GENERAL ANAESTHETIC DRUGS

General anaesthetic depress the CNS and cease a loss of consciousness associated with an inability to
perceive pain.

An ideal anaesthetic would produce amnesia with unconsciousness, analgesia and muscle relaxation
suitable for all surgical procedures and would be metabolically inert and rapidly eliminated.

No single anaesthetic fulfils all these requirements in safe concentrations and so a number of drugs
are often used to achieve the required conditions while minimizing the risk of toxicity.

General anaesthetics are administered either by inhalation or intravenously.

IV anaesthetic agents include;

The Barbiturates e.g. Thiopentone

Phenol e.g. Propofol

Carboxylated imidazole e.g. etomidate

Phencyclidine e.g. ketamine

Inhalational anaesthetics include Halothane, enflurane, isoflurane, nitrous oxide, anaesthetic ether.
The activity of any anaesthetic is dependent on its ability to reach the brain. With the injectables
anesthetics, their activity is dependent on their ability to cross the blood brain barrier and recovery
from their effects is determined their redistribution and excretion.

Conventional general anaesthesia may be divided into a number of stages including:

 Premedication.
 Induction
 Muscle relaxation and intubation
 Maintenance
 Analgesia
 Reversal

For premedication – Benzodiazepines may be given to sedate and relieve anxiety in apprehensive
patients. Antimuscarinics e.g. atropine may be given to inhibit excessive bronchial and salivary
secretions induced by intubation and some anaesthetics. They are also given to reduce intra operative
bradycardia and hypotension induced by drugs such as suxamethonium, propofol etc.

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Induction – the main aim of induction is to produce anaesthesia rapidly and smoothly. It is the
process of taking patient from the awake state to one in which surgery can be started. They may be
achieved with intravenous or inhalational anaesthetics. Intravenous drugs used include the ultra-short
acting barbiturates such as thiopentone. Benzodiazepines such as midazolam and others such as
etomedate, propofol or ketamine may also be used.

Small doses of opiods/narcotics such as fentanyl given before or after induction allow the use of
smaller induction doses of thiopentone. Giving a narcotic for induction is particularly useful for
patients with cardiac disease, in whom it is necessary to maintain stable cardiac output and blood
pressure.

Following induction, muscle relaxation with a rapidly acting neuromuscular blocker e.g.
suxamethonium facilitates intubation of the patient.

Maintenance of anaesthesia may be achieved with an inhalational, intravenous anaesthetic or IV

opiod either alone or in combination.

The most widely used techniques for maintenance use inhalational anaesthetics, with the patient
breathing a mixture of oxygen, nitrous oxide and one of the 3 volative anaesthetic liquids (enflurane,
isoflurane or halothane).

At the end of surgery, drugs are administered to accelerate recovery by reversal of the effects of
various agents used during anaesthesia.

The neuromuscular block produced may be reversed with anticholinesterases such as neostigmine
and edrophonium. An anticholinergic such as atropine may be administered at the same time to
counteract or prevent bradycardia developing.

The opioid antagonist, naloxone, may be given to reverse respiratory depression caused by opiods.
The increasing use of short acting opioids should reduce the need for this as it may interfere with the
analgesic action required post operatively.

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PROPOFOL

It is an anaesthetic given IV for induction and maintenance of anaesthesia. Also used for sedation in
patient undergoing diagnostic procedures. May be given in conjunction with local anaesthesia or in
ventilated adult patients under intensive care. Propofol induces unconsciousness within 1 minute of
injection. Its effects are also brief.

It is safe for use in patients with porphyria (for whom barbiturates are contraindicated) or a
susceptibility to malignant hyperthermia (which contraindicates the use of halothane and related
inhaled drugs). Propofol is available as a 1% or 2% emulsion.

The 1% emulsion may be given by IV injection or infusion but the 2% is for infusion only.

Dose: Individual requirements vary so recommended dose is only a guide.

Induction of anaesthesia by IV injection or infusion 1.5 – 2.5mg/kg at a rate of 20-40mg every 10

seconds.

Maintenance of anaesthesic by IV injection 25-50mg repeated according to response or by IV

infusion 4 – 12mg/kg/hour

Sedation in intensive care by slow IV infusion 0.3 – 4mg/kg/hour

LIMITATIONS OF PROPOFOL

Intravenous injections can be painful. Pain can be reduced by giving the drug into a large vein or by
IV injection of a local anaesthetic first. Propofol should be used continuously in patients with
ischaemic coronary or peripheral vascular disease especially when it is used with nitrous oxide or
narcotics. Depression of cardiac contractility, blood pressure, respiration can occur.

Hypotension may be a particular problem in the elderly.

Trade Names – Diprivan (Astra Zeneca), etc.

