General Anesthetics
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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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General Anesthetics

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General anesthetics

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.


General anesthetics

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.


General anesthetics

Adjuncts to general anesthetics

I. Muscle relaxants

II. Pre-anesthetic medications.

Muscle relaxants

Facilitate intubation.

Suppress muscle tone.

Atracurium, Vecuronium, Succinylcholine.


General anesthetics

  • 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.


General anesthetics

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.


General anesthetics

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.


General anesthetics

  • Classification

  • 1. Inhalation Anesthetics

  • Gases: nitrous oxide

  • Volatile Liquids:

    • Ether

    • Halogenated compounds

  • 2. Intravenous Anesthetics


General anesthetics

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


General anesthetics

  • Inhalation Anesthetics

  • Methoxyflurane

  • Halothane

  • Enflurane

  • Isoflurane

  • Desflurane

  • Sevoflurane

  • Nitrous oxide .


General anesthetics

Pharmacokinetics of general anesthetics

  • Induction of anesthesia

  • Maintenance of anesthesia

  • Depth of anesthesia.

  • Recovery of anesthesia

  • MAC value


General anesthetics

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.


General anesthetics

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).


General anesthetics

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


General anesthetics

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.


General anesthetics

POTENCYMAC

Methoxyflurane 0.16

Halothane 0.75

Isoflurane 1.4

Enflurane 1.7

Sevoflurane 2

Desflurane 6-7

Nitrous oxide >100


General anesthetics

Pharmacological Actions

CNS

-  metabolic rate.

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

- Dose - dependent EEG changes (Enflurane).


General anesthetics

CVS

  • Hypotension

  • Bradycardia except ( Isoflurane, Desflurane)

  • Myocardial depression (Halothane , Enflurane)

    - Sensitize heart to catecholamines (Halothane)


General anesthetics

Respiratory system

- All respiratory depressants.

  • Bronchodilators (Halothane – Sevoflurane).

  •  mucociliary movement.

  • Airway irritation (Desflurane- Enflurane).

    Liver

    - Decrease hepatic flow.

    - Hepatotoxicity (Only halothane ).


General anesthetics

Uterus

  • Uterine relaxation

  • Nitrous oxide: has minimal relaxant effect (labor).

    Skeletal muscles

    - All are skeletal muscle relaxants to varying degree.


General anesthetics

Methoxyflurane

  • The most potent (high lipid solubility).

  • 50 % is metabolized to fluoride (nephrotoxic).

  • Slow induction (20 minutes).

  • For veterinary use only.


General anesthetics

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.


General anesthetics

  • CVS depression

    • Hypotension

    • Bradycardia (vagomimetic action)

    •  Myocardial contractility.

    •  Cardiac output

  • Respiratory depression.

  • Uterine relaxant.

  • The agent of choice in children (Pleasant).


General anesthetics

Adverse Effects

  • Hepatotoxicity (repeated use).

  • Malignant hyperthermia.

  • Decrease the cardiac output.

  • Sensitizes heart to action of catecholamines cardiac arrhythmias.


General anesthetics

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


General anesthetics

  • 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).


General anesthetics

Contraindications

  • patients with seizure disorders.

  • renal failures.


General anesthetics

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.


General anesthetics

  • CVS depression

    • Hypotension ( VR)

      - Potent coronary vasodilator.

      -  H R

      Disadvantages

      Pungent (not for pediatrics).


General anesthetics

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


General anesthetics

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


General anesthetics

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.


General anesthetics

Adverse Effects

  • Diffusion hypoxia: (respiratory diseases).

  • Nausea and vomiting.

  • Inactivation of B 12  megaloblastic anemia.

  • Chronic use:

    Bone marrow depression- leukopenia

    Abortion - Congenital anomalies


General anesthetics

Therapeutic Uses

  • Outpatient anesthesia (dental procedures).

  • As a component of balanced anesthesia.

  • Neuroleptanalgesia.

  • Delivery

    Contraindications

    1. Pregnancy.

    2. Pernicious anemia.

    3. Immunosuppression.


General anesthetics

Intravenous Anesthetics

1. Ultra short acting barbiturates.

2. Benzodiazepines.

3. Opioids.

4. Ketamine.

5. Propofol

6. Etomidate.

7. Neuroleptics


General anesthetics

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).


General anesthetics

Ultra Short acting Barbiturates

Thiopental (Pentothal)

Methohexital (Brevital)

Thiamylal (Surital)


General anesthetics

Thiopentone

Rapid onset of action 1 min (high lipid solubility)

Ultra short duration of action 15 - 20 min

Metabolized slowly by the liver.


General anesthetics

Pharmacodynamics

  • Potent anesthetic.

  • No analgesic activity

  • No skeletal muscle relaxation.

  • CNS:  ICP (Used in head injuries).

  • CVS: Hypotension & Dysrhythmia.

  • Respiratory depression (dose-dependent).


General anesthetics

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.


General anesthetics

Contraindication

1. Chronic obstructive lung disease.

2. Porphyria.

3. Hypersensitive patients.

4. Severe hypotension (hypovolemic & shock patient).


General anesthetics

Benzodiazepines

Midazolam (Versed)

Diazepam (Valium)

Lorazepam (Ativan)

  • The best one is Midazolam

  • Amnesic action.

  • Reduce anxiety.

  • No analgesic activity


General anesthetics

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.


General anesthetics

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


General anesthetics

Side Effects

  • Involuntary movements during induction (diazepam).

  • Postoperative nausea -vomiting.

  • Adrenal suppression (inhibition of steroidogenesis)

  • Pain at sit of injection.

  • Teratogenic.


General anesthetics

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).


General anesthetics

Side Effects

1. Hypotension (PVR).

2. Excitation (involuntary movements).

3. Pain at site of injection.

4. Expensive.

5. Clinical infections due to bacterial contamination.


General anesthetics

Ketamine

  • Non barbiturate

  • Dissociative anesthesia

    • Analgesia.

    • Amnesia.

    • Immobility.

    • Complete separation from the surrounding environment.

      Pharmacokinetics

      - Rapid onset of action (slower than thiopental)


General anesthetics

- 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).


General anesthetics

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


General anesthetics

Contraindications

  • CVS diseases (hypertension-stroke).

  • Head injuries.

    Uses

  • Minor operations (children, elderly, shock patients .

  • Short duration diagnostic procedures


General anesthetics

Opiate Drugs

Fentanyl (Sublimaze)

Alfentanil(Alfenta)

Sufentanil(Sufenta)

Fentanyl

-Rapid onset

- Short duration of action.

- Potent analgesia.

- No muscle relaxation


General anesthetics

Uses

  • Cardiac surgery ( + nitrous oxide).

  • Neuroleptanalgesia (fentanyl + droperidol ).

  • Neuroleptanesthesia (Fentanyl + droperidol+ nitrous oxide).

    Side Effects

  • Respiratory depression, bronchospasm (wooden rigidity).

  • Hypotension.

  • Nausea & vomiting.


General anesthetics

  • 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).


General anesthetics

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).


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