general anaesthesia by dr. nimer khraim. mode of action of anaesthetic drugs the mechanism by which...

General Anaesthesia

By

Dr. Nimer Khraim

Mode of action of anaesthetic drugs

The mechanism by which the anaesthetic drugs produces their action is not very well known.

But simply they may act by switching off excitatory systems & turning on inhibitory ones

so that impulses from periphery to the brain are blocked mainly at the thalamic level,


while a similar action on the fusiomotor system may explain the loss of motor control associated with general anacsthesia.

As cerebral cortex being responsible for the maintenance of consciousness, it is the first part of the brain to be affected during induction of anacsthesia


when its function is abolished unconsciousness is lost and the lower parts of the brain are released and become more active

As anaesthesia deepens various hypothetical centers are depressed down until only the neurons in the medulla and spinal cord continue to maintain life.

Stage of General Anaesthesia and their Signs

Four stages of anaesthesia are describing the transition from conciseness to complete anaesthesia.

Stage of General Anaesthesia and Their Signs

Stage I: Introduction stage of voluntary excitement:

The animal is conscious and may make forcible efforts to avoid being anaesthesia.

It characterized by analgesia and disorientation without loss of consciousness and lasts from beginning of anaesthesia to the loss of conscious.


Clinically characterized by:

a. Heart Rate

b. Respiratory rate are deep.

c. Salivation.

d. Pupils = normal or slightly dilated.

e. Struggling.


Stage II. Stage of involuntary excitement:

This stage started from the loss of conscious

to the onset of regular breathing pattern.


Characterized clinically by:

Violent limb movement and exaggerated response to stimuli.

Pupils dilated and brisk nystgmus (eyeball) moving from side to side.


Swallowing and vomiting (pharyngeal reflex) are present, but become progressively depressed and disappear on entering stage III.

Respiration is very irregular and breath-holding is an invariable accompaniment of struggling.


Stage III. Stage of surgical anacsthesia:

Characterized by Unconsciousness loss of sensation to pain and movement.


This stage divided into 3 plans:

First plane (light) anaesthesia: Indicated by: Onset of regular automatic breathing. Cessation of all limp movements.


Nystagmus i.e eyeballs moving from side to side particularly in horses.

The palpebral, conjuctival and corneal reflexes disappear as anaesthesia deepens and are no longer present when the animal enters the second plane.


Many diagnostic investigations and minor operations can be performed in this plane of anaesthesia.


Second plane (medium) anaesthesia:

eyeballs is fixed centrally in horses, cats, sheep and pigs but in dogs the eyeball rotates downwards.

Respiration rate increases but its amplitude decreases.


The laryngeal reflex persist until the middle of the second plane is reached.

Muscle relaxation becomes progressively more pronounced.

Pedal reflex in the dog and cat becomes absent


This plane of anaesthesia is adequate for all except intra-abdominal surgery.


Third plane (deep) anaesthesia:

Automatic breathing is still present, but respiratory rate increases while its depth decreases and a noticeable pause appear between inspiration and expiration.


All body reflexes abolished.

In the dog and cat the eyeballs once again become central as the tone of the eye muscles is lost.


Stage IV. Stage of Over dosage:

In this stage Paralysis of the thoracic muscles is complete and only diaphragmatic activity remains.


The stage characterized by:

irregular respiration & respiratory arrest. The pulse become rapid and the pupils

dilate.


Cyanosis appears & soon replaced by the ashen-grey color, which indicate heart failure & cardiac arrest follows closely.

At this point immediate Vigorous corrective therapy is required to successfully resuscitable patient.

Anesthetic Agents Used for Induction of General Anaesthesia:

Two main types often used to induce. G.A. in veterinary practice:

Intravenous anaesthesia drugs.

Inhalational anaesthesia drugs.


intravenous anaesthesia drugs:

Generally divided into 2 main types

– The Barbiturate I.V anaesthesia agents.– The Non- barbiturate anaesthesia drugs.


Advantages of intravenous anaesthesia agents over inhalation anaesthesia agents:

Minimal equipment required. Economical i.e. simple non-expensive equipments. Quickest method for induction of anaesthesia. Good for short surgical or diagnostic procedures.


Disadvantages of I.V anaesthesia agents:

The plan (level) of anaesthesia can’t be decreased quickly i.e. if over dosage occurred, it cannot be reversed rapidly.

Recovery from anaesthesia depends on the animals ability to detoxify or excrete the drug i.e the general condition of animal is important.


Recovery period may be long & Stormy.

Long surgical procedures which needs administration of I.V anaesthesia agents for longer periods or in larger doses can cause sever physiological and damages in the patient

Oxygen and other respiratory support equipments (e.g., respiratory ventilator) may not be available.

Anaesthesia with Inject able agents

Equipment:

A suitable hypodermic needle and a syringe are all that essential for parental administration of anaesthesia drugs.

