analgesic - a drug which causes an absence of pain in response to stimulation which would normally be painful; often, what is actually achieved following administration of an analgesic is hypoalgesia, or diminished pain in response to a stimulus.

sedative - a drug which produces a state of decreased motor activity, mental calmness, and drowsiness; does not imply analgesia, although most sedatives will increase the pain tolerance threshold by reducing anxiety and fear.

Two main delivery systems are used in veterinary medicine, inhalation and injection; a brief review of common drugs follows:

Inhalation anesthetics are gaseous or volatile agents administered via the respiratory tract. Inhalation anesthetics, when properly administered allow one to control and regulate anesthetic depth. Disadvantages include need for specialized delivery equipment and potential toxicosis to personnel chronically exposed to anesthetic vapors. Endotracheal intubation facilitates effective and safe delivery of inhalation anesthetics. A waste gas scavenging system should be used to minimize exposure to personnel. Examples include: ether, halothane, methoxyflurane, and isoflurane.

Injectable anesthetics can serve as the sole anesthetic agent, be used to induce anesthesia before inhalation anesthesia, or supplement regional anesthesia.

To minimize the chance of drug overdose and to reduce drug-related tissue damage, drugs used for smaller (<4 kg) laboratory animals may need to be diluted.

• Hypnotic/sedative drugs are widely used for inducing or managing general anesthesia. They induce a dose-dependent spectrum of CNS depression, from sleep to deep general anesthesia. Higher doses may cause medullary paralysis, respiratory arrest and death. Examples include: pentobarbital, sodium thiamylal, sodium thiopental and chloral hydrate.

• alpha 2-Adrenergic receptor agonists have tranquilizing, sedative, and potent analgesic proper-ties. Examples include: xylazine (trade name Rompum).

• Dissociative drugs induce anesthesia, have short duration of action, a wide safety margin, and cause minimal cardiopulmonary depression. To decrease undesirable actions such as muscle hypertonus and emergence delirium, they may be used in combination with hypnotics, tranquilizers, or alpha 2-adrenergic agonists. Examples include: ketamine and tiletamine which is often in combination with the tranquilizer, zolazepam.

• Muscle relaxants are predominantly central or peripheral acting. The peripheral acting muscle relaxants are devoid of sedative and analgesic properties. These drugs, when used during surgery, must be administered only in conjunction with general anesthetics. The investigator must remain aware that the animal is unable to respond with purposeful movement to noxious stimulation and the animal must be closely monitored (e.g. heart rate, arterial blood pressure) to ensure adequate general anesthesia. Examples include: succinylcholine and dimethyl tubocurarine.

Local and Regional Anesthesia

Local and regional anesthesia is used most often in large animals, such as horses, cattle or sheep. Localized insensitivity in awake or mildly sedated animals can result from topical application or injection of appropriate anesthetics in the region of the surgical incision (local anesthesia); injection in proximity to nerve trunks (nerve block); or injection into the subarachnoid or epidural spaces (regional anesthesia).

Local and Regional Anesthesia Advantages Include:

the cost of drugs and equipment is low the need for special post-anesthetic care is minimal avoids undesirable complications that accompany unconsciousness and recumbency: regurgitation and aspiration of gastric contents inefficient respiratory gas exchange traumatic complications associated with recovery myopathy (particularly in large, heavy animals)

Local and Regional Anesthesia Disadvantages Include:

some degree of animal cooperation is necessary the anesthetic period is relatively short tissue damage has been associated with injection of large volumes of anesthetic agents rapid absorption or inadvertent intravascular injections of large quantities of anesthetic agents can cause life-threatening reactions.

Analgesic drugs

Analgesic drugs to reduce pain are initiated during the surgical period and continued well into the postoperative recovery period. It is often erroneously presumed that an animal is not in pain, when there is no obvious change in behavior. Pain can be difficult to detect because of individual and species variation. "Typical" signs of pain include guarding the painful area, vocalization, licking, biting, self mutilation, signs of depression, grinding of teeth, restlessness, lack of mobility, failure to groom, abnormal posture, changes in sleep patterns, and failure to eat or drink. Pain can be assumed to have been present if administration of analgesics causes these signs to disappear.

Consultation with the attending veterinarian is recommended since there is tremendous variation between species as to their response to analgesic drugs. Limited animal studies have been conducted and for many species there will be widely different published dosage schedules. Never extrapolate from human data, please consult with the veterinarian.

GUIDELINES FOR THE ADMINISTRATION OF ANALGESIC DRUGS

a) Medical and veterinary reports suggest analgesics are most effective when administered prior to the painful stimulus, before the surgical incision and tissue manipulation. b) Analgesic drugs must be given at the proper initial dose and subsequent doses must be given according to schedule. c) Federal law requires pain relief according to the same guidelines for a human patient undergoing a similar procedure.

In addition to the care which must be taken when choosing the proper dosage and schedule for a particular species, different analgesics are indicated for different types of pain:

Nonsteroidal anti-inflammatory agents (NSAID) are effective against pain associated with inflammation, acute pain associated with soft tissue injury, burns, and pain associated with bone injuries or disease. However, severe pain in any of these categories may be best treated with NSAID's in combination with potent opioid agonists. Examples include: banamine, ibuprofen.

Opioid agonists are effective against most visceral and somatic pain; although generally not as effective as NSAID's against bone pain, they may be used in conjunction with NSAIDs to treat severe bone pain. Examples include: morphine, meperidine.

Opioid agonist-antagonists are effective against mild to moderate visceral and somatic pain. Examples include: buprenorphine, butorphanol.

Neurogenic pain is pain which arises from damaged nerves or from amputation. This pain is difficult to treat and rarely responds well to any of the drugs listed above. More likely to be effective: tricyclic antidepressants such as amitriptyline, anticonvulsants such as carbamazepine, or antiarrhythmics such as lidocaine.

Management of Drugs

Drugs which are considered by the U.S. Department of Justice, Drug Enforcement Agency (DEA) to be controlled substances must be stored in a locked cabinet in a secured area (e.g. behind two locked doors). Controlled substances must never be left unattended since the potential for theft and misuse of these drugs is high. In the past, the DEA allowed some latitude in research facilities and did not closely observe who exactly administered these drugs to the research animal. This is no longer true. Therefore, each investigator with a DEA license must personally supervise the administration of these drugs. In addition, UAC may no longer transfer controlled drugs to research staff.

All drugs, whether or not they are DEA regulated, must be properly labeled and included on the label must be the expiration date. Expiration dates should be checked periodically, at least once every three months, and expired drugs immediately discarded. It is a violation to use expired drugs on animals involved in research procedures (there are a few limited occasions wherein expired drugs may be used for terminal, non-survival procedures). University Animal Care staff will discard any drug they observe to be improperly labeled, or in use after the expiration date has passed.

At the minimum the label on a drug shall include:

name of drug and concentration expiration date (also the mixing date if a combination) name of Investigator (if the drug is not owned by UAC) specific storage requirements (e.g. refrigerate)

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