Tracrium)
Widely used and have an intermediate onset and
duration of action .
Histamine release ,
No direct cardiovascular effects.
Metabolism is spontaneously by Hofmann
degradation and ester hydrolysis in the plasma,
Its duration of action is independent of renal and
hepatic function.
A breakdown product of atracurium, (laudanosine )
may accumulate and cause seizures
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Cisatracurium(Nimbex)
Isomer of atracurium
Relatively slow onset of action.
Less laudanosine .
Not release histamine.
Hofmann degradation and does not
accumulate in renal failure.
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Pancuronium bromide (Pavulon)
The first steroid NMBD in clinical use has a slow
onset and long duration of action.
It does not cause histamine release
Weak sympathomimetic properties and causes
tachycardia.
It is partly metabolised in the liver .
Its action is prolonged in renal and hepatic
impairment.
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Vecuronium
bromide(Norcuron)
Vecuronium is structurally similar to pancuronium
but has a slightly faster onset and shorter
(intermediate) duration of action.
Not release histamine
No cardiovascular effects.
Metabolism in the liver into active metabolites
before being excreted in the bile and urine.
Prolonged clinical effect in elderly patients and
those with liver or renal disease .
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Rocuronium.
An analog of vecuronium
The most rapid onset of the clinically available nondepolarizing NMBDs.
Intubating conditions can be achieved in 60-90 seconds after
an induction dose of 0.6 mg/Kg.
Increasing the dose to 1.2 mg/kg shortens the time.
Used when a rapid sequence induction .
An intermediate duration of action .
Not release histamine
No cardiovascular effects.
Higher incidence of anaphylactic reactions
Metabolised in the liver and excreted in the bile and renal.
In renal failure ------in a longer duration of action
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Clinical Choice of NMBD
Urgency for tracheal intubation,
Duration of the procedure,
Coexisting medical conditions that may affect the
NMJ,
Side effects
Metabolism
Cost-effectiveness
 SCh makes it a good choice for rapid intubation .
 Rocuronium will decrease the risk of hyperkalemia in
patients with burns.
 Pancuronium can produce a tachycardia that is undesirable
in patients with severe IHD, but its vagolytic effects may be
appropriate in pediatrics.
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Anticholinesterases (Neostigmine)
(acetylcholinesterase inhibitors) are agents
that inhibit the action of the acetylcholinesterase
enzyme at the neuromuscular junction.
(Increases concentration of Ach at NMJ)
 Clinical tests of adequate resolution of
neuromuscular block include the ability to lift the
head from the bed for 5 seconds,
 No role for anticholinesterases in reversing the
effects of suxamethonium.
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Neostigmine
Side effects
Bradycardia, miosis, GI upset,
Nausea, bronchospasm, increased bronchial
secretions, sweating and salivation.
For this reason an antimuscarinic such as
glycopyrronium 0.01 mg/kg or atropine 0.02
mg/kg must be administered along with the
anticholinesterase .
Intravenous injection at a dose of 0.05 mg/kg
(maximum 5mg).
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Sugammadex (a cyclodextrin)
Binds irreversibly to rocuronium and
vecuronium, rendering them inactive.
It has a role in failed intubation/ ventilation
scenarios by reversing muscle relaxation
when rapid resumption of airway reflexes and
respiratory function is required.
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Peripheral nerve stimulator
Check the depth of
neuromuscular blockade
Determine that
neuromuscular blockade
is reversed
at least 3 twitches on a
train of four should be
detected before
attempting reversal.
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Local anesthetics (LAs)
67
Local anesthetics
Weak bases
Mechanism : reversibly blocking sodium channels to
prevent depolarization
Lipid solubility: potency, plasma protein binding
determines, duration of action of local anesthetics.
Addition of vasoconstrictor:
 Prolongation of anesthetic action
 Decreased risk of toxicity
 Decrease in bleeding from surgical manipulation.
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Esters (e.g. cocaine, procaine, Tertracaine,
Benzocaine)
 Allergic reactions are common.
 Metabolized by plasma and liver
cholinesterase.
Amides (e.g. bupivacaine, lidocaine,
ropivacaine)
 Allergic reactions are rare.
 Metabolized by the liver.
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Applications of local anesthesia:
Minor nerve blockade, e.g. radial nerve;
Major nerve trunk blockade, e.g. brachial plexus block;
Intravenous regional anaesthesia.
Topical application: to skin for analgesia (e.g., benzocaine)
or mucous membranes (for diagnostic procedures)
 Spinal & epidural anesthesia:
Local infiltration, e.g. laceration suturing, postoperatively to
surgical wounds;
i.v. infusion: for control of cardiac arrhythmias (e.g.,
lidocaine for ventricular arrhythmias)
With propofol injection, e.g. by adding 10 mg lidocaine.
