Anesthetic agent: Any drug used to induce a loss of sensation, with or without unconsciousness.
Adjunct agent: A drug that is not a true anesthetic but is used during anesthesia to produce other desired effects.
Balanced Anesthesia: The practice of using a combination of drugs at lower doses to provide a safer anesthetic compared to a single agent at higher doses.
Pharmacokinetics: The effect that the body has on a drug.
Pharmacodynamics: The effect that the drug has on the body.
Agonists: Drugs that bind to and stimulate tissue receptors.
Antagonists: Drugs that bind to receptors but do not stimulate them, often displacing the agonist; commonly used as reversals.
Partial agonists: Drugs that bind to and partially stimulate receptors.
Agonist-Antagonists: Drugs that bind to more than one receptor type, simultaneously stimulating at least one receptor and blocking at least one other receptor.
Classification of Anesthetic Drugs
Based on route of administration
Based on the time period that they are used
Based on principal effect: Many drugs used have multiple effects.
Based on chemistry or drug class.
Regulations for Controlled Substances
Anesthetic drugs that are at risk for theft and abuse are regulated by the Drug Enforcement Agency (DEA) under the Controlled Substances Act (CSA).
Regulations require strict handling, record-keeping, and storage.
Consequences of misuse: Theft, illegal use, or diversion of a controlled substance are criminal acts punishable by imprisonment and/or fines, which may impact professional licensure eligibility.
Controlled Substance Schedules
The CSA assigns drugs into five drug schedules according to their potential for abuse:
Schedule I: Highest abuse potential; none in veterinary medicine.
Schedule II: High abuse potential; examples include fentanyl, morphine, and hydromorphone.
Schedule III: Medium abuse potential; examples include ketamine, telazol, buprenorphine, and pentobarbital.
Schedule V: Lowest abuse potential; example includes Lomotil.
Record-keeping Requirements
General inventory of controlled drugs must be performed every 2 years.
Daily accounting of drug use is documented in controlled drug logs.
Controlled substance logs:
Must be official documents in a bound booklet with numbered pages filled out in indelible ink.
Kept for a minimum of 2 years.
Schedule II drug logs should be kept separate from other records.
Storage Requirements for Controlled Substances
Controlled substances must be securely locked in a substantially constructed cabinet.
Containers of controlled substances should not be left unattended on countertops or in public areas.
In cases of unexplained significant loss or suspected theft, registrants must notify the DEA and local police within one business day, and complete DEA Form 106.
Preanesthetic Medications
Premedications are given alone or with other drugs as part of balanced anesthesia.
Common premedications include:
Anticholinergics
Phenothiazines
Benzodiazepines
Alpha2-adrenoceptor agonists (alpha2-agonists)
Opioids.
Reasons for Using Preanesthetic Medications
Calm or sedate an excited, frightened, or aggressive animal.
Minimize adverse effects of concurrently administered drugs.
Reduce the required dose of concurrently administered agents.
Produce smoother anesthetic inductions and recoveries.
Decrease pain and discomfort before, during, and after surgery.
Produce muscle relaxation.
Administration of Preanesthetic Medications
The administration route can be IV, IM, or SQ.
After medicating, patients should remain in a quiet area for observation for 20-30 minutes to allow drug effects to take place.
Combining Drugs in a Syringe
Two or more anesthetic agents can be combined as premedications, typically mixed in the same syringe.
Most anesthetic drugs, except for diazepam, are water-soluble and can be combined safely.
Note: Diazepam is non-water-soluble and cannot be mixed with other drugs, except for ketamine (can be safely mixed).
Anticholinergics
Anticholinergics are noncontrolled drugs used to prevent bradycardia and decrease salivary secretions.
Examples:
Atropine
Glycopyrrolate.
Mode of Action of Anticholinergics
Anticholinergics block the parasympathetic nervous system, hence considered parasympatholytic.
Most parasympathetic effects are mediated by the Vagus nerve; stimulation during intubation and surgery can lead to bradycardia and bronchoconstriction.
Anticholinergics effectively prevent bradycardia and decrease salivary secretions.
Anticholinergic Administration
Routes: IV, IM, SC, or IT.
Atropine: Faster onset, shorter peak, shorter duration; preferred in emergencies.
Glycopyrrolate: Slower onset, longer peak and duration; minimally crosses the placenta; preferred in cesarean sections.
Effects of Anticholinergics
Central Nervous System Effects:
Anticholinergics do not act as sedatives and lack CNS effects.
Cardiovascular Effects:
Prevent bradycardia; avoid use in animals with preexisting tachycardia or heart disease.
Respiratory Effects:
Decrease and thicken respiratory and salivary secretions, and induce bronchodilation.
Other Effects:
May cause mydriasis (pupil dilation) and decreased lacrimal secretions
Decreased gut motility.
Tranquilizers and Sedatives
Tranquilizers: Drugs that reduce anxiety without necessarily decreasing wakefulness.
Sedatives: Drugs that cause reduced mental activity and induce sleepiness.
The effects of these drugs often overlap and are interchanged.
Tranquilizer/Sedatives:
Phenothiazines
Benzodiazepines
Alpha2-adrenoceptor agonists (alpha2-agonists).
Phenothiazines: Acepromazine
Use of Acepromazine ("Ace") includes:
Lower dose requirement for general anesthetic.
