Veterinary Adjunct Drugs

• Adjunct drugs can be used in the peri-operative period for veterinary patients.
• Summarization of the drug's MOA, indications, and need for a loading dose is required.
• The MDR1/ABCB1 gene mutation can affect a patient's response to anesthetic drugs.
• Terms describing drug interactions must be defined.
• An isobologram illustrates drug interactions.

Adjunct Drugs Defined

• These are drugs that may not be commonly used clinically.
• Supportive role is played by them, enhancing patient outcomes.

Important Concepts

• Balanced anesthesia involves the simultaneous use of multiple drugs and techniques to produce anesthesia.
• Multimodal analgesia uses two or more drugs or techniques to manage pain.

Maropitant (Cerenia)

• Acts as a neurokinin-1 (NK1) receptor antagonist used for motion sickness.
• It may be used to limit nausea and vomiting, which could lead to aspiration pneumonia.
• It can reduce the incidence of vomiting from certain premedication drugs.
• It improves recovery quality and allows for a faster return to feeding.
• It has potential MAC lowering effects when administered as a CRI.
• Administer 1 mg/kg SQ approximately 45-60 minutes before premedication.
• IV administration results in a faster onset but increases the risk of hypotension.
• Adverse effects of maropitant include: Pain upon injection, drooling, lethargy, inappetence, and diarrhea
• Does not prevent gastroesophageal reflux (GER).
• It is FDA approved for use in dogs (≥ 4 months old) at a dose of 8 mg/kg PO once daily for two consecutive days.
• Requires a prescription from a DVM.
• Same dose sizes available (16, 24, 60, or 160 mg).
• Excessive drooling is a common side effect at higher doses.

Vomiting vs. Regurgitation

• Vomiting involves forceful ejection of stomach and upper intestinal contents which can contain yellow bile; usually smells sour and involves heaving.
• Regurgitation: is the mild ejection of undigested food from the esophagus, doesn't involve abdominal heaving, and tends to happen just after eating; GER can be a precursor.

Ondansetron

• A 5HT3 receptor antagonist useful for preventing vomiting from chemotherapy or anesthetic drugs.
• For example: 0.22 mg/kg IV can reduce the incidence of vomiting when dexmedetomidine is given to cats

Metoclopramide

• Blocks dopamine D2 receptors in the chemoreceptor trigger zone and serotonin receptors to provide antiemetic effects.
• Prokinetic, reducing gastric fluid by increasing the rate of gastric emptying and increases lower esophageal sphincter tone.
• Administer at 1 mg/kg IV bolus, then 1 mg/kg/hr CRI.
• May increase CNS-depressant effects of anesthetic drugs.
• Do NOT give if GI obstruction is suspected, history of seizures, or pheochromocytoma is present.

Histamine Receptor Antagonists

• These decrease acid production in the stomach (H2 antagonists).
• Famotidine dose: 0.5 mg/kg, SQ.
• Diphenhydramine is given for mast cell tumor removal to counter histamine effects (H1 antagonist).
• Diphenhydramine dose: 2.2 mg/kg, IM.

Proton Pump Inhibitors

• They decrease gastric acid production by irreversibly blocking H+/K+ ATPase.
• Omeprazole and pantoprazole are the most commonly used. Long-acting drugs.
• The 2011 study (Tolbert et al) showed that omeprazole (paste or tablets) is more effective at increasing gastric pH than oral famotidine.
• There is inconclusive evidence on the effect of omeprazole on the incidence of GER.
• ACVIM consensus statement: judicious use of acid suppressants is warranted for long-term administration but not recommended for acute, nonerosive gastritis.

NSAIDs

• Has MAC sparing effects so you do not need require as much inhalant
• Carprofen and Meloxicam reduce MAC of Sevo to 2.10% and 2.06% in dogs, respectively.
• Prefer to administer postoperatively in case of hypovolemia or hypotension during anesthesia, leading to decreased renal blood flow.

Glucocorticoids

• NEVER give concurrently with NSAIDs.
• Used for anti-inflammatory, analgesic, immunosuppressive, and physiological support to Addisonian patients (who struggle to produce their own).

Antibiotics

• Cefazolin (22 mg/kg) is usually given IV slowly over 5 min.
• Unasyn (Ampicillin/Sulbactam) is given IV slowly over 15-30 min.
• If Gentamicin is given IV, administer slowly.
• If K-pen is used IV, administer slowly.
• NEVER give PPG IV.
• Naxcel is used in food animals.

Aminocaproic Acid

• It is an antifibrinolytic agent.
• Can be given to Greyhounds to decrease postoperative bleeding by enhancing clot formation and increasing clot strength per 2012 studies.
• Greyhounds often have higher than normal rates of bleeding 24-48 hours past operation, resulting in bruising around surgical site.
• Oral and injectable available but must give slowly IV (over 30 minutes) after diluting in saline to prevent causing CV effects.

Desmopressin

• It temporarily increases von Willebrand factor in dogs with a deficiency before surgery, as it promotes vWf secretion from endothelium storage sites.
• Synthetic replacement for vasopressin which reduces urine production.
• Administer 1 µg/kg SQ.
• Administer 30 minutes before can help, but results are variable vs humans
• Available as a nasal spray, but expensive; owner usually purchases.