Intravenous (I.V) injectable anaesthesia agents

The barbiturate drugs: These are divided into 4 groups of compounds

a. Oxybarbiturates

b. Methylated oxybarbiturates.

c. Thiobarbiturates

d. Methylated thiobarbiturates.


Compounds from group (a) & (c) are mainly used in veterinary anaesthesia, because they produce unconsciousness in few site-brain circulation times.


The barbiturate in clinical use are all sodium salt of barbituric acid or their oxy or thio-deravitives, whose chemical structure had been modified to increase their lipid solubility and hence potency.

Pentobarbiturate

The important barbiturate drugs in veterinary anaesthesia are:

Pentobarbiturate sodium (Segatal® 6% Nembutal ® 10 %; Narkoderm®).

It is an oxybarbiturate drug, available as sterile alkaline solution of 6.10 & 20 mg/ml.

Pentobarbiturate

Pharmacology

A- Effects on CNS relatively crosses the BBB slowly its peak effect delayed for few minutes (5-10 mins.) It is mainly a potent depressor to the motor areas of

the brain (cerebral cortex & probably the hypothalamus)

hence it is used to control convulsive seizures.

Pentobarbiturate

B- Respiratory system: The drug depresses the respiratory centers

at a dose dependent proportion. The sensitivity of the respiratory center for

CO2 is reduced.

Pentobarbiturate

C- cardiovascular system: The drug causes a fall in blood pressure

following direct depression of the vasomotor center.

It has a little direct toxic effect on the myocardium.

Pentobarbiturate

D- Fat in the body:

The drug metabolized by the liver products eliminated by rental excretion.

Pentobarbiturate

Uses & Doses: It is hazardous in most species, particularly in large

animals, to obtain surgical levels of anaesthesia with pentobarbinate alone.

it is used, particularly in large animals to prolong the duration of narcosis following the administration of another anaesthetic agent e.g., chloral hydrate.

in small animals (dogs & cats) it is used a sole anaesthetic agent.

Pentobarbiturate

Small animals: (Dogs & Cats) 20-25 mg/kg B.wt.

Half to Tow-third of the calculated dose is given I.V quickly to avoid excitement during induction, then the remaining is given very slowly until effect of general anaesthesia is obtained.

Pentobarbiturate

Sheep: 20-25 mg/Kg B.wt. It is a useful agent with duration of

anaesthesia ranging 5-10 up to 25 mins when a single bolus dose is given. The short duration of action in these animals are due mainly to the rapid metabolism of the drug by the liver.

Thiopentone sodium

Thiopentone sodium: Pentothal®, Interval®. It is a thiobarbiturate derivatives, with a

shorter duration of action than pentobarbitone due partly to its higher fat solubility & because it is metabolized in the liver quite rapidly during early stages of anaesthesia.

Thiopentone sodium

The drug prepared commercially as a yellowish-white powder.

It is highly soluble in distilled water with an alkaline pH (pH=11).

This it is extremely irritant to the body tissues if given extravascularly.

Thiopentone sodium

Because, theopentone is a highly fatty soluble drugs, it crosses the BBB with very great speed

makes the drug very useful for the production of anaesthesia with rapid induction, short period of narcosis & rapid recovery as the drug redistribute from the plasma to other body tissues such as body muscles and fat.

Thiopentone sodium

Pharmacology:

1- CNS:

Medullary depression.

Thiopentone sodium

2- Respiratory Syetem: Markedly depressed following rapid administration.

Usually there is increase in depth of respiration followed by a short period of apnoea.

Thiopentone sodium

3- Cardiovascular System: Depresses the myocardium sever hypotension may occur if large doses

are given due to peripheral vasodilatation.

Thiopentone sodium

4- Fate in the body. After rapid I.V administration Thiopentone exerts its

effect on the CNS almost immediately. Then the drug level in the plasma fail rapidly due to

its redistribution into body muscles & fat. This is why rapid recovery from Thiopentone occurs. The drug is rapped metabolized in the liver & exerted

by the kidneys.

Thiopentone sodium

Uses & Dosage: 1-Used as a sole anaesthesia agent with

premedication for short surgical procedures in small & large animals.

For larger procedures, additional increments of Thiopentone I.V can be given to maintain anaesthesia for a longer duration of time.

Thiopentone sodium

2- As an induction agent prior to the anaesthesia by inhalation agents.

Thiopentone sodium

Large animals (Horses & Cattle): 1 g/90 Kg B.wt. given to rapid I.V injection (10% solution).

Sheep & Goat: 20-25 mg/Kg B.wt. (2.5-5% solution).

Dogs & Cats: 25-35 mg/Kg 1% sol. Half of the dose is given rapidly & the remaining is given slowly to-effect.

Methohexitone Sodium (Braven ®).

It is a rapidly acting oxybarbiturates with important differences from other barbiturates

a- Potency 2 to 3 times greater than that of Thiopentone.

b- Shorter duration of effect.

c- More rapid recovery to full alerness even after prolonged anaesthesia


Note:

Methohexitone sod. is administrated to small animals as a 1% solution & large animals concentrated solutions of up to 6% used.


