1. General Anesthetics
Drugs used to induce a state of unconsciousness with the overall aim of ensuring hypnosis, amnesia, analgesia, immobility, skeletal muscle relaxation, and loss of control of reflexes of the autonomic nervous system.

2. Features of ideal anesthetic
1. Rapid and smooth induction and recovery.
2. Wide safety margin.
Minimal side effects.
Balanced anesthesia
Use of more than one agent to obtain ideal anesthesia.

3. Adjuncts to general anesthetics
I. Muscle relaxants
II. Pre-anesthetic medications.
Muscle relaxants
Facilitate intubation.
Suppress muscle tone.
Atracurium, Vecuronium, Succinylcholine.

4. Pre-anesthetic medication
Anticholinergics: prevent secretion of fluids into the respiratory tract .
Benzodiazepines: relieve anxiety.
Thiopental-Propofol: rapid induction of anesthesia .
Antiemetic : post surgical N&V.
Antihistaminics: allergic reactions.
H2-receptor blockers: reduce gastric acidity
Opiates: induce analgesia.

5. Depth of anesthesia ( Four stages).
Stage I
- Analgesia.
- Loss of pain sensation.
- The patient is conscious and conversational.
Stage II
- Excitement.
- Increased, irregular blood pressure.
- Increased respiratory rate.
Patient may experience delirium & violent behavior.
Dilated & reactive eye.

6. Stage III
- Surgical anesthesia.
- Regular respiration & relaxation of sk. muscles.
- Eye reflexes decrease until the pupil is fixed.
Stage IV
- Medullary paralysis.
- Severe depression of vasomotor and respiratory centers.
- Death may occur.

7. Classification
1. Inhalation Anesthetics
Gases: nitrous oxide
Volatile Liquids:
Ether
Halogenated compounds
2. Intravenous Anesthetics

8. Mechanism of action
Interaction with membrane ion channels.
Enhancing the action of inhibitory neurotransmitters, GABA and glycine thus decrease neuronal excitability.
Inhibition of excitatory neurotransmitters e.g. ketamine is NMDA receptor antagonist

10. Inhalation Anesthetics
Methoxyflurane
Halothane
Enflurane
Isoflurane
Desflurane
Sevoflurane
Nitrous oxide .

11. Pharmacokinetics of general anesthetics
Induction of anesthesia
Maintenance of anesthesia
Depth of anesthesia.
Recovery of anesthesia
MAC value

12. Induction, Maintenance and Recovery
Time elapsed between onset of administration of anesthetic and development of effective surgical anesthesia.
Maintenance
Time during which the patient is surgically anesthetized.
Recovery
The time from discontinuation of anesthetic drug until consciousness is regained.

13. Factors controlling induction & recovery
The anesthetic concentration in the inspired air (Direct).
Blood solubility: Blood: gas partition coefficient (Inverse relation).
Pulmonary blood flow (Inverse).
Rate and depth of ventilation (Direct).

14. Desflurane 0.42 poor & Rapid Nitrous Oxide 0.47 Rapid
DRUGS Solubility Induction & Recovery
(Blood : gas partition coefficient )
Methoxyflurane Slow
Halothane Slow
Enflurane Medium
Isoflurane Medium
Sevoflurane Rapid
Desflurane poor & Rapid
Nitrous Oxide Rapid

15. Minimum Alveolar Concentration (MAC)
It is the concentration of inhalation anesthetic that produce immobility in 50 % patients in response to surgical incision.
Depends on potency of anesthetic agents.
The lower the MAC value the more potent the drug.
MAC is increased by CNS stimulants.
MAC is decreased by CNS depressants & in old people.

16. POTENCY MAC Methoxyflurane 0.16 Halothane 0.75 Isoflurane 1.4
Enflurane
Sevoflurane
Desflurane
Nitrous oxide >100

17. Pharmacological Actions
CNS
-  metabolic rate.
-  ICP (due to cerebral vasodilatation) # in head injuries.
- Dose - dependent EEG changes (Enflurane).

18. CVS
Hypotension
Bradycardia except ( Isoflurane, Desflurane)
Myocardial depression (Halothane , Enflurane)
- Sensitize heart to catecholamines (Halothane)

19. Respiratory system
- All respiratory depressants.
Bronchodilators (Halothane – Sevoflurane).
 mucociliary movement.
Airway irritation (Desflurane- Enflurane).
Liver
- Decrease hepatic flow.
- Hepatotoxicity (Only halothane ).

