General anesthetics and Preanesthetic medication

History
 In 1844 Horace well-Used nitric oxide for dental procedure
 In 1846 Morton –dentist-used ether anesthesia
 In 1847 Simpson-used chloroform anesthesia
 In1935 thiopentone first i.v anesthesia was introduced
 Before the middle of 19th century-agents like alcohol, opium and cannabis is used.

General anesthetics (GAs) are drugs which produce reversible loss of all sensation and
consciousness.

The cardinal features of general anesthesia are:

• Loss of all sensation, especially pain
• Sleep (unconsciousness) and amnesia
• Immobility and muscle relaxation
• Abolition of somatic and autonomic reflexes.
Properties of an ideal anaesthetic
A. For the patient
 It should be pleasant, non- irritating, should not cause nausea or vomiting.
 Induction and recovery should be fast with no after effects.
B. For the surgeon
 It should provide adequate analgesia, immobility and muscle relaxation.
 It should be noninflammable and nonexplosive.
C. For the anaesthetist
 Its administration should be easy, controllable and versatile.
 Heart, liver and other organs should not be affected.
 It should be potent so that low concentrations
 Rapid adjustments in depth of anaesthesia should be possible.
 Stages of Anesthesia

The general anesthetics can be classically divided in to four stages based on the increasing depth
Of CNS depression

1.Stage of analgesia
 Starts from beginning of anaesthetic inhalation and lasts upto the loss of consciousness.
 Pain is progressively abolished.
 Patient remains conscious, can hear and see, and feels a dream like state;
 Reflexes and respiration remain normal.
2.Stage of delirium
 This is the state of excitement and delirium
 Apparent excitement is seen patient may shout, struggle and hold his breath;
 muscle tone increases, jaws are tightly closed, breathing is jerky;
 vomiting, involuntary micturition or defecation may occur.
 Heart rate and BP may rise and pupils dilate due to sympathetic stimulation.
3. Surgical anaesthesia
Extends from onset of regular respiration to cessation of spontaneous
breathing. This has been divided into 4 planes which may be distinguished as:
Plane 1 Roving eyeballs. This plane ends when eyes become fixed.
Plane 2 Loss of corneal and laryngeal reflexes.
Plane 3 Pupil starts dilating and light reflex is lost.
Plane 4 Intercostal paralysis, shallow abdominal respiration, dilated pupil.

4.Stage of medullary paralysis

Appears due to overdosing
Depression of respiratory center and vasomotor centre in medulla
This stage is fatal
 Mechanism of action

Inhalation anesthetics are non selective in their action.

 Inhaled anesthetics, barbiturates, BZD, etomidate and propofol facilitate GABA mediated
Inhibition of GABA A receptor sites there by increase chrodie ion influx leading to
hyperpolarization and reduce in membrane excitability.
 Ketamine blocks the actions of glutamate (Excitatory neurotransmitter) at NMDA receptors
 Inhalataion anesthetics like enflurane and isoflurane decreases the duration of nicotinic recept
Activated sodium channels-leads to decrease in action of Ach at cholinergic synapse.
 Inhalational anesthetics
Pharmacokinetics

 Administered at specific conc

 Since brain is highly perfused organ steady state is reached quickly
 Minimum alveolar conc (MAC) is the conc that immobilizes 50% of subjects in response to
Surgical skin incision.
 Nitrous oxide
-Swetish odour
-Produce light anesthesia without significant depression of respiration
 Dissociative anesthesia

Ketamine produces trans-like state known as dissociative anesthesia (Feeling of dissociation

From surroundings, profund analgesia, immobility, light sleep.

Mechanism of action
Act by blocking NMDA receptors which is an excitatory amino acid receptor

Pharmacokinetics
Highly lipid soluble
-Rapidly distributed in to highly perfused organs
Dose: 1-2mg/kg slow IV or 10mg/kg IM
 Neuroleptanalgesia

A combination of neurolept(Droperidol) with analgesic agent (fentanyl) is used

Fentanyl is a short acting and potent opiod analgesic

Droperidol is rapidly acting potent neuroleptic related to haloperidol

DRUG INTERACTIONS
1. Patients on antihypertensives given general anaesthetics—BP may fall markedly.
2. Neuroleptics, opioids, clonidine and mono- amine oxidase inhibitors potentiate anaes-thetic
3. Halothane sensitizes the heart to Adr.
 Pre anesthetic medication

The aim is to
Ensure comfort to the patient
Minimize adverse effects of anesthesia
They are give in order to
1.Decrease anxiety
2.Provide amnesia for the preoperative period
3. Relive preoperative pain if present
4.Reduce gastric acidity

Anti anxiety drugs

They reduce anxiety and produce sedation
BZD such as Diazepam (5-10mg ) oral or lorazepam (2mg I.M)
Midazolam (70-100 ug) I.V can be give prior to surgery
Disadvantage : Respiratory depression

Sedative –hypnotics
Promethazine (25mg I.M) –antihistamine property, antiemitic and anticholinergic action
Negligible respiratory depression found useful in children
Opiod analgesics
Morphine (8-12mg I.M) or Pethidine (50-100mg I.M) is used one hour before surgery
Produce pre and post operative analgesia
Helps in reduction of anesthetic dose

Anticholinergics
Atropine(0,5mg I.M) hyoscine (additionalanti emetic and amnesic property )(0.5mg I.M)
are given 1h prior to surgery
To reduce salivary and bronchial secretion, prevent laryngospasm

Antiemitics
Prevent postoperative vomiting
Metoclopramide, Domperidone, ondensetran

Drugs that reduce acidity -GA trigger vomiting –leads to aspiration of gastric acids in to
respiratory system due to blockade of normal airway reflexes.
Ranitidine, famotidine