( Maybe it is a long script .. but its very easy and enjoyable to study ..

GOOD LUCK ^_^ Eman Nazzal )

General Anaesthesia (GA)

Definition : General anaesthesia is defined as a condition in which the patient has lost : 1-consciousness 2- analgesia : loss of pain sensation . 3- amnesia : loss of memory . Why amnesia ??
((Bcz in Any surgery the patient become in a fear situation so it is preferred that the patient loss his memory, in order not to remember anything))

4-muscle relaxation. Why muscle relaxation ??

((In order to enhance surgery we need a good muscle relaxation ))

5- loss of autonomic reflexes . General anaesthetic has . That are administered for induction to make any general anaesthetic which is VERY important before any surgery , in which once the patient go to surgery ( it is a must ) must have lost of consciousness , no pain sensation , amnesia in which the patient cant remember anything .

So,

general anaesthesia is a condition which characterized by

analgesia, amnesia, loss of consciousness, inhibition of sensory and autonomic reflexes, and, in many cases, skeletal muscle relaxation. Local anaesthesia : we induce analgesia, without loss of consciousness , and administered locally to certain area , in which the patient cant sense the pain at the side of administration .
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General anaesthesia Drugs: So general anaesthesia Drugs it is a reversible loss of consciousness

( many of us think that anesthesiologists career is very easy , But it is Not bcz u induce a consciousness , u induce a reversible comma , and in the case of over dose this lead to death .But when the dose calculated carefully this will induce or maintain general anesthesia to facilitate surgery.

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4 Stages of General anaesthesia : The anesthesia goes in 4 main stages , and also some sub stages : 1- Analgesia 2- Excitement 3- Surgical anaesthesia 4- Medullary paralysis

stage 1 : Analgesia Analgesic effect is the partial loss of pain sensation with impairment loss of consciousness , ( start with impairment loss of consciousness. )

Analgesia is partial until stage II is about to be reached.

stage 2 : Excitement It is stage of excitement or stage of dis-inhibition. Here there are excitement , involuntary movement , irregular BP & irregular respiration . ## What did u think ! We now in this stage >> should we go to the next stage rapidly ? or keep the patient in this stage ?? did u think that this is the stage of surgical anaesthesia ?? No , We should go to the next stage as rapid as we can Bcz this as the stage of excitation , there are undesirable effect on the patient and we should go to the next stage rapidly
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stage 3 : Surgical anaesthesia : here we get the anesthetic purpose ( which we mentioned at the beginning of Lecture. e.g : analgesia etc) , at the same time respiratory and the cardiovascular system are maintained , and there is regular respiration , Blood pressure is controlled at the same time I will get the anesthetic purpose >

Once we reach this stage the surgery is proceed.

stage 4 : Medullar paralysis:

Stage of medullary depressor that seen in the case of anesthetic over-Dose and we will have respiratory and cardiovascular depression center in the medulla , and without full control or support : death will occur ( in the case of over-Dose ) .

Induction of anaesthesia 3 123group of drugs can be administered : Drugs that administered as Pre-anesthetic medication ( prior to surgery) Drugs that administered to induce anaesthesia Drugs that administered to maintain anaesthesia
( the doctor say something but it is not clear at (10:10 min ) in the record )

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1- Induction of anaesthesia : what did we mean by induction ? To reach or to start anaesthesia . this is done by administration of Intravenous Drugs anesthetic in which the time from anesthetic administration until the patient reach stage 3
(which is the stage of surgical anesthesia and here the doctor can proceed the surgery ) .

2- maintain anaesthesia : Now , how we can maintain anaesthesia ? How can we maintain the loss the consciousness , analgesia , amnesia , loss of muscle relaxation and autonomic reflexes . HOW TO KEEP THE PATIENT IN All THESE CONDITIONS OR HOW TO KEEP HIM IN STAGE 3 ?? this is done by Inhaled anesthetics 3- Recovery period: is the time of discontinuation of GA until the patient regains to his consciousness. At the end of the surgery ( this is important ) , the dose of inhaled anesthetic is gradually reduced until it stop , during this time the patient return to his/her consciousness ( this is the Recovery period) So Recovery period it is the time from which the general anesthetic administration is stopped, until the patient regain back to his consciousness . This is the phases :

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Summary Administration of GA the period in which from the time of GA administration until the patient go to stage 3 ( loss of consciousness and other effects ) this is known as induction period Then sustained GA is important for maintenance of anaesthesia to keep the patient in stage 3 . Then from the time of discontinuation of GA until return back the full consciousness this is known as recovery period

Over-Dose comma or death , this is mean that no recovery period the patient cant return back to his consciousness , this is mean the paitient go to stage 4 the stage of medullary depression .

