Every veterinary professional knows the list of drugs related to anesthesia and pain management can seem overwhelming. This lecture will cover the following classes of drugs and explain their mechanism of action, when to use them appropriately, and how to create multimodal anesthetic and analgesic plans for your patients. By combining multiple drug classes in your anesthetic protocols, you can provide better pain control (by blocking more pain pathways) with less side effects (as most side effects are dose dependent).

Drug classes covered will include opioids, benzodiazepines, NMDA receptor antagonists, alpha two receptor agonists, induction agents, local anesthetics, non-steroidal anti-inflammatories (NSAIDs), inhalant anesthetics, and emergency drugs.

Part 1. Opioids

Opioids are considered by many to be the prototype analgesic. They have a wide range of analgesic action from ultra-short acting agents, such as remifentanil, to longer acting agents, such as hydromorphone. Their general reversibility makes them especially attractive in higher risk cases. And in some cases, they are relatively inexpensive. They are also extremely versatile in that they can be administered via many different routes. Opioids can be given as oral tablets, intermittent injection, constant rate infusion, transdermally, or epidurally.

The effects of opioid analgesics are dependent upon the receptors at which they act. Currently, there are three major classes of opioid receptors recognized within the CNS. They are as follows: mu, delta, and kappa. All three classes of opioid receptors produce some level of analgesia.

Drugs acting on opioid receptors are also classified as being agonists, partial agonists, mixed agonist/antagonists, and antagonists.

Opioid agonists: These drugs have high affinity for the mu opioid receptors responsible for analgesia and sedation. Opioid agonists include: morphine, hydromorphone, oxymorphone, fentanyl, methadone, etc.

Partial agonists: These drugs by definition are only partially as effective as agonists. This is because its binding with the mu opioid receptor produces an effect that is less pronounced than that of an opioid agonist such as fentanyl. An example of a partial agonist would be buprenorphine.

Mixed agonist/antagonists: These opioids work by exerting an agonist effect at the kappa receptors being responsible for sedation and some analgesic properties. They also act as an opioid antagonist at mu receptor sites. Agonist/antagonist opioids can include butorphanol and nalbuphine. These drugs can also be used to reverse some of the unwanted side effects of full agonist opioids such as excessive sedation. (Wagner, 2009)

Antagonists: These drugs work to fully antagonize and reverse the effects of opioids at the mu and kappa receptors. Drugs in this category include naloxone and naltrexone. These drugs will cause increased alertness. They will also reverse the analgesic effects of opioids so opioid antagonists should be used with caution in the painful patient.

Part 2. Benzodiazepines

Benzodiazepines are a class of drugs used as tranquilizers for their calming and (sometimes) sedative effects. These drugs also provide some muscle relaxation. There are three benzodiazepines commonly used in veterinary medicine today. These are diazepam, midazolam, and zolazepam (the benzodiazepine component of the mixture Telazol).

Diazepam has been traditionally used as an anticonvulsant. Diazepam is not water soluble and is provided in a carrier solution of propylene glycol; therefore, IM administration is not recommended due to pain on injection (Robbins, 2010).

Diazepam is highly protein bound, and it should be used with caution in animals with low total protein levels. Midazolam is water soluble and can easily be combined with opioids in the pre-medication. It is important to note that these drugs do not have analgesic properties. Benzodiazepines have minimal effects on both the cardiovascular and respiratory systems.

Another attractive trait to benzodiazepines is their ability to be reversed via the administration of flumazenil.

Part 3. NMDA Receptor Antagonists

NMDA receptor antagonists are used in veterinary medicine as analgesic adjuncts and agents of chemical restraint. By inhibiting NMDA receptors, ketamine has been shown to reduce the activity of neurons in the spinal cord in response to nociceptive stimuli and reduce sensitization of these neurons (Kerr, 2010). This helps to decrease the “wind-up” pain phenomenon from starting. NMDA receptor antagonists include ketamine and tiletamine (the NMDA antagonist component of the mixture Telazol). NMDA receptor antagonists cause an increased heart rate and blood pressure due to an indirect stimulation of the cardiovascular system (Robbins, 2010). Ketamine can be especially useful at decreasing inhalant gas anesthetic requirements when used as a constant rate infusion.

