Anesthetic Agents and Their Pharmacodynamics

Anesthetic Agents and Adjuncts

• Anesthetic agents are drugs inducing a loss of sensation, potentially with unconsciousness.
• Adjuncts are drugs not true anesthetics, used during anesthesia to enhance desired effects like sedation, muscle relaxation, analgesia, reversal, neuromuscular blockade, or parasympathetic blockade.

Anesthesia Activity & Terminology

• Intrinsic activity is a drug's ability to produce a biological response, measuring efficacy or potency.
• Drug efficacy is the ability to initiate changes after binding to receptors, leading to certain effects.
• Potency is a comparison of different doses needed to reach the same pharmacological effect.
• Agonists bind to and stimulate target tissues; many anesthetic agents and adjuncts are agonists.
• Antagonists bind to tissues but don't stimulate; reversal agents are antagonists.
• Pharmacokinetics describe how the body affects a drug (absorption, distribution, metabolism, excretion).
• Pharmacodynamics describe a drug's effects on the body (mechanism of action, side effects).

Adjunct Classifications

• Drug administration routes (SQ, IM, IV, PO, etc.)
• Administration timing (pre-medication, induction, maintenance, recovery).
• Principle effects (local vs. general, sedatives/tranquilizers vs. analgesics, blockers, anticholinergics).
• Drug chemistry and pharmacology.

Drug Combinations

• Avoid mixing incompatible drugs in a single syringe.
• Verify compatibility before administering drug combinations.
• Most anesthetic agents and adjuncts are water-soluble, but some aren't (Diazepam).
• Check compatibility charts or use resources for safe drug combinations.

Pre-anesthesia Medications ("Pre-meds")

• Calming patients reduces excitement and improves handling.
• Reduces stress, anxiety, and catecholamine release.
• Provides analgesia and muscle relaxation.
• Allows for reduced anesthetic induction and maintenance drug use.
• Improves vital systems stability during surgery.
• Enhances recovery from anesthesia, minimizing excitement and aiding a smoother process.
• Often used as adjunctive agents for local anesthetics.

Pre-medication Routes

• Intravenous (IV) administration provides the fastest onset.
• Intramuscular (IM) administration has a faster onset than subcutaneous (SC) but slower than IV.
• Subcutaneous (SC) administration provides the slowest onset and longest duration of action.
• Oral administration commonly used for some medications with slower onset and duration.

Preemptive Analgesia

• Administering pain medication before pain occurs to prevent pain signals.
• Usually involves adding analgesic drugs during pre-medication.
• Reduces overall analgesic requirements and duration (MAC sparing).
• Prevents pain-related windup, making subsequent pain management easier.

Perioperative Pain Management

• Preemptive analgesia starts before surgery with pre-medication.
• Anesthetic pre-medication can include the administration of analgesics or pain medication.
• Transdermal fentanyl patches offer consistent analgesic release.
• Non-steroidal anti-inflammatory drugs (NSAIDs) can be used in large animals (primary use).
• Multimodal therapy uses more than one pain-control drug in combination (e.g. covering different receptors).
• Dose reduction of individual drugs, while enhancing pain management.

Pre-Med: Phenothiazines (Acepromazine)

• Advantages: Mild sedation, anxiety reduction, lessened interest in surroundings, anesthetic sparing, antiemetic effects, smoother induction, and histamine prevention.
• Disadvantages: Cardiovascular effects (vasodilation, hypotension, hypothermia, increased heart rate), non-reversible, use caution in MDRI Gene Dogs (herding breeds), potential decreased seizure threshold, no analgesic effect, less effective in cats, and can worsen respiratory depression from other drugs.

Pre-Med: Dexmedetomidine

• Advantages: Profound sedation (most profound group), reversible (atipamezole), moderate muscle relaxation, mild analgesia, reduces stress, lessens sympathetic outflow, and anesthetic sparing (50-80%).
• Disadvantages: Profound peripheral vasoconstriction, reflex bradycardia, possible arrhythmias (1st, 2nd AV block), mild bradypnea, reduced GI motility, not suitable for compromised/ill patients, Severe reduction in CO (cardiac output ) likely, and use cautiously only in normal, healthy dogs and cats.

Pre-Med: Opioids (Hydromorphone)

• Advantages: Robust analgesia (strongest), mild to moderate sedation, reversible with naloxone, minimizes direct cardiovascular effects, suitable for compromised patients, lessened nausea and histamine release comparatively to morphine, but more than that.
• Disadvantages: Cardiovascular and respiratory depression, vomiting, nausea, hypersalivation, dysphoria (excitement, especially in cats), ileus (colic in horses), reduced GI motility, histamine release, high abuse potential (Class II narcotic), and chronic pain use not advisable.

Pre-Med: Butorphanol

• Advantages: Mild-moderate analgesia, mild-moderate sedation (kappa receptor stimulation effect), partially reversible with naloxone, antitussive effects, tolerable in GI compromised patients.
• Disadvantages: Weaker analgesic effect if stronger analgesic is needed, analgesia plateau at higher doses, blocks mu receptors, abuse potential (Class IV narcotic).

Pre-Med: Buprenorphine

• Advantages: Mild to moderate analgesia (mu partial agonist), good for mild pain to severe pain (dose-dependent), reversible with naloxone, anesthetic sparing, good for GI compromised/compromised patients, use with caution only with normal healthy dogs/cats, and long-lasting analgesic effects (72-hr).
• Disadvantages: Analgesia plateau with high doses, slower onset (30mins), may not be suitable to administer a pure mu drug since it blocks mu receptor, can also have abuse potential (Class III narcotic).

Opioids Overall

• Vary in potency, duration, and side effects.
• Mu receptors are the strongest for pain control.
• Kappa receptors play a role in sedation.
• Used for pre-medication or intra/postoperative analgesia, diminishes windup pain, induces potent sedation, and/or neuroleptanalgesia.
• Reduced rate and tidal volume can lead to hypoventilation which is also dangerous.

Pre-Med: Benzodiazepines (Diazepam/Midazolam)

• Advantages: Sedative, hypnotic (species-dependent), reversible (flumazenil), muscle relaxation, anti-convulsant, minimizes direct cardiovascular effects, and minimizes respiratory effects while possibly reducing induction amount needed
• Disadvantages: Paradoxical excitation (especially in cats with midazolam.) No analgesia and cannot be administered IM (burns), Diazepam sensitive to plastics/light, potential for abuse (Class IV).

Ampule Medications

• Common ampule medications include Diazepam, Epinephrine, Atropine.
• Safe practices for handling ampules include hand hygiene, following the 5 Rs, understanding the scoring lines and using appropriate safety steps (wrap with alcohol, face away from user).