A student ask a Qs but i cant hear it ..The doctor answer : ((Ok >> analgesic drug , it is drugs that are administered in which we have loss of pain without loss of consciousness , in local anesthetic they produce the same effect , they produce the same wide the analgesic but the term name as an anesthetic. we will talk about it Insha-Allah in next lecture , local anesthetic although there are no loss of consciousness but they are named as anesthetic))

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Pre-anesthetic medications From their name , pre- : mean before So it is a group of drugs that are administered before GA to get multiple purposes .
1) 2) 3) 4) 5) 6) Sedation and amnesia. ex: Benzodiazepaines derivatives like Diazepam Analgesic . ex: Drugs opioids and its derivatives for example morphine . inhibition of parasympathetic reflexes . ex: Atropine or hyoscine H1 receptor antagonist. ex: diphenhydramine H2 receptor antagonist. ex: cimetidine or ratitidine Antiemetics drugs. ex: Metochlopramide

1) Sedation and amnesia. First of all we are looking to sedate the patient and relief anxiety , it is normal that anyone know that he will go to a surgery procedure he will become anxious , in order to relief an anxiety and induce sedation we will give him pre-anesthetic medication . Benzodiazepaines derivatives like Diazepam is administered as a pre-anesthetic medication to relief anxiety , apprehension , to reduce fear . Benzodiazepaines administration 2) analgesic Drugs analgesic agent or pain killer are administered . we should not wait until patient will complain from pain , the post-operative pain , in which an analgesic agent is administered before and at the end of surgery in order to reduce pain . The best analgesic drug is opioids Derivatives as Morphine and Pethidine , and specially they are used with the anesthetic if the anesthetic has a low analgesic effect we should use another analgesic like for example opioids and its derivatives for example morphine .
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3) inhibition of parasympathetic reflexes By using of antimuscarinic drugs in order to:

The lungs in order to reduce the bronchial secretion as a way as we looking to reduce the salivary secretion once we have ??? the salivary secretion will induce laryngospasm that may enter the larynx to will induce laryngospasm. Antimuscarinic agent are also administered with other aim to reduce the risk of cardiac arrhythmia , example of antimuscarinic agent are either Atropine or hyoscine .

Which one did you think is preferred ? Atropine or hyoscine ?

The best is hyoscine . Ok why hyoscine ? Bcz hyoscine is responsible to cause more CNS depression that is required in anaesthesia ( hyoscine is more preferred for CNS depression , loss of memory which is amnesia ) so it is preferred due to its CNS effect and also peripheral affect .

4)H1 receptor antagonist:

They are used to prevent allergic reaction 5)H2 receptor antagonist:

ex: diphenhydramine

They decrease acid secretion ( I am looking to suppress gastric acid secretion In order to prevent the retention of gastric content back to the lungs that may induce a aspiration pneumonia .

: Aspiration pneumonia is bronchopneumonia that develops due to the entrance

of foreign materials into the bronchial tree, usually oral or gastric contents including food, saliva, or nasal secretions. ) . ex: cimetidine or ranitidine

H is related To histamine H1 receptor responsible for allergic manifestation H2 receptor if they are stimulated they induce gastric acid secretion

6)Antiemetic drugs : it is the drugs that prevent emesis , in which emesis can be a verse effect of GA ex: Metochlopramide
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 general anesthetic are represent in 2 main groups : 1) inhaled anesthetic They are given through the respiratory track and they are used for maintenance of anaesthesia . either they are volatile liquids , or Gases like Nitrous oxide . a) Volatile liquids :

in which they are liquids under pressure once the pressure is released they are evaporated. Example of the volatile liquid is the halogenated compounds . what did we mean by halogen ? halogens which are in group 7 . So halogenated compound they are the groups of drugs that contain (Cl , Br ,I , F ) . These are examples of halogenated general anesthetic : Halothane/ Isoflurane / Methoxyflurane / Sevoflurane

b) Gases : example is : Nitrous oxide .

I think you know about nitrous oxide , commonly used by Dentist as an analgesic and it has a powerful analgesic effect , which is N2O and known as a laughing gas bcz it induce laughing.