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Speed of onset of action:
 pKa (pH at which 50% of the drug is in the ionized
form); eg. lidocaine (pKa 7.9) has a quicker speed of
onset than bupivacaine (pKa 8.1)
 Additives effect : bicarbonate
The rate of systemic absorption depends on the site
of administration:
 mucous membranes >intercostals >major nerve block
>infiltration
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Duration of action
 Protein-bound LAs have a longer duration of action
 Ester LAs may have a prolonged duration of action
(pregnancy, liver disease or when the enzyme is
atypical or absent (e.g. pseudocholinesterase
deficiency)
 Addition of vasoconstrictors
Hyperbaric solutions of LA (e.g. by the addition of
dextrose) effect the spread of LA when injected into
the CSF
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Lidocaine
Amide type anesthetic
Lidocaine was introduced in 1948
The most commonly used local anesthetic
Rapid onset and a duration of 60-75 minutes
Extended with epinephrine for up to 2 hours
Metabolized in the liver and excreted by the
kidneys.
Contraindicated in patients with a known sensitivity
to amide type anesthetics
Has also antiarrhythmic action.
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Bupivacaine
Amide-type local anesthetic
Introduced in 1963
Onset of action is slower than lidocaine and
anesthesia is long acting .
Provides 2-4 hours of anesthesia
Extended with epinephrine for up to 7 hours
More cardio-toxic than lidocaine, difficult to treat.
Metabolized in the liver and excreted by the kidneys
Contraindication: known hypersensitivity
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Levobupivacaine
 less serious CNS and CVS toxicity
Ropivacaine
 A less toxic, long-lasting LA.
 Undergoes extensive hepatic metabolism,
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EMLA
 Prilocaine and lidocaine.
 Surface anaesthesia when applied to skin
and left for (>45 min).
 Paediatrics and dressing changes.
Amethocaine gel
 A quicker onset than EMLA.
Other forms of LA are poorly absorbed
through intact skin.
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Intravenous regional anaesthesia (IVRA)
A BP cuff is applied to the upper arm with a cannula in the
hand.
After exsanguination of the limb, the BP cuff is inflated to 100
mmHg above systolic BP.
Prilocaine is the preferred drug and is injected i.v.
Good analgesia for distal limb procedures (e.g. fracture
manipulation or carpel tunnel decompression).
The cuff is let down after at least 20 min to allow the LA to
spread into the adjacent tissues in order to prevent toxic
plasma levels of LA following systemic absorption.
A second cannula must always be sited in the other arm for
emergency use.
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Local Anesthetic Toxicity
Central nervous system
– initially-- lightheadedness, circumoral numbness,
dizziness, tinnitus, visual change
– later-- drowsiness, disorientation, slurred speech, loss
of consciousness, convulsions
– finally-- respiratory depression
Cardiovascular
– Myocardial depression and vasodilation-- hypotension
and circulatory collapse
– Cardiac arrest
Allergic reactions-- rare (less than 1%)
– preservatives or metabolites of esters
– rash, bronchospasm
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Treatment
Supportive, airway /tracheal intubation ,
IV fluids
Vasopressors (e.g. epinephrine),
Control of seizures with, for example, benzodiazepines,
thiopental.
CPR .
IV lipid emulsion Intralipid 20% 1.5 mL/kg for LA
toxicity/cardiovascular collapse.
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Other side effects
o
o
o
o
Allergy :
Common with the esters, especially with procaine
(para-aminobenzoic acid) .
Related to additives such as vasoconstrictors or
preservatives.
Prilocaine metabolism :
Excess prilocine cause methaemoglobinaemia.
Treated with methylene blue.
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Case 9-Muscle Relaxants (Neuromuscular
Junction Blockers)
A 4- years old male patient booked for squint
surgery right eye
 How you will assess this patient preoperatively
 Discuss fasting time and premedication
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 The patient seen in preoperative anesthesia
clinic and cleared for squint surgery under
general anesthesia , Bwt:16 kg
 What are the physiological difference
between adult and pediatric patient
 Discuss anesthesia consideration and
special concern for such this surgery
 Discuss anesthesia plan , induction,
medications methods for securing the
airway , maintenance of anesthesia and
intravenous fluid requirement
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During surgery the patient developed sever
bradycardia
 Discuss the cause and treatment
The surgery lasted 2 hours and the patient
extubated and shifted to recovery room
 what is your post-operative analgesia plan
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Case scenario
A 47-year-old patient is undergoing the
clipping of an intracranial aneurysm of the
anterior communicating artery under general
anesthesia.
The surgery is being even the smallest
movement by the patient could have
devastating consequences performed under
a microscope, so
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 How can the patient be protected and the
surgery allowed to proceed?
 What are the Clinical Pharmacology of
the Neuromuscular Blockers?
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 Maintenance of Blockade: How Much is
Enough?
 Reversal of the Neuromuscular
Blockade and Emergence
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