lecture 12, general anesthesia (script)

8/3/2019 Lecture 12, General Anesthesia (Script)

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General Anesthesia

Some definitions in General Anesthesia:

We have: 1. General Anesthesia: is the process.

2.Anesthetist: the person who is responsible for anesthetizing the

patient.

3.Anesthetic: the chemical or the drug which can produce general

anesthesia.

-As we said in the last lecture, General anesthetics are classified according to the

route of administration into:

1- Inhalational: are given by endotracheal tube and are sub classified into:

A- Volatile liquids.

B- Gases.

2- Intravenous: are usually liquid (we cant give the patient gas intravenously due

to embolism and because of that when they give intravenous injection, they will

hold the syringe in up like position in order to get the air bubbles which are on the

top of the solution outside. If these air bubbles introduced into the vein, they

might produce embolism.)

Inhalational General Anesthetics:

-These drugs are usually halogenated hydrocarbon which means they contain a

halogen group which is usually fluoride.

-Halogens are fluoride, chloride, bromide and iron.


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1. Halothane:

It can produce quick induction and recovery which is an advantage forgeneral anesthetics.

It is regarded as a best agent in pediatric patients because it has a nice,non-irritant smell thats why they are preferred by children.

It is good for asthmatic patients for the same reason; it has a minor irritanteffect.

It can decrease the blood pressure and thats why it is useful to anesthetizepatients who need a blood less field in surgical operation. For example:

joint and eye operations in which we need less bleeding that could be

produced by decreasing the blood pressure.

A drawback for the use of halothane: it has a cardiac depressant effect andmight sensitize the heart to the effect of endogenous catecholamine.

(Catecholamine: the endogenous sympathetic amine such as Adrenaline

and Nor-adrenaline). So halothane will potentiate the effect of endogenous

Adrenaline and produce tachycardia.

Unfortunately it can produce hepatotoxicity especially after repeated use. It could be complicated by whats called Malignant hyperthermia ( Sudden

and progressive rise in body temperature, it might reach 43 or 44 degree

centigrade and if it is not treated, it might be fatal). Arrhythmia.

2. Enflurane:

Induction and recovery: faster than halothane. Muscular relaxation: it can produce good skeletal muscle relaxation. Safe on the heart and the liver: it cant produce Arrhythmia and

hepatotoxicity.

As a drawback: there might be risk of convulsion or epileptic fits.

3. Isoflurane:

It is the fastest in induction and recovery. Muscular relaxation: it can produce marked muscle relaxation.


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It has no convulsion effect. No serious side effect on the liver and the heart.

-To compare between the three halogenated drugs:

Rate of induction

and recovery

Muscular relaxation

Halothane + +

Enflurane ++ ++

Isoflurane +++ +++

We can conclude that the Isoflurane is the best halogenated

hydrocarbon and nowadays it has replaced the Halothane and the

Enflurane.

4. Nitrous oxide (N2O) : it is in the form of gas and there must be a cylinder of it in

each dental clinic. It is characterized by:

Rapid induction and recovery. Good analgesia. Safe and non-irritant. BUT : it cant produce general anesthesia alone (incomplete anesthesia). It has no muscle relaxation

-Because it has good analgesic power, cant produce loss of consciousness alone

and there is no muscle relaxation; it is now used alone or intermittently in

dentistry to relieve pain & as alternative for local anesthetics and it is also used in

obstetrics to relieve severe pain.

-BUT!! Nitrous oxide could be used with other inhalational general anesthetics

such as Halothane, Enflurane and Isoflurane, WHY?!!

To decrease the dose of other general anesthetics and by decreasing the

dose, side effects will be decreased as well.


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Intravenous general anesthetics:

They are used either alone for minor surgical procedure or they are used as

induction agents [Induction agent: an agent that is given to a patient so hisconsciousness will be lost rapidly.].

1. Thiopentone:

It is called Thiopental in American books, and a trade name for it isPentothal.

Rapid onset and recovery. It is a potent anesthetic. But! It has poor analgesia and muscle relaxation effect. It is widely used as an induction agent.(Before giving the patients the inhalational general anesthetic, they will

injected by Thiopentone).

It can produce Laryngospasm. It might produce hangover (feeling sleepy even hours after the recovery

from general anesthesia.