2) intravenous anesthetic drugs

They are given intravenously To induce GA. They are different groups : a) Barbiturate derivatives like : Thiopental b) Benzodiazepaines derivatives like :Midazolam c) Opioid derivitives like : Fentanyl d) Ketamine e) Propofol

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Ideal Characteristics of Inhalational Anesthetics: Rapid & pleasant induction & recovery . Be potent, stable, non irritant and non inflammable
(( Now Ether , you know either? it is a general anesthetic drug by inhalation but one of the most important problem of Ether that it is Flammable . and this is the most thing that make us afraid and carefull in surgery rooms , that the anesthetic drug may become flammable and induce fire.))

Adequate relaxation of smooth muscle Wide margin of safety Absence of toxic effect ( or adverse drug reaction ) (( keep in your mind that during anaesthesia in some cases , if the general anesthetic drug has inadequate relaxation of smooth muscle effect , we will use a neuromuscular blocking agent like Tubocurarine . Also neuromuscular blocking agent are useful in Tracheal intubation for general anesthetic administration .

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Mechanism of Action of inhaled anesthetics Now the mechanism is little difficult , but the general mechanism(?) they produce CNS depression , they will inhibit neuronal excitation in the CNS by different mechanism First mechanism : With the increase in threshold, there is a decrease in neuronal activity. (they will rise the neuronal firing threshold , this is mean they make the neuron difficult for excitation )

Second mechanism :
At the cellular level, anesthetic agents affect synaptic transmission rather than axonal conduction. The release of excitatory transmitters and the response of the postsynaptic receptors are both inhibited.

- (They will inhibit the release of excitatory neurotransmitter in the CNS)

Third mechanism :
- In general the previous 2 mechanisms will induce the CNS depression . BUT the third mechanism will enhance the GABA effect - ( as u remember GABA is a inhibitory neurotransmitter that will cause opening the chloride channels so induce neuronal hyperpolarization this is mean inducing neuronal excitation

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The pre-synaptic neuron for example will inhibit calcium entrance , by that I will inhibit the release of excitatory neurotransmitter . The Post-synaptic neuron they either increase chloride influx , or they will increase potassium efflux , ya3ni they will induce hyper-polarization or re-polarization ( respectively ) , and by that will inhibit neuronal excitation. Rout of admimistration : 1) Inhaled anesthetic : - the anesthetic drug is given by inhalation , the site of action is in the CNS , this is mean given by inhalation they should be absorbed through the alveoli , reaching the blood , distributed through the body , until it reach the site of action which is CNS or the brain . -Keep in your mind that the site of action is the CNS THEY SHOULD REACH THE BRAIN ( CNS ) 2) IV anesthetic They go directly to the blood , reach the CNS in order to produce the anesthetic effect So, regardless to their route of administration(inhaled or IV anesthetic ) BOTH of them , their site of action is the CNS to cause CNS depression

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Inhaled anesthetic
-How they are taken ? they are taken by inhalation , usually they are mixture with Gas , with oxygen , carrier gas , ok ? with air or with oxygen . - Ok , these anesthetic as we said they should be transferred from the alveolar space to the blood and from the blood they should reach the brain . How fast ? this is the pathway

So , inspired Gas to the alveoli arterial blood other tissue and finally it should reach the brain and in the brain to produce their site of action

Vice versa , or the opposite way , or redistribution process is the way of their elimination . How they are eliminated ? what will be the pathway for their elimination ?

From , the brain blood vessels other tissues the major way from the blood return back to the lungs to the alveoli finally by expiration . This is known as ( redistribution process ) for the ( elimination ).

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To get a therapeutic effect the drug should reach the brain from the alveolar space to the blood and from the blood to the brain and this depends on many factors : First factor : Drug solubility :

Something that u have to know ( blood : gas partition coefficient) which will determine the solubility of the drug in the blood . What did u think , if the drug has a high drug solubility does this mean that its induction will be faster or slower ?? SLOW .

As we increase (blood : gas partition coefficient) and increase in gas solubility in the blood increase the onset of induction will be slower bcz as the solubility increase the drug will need more time to reach the partial pressure in the blood .

So there are reverse relationship between drug lipid solubility and its onset of induction ,as it is more the induction onset will be slow.

The more soluble the anesthetic in the blood , the more it should be dissolved in order to reach the desired partial pressure

( bcz we r talking about Gases , the gases is measured with partial pressure Not in mg ) .

