Local and General Anesthetics Study Notes

Unique History:
- Indigenous practices in the mid-1800s involved chewing leaves for pain relief.
- Active ingredient was later identified as cocaine.
- Coca-Cola historically included cocaine; this practice has since ceased.
- 1884: Kohler used cocaine in eye drops; compounds still compounded in pharmacies today.
- Freud used cocaine, observing both central nervous system (CNS) stimulation and potential for toxicity and abuse.

Einhorn: Synthesized procaine (a conjugate of cocaine) in the 1900s.
Lidocaine: A modification of procaine, it became a standard local anesthetic in various medical fields, especially dentistry.
Mepivacaine: Developed alongside lidocaine; both received FDA approval.
Bupivacaine: Introduced in the early 1990s; effectively used for longer procedures due to its longer duration of action.

No perfect anesthetic exists; every anesthetic has certain drawbacks:
- Cost, duration of action, adverse effects, and stability issues.
Desirable characteristics of a perfect anesthetic include:
- Safety, reversibility, ideal duration of action, and minimal adverse effects.

Classification: Local anesthetics are categorized as either esters or amides based on their chemical structure.
- Allergies to esters vs. amides: Safe to administer amides to patients with ester allergies and vice versa.
Chemical Structure: Consists of:
1. Aromatic group - imparts lipophilic properties (fat-loving), essential for tissue penetration.
2. Linkage (ester or amide) - determining factor in drug classification.
3. Amino group - imparts hydrophilicity (water-loving).

Local anesthetics primarily work by blocking sodium channels in nerves:
- Sodium ions normally contribute to action potentials, flipping the membrane potential from approximately -90 millivolts to +40 millivolts.
- Blockage prevents the propagation of pain signals.
- Some anesthetics also modify calcium channel permeability, but sodium channel blockade is the primary mechanism.
During nerve reset, potassium ions move out of the nerve to restore resting membrane potential.

Local anesthetics exist in their free base or hydrochloride salt forms, influenced by pH:
- Free base (lipophilic) is required for tissue penetration.
- Hydrochloric salt (water-soluble) exerts activity at the nerve.
pKa: Measures pH at which 50% of the molecule is in the acid form and 50% in the base form.
Effective administration considers tissue pH, especially in inflamed conditions (lower than 7.4), which can hinder anesthetic action.

Kinetics Variables: ADME (Absorption, Distribution, Metabolism, Excretion)
- Absorption: Affected by tissue vascularity and technique;
- Vasoconstrictors, like epinephrine, used to prolong local action.
- Distribution: Anesthetics can cross the blood-brain barrier and placenta, raising concerns for pregnant patients.
- Metabolism:
- Esters metabolized largely by esterases in plasma.
- Amides metabolized by liver enzymes. Key metabolites can lead to allergic reactions in genetically susceptible individuals.
- Excretion: Metabolites are water-soluble and primarily excreted through kidneys.

Order of Loss:
- Autonomic function → Cold → Warmth → Pain → Touch → Pressure.
Order of Recovery:
- Reverse order of loss; patients regain sensations in the opposite order of their loss due to the anesthetic.

Toxicity: Primarily affects CNS and could manifest as:
- CNS stimulation or depression.
- Cardiovascular toxicity, including arrhythmias.
- Local effects like pain on injection or hematomas.
- Life-threatening reactions such as malignant hyperthermia, particularly in genetically susceptible individuals.
Pregnancy Concerns:
- Lidocaine and prilo-ocaine (Category B); mepivacaine and bupivacaine (Category C), warrant careful consideration due to potential fetal risks.

Local anesthetics often include:
- Excipients for stability and comfort.
- Vasoconstrictors (commonly epinephrine).
- Sodium chloride for isotonicity and sodium hydroxide for adjusting pH.
Color-Coding System: Amides and esters have different identifiers for quick reference in clinical settings.

Lidocaine: Widely used in dentistry; standard for various dental procedures.
Mepivacaine: Often paired with levonordefrin as a vasoconstrictor; used for short procedures.
Prilocaine: Offers longer duration; suitable for extended procedures.
Bupivacaine: Provides prolonged anesthesia; higher toxicity risk.
Articane: Rapid onset; short duration, useful for brief procedures.
Procaine: Historically known as Novocaine; not commonly used due to allergic reactions linked to its metabolite (PABA).
Tetracaine: An ester with long action; less relevant in dentistry today.

Overview: General anesthetics aim for a balanced approach using IV and inhaled methods for surgical procedures to minimize adverse events.
History: Early anesthetic practices involved dangerous methods (e.g., concussion, strangulation) before developing safer techniques.
Stages of General Anesthesia:
1. Stage One: Analgesia but consciousness intact.
2. Stage Two: Loss of consciousness, potential for involuntary movements, discomfort.
3. Stage Three: Surgical anesthesia, characterized by stable physiological responses.
4. Stage Four: Respiratory and cardiovascular failure; not intended or desired.
Mechanism of Action: Not fully understood; likely involves pathway modulation for nerve action potentials and neurotransmitter effects.

Cardiovascular Risks: Arrhythmias and potential blood pressure drops.
Explosions: Flammability of anesthetics during surgical procedures.
Teratogenic Effects: Variability in impact on pregnant patients and fetuses.