MUSCLE RELAXANTS

The junction between the motor nerve and the muscle fibre supplied is termed the neuromuscular
junction. There is a small gap between the end of the nerve and the motor end plate of the muscle
fibre. This gap is bridged by the release of very small amounts of acetylcholine every time a nerve
impulse arrives. The acetylcholine diffuses away and is destroyed after its release by the enzyme

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cholinesterase. The acetylcholine release at the neuromuscular junction is the same substance that is
release at parasympathetic termination but the muscle receptors are different in the 2 cases.

The Acetylcholine receptor of the skeletal muscle is not blocked by atropine but is blocked by muscle
relaxant drugs.

The acetylecholine receptor of the skeletal muscle is not blocked by atropine but is blocked by
Muscle Relaxant Drugs.

Those neuromuscular blockers which do not prevent the release of acetylcholine but stop it acting on
the motor end plate are termed competitive (or non-depolarizing) neuromuscular blocking agents
e.g. curare, gallamine.

Other neuromuscular drugs block neuromuscular transmission by keeping the motor end plate in a
state of depolarization. They are only destroyed slowly by the enzyme psuedocholinesterase. They
are termed depolarizing neuromuscular blocking agents. With the introduction of muscle relaxant
drugs, very light anaesthesia may be used.

One disadvantage of the use of muscle relaxant drugs is that the patient may stop breathing due to a
paralysis of the respiratory muscles (respiration is brought about by voluntary muscles)

Artificial respiration may have to be employed for the duration of the operation and continued until
the effects of the muscle relaxant drugs have worn off.

Muscle relaxant drugs are of 3 main types

1. Centrally acting relaxants e.g. Baclofen

2. Directly acting relaxants e.g Dantrolene
3. Neuromuscular blockers – (i) competitive (ii) non-competitive/depolarizing

Neuromuscular blockers affect transmission at the neuromuscular junction and are used as adjuncts to
general anaesthesia to enable adequate muscle relaxation to be achieved with light anaesthesia.

There are two main types;

The competitive neuromuscular blockers do not stop the production of acetylcholine but compete
with it for receptors on the motor end phase. Their action can be opposed by increasing the local
concentration of acetylcholine for e.g. by giving an anticholinestease such as neostigmine.

Examples of competitive neuromuscular blockers are:

Atracurium

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Tubocurarine

Vecuronium and Pancoronium

The depolarizing neuromuscular blockers act by depolarizing the motor end plate to prevent the
normal response to acetylcholine.

Their action is not reversed by anticholinesterases but by pseudocholinersterases

e.g. is Suxamethonium (succinylcholine)

Generally competitive neuromuscular blockers have a slower onset and a longer duration of action
and are used in major operations while the depolarizing neuromuscular blockers have a faster onset
and a shorter duration of action and are used in minor operations or manipulations and particularly for
intubation.

Neuromuscular blockers are used as;

1. Adjuncts in anaesthesia
2. To ventilate the lungs in cardiothoracic surgery or intensive care when patients require
mechanical ventilation. Here they provide additional relaxation and facilitate ventilator
support in patients who fail to respond to sedation alone.
3. They facilitate tracheal intubation

SUXAMETHONIUM

Should be used with caution in patients with reduced plasma cholinesterase activity e.g. In pregnancy,
severe liver disease, hypothyroidism, anaemias, cancer, malnutrition.

It is contraindicated in patients with burns, massive trauma, renal impairment with a raised plasma
potassium concentration.

It may cause hypersensitivity reactions.

Following IV injection, Suxamethonium acts in about 30 – 60 seconds and has a duration of action of
2 – 6 minutes.

Following IM injection, onset is 2 – 3 minutes and duration is 10 – 30 minutes. It is used in surgical

and other procedures in which a rapid onset and brief duration of muscle relaxation is needed – e.g in
intubation, endoscopies, etc. Normally given by IV injection.

In anaesthesia, it is given after induction. Assisted respiration is necessary.

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The usual single dose for an adult is 0.3 – 1.1mg/kg body weight by IV injection with a usual range
of 20mg – maximum total of 100mg.

Supplementary doses of 50 – 100% of the initial dose may be given at 5-10 minutes intervals if
required but the total dose by repeated IV injection or continuous infusion should not exceed
500mg/hour. When a suitable vein is inaccessible, suxamethonium has been given by IM injection.

LOCAL ANAESTHETICS

They are drugs used to prevent or suppress unpleasant sensations usually pain in or on a discrete area
of the body. They are also called Regional Analgesics. They produce a reversible loss of sensation by
preventing or diminishing the conduction of sensory nerve impulses near to their site of application or
injection.