Part 4. Alpha-2 Adrenergic Agonists

Alpha 2 drugs such as medetomidine, xylazine and the newest form dexmedetomidine function as both sedatives and analgesics. Alpha-2s have analgesic properties that are primarily mediated via alpha-2 adrenergic receptors located in the dorsal horn of the spinal cord. These receptors modulate the release of neurotransmitters responsible for transmission of nociceptive signals to higher centers (Kerr, 2010) It is recommended that alpha-2s be used on only cardiac healthy patients as they can have significant cardiovascular side effects. Alpha-2 agonists cause increased systemic vascular resistance, peripheral vasoconstriction, and therefore increased systemic arterial blood pressure. Because of this increase in blood pressure, a decreased heart rate is often seen as the body’s normal response. Dexmedetomidine can be used as a premedication, and when combined with an opioid can sometimes be enough to preform minor surgical procedures (Shaffran, 2011). Dexmedetomidine can also be used as a constant rate infusion for overly anxious patients that require treatment and hospitalization.

Part 5. Local Anesthetics

Local anesthetics are used to block transmission of nerve endings or fibers. Local anesthetics inhibit the generation and propagation of nerve impulses by blockage of sodium channels in the nerve membrane (Mama, 2009) Bupivacaine and lidocaine are the two most commonly used local anesthetics in veterinary medicine. Local anesthetics can be administered intravenously, epidurally, and directly infiltrated. They can be especially useful as a part of multimodal analgesic plans.

Part 6. Induction Medications

Propofol can produce general anesthesia in animals, as a sole agent with continuous infusion for surgery, or as a pre-anesthetic for endotracheal intubation. It is valued for its fast recovery time, even after prolonged administration. Propofol has minimal analgesia at sub-anesthetic doses. It can be a profound respiratory depression, and may also cause hypotension. Because of its rapid elimination, it must be administered IV. Propofol can be used as a constant rate infusion for cases of total intravenous anesthesia.

Alfaxalone is another option for induction. Alfaxalone is a neurosteriod anesthetic and is similar to propofol in administration and use. Alfaxlone has been associated with less respiratory depression than propofol and less subsequent hypotension.

Another option for induction is a ketamine/diazepam combination. This combination works well for young healthy animals. The drug profiles for each of these drugs can be found above.

Part 7. Non-steroidal Anti-inflammatory Drugs

The advent of newer, more potent, more specific anti-inflammatory agents has increased their usefulness in veterinary patients. NSAIDs are used to reduce fever, reduce inflammation, and provide varying degrees of analgesia. Carprofen, ketoprofen, ketorolac, and meloxicam may have duration of analgesic action up to 24 hours. They may be used concurrently with anesthetics, with opioid analgesics, and with local anesthetic/analgesics. Injectable NSAIDs are useful for accurate dosage and administration. NSAIDs may decrease clotting ability, of possible concern following surgery. Gastric upset and even ulceration may occur, especially with prolonged use. Prolonged use carries the risk of kidney or liver disease. Cats can be particularly susceptible to toxic effects of NSAIDs. Acetaminophen is never administered to cats; other NSAIDs should be used only at the dose and frequency recommended by your clinician.

Part 8. Inhalant Anesthetics

A variety of inhalant anesthetics are available, but isoflurane is the most commonly used. Isoflurane produces rapid induction and recovery from anesthesia. The depth of anesthesia can be easily and quickly altered. Virtually no metabolism occurs in the body because isoflurane is almost completely eliminated in expired air. Liver microsomal enzymes are minimally affected which results in little interference with drug metabolism or toxicology studies. The use of isoflurane requires an anesthetic machine fitted with a precision vaporizer to deliver controlled amounts of anesthetic and oxygen.

Part 9. Emergency Drugs

Atropine, glycopyrrolate, epinephrine, lidocaine, flumazenil, naloxone, and atipamezole are all drugs that should be calculated for each patient prior to general anesthesia.

Should an anesthetic emergency develop, refer to your clinician for guidance and specific drug dosages.

Further Reading

1.  www.IVAPM.org

2.  www.vasg.org

References

1.  Kerr, C. Pain Management 1: Systemic Analgesics. In BASVA Manual of Canine and Feline Anaesthesia and Analgesia 2nd Edition. British Small Animal Veterinary Association Press. 2010;89–90.

2.  Mama, K. Local Anesthetics. In Handbook of Veterinary Pain Management 2nd edition. Editors: Gaynor J, Muir W. Mosby-Elsevier, St. Louis. 2009.

3.  Robbins, S. Premedication and Sedation Drugs. In Anesthesia for Veterinary Technicians Editor: Bryant S. Ames, IA: Wiley Blackwell. 2010.

4.  Shaffran, N. Alpha-Two Agonists: Much More than Sedation. In American Animal Hospital Association Conference Proceedings. 2011.

5.  Wagner, AE. Opioids. In Handbook of Veterinary Pain Management 2nd edition. (Editors: Gaynor J, William Muir W), Mosby-Elsevier, St. Louis. 2009.