Lecture 20: Neuropharmacology (Alpha2 drugs, Phenothiazines, Opioids)

What is the preferred sedative in ruminants?

Xylazine; widely used in cattle and other ruminants but ineffective in swine.

What is the preferred reversal agent for xylazine?

Yohimbine; an alpha2 antagonist effective across species, especially in ruminants.

What is the drug of choice for sedating dogs for allergy skin testing?

Dexmedetomidine; does not interfere with allergen-induced vasoactivity.

What is unusual about dexmedetomidine dosing?

Dosed by body surface area (mcg/m²) rather than mg/kg.

What is the preferred antagonist for dexmedetomidine?

Atipamezole; though yohimbine also works.

What is romifidine used for?

Equine-specific alpha2 agonist used for colic pain; longest duration and very safe.

What is medetomidine + vatinoxan used for?

Sedation; vatinoxan minimizes cardiovascular side effects while medetomidine provides sedation.

What is the MOA of alpha2 agonists?

Activate presynaptic alpha2 autoreceptors, reducing norepinephrine release and causing sedation, bradycardia, and hypotension.

What is the MOA of alpha2 antagonists?

Block alpha2 receptors; used only to reverse alpha2 agonist effects.

Which alpha2 agonists are used in veterinary medicine?

Xylazine, detomidine, medetomidine, dexmedetomidine, romifidine, clonidine.

Which alpha2 antagonists are used in veterinary medicine?

Yohimbine, atipamezole, tolazoline, vatinoxan.

What are non-sedative uses of xylazine?

Colic relief in horses, anti-emesis in cats (low dose), emesis induction (high dose).

What is clonidine used for?

Minimizes physical signs of fear (tachycardia, tachypnea) when combined with SSRIs or buspirone.

What is a safety note for alpha2 agonists?

Can cause vomiting at sedating doses (except in horses); fasting recommended.

What is a lethal dose effect of xylazine in cattle?

>10x sedating dose IV can euthanize; used as alternative to pentobarbital.

What is the common MOA for phenothiazines?

Antagonism of postsynaptic dopamine D2 receptors; confers sedation and tranquilization.

What additional receptor activities do phenothiazines have?

Antihistaminic, anticholinergic, anti-adrenergic, anti-serotonergic effects depending on the drug.

What are five uses of acepromazine?

Anti-emesis, exam room sedation, travel sedation, equine laminitis, foal rejection.

How does acepromazine treat foal rejection?

DA antagonism increases prolactin, improving maternal bonding.

How does acepromazine help equine laminitis?

Anti-adrenergic vasodilation improves blood flow to the laminae.

Why is acepromazine not recommended before CV exams?

Anti-NE activity causes hypotension; interferes with cardiovascular assessment.

Why is acepromazine not recommended for air travel?

Can cause oversedation and airway obstruction; not endorsed by IATA.

What is the genital side effect of acepromazine in horses?

Persistent penile prolapse; may indicate recent sedation when evaluating sale barn horses.

What are other side effects of acepromazine?

Hypotension, seizures, sensitivity to temperature extremes; boxers and bulldogs are especially sensitive.

What is trimeprazine used for?

Anti-itch medication; anti-histamine and DA2 antagonism reduce pruritus and sedation.

What is fluphenazine used for?

Long-acting sedative in racehorses; used to calm during training or transport.

What is cyproheptadine used for?

5HT receptor antagonist; treats severe serotonin syndrome.

What is azaperone used for?

DA2 antagonist used in swine to prevent fighting during litter co-mingling; currently unavailable.

What is the common mechanism of action for opioids?

Activate mu, kappa, and delta opioid receptors (GPCRs) to suppress pain transmission and enhance pain-blocking neurons.

What are the three most important side effects of opioids?

Respiratory depression, constipation, and vomiting.

What is the difference between an opioid and an opiate?

Opiates are natural (e.g., morphine); opioids are synthetic or semi-synthetic derivatives.

What is the most useful opioid receptor antagonist?

Naloxone; fast-acting reversal agent for overdose and behavior modification.

How does catnip work?

Contains nepetalactone, a mu and kappa opioid receptor agonist; causes euphoria in cats with a dominant trait.