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In the figure : Different anesthetic drugs , you will see the ratio of partial pressure of the anesthetic in the blood compared to the alveoli , we find that 1) Nitrous oxide : has low blood solubility / halothane is medium / methoxyflurane is high , this is the type of induction. This is mean bcz of low blood solubility of Nitrous oxide its onset of induction will be FAST . At the same time the onset of the speed of recovery will be FAST , this is ,mean the drug will leave the brain and returned back to the blood , from the blood to the alveoli to get a recovery phase Also will be fast .

2) Halothane: It has a high blood gas partial coefficient in which the solubility in the blood higher than Nitrous oxide , so it will induce a slow speed of induction or for anaesthesia comparing with nitrous oxide . - These is the differences . There is a reverse relationship comparing between nitrous oxide and Halothane . ok? Low solubility in the blood fast induction . comparing with halothane - usually nitrous oxide is mixed with halothane to fasten its onset of action , So are given in combination .
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Second Factor : Anesthetic Concentration in the inspired air This factor That depend or that can control or that affect onset of drug effect is its concentration in the inspired Air

What did you think the relationship ? direct ? or reverse ? DIRECT **this is mean as its concentration of the inspired air increase this is mean it will reach the blood very fast , this is mean it will reach the brain in very fast onset , the speed of induction or onset of action will be FAST .

SO , increase the concentration of the anesthetic in the inspired air will increase the speed of induction on anaesthesia , by increasing the rate of transfer to the blood ( DIRECT RELATIONSHIP )

Thirs Factor : Pulmonary Ventilation What did u think ? direct or indirect ? DIRECT .

Hyperventilation , this is mean the amount of anesthetic drug that go to the lungs will be more , so it will reach the blood very fast , and also the amount that reach the CNS also will be very FAST .

So , increasing Pulmonary Ventilation will increase in arterial tension

( Tension here mean concentration but bcz we are talking about gases we substitute concentration with tension )
The more Pulmonary Ventilation the more the drug that go to the blood so its tension will be more ( its conc. Will be more ) and this will induce( NOT Clear) effect.

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Fourth Factor : Pulmonary Blood Flow

What did u think ? direct or reverse ? REVERSE / INDIRECT As there is an increase in the blood flow to the lungs this is mean the volume of the blood will be more , this is mean the amount of anesthetic that should be dissolved also should be more ( high anesthetic concentration ) , so the onset of speed of induction will be slow . So ..

As pulmonary blood flow increase the Onset of induction will decrease

SUMMARY So they are 4 factors 2 of them Direct and 2 of them Indirect L concentration of anesthetic inspired air

2 factors with DIRECT relationship pulmonary ventilation

pulmonary blood flow .

2 factors with INDIRECT relationship solubility of the drug in the blood.

another factor : blood capacity Increasing in blood capacity this is mean more anesthetic concentration , more tension will rises very slowly .

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Elimination

The ways of elimination as we said they are eliminated mainly by the lungs by expiration Other way of clearance is done by other tissue like liver liver play an important rule in drug metabolism like in case of halothane and methoxyflurane in which these metabolize are excreted by kidney , but the major process of their elimination is by the lungs - This is seen specially in Nitrous oxide bcz it is inorganic , No need for metabolism and mainly eliminated by the lungs .

Duration is very important : Duration of the exposure of the inhaled anesthetic will affect the time of recovery , as the duration of exposure will be more the recovery ( returning back of consciousness) will be slow .

AGAIN as we said , If the drug has low blood gas partition coefficient this is mean its onset of action will be fast on the same time its recovery also will be fast . So , it is very important , KEEP this in your mind .

NOW Comparing between Nitrous oxide and halothane

which one has the fast onset of action ? Nitrous oxide . why? - Bcz it has low blood gas partition coefficient and low blood solubility , it has fast induction or fast onset of action . Which one will produce a fast recovery ? Nitrous oxide .

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compare between them in the case of potency

- potency is how much of drug is required to produce an effect , for drugs the potency it is expressed by mg / units , in case of inhaled drugs partial pressure) - drug potency is depend on drug lipid solubility as there is an increase in solubility the potency will be more this is mean that the amount of drug that needed to produce an effect will be small .