Thiopentone belongs to a group of drugs called Barbiturate which well talkabout them later on.

Usually anesthetists will select a visible vein on the dorsum of the hand

and they choose the dorsum because there is no superficial artery there and

there is no possibility of mistaken the artery by the vein.

If the Pentothal is injected inside the artery it might produce severe

prolong arterial spasm which might lead to gangrene.


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2. Ketamine:

Slow onset and recovery. Produces marked Analgesia and Amnesia (memory loss). Produces whats called Dissociative Anesthesia.

-The patient cant feel pain and he is completely dissociated from his

environment, he is unable to respond to any stimuli whether tactile or

painful.

It can stimulate central sympathetic outflow that will result in increase inheart rate, blood pressure, and cardiac output and because of that it is

useful in shocked (hypotensive) states (it will increase blood pressure) and

in asthmatic patients because it can produce bronchodilatation. On the

other hand and as a drawback of these results, it can increase the

intracranial pressure (ICP) and cerebral heart flow, therefore, it should

not be used in hypertensive and stroke patients.

3. Propofol:

Rapid induction and very rapid recovery. Poor analgesia. Decreases blood pressure. It may depress respiration with period of apnea. Stoppage of respiration

might take up to 30 seconds and here it decreases the intracranial

pressure (ICP).

No post operative vomiting and nausea. Widely used for induction and sedation in Intensive Care Unit (ICU).

SO..

Ketamine increases blood pressure while Propofol decrease it.

Ketamine increases ICP while Propofol decrease it.

Ketamine should not be given to hypertensive patients and patients with

elevated ICP and can be replaced by Propofol in these types of patients.

Thats enough for General Anesthesia


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The most common drugs that are used by dentists are the Local

Anesthetics, the General Anesthetics (especially Nitrous oxide) and the Analgesic

drugs.

-Analgesic drugs are classified into two main types:

1. Narcotic Analgesic drugs: they relieve pain and they can depress the central

nervous system inducing sleepiness.

- They are reserved for severe pain.

2. Non-Narcotic Analgesic drugs: they can relieve pain but they cannot depress

the central nervous system.

- They are reserved for moderate to mild intensity pain.

-Toothache is between mild and moderate pain so it needs non-narcotic

analgesics and if you use narcotic analgesics in dental practice, most of patients

will be addicted on them.

The Non-narcotic drugs are called Non-steroidal anti-inflammatory

drugs. And before dealing with this group of drugs, I want you to have an ideaabout the following:


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-Cell membrane contains phospholipids

-Under the effect of the enzyme phospholipase A2, Arachidonic acid will be

synthesized and it will go through either Cox or Lox pathways.

Cox: is an abbreviation of Cyclooxygenase enzyme. Lox: is an abbreviation of Lipoxygenase enzyme.

-Arachidonic acid will produce prostaglandins under the effect of Cox enzyme.

-We have two types or two isozymes Cox:

1. Cox-1: is prevalent or predominant in the GI tract, and thats why its effecton Arachidonic acid in the GIT will lead to the formation of prostaglandinsin it.

- Prostaglandins in the GI tract have a protective effect on the mucosa of

the GIT; it can increase the defense mechanism of the mucosa of the

stomach and the duodenum.

2. Cox-2: is prevalent in other sites outside the GIT. Therefore, theprostaglandins which are produced in other sites have an action in

mediation of inflammation, pain and fever.

-Pain, fever and inflammation which are produced in the periphery (in the

joint, bones or in any other peripheral tissue) are due to the release of large

amount of prostaglandins.

-Phospholipase A2 could be inhibited by Steroid hormones while Cox-1 and Cox-2

could be inhibited by drugs such as Aspirin, Paracetamol and other anti-

inflammatory drugs.

-To differentiate this group of drugs that has anti-inflammatory effect from

steroids we give them a new name which is " Non- steroidal anti- inflammatory

drugs.

Because we have steroidal anti- inflammatory drugs like: steroids and

corticosteroids which are produced by adrenal cortex. To differentiate this

steroidal anti- inflammatory drugs which inhibits Phospholipase A2 to high up ( in


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the schematic diagram above ). From those groups of drugs that inhibits Cox

enzyme; we call them non- steroidal anti- inflammatory drugs.