LA’s (local anaesthesia) suppress pain through actions on peripheral sensory nerves without causing
sedation or unconsciousness without the risks of putting a patient to sleep and allow a quicker return
to normal activity.

Classification is based on their clinical structure;

1. Ester type e.g. procaine, cocaine, benzocaine, amethocaine, tetracaine

2. Amide type e.g. lignocaine/lidocaine (xylocaine®), bupivacaine, prilocaine

The chemical differences determine how they are metabolized in the body and help to tell whether a
patient who experiences an adverse reaction to one local anaesthetic can safely receive another.

The drugs vary widely in their potency, toxicity, duration of action, ability to penetrate mucous
membranes and it’s these differences that determine how suitable they are for use by various routes.

Local anaesthetics are not given orally because they are inactivated by gastric acid. They are injected
near the region to be anaesthetized or applied topically. The aim is to place the drug near its desired
site of action or at the nerve supply to that region.

At the normal pH of healthy body tissues, LA molecules are in the non ionized form and can diffuse
readily from their site of application to nearby nerves. Lidocaine and other amide type local
anaesthetics are metabolized by hepatic drug metabolizing enzymes. Their actions are intensified and
prolonged in persons with impaired hepatic function.

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PHARMACOLOGICAL EFFECTS

Sensory nerves are most sensitive to the effects of local anaesthetics and their function is inhibited
first. Pain disappears first followed by sensations of cold, heat, touch and pressure. With increasing
concentration or doses, larger nerve fibres including autonomic nerve fibres and motor nerves are also
inhibited. This often occurs with spinal anaesthesia.

Recovery from anaesthesia occurs in the opposite order i.e. motor nerves first followed by autonomic
nerves and lastly sensory nerves. Pain is generally the last sensation to return. LA’s used for relief of
pain or prevention of regional pain are administered in several ways.

1. SURFACE OR TOPICAL ANAESTHESIA

Surface anaesthesia blocks the sensory nerve endings in the skin or mucous membranes. Mucosal
surfaces are permeable to many drugs and they are rich in sensory nerve endings so they can be
anaesthesized easily by topical administration of anaesthetic solutions, ointments, creams or gels.

Topical application is mainly used and is sufficient for procedures such as inserting a device into an
orifice e.g. a urethral catheter or an endotracheal tube.

Special uses of topical local anaesthetics include;

 Anaesthetizing the cornea during ophthalmological procedures.

 The throat and larynx before intubation and bronchoscopy.
 Anaesthetizing the urethra in which case great care is necessary because if trauma has
occurred rapid absorption of the drug occurs and can give rise to serious adverse effects.
 LA’s have also been included in topical preparations to relieve pain of haemorrhoids and for
pain relief in pruritus and anal fissure

Penetrations of intact skin by LA’s is generally poor whereas absorption through mucous
membranes may be rapid.

NURSING IMPLICATIONS

Applying any LA to the throat may suppress normal swallowing and cough reflexes that are
necessary to prevent aspiration into longs of secretions, gastric juice, food or beverages. Hence
instruct patients who have received topical LA’s on the mouth or throat to avoid eating or drinking

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for at least 1 hour after drug administration to reduce the risk of aspiration, chocking or accidentally
biting the tongue, lips or cheek.

Topical application of a LA to large areas or to lacerated surfaces can lead to excessive drug
absorption into the blood stream and systemic toxicity

2. INFILTRATION ANAESTHESIA

This is produced by injecting the LA directly into and around the field of operation without
attempting to identify individual nerves. Subcutaneous or intradermal injection (infiltration) of LA’s
is often used to suppress pain associated with suturing lacerations making small surgical incisions and
performing some dental procedures.

Lidocaine solution of concentration between 0.5% and 1% are generally used. To minimize toxicity,
total dose should not exceed 300mg for small wounds, this is more than adequate but when large
areas are involved and the procedure is long and more drug is given, the risk of toxicity increases. An
alternative technique is to add a vasoconstrictor in low concentrations to achieve the desired effect
without exceeding the maximum dose. Adrenaline 1:100, 000 or 1:200,000 is often used. They reduce
rate of absorption into the blood stream. Vasoconstrictors shorten the onset of LA action, increase the
potency and prolong LA action.

NURSING IMPLICATIONS

Vasoconstrictors should not be used in LA’s given to highly vascularized areas of skin or body that
have single path for blood supply including fingers or toes, the earlobes or the penis. Doing so to
these sites, may reduce blood flow enough to cause tissue ischaemia and necrosis. Vasoconstriction is
also damaging to inflamed or infected tissue.

Children, geriatric and debilitated patients are more sensitive to vasoconstrictors and to LA’s so dose
should be reduced.