Smooth induction and recovery.
Provides sedation/tranquilization for minor procedures.
Approved for dogs, cats, and horses and administered via IV or IM.
Responses to the drug vary based on species and breed; doses should be reduced in collies and Australian shepherds to minimize prolonged sedation.
Effects of Phenothiazines
Central Nervous System Effects:
Causes sedation but does not provide pain control, decreases anxiety, and may lower seizure threshold.
Occasionally might induce excitement or aggression.
Cardiovascular Effects:
Possess antiarrhythmic properties; cause hypotension and hypothermia.
Other Effects:
Anti-emetic effects, may lead to prolapse of the penis in horses, reduced PCV due to spleen uptake of RBCs, and prevents release of histamine.
Benzodiazepines
Benzodiazepines are tranquilizers used with other agents for muscle relaxant and anticonvulsant properties.
Alone, they produce unreliable sedation and may cause dysphoria.
Examples:
Midazolam – IV or IM
Zolazepam – IV or IM
Diazepam – IV (irritating IM)
Flumazenil – Reversal drug for benzodiazepines.
Diazepam and midazolam are light-sensitive and stored in brown glass vials; Zolazepam is available only mixed with tiletamine.
Effects of Benzodiazepines
Central Nervous System Effects:
Produce unreliable sedation unless used with other drugs, have anticonvulsant activity, and have no analgesic properties.
Cardiovascular and Respiratory Effects:
Minimal effects on cardiovascular and respiratory systems, leading to a high margin of safety; diazepam or midazolam are used for active seizures.
Other Effects:
Excellent muscle relaxants; decrease anesthetic requirements; cross the placenta and may cause CNS depression in neonates following cesarean.
Alpha2-Adrenoceptor Agonists
Also referred to as alpha2-agonists, they are used alone or in combination for sedation, analgesia, and muscle relaxation; administered IV or IM.
Safe for young, healthy patients but should be avoided in geriatric, diabetic, pregnant, pediatric, or sick patients.
Examples:
Xylazine
Dexmedetomidine
Detomidine.
Effects of Alpha2-Adrenoceptor Agonists
Central Nervous System Effects:
Potent sedatives that provide short-lived analgesia and may alter behavior; horses may tremble or kick; cattle may frequently lie down or fall over.
Cardiovascular effects:
Initial vasoconstriction, hypertension, reflex bradycardia (pale mucous membranes); dramatic bradycardia (30 to 50 bpm in dogs) and possible hypotension with decreased cardiac output may occur, alongside cardiac arrhythmias.
Respiratory Effects:
Respiratory depression, especially in cattle.
Other Effects:
Muscle relaxation; increased effects of other anesthetics; vomiting; transient hyperglycemia; hypothermia; potentially induces abortion in cattle during last trimester; horses may sweat.
Monitoring and Reversal of Alpha2-Adrenoceptor Agonists
Vital signs should be carefully monitored in patients receiving alpha2-agonists.
Administration of anticholinergics to mitigate bradycardia is ineffective and may strain the heart.
Effective management: If excessive bradycardia occurs, the superior approach is to reverse the alpha2-agonist using specific antagonists.
Reversals:
Yohimbine and tolazoline can reverse xylazine effects.
Atipamezole reverses dexmedetomidine effects; administer IM only in cats, IM in dogs or IV slowly in emergencies.
Opioids
Opioids are used for analgesia, sedation, and to reduce the dosage required for other anesthetics.
They possess a wide margin of safety and can be used in debilitated patients.
Opioids act on receptors located in the brain and spinal cord.
Types of opioid receptors:
Mu (μ) agonism: causes analgesia, bradycardia, hypothermia, hypoventilation, vomiting, constipation.
Kappa (κ) agonism: induces minor analgesia, sedation, dysphoria.
Delta agonism: leads to hypoventilation, constipation, urinary retention.
Effects of Opioids
Central Nervous System Effects:
Opioids are strong analgesics that may induce CNS depression (sedation) or excitement; cats, horses, and ruminants might show CNS stimulation.
Can elevate intraocular and intracranial pressures; use cautiously in head trauma and CNS disorders.
Cardiovascular System Effects:
May result in vagus-induced bradycardia.
Respiratory System Effects:
Dose-dependent respiratory depression; panting commonly seen in dogs.
Other Effects and Adverse Effects:
Hypothermia in dogs; hyperthermia in cats; increased salivation, vomiting, diarrhea, gastrointestinal stasis, constipation; noise sensitivity; miosis in dogs; mydriasis in cats, ruminants, and horses; increased sweating in horses; decreased urine production and retention.
Morphine and meperidine can cause facial swelling and hypotension due to histamine release.
Neuroleptanalgesia
Definition: Neuroleptanalgesia is defined as a state of sedation and analgesia induced by simultaneous administration of an opioid and a tranquilizer.
Example: Combination of dexdomitor and butorphanol primarily used for minor procedures.
Preparedness: Anesthetists should be ready to intubate and ventilate patients as required during procedures where neuroleptanalgesia is applied.
Opioid Antagonists (Reversals)
Reversal: Opioids can be reversed with an antagonist, such as naloxone.
These antagonists will reverse both desirable and undesirable effects of the opioid.
An agonist–antagonists, such as butorphanol, can be employed to partially reverse effects of pure agonists.