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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. Features of ideal anesthetic

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slide1

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.

slide2

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.

slide3
Adjuncts to general anesthetics

I. Muscle relaxants

II. Pre-anesthetic medications.

Muscle relaxants

Facilitate intubation.

Suppress muscle tone.

Atracurium, Vecuronium, Succinylcholine.

slide4

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.
slide5
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.
slide6
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.

slide7

Classification

  • 1. Inhalation Anesthetics
  • Gases: nitrous oxide
  • Volatile Liquids:
    • Ether
    • Halogenated compounds
  • 2. Intravenous Anesthetics
slide8
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
slide10

Inhalation Anesthetics

  • Methoxyflurane
  • Halothane
  • Enflurane
  • Isoflurane
  • Desflurane
  • Sevoflurane
  • Nitrous oxide .
slide11

Pharmacokinetics of general anesthetics

  • Induction of anesthesia
  • Maintenance of anesthesia
  • Depth of anesthesia.
  • Recovery of anesthesia
  • MAC value
slide12
Induction, Maintenance and Recovery

Induction

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.

slide13
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).
slide14
DRUGS Solubility Induction & Recovery

(Blood : gas partition coefficient )

Methoxyflurane 12 Slow

Halothane 2.3 Slow

Enflurane 1.8 Medium

Isoflurane 1.4 Medium

Sevoflurane 0.69 Rapid

Desflurane 0.42 poor & Rapid

Nitrous Oxide 0.47 Rapid

slide15
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.
slide16
POTENCYMAC

Methoxyflurane 0.16

Halothane 0.75

Isoflurane 1.4

Enflurane 1.7

Sevoflurane 2

Desflurane 6-7

Nitrous oxide >100

slide17
Pharmacological Actions

CNS

-  metabolic rate.

-  ICP (due to cerebral vasodilatation) # in head injuries.

- Dose - dependent EEG changes (Enflurane).

slide18
CVS
  • Hypotension
  • Bradycardia except ( Isoflurane, Desflurane)
  • Myocardial depression (Halothane , Enflurane)

- Sensitize heart to catecholamines (Halothane)

slide19
Respiratory system

- All respiratory depressants.

  • Bronchodilators (Halothane – Sevoflurane).
  •  mucociliary movement.
  • Airway irritation (Desflurane- Enflurane).

Liver

- Decrease hepatic flow.

- Hepatotoxicity (Only halothane ).

slide20
Uterus
  • Uterine relaxation
  • Nitrous oxide: has minimal relaxant effect (labor).

Skeletal muscles

- All are skeletal muscle relaxants to varying degree.

slide21
Methoxyflurane
  • The most potent (high lipid solubility).
  • 50 % is metabolized to fluoride (nephrotoxic).
  • Slow induction (20 minutes).
  • For veterinary use only.
slide22
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.
slide23
CVS depression
    • Hypotension
    • Bradycardia (vagomimetic action)
    •  Myocardial contractility.
    •  Cardiac output
  • Respiratory depression.
  • Uterine relaxant.
  • The agent of choice in children (Pleasant).
slide24
Adverse Effects
  • Hepatotoxicity (repeated use).
  • Malignant hyperthermia.
  • Decrease the cardiac output.
  • Sensitizes heart to action of catecholamines cardiac arrhythmias.
slide25
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
slide26
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).
slide27
Contraindications
  • patients with seizure disorders.
  • renal failures.
slide28
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.
slide29
CVS depression
    • Hypotension ( VR)

- Potent coronary vasodilator.

-  H R

Disadvantages

Pungent (not for pediatrics).

slide30
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

slide31
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

slide32
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.
slide33
Adverse Effects
  • Diffusion hypoxia: (respiratory diseases).
  • Nausea and vomiting.
  • Inactivation of B 12  megaloblastic anemia.
  • Chronic use:

Bone marrow depression- leukopenia

Abortion - Congenital anomalies

slide34
Therapeutic Uses
  • Outpatient anesthesia (dental procedures).
  • As a component of balanced anesthesia.
  • Neuroleptanalgesia.
  • Delivery

Contraindications

1. Pregnancy.

2. Pernicious anemia.

3. Immunosuppression.

slide35
Intravenous Anesthetics

1. Ultra short acting barbiturates.

2. Benzodiazepines.

3. Opioids.

4. Ketamine.

5. Propofol

6. Etomidate.

7. Neuroleptics

slide36
IntravenousAnesthetics
  • 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).
slide37
Ultra Short acting Barbiturates

Thiopental (Pentothal)

Methohexital (Brevital)

Thiamylal (Surital)

slide38
Thiopentone

Rapid onset of action 1 min (high lipid solubility)

Ultra short duration of action 15 - 20 min

Metabolized slowly by the liver.

slide39
Pharmacodynamics
  • Potent anesthetic.
  • No analgesic activity
  • No skeletal muscle relaxation.
  • CNS:  ICP (Used in head injuries).
  • CVS: Hypotension & Dysrhythmia.
  • Respiratory depression (dose-dependent).
slide40
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.
slide41
Contraindication

1. Chronic obstructive lung disease.

2. Porphyria.

3. Hypersensitive patients.

4. Severe hypotension (hypovolemic & shock patient).

slide42
Benzodiazepines

Midazolam (Versed)

Diazepam (Valium)

Lorazepam (Ativan)

  • The best one is Midazolam
  • Amnesic action.
  • Reduce anxiety.
  • No analgesic activity
slide43
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.
slide44
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

slide45
Side Effects
  • Involuntary movements during induction (diazepam).
  • Postoperative nausea -vomiting.
  • Adrenal suppression (inhibition of steroidogenesis)
  • Pain at sit of injection.
  • Teratogenic.
slide46
Propofol

- 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).
slide47
Side Effects

1. Hypotension (PVR).

2. Excitation (involuntary movements).

3. Pain at site of injection.

4. Expensive.

5. Clinical infections due to bacterial contamination.

slide48
Ketamine
  • Non barbiturate
  • Dissociative anesthesia
    • Analgesia.
    • Amnesia.
    • Immobility.
    • Complete separation from the surrounding environment.

Pharmacokinetics

- Rapid onset of action (slower than thiopental)

slide49
- 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).

slide50
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
slide51
Contraindications
  • CVS diseases (hypertension-stroke).
  • Head injuries.

Uses

  • Minor operations (children, elderly, shock patients .
  • Short duration diagnostic procedures
slide52
Opiate Drugs

Fentanyl (Sublimaze)

Alfentanil(Alfenta)

Sufentanil(Sufenta)

Fentanyl

-Rapid onset

- Short duration of action.

- Potent analgesia.

- No muscle relaxation

slide53
Uses
  • Cardiac surgery ( + nitrous oxide).
  • Neuroleptanalgesia (fentanyl + droperidol ).
  • Neuroleptanesthesia (Fentanyl + droperidol+ nitrous oxide).

Side Effects

  • Respiratory depression, bronchospasm (wooden rigidity).
  • Hypotension.
  • Nausea & vomiting.
slide54
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).

slide55
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).