Lecture 18-20 Behavior-Modifying Drugs

Know that uncontrollable situational anxieties, compulsive behaviors, and cognitive dysfunction can be addressed with drugs alone.

• uncontrollable situational anxieties such as thunderstorms, vet office visit anxiety, owners not wanting to do behavior modification training

• compulsive behaviors: urine marking, acral licking, tail chasing, flank sucking, spinning

Know which neurotransmitter often underlies most behavior problems and is the target for most behavior-modifying drugs.

serotonin

Know the three intervention points for modulating the major neurotransmitter involved in behavioral issues.

1. NT production and synthesis

2. NT receptor interaction

3. NT elimination/reuptake

Why is combination therapy of behavior-modifying drugs not recommended?

because of the crossover nature of NTs, combination therapy should be relegated to refractory problems because of side effects

What is selegiline?

a selective and irreversible MAO-B inhibitor in dogs → increases dopamine in the synapse → used to treat multiple manifestations of cognitive dysfunction in dogs and cats, also activates free radical-scavenging enzymes which results in decreased nerve damage that occurs as part of aging

What are the side effects of selegiline?

GI upset, cardiovascular effects (BP and HR), respiratory (tachypnea)

What is the difference between NSRIs and SSRIs?

NSRIs block the uptake of serotonin and norepi and other NTs, whereas SSRIs block ONLY serotonin uptake

What NSRI is used in cats?

clomipramine → not for use in hepatic patients or geriatric patients, patients with CV disease or glaucoma

What are the uses for clomipramine?

• separation anxiety in dogs

• compulsive disorders and general anxiety in dogs and cats

• urine making in cats

What SSRI is used in veterinary medicine and has fewer side effects than TCAs?

fluoxetine

What caution needs to be taken with fluoxetine?

works so well that it can lead to an inhibition of subservience, which can result in aggression

What drug is used in horses for cribbing?

fluoxetine

The TCAs and SSRIs both enhance serotonin in the synapse so that it can interact with a post-synaptic receptor, so why would serotonin-R antagonists have the same effect on behavior?

5HTR loci and subtypes and other effects unrelated to 5HT

What are the two serotonin receptor antagonists commonly used in vet med?

trazodone and mirtazapine

How does trazodone work?

antagonizes the pre-synaptic autoreceptor for serotonin → pre-synaptic side unable to recognize serotonin in synapse and thus serotonin-containing pre-synaptic vesicles are ocntinually released → used vs situational anxiety and thunderstorm phobias

How does mirtazapine work?

antagonizes multiple receptor subtypes, ultimately resulting in dopamine release, also has anti-adrenergic and antihistamine activity → available for cats as transdermal gel for appetite stimulation

What is serotonin syndrome?

a side effect occurring when serotonin accumulates because of:

• high dose SRIs, whether selective or non-selective

• combinations of serotonin-modulating drugs including MAOIs and 5HT-R agonists

• nutraceuticals + a serotonin modulating drug

• certain foods + a serotonin modulating drug

• certain other drugs + a serotonin modulating drug

What nutraceuticals are associated with serotonin syndrome?

St. John’s wort, SAMe, tryptophan

What foods are associated with serotonin syndrome?

foods containin tyramine, a catecholamine precursor: dried meats, nuts and cheese, pickles and bananas

What drugs are associated with serotonin syndrome?

tramadol or any opioid, linezolid, metoclopramide

What are the clinical signs of serotonin syndrome?

• restlessness, confusion, hyperesthesia, seizures, coma

• increased HR, RR, temp, twitching/tremors

• salivation/vomiting, diarrhea, shivering/shaking, abdominal pain

How is serotonin syndrome treated?

Mild → stop drugs or supplements that enhance serotonin

Severe→ serotoninR blocker (cyproheptadine), diazepam/phenobarbital for sz and tremors, fluid therapy fo CV support, fans/cold baths for hyperthermia

What is the only BZD that MUST be injected?

midazolam

What is alprazolam?

a short-acting BZD used to address certain types of anxiety

What is diazepam?

a long-acting BZD used to address certain types of anxiety.

Why are BZDs not first choice behavior-modifying drugs?

tolerance dependence

What is alfaxalone?

a GABA receptor-modulating drug used as a swine sedative.

What species can diazepam not be used in and why?

cats because it causes fatal idiopathic hepatic necrosis

What is flumazenil and when is it used?

GABA receptor antagonist that specifically blocks the BDZ-binding site → mostly used to reverse CV complications from midazolam during anesthesia but can be used to treat accidental overdoses in any species

What is the general MOA of a benzodiazepene?

GABA-R agonist → inhibition of excitatory NT release, especially glutamate → calming effect

What behavior conditions are BDZs used to treat?

• separation anxiety

• noise phobias

• feline inappropriate elimination

• situation anxiety

• middle of night waking or waking too early

• appetite stimulation in cats

What is alprazolam used to treat?

• anxiety in mares that have recently foaled, or for orphaned foals

• fear and aggression in dogs especially in dogs that develop motor issues while on diazepam

• thunderstorm phobia/anxiety conjunction with clomipramine

• middle of night anxiety