-The mechanism of action of the NSAIDs is: the inhibition of Cox enzymes, if we

inhibit Cox-1, prostaglandins synthesis will be inhibited and therefore, the

protective effect of prostaglandins on GI tract mucosa will be reduced. Thats why

this group of drugs is complicated by GIT irritation or ulceration as side effects of

the NSAIDs.

-While the inhibition of prostaglandins in other sites (inhibition of Cox-2) will

reduce the inflammation, pain and fever and thats why these drugs have three

main pharmacological actions:

1. They are regarded asAnti-inflammatory drugs because they depress the

inflammation.

2. They relieve pain so they have analgesic effect (Analgesic drugs).

3. They decrease elevated body temperature so they are called Antipyretic

drugs.

As a conclusion: Inhibition of the Cox enzyme will have a therapeutic

effect as Anti-inflammatory, Analgesic and Antipyretic and it will have an adverse

drug reaction in the form of GI tract irritation and ulceration.

- The Non-narcotic analgesics (NSAIDs) are classified according to their anti-inflammatory effect into:

1. Strong anti-inflammatory effect:

a. Salicylic acid derivatives (or Salicylate):-Aspirin is a prototype of it.

b. Pyrazolone derivatives:-Phenylbutazone.

c. Acetic acid derivatives:-Indomethacin.

-Diclofenac (voltaren).

d. Oxicam derivatives:-Piroxicam (Feldene).


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2. Mild to moderate anti-inflammatory effect:

a. Priopionic acid derivatives:

-Ketoprofen or profen in general.

b. Fenamic acid derivatives:

- Ponstan.

c. Non-acidic drugs:

- Nabumetone.

3. No or weak anti-inflammatory effect:

- Acetaminophen (paracetamol, panadol).

We said that this group of drugs might have antipyretic effect (drugs

which can reduce an elevated body temperature) but they have no effect on

normal body temperature and they will never decrease the temperature below

the normal limit.

-Drugs that decrease the body temp below the normal limit are called

Hypothermic drugs.

Lets discuss a prototype of the NSAIDs

Aspirin:- The first non-steroidal anti-inflammatory drug.

- Used for the first time in the form of tablets at the end of the 18 century but

before that it was used as an herbal medicine (It is derived from willow bark).

-Protective against cardiac diseases (ischemic heart disease).


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-Protective against some types of cancers such as colorectal cancer and thats

done by repeated intake of aspirin.

-It belongs to salicylate.. it is a derivative from Salicylic acid (SA)... it is Acetyl

Salicylic Acid (ASA).

In the picture above:

There is a Salicylic acid on the left of the picture and it contains a Carboxyl

group (-COOH).

- If (H) in the -COOH is replaced by Sodium, it will be Sodium salicylate. And

Sodium salicylate will produce Acetyl Salicylic Acid (Aspirin) when it is attached to

Acetyl group (-COCH3).

-Salicylic acid is highly irritant substance while Sodium salicylate and Acetyl

Salicylic acid are less irritant substances so they are used therapeutically as anti-

inflammatory, analgesic and antipyretic.

-Because it is highly irritant, Salicylic acid can be used as keratolytic (it has a

keratolytic effect).

Keratolytic: it will dissolve a hyperkeratinized layer of the skin when it is

locally applied on this layer) examples: when it is applied on warts and corns.

-Other fault of Salicylic acid, it could be used systemically as Antipyretic, anti-

inflammatory and analgesic and It is very dangerous to use it orally.


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**A brief review of Aspirins pharmacological action:

It decreases signs and symptoms of inflammation as pain, redness and immobility

by the inhibition of prostaglandins synthesis and as a minor effect, it decreases

ACTH (Adrenocorticotropic hormone) and capillary permeability.

-I want you to concentrate on the anti-inflammatory effect which due to an

inhibitory effect on prostaglandins synthesis in the periphery NOT in the GI tract

because the inhibition of GI tracts prostaglandins will not have therapeutic effect

but it has an adverse drug reaction in form of GI tract irritation or ulceration.

-Due to inhibition of prostaglandins both centrally and peripherally.

-The type of pain that is relieved by Aspirin and other NSAIDs is mild to moderate

intensity pain usually superficial pain. So it cant be used in relieving post-

operative or severe pain (deep-seated visceral pain).

