Medicine Lecture One General Anaethsia 19th Nov

7/30/2019 Medicine Lecture One General Anaethsia 19th Nov

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GENERALANAESTHETIC

AGENTS


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OUTLINE

DEFINATION

INTRODUCTION

CLASSIFICATION

MECHANISM OF ACTION

INDUCTION STAGES OF GA

GENERAL PRECAUTIONS DURING USE OF

GA

PRE-MEDICANTS


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Definition

An anesthetic is a drug or agent that produces

a complete or partial loss of feeling.

There are three kinds of anesthetics:

GENERAL,

REGIONAL

LOCAL


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Regional anaestheticor nerve block.

For example, a woman giving birth by

caesarean section may have an epidural.

This is an injection into the spine that numbs

the body from the waist down.


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Local anaesthetic anaesthetic is injected

into the immediate area to be operated on.

For example, your dentist may inject local

anaesthetic into your gum before removing atooth.


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When a patient undergoes a general

anesthetic, they lose sensation and become

unconscious.

General anaesthetic may be given as aninjection or as a gas.

An anaesthetist will administer a general

anaesthetic.


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BEFORE ANAESTHESIA

The following is critical

Medical history, including any pre-existing

conditions, such as diabetes or heart problems

Surgical history

Allergies, for example, to drugs or foods

Drugs you may be taking, including cigarettes

and alcohol.


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INTRODUCTION

General anaesthetics are used to make

patients unaware or unresponsive to painful

stimulation

They are given systemically and main effect ison the CNS

Modern medicine would not be possible

without these agents


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HISTORY

Inhalational anaesthetics(I.A) were discovered

in 1846

Before operations done on struggling patients

and done at lightening speed

Most operations were amputations

Nitrous oxide(laughing gas) used in

1800,tested on the PM Then ether, given in parties to cause euphoria,

then chloroform


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Types

Old ,obsolete

Chloroform

Ether

Xenon

Trichloroethylene

cyclopropane


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Intravenous agents

Ketamine

Propofol

Thiopental

Etomidate

midazolam


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inhalational

Nitrous oxide

Isoflurane

Desflurane

Sevoflurane

Halothane

Enflurane

Ether

Methoxyflurane


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Several different types of drug are given

together during general anaesthesia

Anaesthesia is induced by

volatile drug given by inhalation,

with an intravenously administered drug

anesthesia is maintained with an intravenous

or inhalational anesthetic.


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G. A characteristics

They induce

analgesia,

amnesia,

loss of consciousness,

inhibition of sensory and autonomic reflexes,

Skeletal muscle relaxation.


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The extent to which an individual drug can

exert these effects varies with

the drug,

route of administration

clinical situations.


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roper es o an ea anes e cagent

Result in rapid loss of consciousness, which

eliminates awareness, memory of pain,

anxiety, and stress throughout the surgicalperiod;

Provide a level of analgesia sufficient to

abolish the reflex reactions to pain, such asmuscular movement and cardiovascular

stimulation;


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Have minimal and reversible influence on vital

physiological functions, such as those

performed by the cardiovascular and

respiratory systems; Lead relaxation of skeletal muscle to facilitate

endotracheal intubation, provide the surgeon

ready access to the operative field, and

reduce the dose of anesthetic required to

produce immobility;


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Lack operating room safety hazards, such as

flammability and explosiveness

Prompt patient recovery to psychomotor

competence, facilitating the cliniciansassessment of the patient and the patients

ability to become physiologically self-

supporting.


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ANAESTHETIC ACTION

Anaesthetic agents were originally thought to

act by interacting physically rather than

chemically with lipophilic membrane

components to cause neuronal depression. However this theory implies that all

anaesthetics interact in a common way

(unitary theory of anaesthesia)


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This is being challenged by more recent

studies which demonstrate that specific

anaesthetics exhibit selective and distinct

interactions with neuronal processes These interactions are not easily explained

by a common physical association with

membrane components.


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ACTION

Anaesthesia from Physical Interaction With

Lipophilic Membrane Components

The importance of physical interaction in

anaesthesia is supported by the observationthat noble gases such as xenon, which do not

chemically interact with tissues, produce

unconsciousness.


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Theory 1

Membrane conformational changes are

observed on exposure to anesthetics, further

supporting the importance of physical

interactions that lead to disruption ofmembrane macromolecules.


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For example, exposure of membranes to

clinically relevant concentrations of

anesthetics causes membranes to expand

beyond a critical volume (critical volumehypothesis) associated with normal cellular

function.