3. REGIONAL CONDUCTION BLOCK ANAESTHESIA OR REGIONAL NERVE BLOCK

ANAESTHESIA

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This is a modification of infiltration anaesthesia which can also be used when the area to be
anaesthesized is large, difficult to reach directly or requires many injections. It is also used when the
site to be anaesthetized is ischaemic, necrotic or encapsulated by a cysts.

LA’s will not work well when injected into these areas because of reduced blood flow which will
prevent the LA from reaching the nerves.

These are variations of the Regional Block Techniques among them are central Nerve Blocks
Comprising Spinal and Epidural (Peridureal) Anaesthsia

The epidural is achieved by injecting the drug into the epidural space, located in the spinal canal
between the bone and dura mater, usually in the lower lumbar region.

The technique is often used in obstetrics, orthopaedic surgery and other surgical procedures involving
the lower half of the body. Today epidural can be used for cervical thoracic as well as abdominal
procedures.

Spinal anaesthesia is also often used to suppress pain in the abdomen, pubic region or legs. Here,
relatively small amounts of LA are injected beneath the dura in the spinal fluid of the lower lumbar
region.

ALLERGIC REACTIONS

The only major contraindication to the use of a local anaesthetic is a history of allergic reactions to
that agent, to a local anaesthetic that belongs to the same chemical class, or to a preservative in the
anaesthetic.

They are more common with ester type local anaesthetics and rare with the amides. Many allergic
reactions are due to the LA or its metatolites or by paraben, sulfite or bisulfite preservatives.

GENERAL NURSING IMPLICATIONS FOR THE ADMINISTRATION OF LOCAL

ANAESTHETICS.

General anaesthesia renders the patient unconscious and so alleviates much emotional stress. With
LA, the patient is awake and it is essential for the nurse to help allay fear and anxiety before and
during the procedure.

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Always double check the LA container especially during emergencies, to use the correct
concentration and ingredients. Check for preservatives which should not be used for spinal
anaesthesia or those with previous allergic reactions to it.

Do not use solutions that are outdated and are not colourless or precipitate free.

The initial injection of a LA will cause minor pain like a mild bee sting until its effects develop
(usually a few seconds) inform the patient.

Take precautions to prevent accidental trauma to regions of the body that have been anaesthetized
(especially oral tissues and extremities).

If a patient has received a LA that can affect blood pressure or lower extremity function such as
spinal anaesthesia, confine the patient to bed, with side rails, until full sensation has returned and vital
signs have normalized.

To reduce contact with the drug and the risk of allergic reactions, always wear gloves when
administering LA by any route.

LIGNOCAINE

It is a local anaesthetic of the amide type used for surface, infiltration and regional nerve block. It is
the overall prototype and the most widely used LA because it has properties which makes it almost
ideal.

It is effective whether administered topically or by several parenteral routes.

It is effective even when used without vasoconstrictors

It has a prompt onset of action yet a duration of action sufficient for most surgical procedures to be
completed without need for frequent drug administration

It has satisfactory potency

Its toxicity is sufficiently low so therapeutic doses if administered correctly are not likely to produce
significant side or adverse effects.

It is much less likely to cause allergic reactions than ester type LA’s

Lignocaine has both local and systemic effects

Local effects include loss of pain and other sensations. Vasodilation and loss of motor power

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Systemic effects occur following absorption from the site e.g. local administration.

Adverse effects are due to over-dosage and include anxiety, excitement, progressing to sedation,
disorientation, restlessness, tremors, convulsions and unconsciousness.

The doses used depend on the site of application and the procedure used.

Ligcocaine is available in a variety e.g. formulations.

For surface anaesthesia, strength is usually between 2% - 4%

 Lignocaine ointment for anaesthesia e.g. skin and mucous membranes

Lignocaine gel for anaesthesia of the urinary tract
 Topical solutions for surface anaesthesia of mucous membranes of the mouth, throat and
upper GI tract
 It is also available as a 10% spray for application to mucous membranes, during procedures
such as endoscopy and bronchoscopy.
 May be used rectally as suppositories, ointments and crease in treatment of haemorrhoids and
other peri-anal conditions.
 Eye drops containing 4% lignocaine HCl are used in tonometry

For infiltration anaesthesia, a concentrating 0.5 – 1% is normally used.

The max safe dose for a 70kg man is 200mg without Adrenaline (3-4mg/kg) and 400-500mg with
Adrenaline (6-7mg/kg). effects are noted 5-10 minutes after administration and duration of action is
of order of 2-3 hours.

Lignocaine is also used in treatment of ventricular arrythmias.

Initial dose 1 – 1.5mg/kg IV bolus over 2-3 minutes may repeat doses of 0.5-0.75mg/kg in 5-10
minutes up to a total e.g. 3mg/kg.

By continuous infusion: 1 – 4mg/minute

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