General Anaesthetics/ classification, pharmacological action -

General Anaesthetics

A family of medications known as general anesthetics causes a reversible loss of consciousness, enabling patients to receive medical treatments without experiencing pain or awareness of the operation. Usually, an anesthesiologist or anesthetist will deliver these medications in a regulated setting, like a hospital or surgery center. Surgical techniques, diagnostic treatments, and other medical interventions frequently include the use of general anesthesia.

Here are some key points about general anesthetics:

Mechanism of Action: General anesthetics work by altering the activity of neurotransmitters in the brain, particularly gamma-aminobutyric acid (GABA) receptors. They enhance inhibitory signals in the brain, leading to a decrease in neuronal activity and a loss of consciousness.
Administration: General anesthetics can be administered through inhalation (inhaled anesthetics) or intravenous injection (intravenous anesthetics). Inhalation anesthetics are gases or vapors that patients breathe in, while intravenous anesthetics are injected directly into the bloodstream.
Types of General Anesthetics:
- Inhalation Anesthetics: Examples include nitrous oxide, desflurane, sevoflurane, and isoflurane.
- Intravenous Anesthetics: Examples include propofol, etomidate, and barbiturates.
Monitoring: Patients under general anesthesia are closely monitored for vital signs such as heart rate, blood pressure, oxygen saturation, and respiratory rate. Advanced monitoring devices are used to ensure the patient’s safety during the procedure.
Reversal Agents: Some general anesthetics can be reversed or antagonized using specific drugs. For example, medications like flumazenil can reverse the effects of certain intravenous anesthetics that act on GABA receptors.
Side Effects and Risks: While general anesthesia is generally safe, it is not without risks. Side effects and risks can include nausea, vomiting, respiratory issues, allergic reactions, and rare complications such as malignant hyperthermia. The risks are usually weighed against the benefits of the medical procedure being performed.
Postoperative Recovery: After the procedure, patients are carefully monitored during the initial recovery period. The anesthetic agents are discontinued, and patients gradually regain consciousness. Postoperative pain management and monitoring for any complications are essential components of the recovery process.

Classification:

General anesthetics can be classified based on their chemical structure and mode of administration. Here’s a classification of general anesthetics:

Based on Chemical Structure:

Classifying general anesthetics based on their chemical structure helps to categorize these agents according to their molecular composition. Here are some common categories based on chemical structure:

Halogenated Hydrocarbons:
- These are volatile inhalation anesthetics. Examples include:
  - Isoflurane
  - Desflurane
  - Sevoflurane
Ether Derivatives:
- While ethers are not as commonly used today, some historical examples include:
  - Ether (diethyl ether) – historically used, but largely replaced by safer agents
  - Methoxyflurane – used in the past but has fallen out of favor due to renal toxicity
Inert Gases:
- Nitrous oxide (N2O) is an inert gas used as an inhalation anesthetic. It is unique among anesthetics due to its low potency and analgesic properties.
Alkyl Ethers:
- Some intravenous anesthetics fall into the alkyl ether category. For example:
  - Etomidate
  - Methohexital
Alkylphenols:
- Propofol is an intravenous anesthetic belonging to the alkylphenol class.
Barbiturates:
- Barbiturates are a class of compounds, some of which have been used as intravenous anesthetics. An example is:
  - Thiopental

Each of these classes has distinct properties and characteristics, and the choice of a specific agent depends on factors such as the patient’s health, the type of surgery, and the preferences of the anesthesia team. Modern anesthesia often involves the use of a combination of agents to achieve a balanced and effective state of anesthesia while minimizing side effects.

Based on Mechanism of Action:

Based on the mechanism of action, general anesthetics can be categorized into different groups. Here are the main classes based on their mechanisms:

GABAergic Agents:
- Mechanism: Enhance the activity of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain. This results in increased chloride ion influx into neurons, leading to hyperpolarization and inhibition of neuronal activity.
- Examples:
  - Isoflurane
  - Desflurane
  - Sevoflurane
  - Propofol
NMDA Receptor Antagonists:
- Mechanism: Block the N-methyl-D-aspartate (NMDA) receptors, which are glutamate receptors responsible for excitatory neurotransmission. This inhibition contributes to the analgesic and dissociative effects.
- Example:
  - Ketamine
Sodium Channel Blockers (Local Anesthetics):
- Mechanism: Act on sodium channels, inhibiting the generation and propagation of action potentials. While local anesthetics primarily target peripheral nerves, they can also affect the central nervous system.
- Examples:
  - Lidocaine (used more commonly in regional anesthesia)
  - Bupivacaine
Inhalation Anesthetics – Unknown Mechanism:
- Mechanism: The exact mechanism of action for some inhalation anesthetics is not fully understood. It is believed that they may affect multiple targets, including ion channels and neurotransmitter receptors.
- Examples:
  - Nitrous oxide
  - Halogenated hydrocarbons (e.g., isoflurane, desflurane, sevoflurane)
Opioids (Adjunctive Analgesics):
- Mechanism: Opioids are often used in combination with other general anesthetics for analgesia. They act on opioid receptors in the central nervous system, modulating pain perception.
- Examples:
  - Fentanyl
  - Morphine

Understanding these mechanisms is crucial for anesthesiologists and healthcare professionals to select the appropriate agents and tailor anesthesia regimens for individual patients and specific surgical procedures. The combination of agents with different mechanisms allows for balanced anesthesia, optimizing the desired effects while minimizing side effects.