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Theory 2

Additionally, membrane structure becomes

disorganized, so that the insertion of

anesthetic molecules into the lipid membrane

causes an increase in the mobility of the fattyacid chains in the phospholipid bilayer

(membrane fluidization theory)


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Theory 3

prevent the interconversion of membrane

lipids from a gel to a liquid form, a process that

is assumed necessary for normal neuronal

function (lateral phase separation hypothesis).


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Theory 4

Anaesthesia from Selective Interactions of

Anaesthetics With Specific Cellular

Components

Various anesthetics interact specifically withdifferent components of the GABAA- receptor

chloride ionophore and enhance chloride

conductance, some directly and others by

enhancing the action of GABA.


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Inhalational agents directly activate thechloride channel as well as facilitate the action

of GABA.

Barbiturates, propofol, benzodiazepines,and etomidate primarily enhance the action ofGABA by interacting with specific receptor

sites.


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Also, anesthetics enhance other processes

known to inhibit neuronal function, such as the

glycine receptorgated chloride channel.

A smaller number of anesthetics, includingketamine, N2O, and xenon, produce neuronal

inhibition by antagonizing excitatory neuronal

transmission mediated via the N-methyl-D-

aspartic acid (NMDA) receptor.


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Some inhalational drugs activate K channels

and so contribute to hyperpolarization and

reduced neuronal excitability.

These agents also inhibit the function of theprotein complex involved in neurotransmitter

release.


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Many compounds produce

anaesthesia,including inert gas like xenon

Potency is related to lipid solubility not with

chemical structure


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Summary of M.O.A..

Earlier theories suggested interaction with lipid

bylayer,recent evidence favours interation with

membrane ion channels

Most enhance activity of GABA receptors Others effects include activation of pottassium

channels and inhibition of excitatory NMDA

receptors

STAGES OF ANESTHESIA


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STAGES OF ANESTHESIA

The traditional description of the stages of

anesthesia (the so-called Guedel's signs) were

derived from observations of the effects of

diethyl ether, which has a slow onset of centralaction owing to its high solubility in blood.

Using these signs, anesthetic drug effects can

be divided into four stages of increasing depth

of central nervous system depression:


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STAGE 1- Stage of analgesia

The patient initially experiences analgesia

without amnesia.

Later in Stage I, both analgesia and amnesiaare produced.


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STAGE 2-Stage of excitement

: During this stage, the patient often appears

to be delirious and may vocalize but is

definitely amnesic.

Respiration is irregularboth in volume and rate vomiting may occur if the patient is

stimulated. Therefore efforts are made to limit

the duration and severity of this stage, whichends with the re-establishment of regular

breathing.


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STAGE 3-Stage of surgical

anesthesia

This stage begins with the recurrence of

regular respiration and extends to complete

cessation of spontaneous respiration (apnea).

Four planes of stage III have been describedin terms of changes in ocular movements

eye reflexes, and pupil size, which under

specified conditions may represent signs ofincreasing depth of anesthesia.

S G


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STAGE 4-Stage of medullarydepression

This deep stage of anesthesia includes

severe depression of the vasomotor center in

the medulla, as well as the respiratory center.

Without circulatory and respiratory support,death rapidly ensues.


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NOTE-ONE

In current anesthetic practice, the distinctive

signs of each of the four stages described

above are usually obscured because of the

more rapid onset of action of modernintravenous and inhaled anesthetics

(compared with ether),


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NOTE 2

Ventilation is often controlled mechanically.


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NOTE 3

In addition, the practice of administering other

pharmacologic agents preoperatively (eg,

preanesthetic medication) or intraoperatively

(eg, opioid analgesics, cardiovascular drugs)can also alter the clinical signs of anesthesia.


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The most reliable indication that stage III

(surgical anesthesia) has been achieved is

loss of responsiveness to noxious stimuli and

reestablishment of a regular respiratorypattern.


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The adequacy of the depth of anesthesia for a

specific surgical stimulus is assessed by

monitoring changes in

respiratory cardiovascular responses to the surgical

stimulation.

Surgery and Long term


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Surgery and Long-term

Medication

The risk of losing disease control on stopping

long term medication before surgery is often

greater than the risk posed by continuing it

during surgery. It is vital that the anesthetist knows about all

drugs that a patient is (or has been) taking.