So

Onset of action depend on the blood solubility , Potency of the drug depends on its lipid solubility ( as it is more the potency will be more )

Minimum Alveolar concentration (MAC) The potency is measured by Minimum Alveolar concentration (MAC) which is : The minimum concentration of the inhaled anesthetic that is looking to induce immobility or prevent movement in response to surgical incision in 50% of patient

Comparing with other drug , the potency of other drug is expressed by ED50 ( effective dose in 50% of population ) . While in the inhaled anesthetic its potency is expressed by or depends on MAC 50 . it is defined as how much is the anesthetic is needed to produce immobility or prevent movement or response to such stimulus like surgical incision in 50% of population . - As it Is small the potency of the drug will be more , and as it is high , the potency of the drug will be low .

The MAC depends on the drug lipid solubility high lipid solubility Low MAC the drug will be highly potent

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Now we finish from the introduction and we will talk about examples : ** INHALED ANESTHETIC

1) Halothane -

It is one of the inhaled anesthetic it is halogenated not irritant Colorless

High blood solubility slow induction and recovery . High fat solubility low MAC highly potent . Mainly this drug can be metabolized by liver enzymes Cyt-P450 One of its adverse effect Sensitize the myocardium to the effect of catecholamine and it will induce cardiac arrhythmia. - Repeated administration over a short period of time has been implicated to produce halothane hepatitis , and induce the liver damage . why? They said that halothane metabolism will induce reactive metabolites , and these reactive metabolites either cause direct damage to the liver cells or they will induce immune-mediated response ( all of this due to the reactive metabolites ) .

2) Nitrous Oxide (N2O) laughing gas

It is a good analgesic drug Low blood solubility rapid induction and recovery Most rapid induction Most rapid rate of recovery least potent, highest MAC value bcz of low lipid solubility Not metabolized, totally eliminated by lungs Bcz of its good analgesic effect it can be used in dental procedure and obstetrics. - Given by inhalation and mixed with oxygen 50 to 50 percent bcz of its powerful analgesic effect . - One of its problems is its short duration of action , you put the mask and if there is pain you must return the mask ( y3ni it needs repetitive administration bcz of its short duration of action ) - Multiple adverse effect ( bcz of rapid recovering it may cause washout of oxygen from the alveoli and this will induce hypoxia , it is very important to prevent hypoxia development by administration of significant amount of pure oxygen.
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** INTRAVENOUS ANESTHETIC :

1) Barbiturates : thiopental it is ultra short acting barbiturates in which its onset of action within seconds , can be induce unconsciousness very rapid .

rapid onset induction and recovery good anesthetic with poor analgesic effect ( in opposite to Nitrous oxide in which nitrous oxide is a poor anesthetic with good analgesic effect ).

Dissociative Anesthesia
This term is defined in which we have analgesic effect as well as we have amnesia , minimal effect of the respiratory function . The patient is conscious , analgesic , amnesic But he can open his eyes and can swallow , but doesnt process any information ( decrees of awareness of external environment ) How we get Dissociative Anesthesia ?

This is seen by the administration of Ketamine HCl . and its effects are : 1) muscular relaxation is poor 2) this drug can increase Stimulates central sympathetic outflow increasing HR, BP and CO. 3) Not used in hypertensive patients 2)Propofol It is a dug that produces anesthesia at a rate similar to that of barbiturates ( in compared with thiopental) in which it has a fast onset of action . post operative vomiting is less common and may have anti-emetic property hypersensitivity is less common
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3)BENZODIAZEPINES Benzodiazepine derivatives (Diazepam, midazolam, lorazepam ) Not complete GA produces amnesia , muscle relaxation , sedation , no analgesia . Used for: 1) Premedication To relieve anxiety & prevent sympathetic activity. 2) Conscious sedation along with Opioids (for short surgical & diagnostic procedures e.g : Endoscopy and Bronchoscopy Neuroleptanalgesia: It is a state in which there is an analgesia , amnesia , sedation BUT he is consciousness and cooperative that mean he is able to respond to commands or external orders .

Anxiety, motor activity, and sensitivity to painful stimuli are reduced; the person is quiet and indifferent to surroundings
How we get Neuroleptanalgesia? by administration of 2 drugs : 1) narcotic analgesics (Opioids derivatives) like Fantanyl

2) Neuroleptic drugs (antipsychotic drugs) like Droperidol Droperidol+ Fantanyl Neurolept analgesia If we add Nitrous Oxide to Droperidol and Fantanyl we will have Neurolept anaesthesia ( NOT Neurolept analgesia)

Droperidol+ Fantanyl + Nitrous Oxide Neurolept anaesthesia

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THE END GOOD LUCK Im sorry for any mistake .. Done By : Eman Nazzal

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