What are key facts about tramadol?

Effective in birds; questionable in dogs; lowers seizure threshold due to SSRI/SNRI and alpha2 activity.

What is the activity and use of butorphanol?

Mixed agonist-antagonist (kappa agonist, mu antagonist); used for mild-moderate pain, visceral pain, and anti-tussive.

What is the activity and use of buprenorphine?

Partial mu agonist and kappa antagonist; potent analgesic with low dependence and respiratory depression; approved in cats.

What is the use of hydrocodone in veterinary medicine?

Anti-tussive; suppresses cough via mu receptor; formulated with homatropine to reduce secretions and abuse potential.

How do you prevent the wind-up phenomenon?

Use pre-emptive analgesia before and after surgery to reduce central sensitization and chronic pain.

What is the wind-up phenomenon?

Centralized hypersensitization to pain after acute injury; leads to chronic pain if not prevented.

What are the clinical uses of opioids?

Pre-anesthesia, neuroleptanalgesia, wildlife restraint, pain management, anti-diarrhea, emesis induction, anti-tussive.

What is the role of opioids in preventing chronic pain?

Prevents maladaptive transformation of acute pain into chronic pain during peri-operative period.

What are the opioid receptor subtypes?

Mu, kappa, delta; all mediate analgesia, with mu being most abundant in pain pathways.

What is the role of opioid receptors in pain modulation?

Post-synaptic activation dampens pain signals; pre-synaptic inhibition of GABA disinhibits pain-blocking neurons.

What is a full opioid agonist?

Morphine; high receptor affinity and maximal activation.

What is a partial opioid agonist?

Buprenorphine; moderate affinity and partial activation.

What is an opioid antagonist?

Naloxone; high affinity with no activation, blocks other opioids.

What is a mixed agonist-antagonist opioid?

Butorphanol; kappa agonist and mu antagonist.

What is morphine used for?

Peracute analgesia for severe trauma; used post-stabilization and peri-operatively; not for chronic pain.

What is butorphanol used for?

Mild-moderate pain, visceral pain, soft tissue injuries, anti-tussive; less respiratory depression and dependence.

What is buprenorphine used for?

Subacute/chronic pain; potent mu1 agonist; approved in cats for injectable and transdermal use.

What are fentanyl patches used for?

Subacute analgesia; applied pre-op; lasts 3-6 days; avoid heat; extra-label for chronic pain.

What are tramadol's mechanisms?

Weak mu agonist, SSRI/SNRI activity, alpha2 agonist; bitter taste; lowers seizure threshold.

What are tramadol's contraindications?

Epileptic dogs; bitter taste makes it unsuitable for cats and horses.

What is hydrocodone's mechanism and formulation?

Mu agonist suppresses cough; combined with homatropine to reduce secretions and abuse.

What is carfentanil used for?

Wildlife immobilization; ultra-potent; reversed with naltrexone; requires PPE and emergency plan.

What is loperamide used for?

Anti-diarrheal; mu agonist reduces GI motility; no central effects due to MDR1 exclusion.

Why is loperamide risky in infectious diarrhea?

Slows motility, allowing pathogens to invade mucosa.

What breeds are sensitive to loperamide?

Collies and MDR1-deficient breeds; may show central sedation.

What is naloxone's behavioral use?

Enhances pain perception to prevent self-mutilation in dogs, cats, and horses.

What are other common opioid side effects?

Miosis, urine retention, panting, hyperexcitability (cats/horses), mydriasis in cats.

What are opioid contraindications?

Epilepsy, uremia, toxemia, juvenile animals, hepatopathy, possibly neoplasia.

What is renarcotization?

Return of sedation after antagonist wears off; common with naloxone; naltrexone preferred for longer reversal.

What are opioid effects in birds?

Agonists may cause hyperalgesia; tramadol effective; mixed agonist-antagonists preferred.

What are good opioid choices for birds?

Butorphanol, buprenorphine, hydrocodone (species-dependent), meloxicam.

What is bupivacaine liposomal injection used for?

Long-acting post-op analgesia in dogs (ACL surgery) and cats (nerve block); reduces need for opioids.