-Due to inhibition of prostaglandins in the central nervous system because it has

been found that Pyrogens (the substances which can increase the body

temperature) will elevate the prostaglandins in the central nervous system.

Anti-inflammatory effect

Analgesic:

Antipyretic:


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To understand the Aspirins anti-platelet effect I want you to understand this

diagram:

We have: 1.) vascular endothelium. 2.) The platelets.

-Both of them contain phospholipids and Arachadonic acid.

-In vascular endothelium:

Under the effect of an enzyme called Prostacyclin synthetase, Arachidonic

acid (AA) will produce prostaglandins called Prostacyclins (PC) which have a

vasodilator effect.

-In platelets:

Arachadonic acid here under the effect of an enzyme called Thromboxane-A2

synthetase will lead to the formation of prostaglandin called Thromboxane A2

(TX -A2) that has a platelet aggregatory effect.

***Platelet aggregation: is the attachment of platelets to each other.

***Platelet adhesion: is the attachment of platelets to the vascular endothelium.

Anti-platelets:


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-Large doses of aspirin (300 mg &more) will inhibit the formation of Prostacyclin

and this will inhibit the vasodilatation which could be regarded as a harmful

effect.

-While low doses of it (75-150 mg) will inhibit Thromboxane-A2 synthetase which

means less formation of Thromboxane A2 that leads to the inhibition of platelets

aggregation which is a useful effect.

Therefore, for protective effect of aspirin, patients are asked to take small

doses (100mg daily to have anti-aggregatory effect) and we need this protective

effect for the protection against ischemic heart disease. Also large doses of aspirin

have more ulcerative effect than low doses of it.

*** Because the ulcerative effect of aspirin is mainly due to the inhibition of

prostaglandins synthesis in the GI tract (not the direct contact of aspirin with GI

tract mucosa that will have minor irritative effect), when we give aspirin whether

orally or systemically it might have ulcerative effect and this is the same for any

other NSAIDs.

The effect of normal doses (1-2gm): it will inhibit the tubular secretion of uric acid

so uric acid will stay in the blood. In other words, normal doses of aspirin will lead

to hyperuricemia (increase in serum uric acid).

The effect of high or very high doses (>5gm): it will inhibit tubular reabsorption

and this means increase in the elimination of uric acid with urine (decrease in

serum uric acid) so it can be used for the treatment of Gout.

BUT!! For patient with Gout, its better not to take aspirin whether in low or hight

doses because low doses might aggravate the condition and high doses mighthave high incidence of GI tract irritation and ulceration.

Effect on uric acid:


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Therapeutic dose has no effect but large doses might stimulate respiratory center

to produce respiratory alkalosis due to carbon dioxide wash out which will lead

to increase in blood pH.

Toxic doses will inhibit the respiratory center and will lead to a condition called

respiratory acidosis and then metabolic acidosis due to accumulation of acids of

metabolic processes.

Large doses will inhibit the vasomotor center and can produce vasodilatation andsever hypotension.

-Irritation and ulceration.

** So at the end of this lecture

The mechanism of action of Aspirin is the inhibition of the enzymes that are

responsible for the production of prostaglandins and these enzymes are: Cox-1

and Cox-2.

Because aspirin can inhibit the two isozymes of Cox (Cox-1 and Cox-2), it is called

Non-selective Cox inhibitor which might have therapeutically useful effect and

undesirable effect due to the non-selectivity in blocking the two isozymes.

Nowadays, a new group of drugs have been synthesized and they are called

Selective Cox-2 inhibitors and they have more powerful inhibitory effect on Cox-2

as compared to Cox-1.

Therefore, they can retain their therapeutic efficacy without a major undesirable

GI tract ulcerative effect because they cant inhibit Cox-1. So prostaglandins

Effect on respiration:

Cardiovascular:

GI tract:


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synthesis in the GI tract will not be that much affected and therefore, they might

lack the ulcerative effect of aspirin.

The end!!

Yesterday is over! We can't go back and redo anything that happened...But we

can make better choices today! With God's grace we have a NEW chance

everyday!

Special thanks goes to Eman Tawalbeh for her help

Done by: Walaa Al-khdour

lecture 12, general anesthesia (script)

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