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Patients with adrenal atrophy resulting from

long-term corticosteroid use may suffer a

precipitous fall in blood pressure unless

corticosteroid cover is provided duringanesthesia and in the immediate postoperative

period

Anesthetists must therefore know whether a

patient is, or has been, receiving

corticosteroids (including high-dose inhaled

corticosteroids).

DRUGS THAT MUST BE


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DRUGS THAT MUST BE

STOPPED

Antiepileptics,

Antiparkinsonian

antipsychotics

Cardiovascular

Anxiolytics

bronchodilators


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glaucoma drugs

immunosuppressant's,

drugs of dependence

thyroid or antithyroid drugs


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Patients taking Antiplatelets medication or an

oral anticoagulant present an increased risk of

surgery.

Heparin therapy should be considered


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others

combined oral contraceptives

If antidepressants need to be stopped, they

should be withdrawn gradually to avoid

withdrawal symptoms. In view of their hazardous interactions MAOIs

should normally be stopped 2 weeks before

surgery


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Tricyclic antidepressants need not be stopped,

but there may be an increased risk of

arrhythmias and hypotension (and dangerous

interactions with vasopressor drugs); therefore the anaesthetist should be informed

if they are not stopped.


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Lithium should be stopped 24 hours before

major surgery

Normal dose can be continued for minor

surgery monitor fluids and electrolytes


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Anaesthesia and driving

Patients given sedatives and analgesics

during minor outpatient procedures should be

very carefully warned about the risk of driving

afterwards. For intravenous benzodiazepines and for a

short general anaesthetic the risk extends to at

least 24 hours after administration

Alcohol should be avoided


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Potassium-sparing diuretics may need to be

withheld on the morning of surgery because

hyperkalaemia may develop if renal perfusion

is impaired or if there is tissue damage Angiotensin-converting enzyme (ACE)

inhibitors and angiotensin-II receptor

antagonist can be associated with severe

hypotension after induction of anesthesia;

these drugs may need to be discontinued 24

hours before surgery.


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Prophylaxis of acid aspiration

Regurgitation and aspiration of gastric

contents (Mendelsons syndrome) is an

important complication of general anesthesia,


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worse in obstetrics and during emergency

surgery, and requires prophylaxis against acid

aspiration.

Prophylaxis is also needed in those withgastro-oesophageal reflux disease

prophylaxis needed where gastric emptying

may be delayed.


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An H2-receptor antagonist or a proton pumpinhibitor such as Omeprazole may be usedbefore surgery to increase the pH and reducethe volume of gastric fluid.

They do not affect the pH of fluid already inthe stomach and this limits their value inemergency procedures;

oral H2-receptor antagonists can be given 1-2hours before the procedure but Omeprazolemust be given at least 12 hours earlier


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Antacids are frequently used to neutralize the

acidity of the fluid already in the stomach;

clear (non-particulate) antacids such as

sodium citrate are preferred. Sodium citrate 300 mmol/litre (88.2 mg/mL)

oral solution is normally used


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Pre-medication

PRE-ANAESTHETIC MEDICATION

(ANAESTHETIC ADJUNCTS)

A general anesthetic is usually given with

adjuncts that augment specific components ofanesthesia thus permitting lower doses of

general anesthetics and resulting in fewer

side effects.


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Premedication:

These drugs are given to

allay fear and anxiety in the pre-operative

period (including the night before an

operation), to relieve pain and discomfort when present,

and to augment the action of subsequent

anesthetic agents..


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A number of the drugs used also provide some

degree of pre-operative amnesia.

The choice will vary with

I. the individual patient

II. the nature of the operative procedure

III. the anesthetic to be used


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other prevailing circumstances such as

Outpatient

obstetrics and recovery facilities.

The choice also varies between elective and

emergency operations


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Classes of premeds

Antimuscarinic-hyoscine

Benzodiazepines-diazepam

lorazepam,temazepam,midazolam

Analgesics-Nsaids. opioids

2-adrenoceptor agonists-clonidine

Neuromuscular blocking drugs-

Antimuscarinic Drugs


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Antimuscarinic Drugs

Antimuscarinic drugs are used (less commonly

nowadays) as premedicants to dry bronchial

and salivary secretions

They are also used before or withNeostigmine to prevent bradycardia, excessive

salivation, and other Muscarinic actions of

Neostigmine.

They also prevent bradycardia and

hypotension associated with drugs such as

halothane, Propofol, and suxamethonium.


