DRUGS ACTING ON THE Central

Nervous System (CNS)

General anaesthetics with

pre-anaesthetic medications

Dr. Olorunfemi OWA MBBS, MSc., MPA, FWACS(O&G), FICS

Department of Pharmacology and Therapeutics, UNIMED,
Ondo
 Outline
 Pre-anaesthetic Medication
 Drugs used in pre-anaesthetic medication
 General Anaesthetics
 History
 Stages of anaesthesia
 Pharmacokinetics
 Mechanism of action
 Complications of general anaesthesia
 Summary
 Preanaesthetic medication
“It is the term applied to the administration of drugs prior to general anaesthesia so as to make
anaesthesia safer for the patient”

Ensures comfort to the patient & to minimize adverse effects of anaesthesia

 Aims
• Relief of anxiety & apprehension preoperatively & facilitate
smooth induction

• Amnesia for pre- & post-operative events

• Potentiate action of anaesthetics, so less dose is needed.

• Antiemetic effect extending to post-operative period

• Decrease secretions & vagal stimulation caused by anaesthetics

• Decrease acidity & volume of gastric juice to prevent reflux &

aspiration pneumonia
Drugs used for Pre-Anesthetic medication

• Anti-anxiety drugs (Anxiolytics)

• Sedatives-hypnotics
• Opioid analgesics
• Anticholinergics
• Antiemetics
• Drugs reducing acid secretion
Drugs used for Pre-Anesthetic medication
Anti-anxiety drugs (Anxiolytics)-
- Provide relief from apprehension & anxiety.
- Post-operative amnesia.
e.g. Diazepam (5-10mg oral/iv), Lorazepam (2mg
i.m.) [Avoided co-administration with morphine,
pethidine]
Sedatives-hypnotics-
Example: Promethazine (25mg i.m.) has sedative,
antiemetic & anticholinergic action.
Causes negligible respiratory depression & suitable
for children
 Opioid analgesics:-
Example:
i. Morphine (8-12mg i.m.) or Pethidine (50-100mg
i.m.) used one hour before surgery. Provide
sedation, pre-& post-operative analgesia,
reduction in anaesthetic dose

ii. Fentanyl (50-100μg i.m. or i.v.) preferred

nowadays (just before induction of anaesthesia)
Anticholinergics-
Examples:
Atropine (0.5mg i.m.) or Hyoscine (0.5mg i.m.) or
Glycopyrrolate (0.1-0.3mg i.m.) one hour before
surgery (not used nowadays).

Reduces salivary & bronchial secretions, vagal

bradycardia, hypotension.

Glycopyrrolate(selective peripheral action) acts

rapidly, longer acting, potent antisecretory agent,
prevents vagal bradycardia effectively
Antiemetics-
Examples:
Metoclopramide (10mg i.m.) used as antiemetic & as
prokinetic gastric emptying agent prior to emergency
surgery (full stomach)

Domperidone (10mg oral) more preferred (does not

produce extrapyramidal side effects)

Ondansetron (4-8mg i.v.), a 5HT3 receptor

antagonist, found effective in preventing post-
anaesthetic nausea & vomiting
 Drugs reducing acid secretion or Antacids
Examples:
Ranitidine (150-300mg oral) or Famotidine (20-
40mg oral) given night before & in morning along
with Metoclopramide reduces risk of gastric
regurgitation & aspiration pneumonia

Proton pump inhibitors like Omeprazole (20mg) with

Domperidone (10mg) is preferred nowadays.
 GENERAL ANAESTHETICS
General Anaesthetics (GA) are drugs which produce
reversible loss of all sensation & consciousness

Neurophysiologic state produced by general

anaesthetics characterized by five primary effects:

Major effects of anaesthesia.

1. Unconsciousness
2. Amnesia and lack of awareness
3. Analgesia
4. Inhibition of autonomic reflexes
5. Skeletal muscle relaxation .
Ideal anaesthetic-
- Rapid induction
- Smooth loss of consciousness
- Rapidly reversible upon
discontinuation
- Possess a wide margin of safety

The cardinal features of general anaesthesia

are:
• Loss of all sensation, especially pain
• Sleep (unconsciousness) & amnesia
• Immobility & muscle relaxation
• Abolition of somatic & autonomic reflexes
Patients Factors in Selection of Anaesthesia
A. Status of Organ Systems
i. Cardiovascular system
ii. Respiratory system
iii. Liver & Kidney
iv. Nervous system
v. Pregnancy
B. Concomitant use of non-anaesthetic drugs
i. Alcohol
ii. Opioids
 Depth of Anaesthesia
Stage I: Analgesia-loss of pain sensation
Stage II: Excitement-Delirium or combative
behaviour.
Stage III: Surgical anaesthesia-Loss of
muscle tone, loss of spontaneous movement
Stage IV: Medullary paralysis-severe
depression of respiratory/vasomotor centers;
death can occur at this stage unless effort is
made to maintain circulation and respiration.
 Stages of Anaesthesia
• Induction: Depends on how fast the drug
gets to the brain and it varies
• Maintenance of Anaesthesia: Period
during which the patient is surgically
anaesthetized. Vital signs & organs are
monitored. IV infusions of various drugs may
be applied.
• Recovery: After the procedure, the various
anaesthetic agents are withdrawn and the
patients gradually recovers consciousness
 Pharmacokinetics
Procedure for producing anaesthesia involves smooth & rapid induction

Maintenance

Prompt recovery after discontinuation

Induction –

“Time interval between the administration of

anaesthetic drug & development of stage of
surgical anaesthesia”

Fast & smooth induction desired to avoid

dangerous excitatory phase
Thiopental or Propofol often used for rapid
induction.

