1. General anesthesia
General anesthesia was not known until the mid-1800’s
Diethylether was the first general anesthetic used for surgery
General Anesthetics are divided into two classes:
Inhaled anesthetics (usually halogenated compounds)
Intravenous anesthetics or induction agents

2. Modern Anesthesia It combines the following: Analgesia
Sleep (loss of consciousness)
Skeletal Muscle relaxation
amnesia
Abolition sensory & autonomic reflexes
No single drug can produce all these effects

3. Ideal anesthesia is No single drug can produce all these effects
Induce loss of consciousness smoothly and rapidly
Allow for prompt recovery of cognitive function after its administration is discontinued
Possess wide margin of safety
Have no side effects
No single drug can produce all these effects

4. Stages of anesthesia Stage 1:analgesia
Decreased pain awareness, sometimes with amnesia ,conscious may be impaired but not lost
Stage 2:disinhibition
Delirium, excitation, amnesia, enhanced reflexes, irregular respiration and incontinence
Stage 3:surgical anesthesia
Unconsciousness ,no pain reflex, regular respiration and maintained blood pressure
Stage 4:medullary depression
Severe CVS and respiratory depression and the patient require pharmacological and ventilatory support

5. Anesthesia protocols
For minor procedure, conscious sedation conscious sedation techniques that combine IV agent with local anesthetics are often used ;these can provide profound analgesia, with retention of the patient ability to maintain a patent airway and response to verbal commands
For extensive surgical procedure protocol commonly includes IV drug for induction, inhaled agent(with or without IV)for maintenance and neuromuscular junction blockers to cause muscle relaxation

6. General Anesthetics
Absence of sensation associated with a reversible loss of consciousness, skeletal muscle relaxation, and loss of reflexes.
Drugs used for anesthesia are CNS depressants with action that can be induced and terminated more rabidly than conventional sedative and hypnotics
Most sensitive site of action for general anesthetics is the reticular activating system of the brainstem (RAS)
Anesthetic dose: does not cause depression of cardiac, vasomotor or respiratory centers
Has a small margin of safety

7. Inhaled Anesthetics Include: Nitrous oxide Halothane Enflurane
Isoflurane
Desflurane

8. Intravenous Anesthetics
Include:
Barbiturates
Thiopental & Methohexital
Opioids
Alfentanil, Meperidine, Fentanyl, Sufentanil (agonists)
Naloxone (antagonist)
Benzodiazepines
Diazepam, Midazolam
Flumazenil (antagonist)

9. Intravenous Anesthetics
Miscellaneous Agents
Etomidate – non-barbiturate hypnotic agent without analgesic properties
Droperidol - Neuroleptic (similar to Haloperidol) - combined with Fentanyl and is used for neuroleptanalgesia (state of analgesia and amnesia)
Ketamine - dissociative anesthetic
Propofol

10. General Uses of IV Anesthetics
Primary Use = induction of general anesthesia
Supplement general anesthesia
maintain general anesthesia
provide sedation
control Blood Pressure

11. Intravenous agents Mechanism of action Act at cell surface receptors
Barbiturates and benzodiazepine act at GABA-A receptors to increase Cl- influx
Opioids act on m and other subtypes
Ketamine antagonizes PCP site on NMDA receptors (prevent excitation)
Pharmacokinetics
Rapid induction = shorter acting
Duration of effect proportional to redistribution from brain to other tissue

12. Barbiturates: Thiopentone
Ultra-short acting hypnotic with no analgesic action
High lipid solubility promotes rapid entry to the brain
Eliminated by the liver
Has rapid onset of action and recovery
M.O.A.= potentiates GABA, decrease glutamate activity, increase chloride ion conductance
Adverse reactions: decreased myocardial and respiratory activity

13. Etomidate
Imidazole derivative that provide induction with minimal change in cardiac function and respiratory rate and has short duration of action
It is not analgesic , and its primary advantage is in anesthesia for patient with limited respiratory and cardiac reserve
Activates GABA receptors
Uses
Induction of anesthesia
Side effects
Myoclonus
Post-operative nausea and vomiting

14. Ketamine
This drug produce dissociative state in which the patient is patient remains conscious but has marked catatonia, analgesia, and amnesia
It is a chemical congener of the psychotomimetic agent, phencyclidine (PCP)
It is a cardiovascular stimulant drug and this action may cause increase ICP
Emergency reactions include disorientation ,excitation and hallucination which can be reduced by preoperative administration of benzodiazepines

15. Uses- Induction of anesthesia
in children
in severely hypovolemic patients
Contraindications
Increased intracranial pressure
Ischemic heart disease
Psychological disorders
Effects
Analgesic with dissociative anesth. properties
Dreaming in children