20. Uterus
Uterine relaxation
Nitrous oxide: has minimal relaxant effect (labor).
Skeletal muscles
- All are skeletal muscle relaxants to varying degree.

21. Methoxyflurane
The most potent (high lipid solubility).
50 % is metabolized to fluoride (nephrotoxic).
Slow induction (20 minutes).
For veterinary use only.

22. Halothane (Fluothane)
Non irritant (pleasant odor)
Potent anesthetic.
Weak analgesic.
Weak skeletal muscle relaxant.
Slow induction and recovery (blood solubility).
Metabolized to hepatotoxic metabolite, trifluroethanol.

23. CVS depression
Hypotension
Bradycardia (vagomimetic action)
 Myocardial contractility.
 Cardiac output
Respiratory depression.
Uterine relaxant.
The agent of choice in children (Pleasant).

24. Adverse Effects
Hepatotoxicity (repeated use).
Malignant hyperthermia.
Decrease the cardiac output.
Sensitizes heart to action of catecholamines  cardiac arrhythmias.

25. Enflurane (Ethrane) More rapid induction and recovery than halothane.
Less potent than halothane.
Better muscle relaxation.
Better analgesic properties.
is metabolized to fluoride (8%).
Excreted in the kidney

26. CVS depression
- Hypotension
-  Cardiac output
- No sensitization of the heart to catecholamines
Disadvantages
Pungent (less induction -not for pediatrics).
CNS stimulation (Epilepsy-like seizure- abnormal EEG).

27. Contraindications
patients with seizure disorders.
renal failures.

28. Isoflurane (Forane) Less potent than halothane
Better analgesic action.
More rapid induction & recovery than
halothane
Stable compound (2%).
Low biotransformation (less fluoride).
No hepatotoxicity.
No sensitization of the heart.
No cardiac arrhythmias.

29. - Potent coronary vasodilator. -  H R Disadvantages
CVS depression
Hypotension ( VR)
- Potent coronary vasodilator.
-  H R
Disadvantages
Pungent (not for pediatrics).

30. Desflurane (Suprane) Pungent odor (irritation - cough)
Rapid induction & fast recovery (low blood solubility).
Less potent than halothane.
Less metabolized (0.05 %).
CVS
- Hypotension
-  VR
-  H R

31. Sevoflurane Less potent than halothane Rapid induction and recovery.
Less metabolized (3- 5% fluoride)
Better smell
No airway irritation (children)
CVS
- Hypotension
-  VR
- Little effect on HR

32. Nitrous Oxide (N2O) The most potent analgesic.
Weak anesthetic (low potency, combined).
The most rapid induction & recovery
due to low blood solubility.
No muscle relaxation.
No respiratory depression.
Not hepatotoxic.
Minimal CVS adverse effects.

33. Adverse Effects Diffusion hypoxia: (respiratory diseases).
Nausea and vomiting.
Inactivation of B 12  megaloblastic anemia.
Chronic use:
Bone marrow depression- leukopenia
Abortion - Congenital anomalies

34. Therapeutic Uses Outpatient anesthesia (dental procedures).
As a component of balanced anesthesia.
Neuroleptanalgesia.
Delivery
Contraindications
1. Pregnancy.
2. Pernicious anemia.
3. Immunosuppression.

35. Intravenous Anesthetics
1. Ultra short acting barbiturates.
2. Benzodiazepines.
3. Opioids.
4. Ketamine.
5. Propofol
6. Etomidate.
7. Neuroleptics

36. Intravenous Anesthetics
Rapid induction & recovery except BZs
Should be injected slowly.
Recovery is due to redistribution from CNS.
Can be used alone in short operation.
Outpatients anesthesia.
NO need for special equipments.
Analgesic activity (Opioids & ketamine ).
Amnesic action (BZs & ketamine).

37. Ultra Short acting Barbiturates
Thiopental (Pentothal)
Methohexital (Brevital)
Thiamylal (Surital)

38. Thiopentone Rapid onset of action 1 min (high lipid solubility)
Ultra short duration of action min
Metabolized slowly by the liver.