Doses Cats: I.V doses of 5mg/Kg at 0.5% solution. Cattle: because recovery after

methohexitone Na is more rapid than that after thiopentone, it might be better for use in cattle. In adult cattle 25 mg/kg by rabid I.V 2.5-5% sol.


Horses: used in horses premedicated with acepromazine (0.04 mg/kg)

the I.V does of methohoxitone being used for induction of anaesthesia is 0.5g 90kg. B.wt. (6% solution).

Accidental extravascular injection does not cause tissue nerosis as occur with thiopentone & recovery is more rapid & complete than after thiopentone.

Non- barbiturate intravenous anaesthesia agents:

1- Chloral hydrate: A white translucent crystals substance which has a

pungent smell. It is water soluble. The drug is primarily a hypnotic but when given in

large quantities, it will produce narcosis and anaesthesia with low analgesic action.

The drug is irritant (pH=11) when given a perivascularly it will cause sever

tissue damage.


Effects on Respiratory systems: In hypnotic doses the drug produce

depression, due to failure of respiratory center.

C.V.S: Myocardial contractility is reduced & arterial blood pressure falls.


It is administered in large animal in solution of 10% concentration.

Doses for Horses and Cattle: 5g./50kg B.wt. one third is run in over 4 minutes and as soon as the animal becomes ataxic & then on the ground the remainder is given to effect.

2- Chloral hydrate Magnesium Sulphate Mixtures:

A dose of 5 gm of each (i.e. Chloral hydrate and magnesium Sulphate)/50 kg. B.wt. in 10% solution claimed to hastened to onset of anaesthesia muscle relaxation & increases the depth of anaesthesia and reduce the toxicity produced by chloral hydrate when given alone.


3- Equithesin ® Army preparation: It is a mixture from the following

components:

1. Chloral hydrate 28gm.

2. Mag. Sulphate 14 gm.

3. Pentobarbitone Na 6.5 gm.

4. Distilled water up to 1000 c.c.


Note: This solution must be prepared within one

hour before administration to prevent precipitation occurs as a result of reaction between chloral hydrate and pentobarbonate.


Advantages:

1. The mixture has low toxicity.

2. Low quantity required for anaesthesia.

3. Excitement during induction is less.


Disadvantages:

the solution is very irritant if given perivascularily.


Doses: Horses and Cattle 20-30 ml/50kg. B.wt I.V.

slowly.


4- Dissocitative agents (Cyclohexylamine derivatives)

A group of chemically related compounds of which 3 are of clinical importance, namely: Phenecyclidine, Tiletamine & Ketamine. But the last agent i.e. Katamine is the most widely for use in men animals.


These agents are described as having a cataleptic, analgesics & anaesthetic actions, but without hypnotic properties.

Catalepsy is defined as a characteristic akmetic state with loss of orthostatic reflexes but without loss of consciousness in which the extremities appear to paralyzed


Ketamine : is the only dissociative agent Widely accepted for chemical use

The drug metabolized by the liver In cat a large part is excreted unchanged by

the kidney and the reminder metabolized by the liver


Effects on the body:

CNS Ketamine alters the reactivity of CNS to various

sensory impulses without blocking sensory input at spinal or brain stem levels.

Its anaesthetic action requires the presence of a functional cerebral cortex.

The drug increases the intracranial pressure due to increased cerebral blood flow.


CVS

It causes a transient hypotension & Brady cardia followed by an increase in HR and BP.


Respiratory system: It doesn't dependent ,respiratory depression Salivation simulated by Ketamine, but can be

controlled with atropine.


Uses and Dosage: Horse: used in combination with xylazin which

produce a smooth & slow induction & provide 5-15 mins of anaesthesia &10-20 mins. of recumbency.

Xylazine 1.1 mg/kg I.V after 2-5 mins. and katamine 2.2 mg/kg I.V.

Either mixed in the same syring or given separately.


Sheep: 0.05 mg/kg xylazine and 4mg/kg katamine. The two drugs either mixed or given separately and gives 50-90 minutes of analgesia & restraint.


Small animals: Dogs: Atropine sulphate 0.6 mg I.M or S.C. Xylazine 2mg/kg I.M.Katamine10-15 mg/kg I.M 10 to 15 min. better. Cats: Atropine sulphate 0.3 mg/kg S.C. Xylazine 1.1mg/kg I.M. Katamine 15-20 mg/kg I.M 10 to 20 min.

better.

Disoprofol

Is a very new anaesthetic agent. Its active ingredient is 2.6-

disoprophylphenol. It is a rapidly acting agent which produce

anaesthesia for short duration & without excitatory side-effects.

Disoprofol

This agent has shown to be compatible with a wide range of drugs used for premedication, inhalation anaesthesia & neuromuscular agents.

2mg/kg of Disoprofol I.V is an effective agent for smooth induction of anaesthesia in horses after xylazine premedication. anaesthesia

general anaesthesia by dr. nimer khraim. mode of action of anaesthetic drugs the mechanism by which...

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