Based on Clinical Characteristics:

Based on clinical characteristics, general anesthetics can be categorized into two main types: volatile (inhaled) anesthetics and intravenous (IV) anesthetics. Each type has its own set of characteristics and administration methods.

Volatile Anesthetics (Inhaled Anesthetics):
- Physical State: These agents exist as gases or vapors at room temperature.
- Administration: Administered through inhalation via a vaporizer, either through a mask or an endotracheal tube during intubation.
- Examples:
  - Isoflurane
  - Desflurane
  - Sevoflurane
- Advantages:
  - Precise control over depth of anesthesia.
  - Rapid induction and emergence.
Intravenous Anesthetics:
- Physical State: These agents are typically administered as liquids through intravenous injection.
- Administration: Administered directly into the bloodstream via an IV line.
- Examples:
  - Propofol
  - Etomidate
  - Thiopental (barbiturate)
  - Ketamine
- Advantages:
  - Rapid onset of action.
  - Smooth induction and emergence.
  - Reduced risk of irritation to the respiratory tract (compared to inhaled agents).
Balanced Anesthesia:
- Definition: This approach involves the use of a combination of both inhaled and intravenous agents to achieve balanced and effective anesthesia.
- Benefits:
  - Allows for lower doses of each agent, reducing the risk of side effects.
  - Provides flexibility and customization of anesthesia based on patient and procedural requirements.
Reversal Agents:
- Definition: Some agents used in general anesthesia have specific reversal agents that can be administered to counteract their effects.
- Example:
  - Flumazenil is a reversal agent for certain intravenous anesthetics, such as benzodiazepines.
Local Anesthetics (Adjuncts to General Anesthesia):
- Definition: These agents block nerve conduction in a specific area, providing analgesia and contributing to the overall anesthesia plan.
- Example:
  - Lidocaine is sometimes used in combination with general anesthetics to reduce pain during intubation or to decrease the dose of other anesthetic agents.

The choice between inhaled and intravenous anesthesia often depends on factors such as the type of surgery, patient preferences, and the expertise of the anesthesia team. The use of balanced anesthesia and adjuncts allows for a more tailored approach to meet the specific needs of each patient and procedure.

General Anaesthetics pharmacological action:

General anesthetics work pharmacologically by modifying neurotransmitter activity in the central nervous system, which results in muscular relaxation, analgesia (pain alleviation), and a reversible loss of consciousness. The particular mechanisms of action can change based on the kind of general anesthetic that is used. The general pharmacological activities are as follows:

Enhancement of Inhibitory Neurotransmission:
- Many general anesthetics, both inhalation and intravenous, enhance the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
- GABA is the major inhibitory neurotransmitter in the brain, and its activation leads to hyperpolarization of neurons, reducing their excitability.
- Agents like isoflurane, desflurane, sevoflurane, and propofol exert their effects, at least in part, by enhancing GABAergic neurotransmission.
Inhibition of Excitatory Neurotransmission:
- Some general anesthetics, such as ketamine, act as antagonists at the N-methyl-D-aspartate (NMDA) receptors, inhibiting excitatory neurotransmission mediated by glutamate.
- This NMDA receptor blockade contributes to the dissociative anesthesia and analgesic effects of ketamine.
Modulation of Ion Channels:
- General anesthetics, particularly inhalation agents, can modulate ion channels, affecting the flow of ions across neuronal membranes.
- Examples include the modulation of potassium and calcium channels, leading to changes in neuronal membrane potential and decreased neuronal excitability.
Depression of the Central Nervous System:
- General anesthetics depress the central nervous system, leading to a progressive reduction in the level of consciousness.
- This depression affects higher brain functions, resulting in amnesia, immobility, and a decreased response to sensory stimuli.
Analgesia:
- General anesthetics provide analgesia by reducing the perception of pain. This is achieved through their effects on pain pathways in the brain and spinal cord.
Muscle Relaxation:
- General anesthetics induce muscle relaxation by interfering with the transmission of nerve impulses at the neuromuscular junction.
- This allows for surgical procedures that require muscle relaxation, such as abdominal surgeries or orthopedic procedures.
Cardiovascular Effects:
- Some general anesthetics can affect cardiovascular function, leading to changes in heart rate, blood pressure, and cardiac output.
- These effects are carefully monitored during anesthesia administration.
Respiratory Depression:
- General anesthetics can depress respiratory function, leading to a decrease in respiratory rate and tidal volume. Mechanical ventilation is often used to support respiratory function during surgery.

It’s important to note that the pharmacokinetics and pharmacodynamics of individual anesthetic agents can vary, and the choice of anesthetic is tailored to the patient’s specific needs, the type of surgery, and other relevant factors. The administration and monitoring of general anesthesia are performed by trained anesthesia professionals to ensure the safety and well-being of the patient.