Lecture 12: Adjunctive Drugs & Interactions

What are drugs that play a supportive role by the benefit that they provide the patient pre-, peri-, or post-anesthesia?

adjunctive drugs

What are the two uses of adjunctive drugs to anesthesia and analgesia?

• balanced anesthesia = simultaneous use of multiple drugs & techniques to produce anesthesia

• multimodal (balanced) analgesia = using 2 or more different drugs or techniques to manage pain

What is the difference between vomiting and regurgitation?

• vomiting (active) = forceful ejection of stomach and upper intestinal contents, can contain yellow bile or partially digested dog food, usually smells sour and involves heaving

• regurgitation (passive) = mild ejection of undigested food from the esophagus, does not involve abdominal heaving, tends to happen just after eating

What is the neurokinin-1 recepgtor antagonist, often used for motion sickness?

maropitant

What are the benefits of maropitant in the perioperative period?

1. Reduced incidence of vomiting from certain premedication drugs

2. Improvement in recovery quality and a faster return to feeding

3. Potential MAC lowering effects (dose and route), analgesia, antitussive

True or false: maropitant does not prevent gastroesophageal reflux (GER).

true

How is maropitant administered?

1-2 mg/kg SQ, approx 45-60 min prior to premed

What is the common side effect of higher doses of maropitant?

excessive drooling

What is the MOA of ondansetron?

5HT3 (serotonin) receptor antagonist - central and GI

What antiemetic is particularly useful for prevention of vomiting due to chemotherapy drugs or from anesthetic drugs that induce vomiting?

ondansetron

What is the MOA of metoclopramide?

dopamine (D2) receptor antagonist in chemoreceptor trigger zone and also 5HT receptor antagonist to contribute to aniemetic effects

What are teh GI prokinetic effects of metoclopramide?

decrease gastric contents (via increasing the rate of gastric emptying) and increasing lower esophageal sphincter tone

Metoclopramide may _______ CNS depressant effects of anesthetic drugs.

increase

When should metoclopramide NOT be given?

• if GI obstruction suspected

• history of seizures

• pheochromocytoma

When are histamine receptors antagonists, such as famotidine (H2 antagonist), given?

to decrease acid production in the stomach

What drug is commonly given prior to mast cell tumor removal to competitively counter the effects of histamine?

diphenhydramine (H1 antagonist)

What drug class (give example) are very effective at lowering gastric pH when given IV?

proton pump inhibitors (omeprazole and pantoprazole)

What is the inhalant anesthetic sparing effect of NSAIDs?

• carprofen → decreased MAC of sevo to 2.1% in dogs

• meloxicam → decreased MAC of sevo to 2.06% in dogs

What drug class should NEVER be given concurrently with NSAIDs?

glucocorticoids

What are glucocorticoids used for?

Used for anti-inflammatory, analgesic, immunosuppressive, and for physiologic support → hypoadrenocorticism

What antibiotics are commonly given during anesthetic episodes?

• cefazolin

• unasyn (amplicillin/sulbactam)

• gentamicin

• K-pen (give slowly)

• PPG (NEVER give IV)

• Naxcel

What anti-fibrinolytic agent can be given to greyhounds to decrease postoperative bleeding by enhancing clot formation and increasing clot strength?

aminocaproic acid

What is desmopressin used for?

hormone given to temporarily increase von Willebrand factor in dogs prior to surgery → promotes vWf secretion secretion (if able) from endothelium storage sites

What hormone is desmopressin a synthetic replacement for?

vasopressin → hormone that reduces urine production

What hormone replacement drug is available as a nasal spray and is expensive, so the owner should usually purchase it at a human pharmacy?

desmopressin

What is dantrolene and what is it used for?

peripherally acting skeletal muscle relaxant for the treatment and prevention of malignant hyperthermia and exertion rhabdomyolysis

What CNS stimulant should not be used to arouse from anesthesia or should not be used to stimulate respiration in neonates or adults?

doxapram

Doxapram is a good assessment of ________ function (dogs & horses).

laryngeal

What is guaifenesin?

central acting muscle relaxant with sedative properties

Why is guaifenesin co-administered with IV anesthetics (ex. ketamine) in horses and ruminants?

• to induce anesthesia

• to maintain anesthesia

_________ is a local anesthetic drug used to provide locoregional analgesia and also used systemically to treat ventricular arrhythmias.

lidocaine

In many species (humans, dogs, horses), lidocaine shows _______ sparin, anti-inflammatory, and analgesic effects.

lidocaine

What is lidocaine used in equine medicine for?

– Ileus ➔ stimulates intestinal muscle contraction (in vitro) + analgesia

– Impactions

– Duodenitis-jejunitis

– Inflammation ➔ preserves microvascular integrity, prevents neutrophil migration, and inhibits cytokine production

– Laminitis

– Post-operative pain

What are the signs of lidocaine toxicity?

– Muscle fasciculations, weakness, GI

– Discontinue lidocaine immediately ➔ signs should quickly disappear

What NMDA receptor antagonist is given as an intraoperative CRI or individually to manage central sensitization types of pain, especially if the pain is chronic and the patient has not responded well to other analgesic options?

ketamine

What drug is excellent for reduction of inhalant with CV benefits?

ketamine

What opioids should be used as a CRI?

• fentanyl

• remifentanil

• morphine

• hydromorphone

What opioids should not use as a CRI?

• butorphanol

• buprenorphine

What is conscious perception inhibited by?

general anesthetics, opioids, and alpha 2 agonists

What is spinal cord sensitization inhibited by?

opioids, NSAIDs, NMDA antagonists, alpha 2 agonists, and local anesthetics

What is transmission along peripheral nerves inhibited by?

local anesthetics and alpha 2 agonists

What is nocicpetion inhibited by?

local anesthetics, opioids, and NSAIDs

What can happen during in vitro pharmaceutical interactions?

drugs precipitate, toxic products formed, drug could be inactivated

What can happen during in vivo pharmaceutical interactions?

PK and PD can be affected:

• absorption

• ABCB1 (MDR1)

• hepatic clearance

• drug protein binding

What is the MDR1 gene mutation?

single mutation in gene coding for protein (P-glycoprotein) that affects drug action

What is P-glycoprotein important for?

the BBB → protects body from toxic accumulations of substances

What are two anesthesia drugs affected by MDR1 gene mutation?

butorphanol and acepromazine

Why does the MDR1 gene mutation matter?

• dogs with mutation may have more serious side effects, such as CNS and/or respiratory depression, from certain anesthetic drugs

• recovery may take longer, sedation may last longer

What is recommended for dogs with homozygous MDR1 gene mutation?

25-50%

What is simple additivity of fractional doses of two or more drugs?

addition

What is synergism?

response to fractional doses is greater than the response to the sum of the fractional doses

What is potentiation?

enhancement of action of one drug by a second drug that has no detectable action of its own

What is antagonism opposing action of one drug toward another, can be competitive (drugs compete for same receptor site) or noncompetitive ( drugs act via different receptors)?

antagonism

What drug will have precipitation occur with aqueous solutions and significant absorption into soft plastic (i.e. fluid bags or tubing) within 24 hours, also incompatible with heparin flush?

diazepam

What anesthetic drugs are incompatible with alkaline solutions?

epinephrine, dobutamine, and dopamine

What solution does phenylbutazone precipitate in?

phenylbutazone

What anesthetic drug should not be mixed with solutions that contain calcium (ex. LRS) because precipitation may occur?

sodium bicarbonate