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Atropine sulphate

Rarely used for premedication

Has an emergency role in the treatment of

vagotonic side-effects


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Dose

Premedications, by intravenous injection, 300

600 mcgs immediately before induction of

anaesthesia; CHILD 20 mcgs/kg (max 600mcgs)

By subcutaneous or intramuscular injection,

300 600 mcgs 30 60 minutes before

induction; CHILD 20 mcgs/kg (max. 600 mcgs)


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Hyoscine hydrobromide

reduces secretions and also provides a degree

of amnesia, sedation and anti-emesis.

Unlike atropine it may produce bradycardia

rather than tachycardia. In some patients, especially the elderly,

hyoscine may cause the central ant cholinergic

syndrome (excitement, ataxia, hallucinations,

behavioral abnormalities and drowsiness).

Gl i b id


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Glycopyrronium bromide

reduces salivary secretions. When given

intravenously it produces less tachycardia than

atropine.

It is widely used with Neostigmine for reversalof non-depolarising neuromuscular blocking

drugs.

Phenothiazines do not effectively reduce

secretions when used alone.

Benzodiazepines


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Benzodiazepines

Benzodiazepines possess useful properties for

premedication including

relief of anxiety,

sedation, and amnesia.


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Short-acting benzodiazepines taken by mouth

are the most common premedicants.

They have no analgesic effect so an opioid

analgesic is required for pain


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Benzodiazepines can alleviate anxiety at does

that do not necessarily cause excessive

sedation

They are of particular value during shortprocedures or during operations under local

anesthesia


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Amnesia reduces the likelihood of any

unpleasant memories of the procedure

Benzodiazepines are also used in intensive

care units for sedation, particularly in thosereceiving assisted ventilation


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Benzodiazepines may occasionally cause

marked respiratory depression and facilities for

its treatment are essential

flumazenil is used to antagonize the effects ofbenzodiazepines.

They are best avoided in myasthenia gravis

especially pre-operatively.

di


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diazepam

Diazepam is used to produce mild sedation

with amnesia.

It is a long-acting drug with active metabolites

and a second period of drowsiness can occurseveral hours after its administration.

Peri-operative use of diazepam in children is

not generally recommended; its effect and

timing of response are unreliable and

paradoxical effects may occur.


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Diazepam is relatively insoluble in water andpreparations formulated in organic solvents

are painful on intravenous injection

a high incidence of venous thrombosis isreported (which may not be noticed for several

days after the injection).

Intramuscular injection of diazepam is painful

and absorption is erratic


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An emulsion formulated for intravenousinjection is less irritant and reduces the risk of

venous thrombosis

it is not suitable for intramuscular injection.Diazepam is also available as a rectal solution

but this preparation is not used for

premedication or sedation.

t


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temazepam

Temazepam is given by mouth and has ashorter duration of action and a more rapid

onset than diazepam given by mouth

It has been used as a premedicants ininpatient and day-case surgery;

anxiolytic and sedative effects last about 90

minutes although there may be residual

drowsiness.

l


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lorazepam

Lorazepam produces more prolonged sedationthan temazepam and it has marked amnesic

effects.

It is used as a premedicants the night beforemajor surgery

a further, smaller dose may be required the

following morning if any delay in starting

surgery is anticipated.

Alternatively the first dose may be given early

in the morning on the day of operation.

id l


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midazolam

Midazolam is a water-soluble benzodiazepinethat is often used in preference to intravenous

diazepam;

recovery is faster than from diazepam, but may be significantly longer in the elderly


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Midazolam is associated with profoundsedation when high doses are given

intravenously or when used with certain other

drugs.

overdosage


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overdosage

There have been reports of overdosage whenhigh strength midazolam has been used for

conscious sedation.

The use of high-strength midazolam (5 mg/mLin 2 mL and 10 mL ampoules, or 2mg/mL in 5

mL ampoules) should be restricted to general

anaesthesia,


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It is advised that flumazenil is available whenmidazolam is used, to reverse the effects .


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Benzodiazepines

Benzodiazepines can produce anesthesia

similar to that of barbiturates, but are morecommonly used for sedation rather than

anesthesia because prolonged amnesia and

sedation may result from anesthetizing doses.


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As adjuncts, benzodiazepines are used foranxiolysis, amnesia, and sedation prior to

induction of anesthesia or for sedation during

procedures not requiring general anesthesia.The benzodiazepine most frequently used in

the perioperative period is midazolam

followed distantly by diazepam and

lorazepam.


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Midazolam has several advantages over bothdiazepam and lorazepam.


