Neuro-physiology of anxiety.pptxNeuro-physiology of anxiety.pptx

Neuro-physiology of anxiety.pptx

1. Neuro -physiology of anxiety/pain controle By Dr : farzana lakho Senior registrar omfs

2. The desirable properties of local anesthesia 1 . Effectiveness: It should provide complete and predictable pain relief in the targeted area . 2 . Rapid Onset: It should act quickly to provide relief within a short period after administration . 3 . Duration of Action: It should maintain its effect for a sufficient period of time to allow the procedure to be completed without causing discomfort . 4 . Safety: The anesthesia should have a low incidence of toxicity and side effects, with minimal risk to the patient . 5 . Non-irritating: It should not cause excessive irritation to the tissues when administered.

3. 6. Reversible: Once the procedure is finished, the effects should wear off without long-lasting complications . 7. Minimal Systemic Absorption: It should have limited absorption into the bloodstream to reduce the risk of systemic toxicity . 8 . Ease of Administration: The technique for administration should be straightforward and suitable for the clinical procedure . 9 . Low Allergic Potential: The agent should be safe for most patients, with minimal risk of allergic reactions . 10 . Compatibility with other Drugs: It should not interfere with other medications or conditions, especially in patients who are on long-term treatments.

4. Fundamentals: Impulse Generation and transmission 1 . Resting Membrane Potential: Cells, especially neurons, maintain a resting potential across their membrane due to differences in ion concentrations inside and outside the cell (mainly sodium, potassium, chloride, and calcium ions ). 2 . Stimulus: A stimulus, which could be mechanical, chemical, or electrical, causes a temporary change in the membrane's permeability to ions. This leads to depolarization, where sodium channels open and sodium ions rush in . 3 . Action Potential: When the depolarization reaches a certain threshold, an action potential is generated. This is a rapid, all-or-nothing electrical signal that travels along the nerve axon . 4. Repolarization: After the action potential peaks, potassium channels open, allowing potassium ions to exit the cell, which helps restore the negative membrane potential (repolarization ). 5 . Hyperpolarization: Sometimes, the membrane potential becomes more negative than the resting potential for a short time, which helps in preventing the neuron from firing again too soon.

5. Impulse Transmission: Impulse transmission refers to the movement of the action potential along the nerve and across synapses to other cells (such as muscles or other neurons). This process involves : 1 . Saltatory Conduction: In myelinated axons, action potentials jump between the nodes of Ranvier (gaps in the myelin sheath), making the signal transmission much faster compared to unmyelinated axons . 2. Synaptic Transmission: At the end of the axon, the electrical impulse reaches the synaptic terminal. Here, it triggers the release of neurotransmitters from synaptic vesicles into the synaptic cleft. These neurotransmitters bind to receptors on the next neuron or muscle cell, transmitting the signal further . 3 . Refractory Period: After an action potential, neurons enter a refractory period where they cannot generate another action potential immediately. This ensures that impulses travel in one direction along the nerve and prevents overstimulation.In mechanical systems, such as engines or hydraulic systems, impulse generation typically refers to a rapid force or pressure change, while transmission involves the transfer of this force through components like gears, levers, or fluids .

6. Mode of action : . Local anesthetics primarily work by inhibiting the function of voltage-gated sodium channels in nerve cells. These channels are responsible for transmitting nerve impulses. When the anesthetic is applied to a nerve, it binds to these channels, preventing the influx of sodium ions, which are necessary for the depolarization and conduction of nerve impulses. Without the ability to conduct these signals, the brain doesn't receive pain information from the affected area, causing numbness.

7. 1. Sodium Channel Blockade: Local anesthetics primarily act by binding to voltage-gated sodium channels on the nerve cell membrane. This prevents sodium ions from entering the nerve cell, inhibiting the depolarization necessary for nerve impulse transmission . Preventing Action Potential Propagation: By blocking sodium influx, local anesthetics prevent the generation and propagation of action potentials along the nerve fibers. This means that the nerve can't transmit pain signals to the brain, effectively blocking the sensation of pain . 3. Use-Dependent Block: Local anesthetics block sodium channels more effectively when the nerve is actively firing (i.e., during depolarization), which is why they are particularly effective in areas of high nerve activity.

8. Site of action: The site of action is the nerve membrane, specifically the sodium channels located in the axons of sensory nerves. Local anesthetics can be applied via injection or topical methods to affect the nerves in the area of interest, usually blocking sensation in skin, tissues, or other areas where the anesthetic is delivered.

9. Mechanism of action : Local anesthetics work by blocking sodium channels, preventing nerve signal transmission, and leading to temporary loss of sensation in a specific area. The active forms of local anesthetics generally exist in two forms: the ionized (charged) form and the unionized (neutral) form. Both forms play a role in the drug's mechanism of action.

10. Forms of local anaesthesia : 1. Unionized (Neutral) Form: This form is lipophilic (fat-soluble), allowing the anesthetic to cross cell membranes, particularly the nerve membrane.Once the drug crosses the membrane, it enters the cytoplasm and then converts to the ionized form, which is essential for binding to the sodium channels . 2. Ionized (Charged) Form : The ionized form is hydrophilic (water-soluble), which allows it to interact with the sodium channels located inside the nerve.The anesthetic binds to specific sites on the sodium channels, blocking sodium influx and inhibiting action potential propagation, which leads to the local anesthetic effect .

11. The relative amounts of the unionized and ionized forms depend on the pH of the tissue and the pKa (acid dissociation constant) of the anesthetic. In acidic environments (such as inflamed tissue), the drug tends to remain more ionized, which can decrease its effectiveness. In contrast, in less acidic (or more basic) environments, the anesthetic is more likely to exist in its unionized form, enhancing its ability to penetrate nerve membranes.Active Forms:For the anesthetic to be effective, it needs to be in its unionized form to cross the nerve membrane, but once inside, the ionized form binds to the sodium channels and exerts the anesthetic action.This dynamic interplay between the two forms (

12. The kinetics of local anesthetics (LAs ): include both their onset of action and duration, which are influenced by several factors like the drug's chemical properties, tissue pH, and the specific site of injection. Here's a brief overview : The onset of a local anesthetic : refers to the time it takes to produce an effective block after injection. The factors that influence the onset include:1. pKa (Dissociation Constant): The pKa determines how much of the anesthetic is in its uncharged (lipophilic) form, which can more easily cross nerve membranes. Local anesthetics with a lower pKa generally have a faster onset because more of the drug is in its uncharged form at physiological pH. For example, lidocaine has a pKa around 7.8 and works faster than bupivacaine ( pKa ~8.1).

13. Duration of action : The duration of action refers to how long the anesthetic effect lasts. Several factors influence this, including : 1 . Protein Binding: Local anesthetics that bind more strongly to plasma proteins (such as bupivacaine and ropivacaine ) tend to have a longer duration because the bound drug is slowly released into the bloodstream, prolonging its effect . 2 . Vasodilation: Drugs that cause vasodilation (e.g., lidocaine ) are usually cleared more rapidly because they are washed away from the site of action by the bloodstream, leading to a shorter duration. Drugs with lower vasodilation (e.g., bupivacaine and ropivacaine ) have a longer duration due to reduced systemic absorption.

14. Metabolism and elimination: The metabolism of the local anesthetic can also affect its duration. For example, lidocaine is metabolized in the liver (and has a relatively short duration ).

15. Thanks for attention