General anaesthetics

1. General
Anesthetics
Mr. Dipak B. Bari
KES’s College of Pharmacy, Amalner

2. General Anesthetics
Definition : Anesthesia (an =without, aesthesis = sensation)
The drugs which produce reversible loss of all sensations and
consciousness.
Generally administered by an anesthesiologist in order to induce or
maintain general anesthesia to facilitate surgery.

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4. 1. General Anesthesia
General anesthesia (GA) is the state produced when a patient receives medications
for amnesia, analgesia, muscle relaxation, and sedation.
General anesthetics depress the central nervous system to a sufficient degree to
permit the performance of surgery and other noxious or unpleasant procedures.

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General anesthesia uses intravenous and inhaled agents to allow
adequate surgical access to the operative site.
A point worth noting is that general anesthesia may not always be
the best choice; depending on a patient’s clinical presentation, local
or regional anesthesia may be more appropriate.

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7. Preanesthetic Medication
▹ Drugs are to be used to counteract the undesirable effects of anesthetic agent.
▹ Pre-anesthetics refer to the use of drugs prior to the administration of anesthetics
agents.
Importance:
To relief from Anxiety.
To maintain patient in Amnesia.
To support Analgesic action to potentiate anesthetics.
Decrease secretion caused by Anesthesia.
To maintain Antiemetic effect during & post operating procedure.
Decrease Acidity & gastric juice.

8. Pre-anesthetics drugs:
1. Narcotic analgesics: They are helps by depressing CNS. They
also produce analgesia. E.g. Morphine & pethidine.
2. Anticholinergic agents: They reduces body secretion;
specially salivary & respiratory tract secretions. E.g. Atropine
& Hyoscine.
3. Transquillizers: Its helps to reduces anxiety. E.g. Diazepam &
Chlorpromazine.
4. Antihistaminic agent: Its Shows antiemetic action.

9. Stages of Anaesthesia
1. Stage of Analgesia & Amnesia:
This stage start with a induction of anesthesia to loss
consciousness characterized by feeling numbness &
analgesia.
This stage is compatible for dental surgery & obstetrical
procedure.
This stage is does not last for long.
With continued administration of anesthetics agent patient
passes to second stage.

10. 2. Stage of Delirium or excitement
This stage start with lass of consciousness to the
beginning of surgical anesthesia.
This stage is characterized by excitement,
laughing, increased muscular activity, & vomiting.
Pupils may dilate & the patient may show
hypertension & tachycardia.

11. 3. Stage of Surgical Anesthesia:
Patient excitement will stop in this stage & breathing will regularized.
Characteristics of this stage by fixed eye balls & shallow abdominal
pain.
The physical signs during surgical anesthesia are divided into four
different planes.

12. Plane 1
The pupils are
normal in size.
Eyeball roving.
Respiration will
full, regular. The
blood pressure &
pulse rate will
normal. At the last
eye ball will fixed.
Plane 2
Starting from the eye
ball fixation. Corneal
reflexes will loss.
The respiration will
regular.
The increase in
respiration rate or
breath holding in
response to skin
incision is abolished.
Plane 3
The blood pressure
will begins to fall.
The intercostals
muscle will slowly
paralyzed. The pupil
light reflux will lost.
The muscular
relaxation will
complete.
Plane 4
With completely IC
muscle relaxation,
Pupil will dilates &
will not respond to
light.
Blood pressure will
be low & all the
secretion will
completely
abolished.

13. 4. Respiratory paralysis (Medulary paralysis)
Due to excessive administration of anaesthetic agent, the patient
passes into this fourth stage of anaesthesia. This stage shows
severe depression of vital medullary centers. The complete
respiratory arrest occur due to paralysis of intercostals muscles &
diaphragm.
Cessation of breathing to failure of circulation & finally death will
occur.

14. Classification of General Anaesthetics:
1. Volatile General Anaesthetics:
A. Liquid: Diethyl ether, Chloroform, Halothane, Methoxy furane, Ethyl
chloride, & Trichloroethylene.
B. Gases: Nitrous oxide, Ethylene, & Cyclopropane.
2. Non-Volatile General Anaesthetics:
A. Short acting Barbiturate: Thiopentale sodium & Methohexital
B. Non Barbiturate: Propanidid, Ketamine, & Ethomidiate.

