PHARMACOLOGY OF THE

CENTRAL NERVOUS
SYSTEM
DRUGS FOR LOCAL AND GENERAL
ANESTHESIA
Kirsten Culver, PhD
Local Anesthesia
 Loss of sensation to a specific area of the body
without the loss of consciousness
Local Anesthesia
Local Anesthesia
 Most local anesthetics exert
their effect through a common
mechanism of action
 Block voltage-gated sodium
channels
 Inhibit both motor and sensory
neuronal signalling
 Bind to open sodium channels
 Active neurons are the most
susceptible
 To improve their duration of
action, local anesthetics are
sometimes co-administered
with epinephrine
 Local Anesthetics

Ester Anesthetics Amide Anesthetics

Rapidly metabolized in the bloodstream Metabolized in in the liver


(esterases) Longer half-lives (30-60 minutes)


 Short half-life (1 – 2 minutes) pKa’s range from 7.5 - 8.0


 pKa’s range from 8.6 - 8.9

Axon Sensitivity to Local
Anesthetics
 Not all nerves are equally susceptible to local anaesthesia
 The thinnest axons and those without myelin are most easily
paralysed
 Somatic motor nerves are thick and myelinated
 A fibres
 Somatic pain (sharp pain) fibres are thick fibres with some
myelin
 A fibres
 Sympathetic nerves are thin but myelinated
 B fibres
 Visceral pain (dull, aching pain) fibres are thin and
unmyelinated
 C fibres
Local Anesthesia in Labour
 More than 60% of Canadian women will chose
some form of regional anesthesia during labour
 Epidural or intrathecal (spinal) injection of local
anesthetics
 Epidural administration of opioids
 Opioids are not local anesthetics – they do not induce a
complete blockade of nerve impulses
 Excellent pain control agents
 Local Anesthesia in Labour

The spinal cord ends at L1

Below L1, the spinal nerves continue as the
cauda equina
Epidural Local Anesthesia
 Injection of drug into the fat-filled epidural space
 Highly vascularised area
 Much more anaesthetic is required compared to intrathecal
administration
 Bupivacaine (Marcaine)
 Exerts an effect on any nerve that comes into contact
with the drug
 Some drug will diffuse into the arachnoid space
 However, if properly applied, the drug should
predominantly affect the nerve roots passing through the
epidural space (somatic sensory fibres)
Intrathecal Local Anesthesia
 Injection of a local anaesthetic (or other analgesic)
directly into the CSF
 Administered in the space below the second lumbar
vertebra (or further down) but before the coccyx
 Somewhat easier to administered since it has a clear
endpoint (withdrawal of CSF)
 Typically administered during scheduled surgical
procedures, rarely used during labour
 Higher rate of efficacy compared to epidural anesthesia
 Requires less anesthetic than epidural anesthesia
Opioids and Epidural/Spinal Anesthesia

 When administered in either the epidural space or

in the CSF opioids...
 Bind to presynaptic receptors in the substantia
gelatinosa inhibiting the release of pain signalling
neurotransmitters
 Bind to postsynaptic receptors decreasing neuronal
excitability
 Ultimately, both mechanisms inhibit the firing of
ascending neurons, resulting in a decrease in pain
signals received by the brain
Opioid Regional Anesthesia
 This class of drugs has no effect (blockade) on the
activity of motor neurons
 Mobility, proprioception, and a sense of touch are
maintained
 Very effective in controlling visceral pain
 Adverse Effects
 Pruritus is common and can be treated with antihistamines
 Nausea and vomiting may occur if the drug reaches the area
postrema in the brain stem
 Respiratory depression (rare if administered correctly)
Side Effects of Epidural and Spinal Anesthesia

 Backache (approximately 20%)

 Infection (<<1%)
 Inadequate anesthesia
 Arachnoiditis
 Spinal headache (approximately 1%)
 CSF leak, causing traction on the brain from the
meninges
 Treated with a blood patch
 15-20 ml autologous blood transfusion to the puncture site
General Anesthesia
 Loss of sensation (and movement) occurring throughout the
entire body, accompanied by a loss of consciousness
 Requires the administration of multiple drugs to induce...
 Unconsciousness
 Muscle relaxation
 Maintenance of deep anesthesia
General Anesthesia
 Intravenous general anesthetics
 Typically co-administered with inhaled general
anesthetics
 Use of IV general anesthetics decreases the dose of inhaled
anesthetic required to induce anesthesia
 Induce analgesia and muscle relaxation
 Can be used alone if surgical procedures require less than
15 minutes of anesthesia
 Opioids, barbiturates and benzodiazepines
General Anesthesia
 Inhaled general anesthetics
 Used to maintain anesthesia
 Prevent flow of sodium ions into neurons in the CNS,
reducing neural activity
 Gaseous inhaled anesthetics
 Nitrous oxide
 Used in dental procedures, during labour and brief surgical
procedures
 Volatile Liquids
 Isoflurane
 High safety profile – does not induce the same respiratory and
cardiovascular depression as other drugs in this class
General Anesthesia
 Postoperatively, patients should be monitored for
 Nausea and vomiting
 CNS depression
 Respiratory depression
 Changes in vital signs
Drugs as Adjuncts to General Anesthesia
 Preoperative
 Barbiturates and benzodiazepines
 Anti-anxiety and mild sedation effects
 Anticholinergics
 Dry respiratory and oral secretions
 During surgery
 Ganlglionic receptor blockers
 Induce relaxation of skeletal muscles (for surgery and intubation)
 Postoperative
 Opiates
 Reduce post-operative pain
 Antiemetics
 Reduce the nausea and vomiting associated with general anesthetics
 Cholinergics
 Stimulate smooth muscle contraction in the GI tract and bladder to induce
peristalsis and urination