16. Propofol Uses Induction and maintenance of anesthesia
As anesthetic agent at outpatient surgery
Also effective in producing prolog sedation in patient in critical care setting
Contraindications
Cardiovascular instability due to marked reduction in the peripheral resistance
Effects
Hypnosis ,Antiemetic
Fast acting, short duration. Fewer peripheral side effects compared to barbiturates

17. Opiates Potent analgesics Fentanyl -Potency 50-100X >Morph
Alfentanil -Potency 25-30X > Morph
Sufentanil -Potency 5-10X >Fentanyl
Meperidine
Uses
Supplementation of general anesthesia or analgesia
Effects
respiratory depression
nausea and vomiting
muscle rigidity

18. INHALATION ANESTHETICS

19. MAC(minimal alveolar concentration)
MAC of anaesthetic measures potency of anaesthetic vapour. High MAC means low potency
Defined as the concentration of anesthetic that prevents movement induced by a painful stimulus in 50 % of subjects.

20. Mechanism of Action Potency is correlated with lipid solubility
Olive oil:gas partition coefficient
The greater the number, the more potent the anesthetic Methoxyflurane>halothane>isoflurane etc.

21. Theories for Mechanism of Action
Theory #1
Gas movement into lipid membrane disrupting ion channels and action potential propagation
Increased Atmospheric pressure will reverse effects
Theory #2
Binding theory = anesthetics bind to hydrophobic portion of the ion channel
Theory #3
Neuromodulator theory = anesthetics bind to cell-surface receptors.
increased Cl- flux (possible GABA mediation)

22. Pharmacokinetics of Inhaled Anesthetics
Factors influencing the effects of inhaled anesthetics
Amount that reaches the brain
Indicated by oil:gas ratio (lipid solubility)
Partial pressure of anesthetic
5% anesthetic = 38 mmHg (10% =76 mmHg)
Solubility of gas into blood
The lower the blood:gas ratio, the more anesthetic will arrive at the brain
Cardiac Output
Increased CO = greater Induction time

23. Rate of Entry into the Brain: Influence of Blood and Lipid Solubility

24. General Actions of Inhaled Anesthetics
Respiration
Depressed respiration
Kidney
Depression of renal blood flow and urine output
Muscle
High enough concentrations will relax skeletal muscle

25. General Actions of Inhaled Anesthetics
Cardiovascular System
Generalized reduction in arterial pressure and peripheral vascular resistance. Isoflurane maintains CO and coronary function better than other agents
Central Nervous System
Increased cerebral blood flow and decreased cerebral metabolism

26. Toxicity and Side Effects
Depression of respiratory drive
Depressed cardiovascular drive
Fluoride-ion toxicity from methoxyflurane
Metabolized in liver = release of Fluoride ions
Decreased renal function allows fluoride to accumulate = nephrotoxicity
Malignant hyperthermia
To treat this, rapidly cool the individual and administer Dantrolene to block release of Calcium from muscle sarcoplasmic reticulum

27. Advantages and Disadvantages of Selected Inhaled Anesthetics
Isoflurane
Cardiac output is maintained
Arrhythmias are uncommon
Potentiates the actions of muscle relaxants
Minimally metabolized and no reports of heptato- or nephrotoxicity
most widely used agent
MAY CAUSE MALIGNANT HYPERTHERMIA

28. Advantages and Disadvantages of Selected Inhaled Anesthetics
Desflurane
More irritating to airways than other agents
Rapid recovery
No reports of malignant hyperthermia

29. Preanaesthetic Medication

30. Focus Points
Induction of anesthesia is through use of any of the IV agents (Barbiturates: Thiopental, Opiate: Fentanyl, Benzodiazepines: Midazolam, Dissociative: Ketamine, Others: Propofol, Etomidate and Droperidol)
Majntenance of anesthesia is through use of any of the ihalation agents
-N2O (70% in oxygen) is not suitable alone
- N2O is usually combined with another inhalation agent or with opioids e.g. fentanyl

31. A comparison
halothane N2O Speed of induction intermediate fast Potency v.potent weak MAC=2% MAC 80% Muscle relaxation some none Cardiac arrhythmia yes no Liver damage yes no Recovery slow rapid

32. NOTES:
Enflurane releases flouride ions which may cause renal failure
All inhalation anesthetics can cause resp. depression, myocardial depression, cardiac arrhythmias, hypotension and PONV
A mixture of N2O(50-70%) and haothane 1% is usually used in anesthesia.

33. Nitrous Oxide Characterized by inert nature with minimal metabolism
Colorless, odorless, tasteless, and does not burn

34. Simple linear compound
Only anesthetic agent that is inorganic
Major difference is low potency
MAC value is %
Weak anesthetic, powerful analgesic
Needs other agents for surgical anesthesia
Low blood solubility (quick recovery)

35. GOOD LUCK