15. Mechanism of Pain Impulse Generation (Synapse)
A cholinergic synapse is one involving the neurotransmitter
substance acetylcholine (ACh).
ACh is mostly concerned with excitatory synapses, i.e. ones
passing on impulses from neuron to neuron in the CNS

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1. As an initiating with the release of Na ions at presynaptic cleft, impulse reaches the end of
the axon, the action potential depolarizes the membrane of the synaptic knob.
2. This causes (voltage-gated) calcium ion channels to open, allowing calcium ions to enter.
3. Calcium ions cause synaptic vesicles containing acetylcholine to move towards, and then fuse
with the (presynaptic) membrane.
4. Acetylcholine leaves the vesicles (exocytosis) and diffuses across the synaptic cleft.
5. ACh binds to (sodium channel) receptors on the postsynaptic membrane, which open.
6. As sodium ions enter, resulting depolarization of the postsynaptic membrane.
Events:

17. Mechanism Of Action
Group A
Etionidiate,
Propofol
Barbiturate.
Group B
Ketamine,
Nitrous
oxide,
Cyclopropane.
Group C
Halothane,
Flurane,
Enflurane.

18. Group 1
Etonidiate, Propofol & Barbiturates much more produce
unconsciousness rather than immobility or analgesia.
They act on GABA A receptor at prosynaptic & presynaptic nerves in
CNS.
They combine with receptor open Chloride channel for chloride ion
which makes hyper polarization resulting difficult to excitatory
neurotransmitter to depolarize neuron & generate action potential.

20. Group 2
Ketamine, Nitrous oxide, & Cyclopropane significantly induce analgesia.
Ability of unconsciousness & sensation loss is relatively week.
They acts on N-methyl-D-aspartate receptor (NMDA) found in nerve cells
of spinal cord which modulating pain sensation.
Neurotransmitter Glutamate binds to receptor NMDA, it cause inflow of
calcium ions in postsynaptic neurons which then activate a signals of pain
frequently.
This drugs inhibit NMDA receptors which prevents Neurotransmitter of
pain.

22. Group 3
Halothane, Flurane & Enflurane shows its intrinsic activity
by acting on GABA A & NMDA receptor as well.
They are more potent to produce immobility.

23. Volatile General Anaesthetics
Diethyl Ether:
It’s a colorless liquid very volatile in nature with boiling point 350 c & its give irritant,
inflamed & explosive vapour.
▹ It is explosive
▹ Irritant to respiratory tract
▹ High incidence of nausea and vomiting during induction and post-surgical emergence
Ph’kinetics: Oxidized in body & eliminated through lungs.
Ph’dynamic: Its acts on GABA A receptor.
Preparation Doses
Ether I.P. 1 to 4 ml
Spirit of Ether I.P. 1 to 4 ml
1. Liquid:

24. Chloroform:
▹ Its clear volatile liquid of boiling point 610 C.
▹ Its non explosive liquid. Which is unstable on storage.
▹ Its has sweet smell.
▹ Its potent anaesthetics producing all stages of anaesthesia.
Adverse effect: Major toxic effect on liver.
Repeated dose can causes cirrhosis.
Impaired heart or kidney.

25. Halothane:
Volatile liquid at room temperature. Light sensitive
Ph’kinetic: High fat solubility. Metabolised in liver by Cyt-P450. small amount
eliminated unchanged via lungs.
Commonly used in children, where preoperative placement of an iv catheter can
be difficult
It is marketed in amber bottles with thymol added as a preservative
Metabolised in liver by Cyt-P450

26. Side effects of halothane :
CVS : Cardiac arrhythmia, depression of myocardial contraction.
Respiratory system : Depression of respiration
Muscles : Malignant hyperthermia
Kidney : Decrease renal blood flow and glomerular filtration rate.
Liver and GIT: Cause halothane induced hepatitis & nausea and vomiting
DRUG INTERACTION : Halothane + adrenaline, theophylline => arrhythmia
may be precipitated.
CONTRAINDICATION : Hepatic dysfunction and/or jaundice.

27. Nitrous oxide:
It’s a colorless gas with a faint sweetish smell. The gas is not explosive & not
inflammable. Its marketed as liq. Under 50 atm pressuer in royal blue
cylinder.
Mixture of Nitrous oxide gas with oxygen containing 80%, causes
unconsciousness & analgesia.
Adverse effect:
Excitement produce may be violent in certain cases. Cardiac irregulation may
observed.
2. Gases:

28. Cyclopropane:
Very heavy colourless gas with ether like odour. Its marketed as liq. Under
pressure in orange colored cylinder.
It is inflammable & explosive liquid.
Adverse effect: Responsible for cardiac irregualtion.
Preparation Doses
Cyclopropane I. P. 30 to 35 % Concentration

29. Non Volatile Anaesthesia:
Thiopentane:
▹ It’s a sodium salt of pentobarbitone used as an anaesthetic agent.
▹ Its administered as a 2.5 to 5% solution.
▹ Undesirable effect: Depress respiration & causecoughing, laryngospasm &
bronchospasm.

30. Properties of Ideal Anaesthetics agents:
Potency
Ease
Of
adminstration
Induction
&
Recovery
Inflammable
&
Explosive
Muscle
Relaxant
property
Analgesic
property
Toxicity
Stability

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Thanks…