39. No skeletal muscle relaxation. CNS:  ICP (Used in head injuries).
Pharmacodynamics
Potent anesthetic.
No analgesic activity
No skeletal muscle relaxation.
CNS:  ICP (Used in head injuries).
CVS: Hypotension & Dysrhythmia.
Respiratory depression (dose-dependent).

40. Uses
As anesthetic alone in minor surgery.
Induction of anesthesia in major surgery.
Adverse Effects
Respiratory depression
CVS collapse.
Extravasations.
Precipitation of porphyria attack.
Hypersensitivity reaction.

41. Contraindication
1. Chronic obstructive lung disease.
2. Porphyria.
3. Hypersensitive patients.
4. Severe hypotension (hypovolemic & shock patient).

42. Benzodiazepines
Midazolam (Versed)
Diazepam (Valium)
Lorazepam (Ativan)
The best one is Midazolam
Amnesic action.
Reduce anxiety.
No analgesic activity

43. Uses
1. Induction of general anesthesia.
2. Alone in minor procedure (endoscopy).
3. Balanced anesthesia (midazolam).
4. Pre-anesthetic medication (diazepam)
Side Effects
Slow induction & recovery.
Respiratory depression.

44. - Ultra-short acting hypnotic (non barbiturates).
Etomidate (Amidate)
- Ultra-short acting hypnotic (non barbiturates).
- No analgesic activity.
Rapid onset of action
Short duration of action.
- Decreases  ICP.
Minimal CVS and respiratory depressant effects.
Uses
Induction of Anesthesia

45. Side Effects
Involuntary movements during induction (diazepam).
Postoperative nausea -vomiting.
Adrenal suppression (inhibition of steroidogenesis)
Pain at sit of injection.
Teratogenic.

46. Propofol - No analgesia.
- Hypnotic (non barbiturates).
- No analgesia.
Rapid onset – Faster recovery than thiopental.
Short duration of action.
- Decreases  ICP.
Antiemetic action.
Uses
Induction of anesthesia
Maintenance of anesthesia (balanced anesthesia).

47. Side Effects
1. Hypotension (PVR).
2. Excitation (involuntary movements).
3. Pain at site of injection.
4. Expensive.
5. Clinical infections due to bacterial contamination.

48. Dissociative anesthesia Analgesia. Amnesia. Immobility.
Ketamine
Non barbiturate
Dissociative anesthesia
Analgesia.
Amnesia.
Immobility.
Complete separation from the surrounding environment.
Pharmacokinetics
- Rapid onset of action (slower than thiopental)

49. - Short duration of action.
- Metabolized in the liver to active metabolite (Norketamine).
Pharmacodynamics
1. BP & cardiac output (central sympathetic activity)
2.  Increases plasma catecholamine levels.
3.  ICP
4. Potent bronchodilator (asthmatics).

50. Advantages
Can be given IV, IM (Children).
No bronchospasm.
Hypovolemic or shock patients.
Side Effects
Post operative hallucination, vivid dreams & disorientation & illusions (Diazepam).
Risk of hypertension & cerebral hemorrhage.
 ICP

51. Contraindications
CVS diseases (hypertension-stroke).
Head injuries.
Uses
Minor operations (children, elderly, shock patients .
Short duration diagnostic procedures

52. Opiate Drugs
Fentanyl (Sublimaze)
Alfentanil (Alfenta)
Sufentanil (Sufenta)
Fentanyl
-Rapid onset
- Short duration of action.
- Potent analgesia.
- No muscle relaxation

53. Uses
Cardiac surgery ( + nitrous oxide).
Neuroleptanalgesia (fentanyl + droperidol ).
Neuroleptanesthesia (Fentanyl + droperidol+ nitrous oxide).
Side Effects
Respiratory depression, bronchospasm (wooden rigidity).
Hypotension.
Nausea & vomiting.

54. Increase in ICP.
Prolongation of labor & fetal distress.
Urinary retention.
Contraindication
1. Head injuries.
2. Pregnancy.
3. Bronchial asthma.
4. Chronic obstructive lung diseases.
5. Hypovolemic shock (Large dose only).

55. Neuroleptanalgesia
A state of analgesia, sedation, muscle
relaxation BUT no loss of consciousness.
Innovar (Fentanyl + Droperidol ).
Contraindicated in parkinsonism.
Diagnostic procedures that require
co-operation of the patient.
Neuroleptanesthesia : a combination of (Fentanyl + Droperidol + nitrous oxide).

56. Thank you