Unconsciousness results in few minutes after

injection

Muscle relaxants(Pancuronium or Atracurium)

co-administered to facilitate intubation.

Lipophilicity is key factor governing

pharmacokinetics of inducing agents
Maintenance

Patient remains in sustained stage of surgical

anaesthesia (stage 3 plane 2)

Depth of anaesthesia depends on

concentration of anaesthetic in CNS

Usually maintained by administration of gases

or volatile liquid anaesthetics (offer good
control over depth of anaesthesia).
Recovery
Recovery phase starts as anaesthetic drug is
discontinued (reverse of induction)

In this phase, nitrous oxide moves out of blood

into alveoli at faster rate (causes diffusion
hypoxia)
Oxygen given in last few minutes of anaesthesia
& early post-anaesthetic period

More common with gases relatively insoluble in

blood
 Major Anaesthetic Drugs
• Inhalation anaesthetics -
they are administered through a face mask.

• Intravenous anaesthetics -
they are administered through intravenous
route.
 Inhalation Anaesthetics
• Inhalation anaesthetics are a diverse group of
compounds that are used in a gaseous form
to render a patient unconscious so that
surgical procedures can be carried out.

• They are administered through a face mask.

• An inhalational anaesthetic is a chemical

compound possessing general anaesthetic
properties that can be delivered via inhalation.
 Mechanism of action of Inhalation
anaesthetics
• Inhalational anaesthetics can hyperpolarize
neurones and hence reduce both pacemaker
neurone and post-synaptic neurone action
potentials.

• Inhalational and intravenous anaesthetics affect

synaptic function by inhibiting excitatory synapses
and enhancing inhibitory synapses.
• Currently-used agents: Halothane, Desflurane,
Isoflurane, Nitrous oxide, Sevoflurane, Xenon,
Methoxyflurane.

• However, inhalation anaesthetic agents are rarely

used alone; other medications are frequently
administered to induce or supplement anaesthesia.

• Volatile anaesthetic agents share the property of

being liquid at room temperature, but evaporating
easily for administration by inhalation.
Intravenous Anaesthetics
a. Fast inducers –
i.) Thiopental, Methohexital
ii.) Propofol, Etomidate
b. Slow inducers –
i.) Benzodiazepines – Diazepam, Lorazepam &
Midazolam.

c. Dissociative anaesthesia – Ketamine

d. Opioid analgesia – Fentanyl

 Intravenous anaesthetics
Thiopentone sodium

Ultrashort acting thiobarbiturate, smooth

induction within one circulation time.

Crosses BBB rapidly.

Diffuses rapidly out of brain, redistributed to

body fats, muscles & other tissues.

Typical induction dose is 3-5mg/kg.

Metabolised in liver
Thiopentone sodium contd
Cerebral vasoconstriction, reducing cerebral blood
flow & intracranial pressure(suitable for patients with
cerebral oedema & brain tumours)
Laryngospasm on intubation
No muscle relaxant action
Barbiturates in general may precipitate Acute
intermittent porphyria (hepatic ALA synthetase)
Reduces respiratory rate & tidal volume
 Propofol
Available as 1% or 2% emulsion in oil

Induction of anaesthesia with 1.5-2.5mg/kg within 30 sec &

is smooth & pleasant

Low incidence of excitatory voluntary movements

Rapid recovery with low incidence of nausea & vomiting

(antiemetic action)

Non-irritant to respiratory airways

No analgesic or muscle relaxant action

 Propofol contd.
Anticonvulsant action

Preferred agent for day care surgery

Apnoea & pain at site of injection are common after bolus

injection

Produces marked decrease in systemic blood pressure

during induction (decreases peripheral resistance)

Bradycardia is frequent
 Ketamine
Phencyclidine derivative

Dissociative anaesthesia: a state characterized by

immobility, amnesia and analgesia with light sleep and
feeling of dissociation from surroundings

Primary site of action – cortex and limbic system – acts by

blocking glutamate at NMDA receptors

Highly lipophilic drug

Dose: 1-2mg/kg i.v.

 Ketamine contd...
Only i.v. anaesthetic possessing significant analgesic
properties & produces CNS stimulation
Increases heart rate, blood pressure & cardiac output
Markedly increases cerebral blood flow & ICP
Suitable for patients of hypovolaemic shock
Recovery associated with “emergence delirium”, more in
adults than children
Use of diazepam or midazolam i.v. prior to administration of
ketamine, minimises this effect
 Fentanyl
Potent, short acting (30-50min), opioid analgesic

Generally given i.v.

Reflex effects of painful stimuli are abolished

Respiratory depression is marked but predictable

 Fentanyl contd..
Decrease in heart rate, slight fall in BP

Nausea, vomiting & itching often occurs during

recovery

Also employed as adjunct to spinal & nerve block

anaesthesia & to relieve postoperative pain
 Complications of Anaesthesia
During anaesthesia: After anaesthesia:

Respiratory depression Nausea and vomiting

Salivation, respiratory Persisting sedation
secretions Pneumonia
Cardiac arrhythmias Organ damage – liver,
Fall in BP kidney
Aspiration Nerve palsies
Laryngospasm and Emergence delirium
asphyxia Cognitive defects
Awareness
Delirium and convulsion
Fire and explosion
 Balanced anaesthesia
General anaesthetics rarely given as sole agents

Anaesthetics adjuvants used to augment specific components

of surgical anaesthesia, permitting lesser doses of GA

General anaesthetic drug regimen for balanced anaesthesia:

Thiopental + Opioid analgesic(pethidine or fentanyl/

benzodiazepine) + Skeletal muscle relaxant
(pancuronium) & Nitrous oxide along with inhalation
anaesthetic(Halothane/other newer agents )
Thanks for listening!