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It is water soluble and typically isadministered intravenously but also can be

given orally, intramuscularly, or rectally.

Oral midazolam is particularly useful forsedation of young children.


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Midazolam produces minimal venous irritationas opposed to diazepam and lorazepam,

which are formulated in propylene glycol and

are painful on injection, sometimes producingthrombophlebitis.


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Midazolam has the pharmacokineticadvantage, particularly over lorazepam, of

more rapid onset and shorter duration of

effect. Sedative doses of midazolam (0.010.07

mg/kg intravenously) reach peak effect in

about 2 minutes and provide sedation for

about 30 minutes


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Elderly patients tend to be more sensitive toand have a slower recovery from

benzodiazepines

thus, titration to the desired effect of smallerdoses in this age group is prudent.


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For either prolonged sedation or generalanesthetic maintenance, midazolam is more

suitable for infusion than other

benzodiazepines, although its duration ofaction does significantly increase with

prolonged infusions

Analgesics


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Analgesics

With the exception of Ketamine and nitrousoxide, neither parenteral nor currently

available inhalational anesthetics are effective

analgesics. Thus, analgesics typically are administered

with general anesthetics to reduce anesthetic

requirement and minimize hemodynamic

changes produced by painful stimuli.


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Nonsteroidal anti-inflammatory drugs,cyclooxygenase-2 inhibitors, or

acetaminophen may provide adequate

analgesia for minor surgical procedures. Because they produce rapid and profound

analgesia, opioids are the primary analgesics

used during the perioperative period.


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Fentanyl , sufentanil , alfentanil , remifentanil ,meperidine , and morphine are the major

parenteral opioids used in the perioperative

period. The primary analgesic activity of each of these

drugs is produced by agonist activity at -

opioid receptors.


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Their order of potency (relative to morphine) is:sufentanil (1000x) > remifentanil (300x) >

fentanyl (100x) > alfentanil (15x) > morphine

(1x) > meperidine (0.1x). The choice of a perioperative opioid is based

primarily on duration of action, given that at

appropriate doses, all produce similar

analgesia and side effects.


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During the perioperative period, opioids oftenare given at induction to prevent responses to

predictable painful stimuli (e.g., endotracheal

intubation and surgical incision). Subsequent doses either by bolus or infusion

are titrated to the surgical stimulus and the

patients hemodynamic response


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Marked decreases in respiratory rate andheart rate with much smaller reductions in

blood pressure are seen to varying degrees with

all opioids. Muscle rigidity that can impair ventilation

sometimes accompanies larger doses of

opioids


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. The incidence of sphincter of Oddi spasm isincreased with all opioids, although morphineappears to be more potent in this regard.

The frequency and severity of nausea,vomiting, and pruritus after emergence fromanesthesia are increased by all opioids toabout the same degree.

A useful side effect of meperidine is itscapacity to reduce shivering, a commonproblem during emergence from anesthesia.

2-adrenoceptor agonists


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These agents have been found to producesedation and analgesia.

The sedative properties may be related to their

action on 2-receptors in the locus cereleus while analgesia likely occurs via 2-receptors

in the spinal cord


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Agents used for sedation include clonidineand IV dexmedetomidine.


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A solution of clonidine is available for epiduralanesthesia.

Cardiovascular side effects such as

bradycardia and hypotension limit the dosesthat can be used.

As adjunctive drugs they reduce the dose

requirement for opioids and anaesthetics

during surgery.

Neuromuscular Blocking Agents


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Depolarizing (e.g., succinylcholine) andnondepolarizing muscle relaxants (e.g.,

pancuronium)

often are administered during the induction ofanesthesia to relax muscles of the jaw, neck,

and airway and thereby facilitate laryngoscopy

and endotracheal intubation


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. Following induction, continued musclerelaxation is desirable for many procedures to

aid surgical exposure and to provide additional

immobility.


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The action of nondepolarizing muscle

relaxants usually is antagonized, once muscle

paralysis is no longer desired, with anacetylcholinesterase inhibitor such as

neostigmine or edrophonium combined with a

muscarinic receptor antagonist e.g.atropine to

offset the muscarinic activation resulting fromesterase inhibition.


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Other than histamine release by some agents,nondepolarizing muscle relaxants used in this

manner have few side effects.


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succinylcholine has multiple serious side effectse.g.

bradycardia,

hyperkalaemia, severe myalgia

induction of malignant hyperthermia in

susceptible individuals.

Medicine Lecture One General Anaethsia 19th Nov

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