Dantrolene

• A peripherally-acting muscle relaxant with higher doses reported to cause cardiac depression.
• Ryanodine receptor antagonism and can reduce Calcium release.
• It can treat and prevent malignant hyperthermia and exertional rhabdomyolysis in pigs, humans, dogs, and horses.
• Can give injectable solution and oral capsules.
• Dosage is species dependent. Dogs, cats, and pigs require 1-3 mg/kg IV for treatment and 5 mg/kg PO once daily for prophylaxis..

Doxapram

• A CNS stimulant used to reverse sedation/anesthesia and stimulate respiration.
• Likely due to both central and peripheral effects and leads to increased activity of the respiratory nuclei of the medulla, unclear MOA.
• Significant increase in minute ventilation with short lived effects through short lived effects.
• It can lead to convulsions due to cortical stimulation.
• Dosages cause differing effects among species.
• Do not use in epileptic patients.

Guaifenesin (aka GG)

• It is a central-acting muscle relaxant with sedative properties with an unknown MOA.
• Can be co-administered with IV anesthetics (e.g., ketamine) in horses and ruminants.
• It can induce and maintain anesthesia.
• No known analgesic properties noted.
• Commonly used in 5-15% solution with 0.9% saline or 5% dextrose solution.
• Perivascular injection may cause necrosis.

Lidocaine CRI

• It is an amide local anesthetic agent that is administered for the purposes of providing local regional analgesia or to treat ventricular arythmias.
• It may have a MAC sparing effect, anti-inflammatory and analgesic effects.
• Can be given to equines at 1.3 to 2 mg/kg IV slowly (over ~ 5 min) for a typical loading dose.
• It also has effects on the GI tract leading to stimualtion of intestinal motility.
• Toxicity in cats is of concern as it may be toxic.
• For equine it is used to treat Ileus, impactions, duodenitis-jejunitis, inflammation, laminitis and post-operative pain.
• Can be givne for 1 to 3 days but must be monitored carefully.
• Muscle fasciculations, weakness, and recumbency are signs of toxicity
• If these signs of toxicity develop, discontinue lidocaine immediately.

Ketamine CRI

• It is an NMDA receptor antagonist that can binds at the CNS receptors and prevents"wind up" pain, otherwise known as, neuropathic pain.
• It may be combined with an opioid or lidocaine infusion.
• It is best used to manage neuropathic pain, mainly If the patient's pain is in chronic and the patient has failed other analgesic options.
• Can be administered at 0.5 mg/kg IV loading dose
• Then a CRI dose for surgery: 10 µg/kg/min,, then decrease to 2 µg/kg/min for the next 24 hours post op.

Opioid CRI

• Fentanyl, Remifentanil, Morphine, Hydromorphone, Butorphanol, & Buprenorphinecan be used as a CRI.
• Dilute the drug in IV fluids for administration via a syringe pump.
• Administer a loading dose first.

Loading Dose

• They are the most efficient and quickly reach desired window and stay there

Morphine-Lidocaine-Ketamine (MLK) CRI

• 2003 study by Muir et al. found the combination significantly lowered isoflurane MAC .
• Not associated with adverse CV effects.

Formulating Morphine-Lidocaine-Ketamine (MLK) CRI

• Add 24mg of Morphine, 60mg of Ketamine, and 300mg Lidocaine per 500ml bag of fluid.
• Remove calculated drug volume from fluid bag
• Before, ly. If adding 50mL drugs,→remare remove 50 mL of fluid from bag to maintain volume)
• Label each bag with the contents, date, and initials.

MDR1 gene mutation (a.k.a. ABCB1 mutation)

• The gene is in some herding-breed dogs where a single mutation affects protein (P-glycoprotein), resulting in drastic affects on adsorption, distribution, metabolism and excretion of drugs.
• Glycoprotein protein leads to toxic accumulation of substances
• It is important part of the blood-brain barrier protects body from toxic accumulations of substances
• Affected Anesthesia drugs include Butorphanol and acepromazine, Ivermectin, chemotherapeutic drugs.

Why MDR1 matters

• These patients can have serious side effects,
• such as CNS or respiratory depression.
• Recovery can take longer.
• It is recommended to reduce normal dose by 25-50% in dogs that are homozygous for the mutation.

Important Anesthetic Drug Incompatibilities

• Diazepam: Precipitation occurs with aqueous solutions and significant absorption into soft plastic within 24 hours. It is also incompatible with heparin flush.
• Epinephrine, dobutamine, and dopamine are incompatible with alkaline solutions.
• Phenylbutazone precipitates with aqueous solutions.
• Sodium bicarbonate can NOT mix with solutions that contain calcium because precipitation may occur.

Terms to Knnow

• Addition leads to simple additivity of fractional doses of two or more drugs
• Synergism can lead to response that is greater than the response to the sum of the fractional doses
• Potentiation leads to enhancement of action of one drug by a second drug that has no detectable action of its own.
• Antagonism is opposing action of one drug toward another.
• This can be competitive (drugs compete for same receptor site) or noncompetitive ( drugs act via different receptors).

Isobologram

• To show a visual representation of drug interactions and their relationship between drug concentrations.