Pharmacology - Behaviour Modifying Drugs & Neoplastic

Veterinary Pharmacology: Behavior-Modifying & Antineoplastic Drugs

Why This Topic Matters

• Behavior-modifying drugs are increasingly used to reduce Fear, Anxiety, and Stress (FAS) in veterinary patients.

• Antineoplastic drugs (chemotherapy) can extend the lives of animals with cancer.

• Safety is critical when handling chemotherapy drugs; only trained personnel should do so.

Part 1: Behavior-Modifying Drugs

Understanding FAS (Fear, Anxiety, Stress)

Why FAS is Harmful

• Self-harm (escape attempts, compulsive licking)

• Harm to others (biting, scratching)

• Increased fear with repeated exposure

• Difficulty learning

• Physiological changes (cortisol, dopamine, serotonin, norepinephrine)

• Health issues (diarrhea, slower healing, anorexia)

• Prevents proper veterinary care

Role of Behavior-Modifying Drugs

• Help manage the situation

• Reduce FAS to allow behavior modification (training) to work

• Used temporarily (stressful events) or lifelong

• Adverse effects: liver, kidney, cardiovascular issues; may reduce inhibitions → aggression

• Onset: Can take 6–8 weeks to see a change

Always Rule Out Medical Causes First

• Hyperthyroidism → agitated cats

• Nerve pathology → compulsive chewing/licking

• Urinary issues → spraying/inappropriate urination

Key Neurotransmitters in Behavior

Pre-Veterinary Pharmaceuticals (PVPs)

• Given before appointments to reduce stress.

• Canine "Chill Protocol" : Acepromazine, Melatonin, Trazodone, Gabapentin, Clonidine (given night before & 1–3 hours prior)

• Feline: Gabapentin

Antianxiety Drugs

Benzodiazepines

• Drugs: Diazepam (Valium), Lorazepam (Ativan), Alprazolam (Xanax), Clonazepam (Klonopin)

• Uses: Anxiety, fear, aggression, urine spraying

• Mechanism: Potentiates GABA (inhibitory)

• Features: Rapid onset, muscle relaxation, reversible

• Adverse effects: Sedation, possible hepatotoxicity in cats

• Caution: May reduce inhibitions → aggression

Supplements

• L-Theanine (Anxitane): Increases GABA

• Casein (alpha-casozepine): High affinity for GABA receptors

• Tryptophan: Precursor to melatonin & serotonin; efficacy in horses questionable, high doses can cause hemolytic anemia

• Probiotics: Blunt cortisol response to stress

• Melatonin: Used in chill protocols, separation anxiety, alopecia in Nordic breeds

Gabapentin

• Uses: PVP, anticonvulsant, pain control

• Mechanism: Inhibits calcium channels → decreased excitatory neurotransmission

• Adverse effects: Sedation, ataxia, possible hepatotoxicity

• Caution: Renal insufficiency; avoid human liquid forms with xylitol

Trazodone

• Class: SARI (Serotonin Antagonist & Reuptake Inhibitor)

• Uses: Anxiety, PVP, post-surgical sedation

• Mechanism: Inhibits serotonin reuptake

• Caution: Risk of serotonin syndrome with other serotonergic drugs

Antidepressants

Tricyclic Antidepressants (TCAs)

• Drugs: Amitriptyline (Elavil), Clomipramine (Clomicalm)

• Uses: Separation anxiety, compulsive disorders, urine spraying

• Mechanism: Block reuptake of serotonin & norepinephrine (non-selective)

• Adverse effects: Anticholinergic (dry mouth, constipation, urinary retention, tachycardia), elevated liver enzymes, possible seizures

• Caution: May interfere with thyroid meds

Selective Serotonin Reuptake Inhibitors (SSRIs)

• Drug: Fluoxetine (Prozac)

• Uses: Aggression, anxiety, phobias, inappropriate urination

• Mechanism: Selectively inhibits serotonin reuptake

• Adverse effects: Lethargy, reduced appetite, vomiting, shaking, diarrhea

• Caution: Serotonin syndrome when combined with other serotonergic drugs

Monoamine Oxidase Inhibitors (MAOIs)

• Drug: Selegiline (Anipryl)

• Uses: Canine Cognitive Disorder, adjunct for anxiety

• Mechanism: Inhibits MAO-B → increases dopamine

• Adverse effects: Anticholinergic-like, hypotension, drowsiness

• Caution: Serotonin syndrome risk

Serotonin Syndrome

• Cause: Too much serotonin (combine TCAs, SSRIs, SARIs, MAOIs, tramadol)

• Symptoms: Vomiting, diarrhea, seizures, hyperthermia

Other Behavior Drugs

Alpha-2 Agonists

• Dexmedetomidine (Sileo) : Noise phobias; transmucosal

• Clonidine: Oral PVP, fear-based behaviors (separation anxiety, noise/storm phobia); give 90 min before event, lasts 4–6 hours

• Adverse effects: Pale mucous membranes, vomiting, dry mouth, increased thirst

• Caution: Cardiovascular, respiratory, liver, renal disease

Hormones

• Progestins (medroxyprogesterone) : Suppress male-like behaviors; many adverse effects (PU/PD, mammary neoplasia, diabetes, pyometra, bone marrow suppression) → last resort

• Melatonin: Rare side effects; OTC

Pheromones (Mild calming, species-specific)

• Canine (DAP – Adaptil) : Lactating female pheromone

• Feline (FFP – Feliway) : Cheek gland secretions

• Equine (EAP – Confidence EQ) : Maternal pheromone

Part 2: Antineoplastic Drugs

Cancer Basics

• Uncontrolled cell growth → blocks blood flow, nutrients

• Immune system role: T lymphocytes, antibodies, interferons, TNF

• Treatment: Surgery, chemotherapy, or both

Cell Cycle & Drug Targeting

• Growth fraction: % of cancer cells dividing. High = more responsive (e.g., leukemia, lymphoma). Low = less responsive (e.g., solid tumors).

• Doubling time: Larger tumor = longer doubling time = less drug effectiveness.

Types of Antineoplastic Drugs

Adverse Effects (Target rapidly dividing cells) – "BAG"

• Bone marrow suppression (neutropenia → thrombocytopenia → anemia)

• Alopecia (rare in animals; some breeds, cat whiskers)

• Gastrointestinal (10–15% of patients; use maropitant or ondansetron)

• Also: cardiotoxicity, nephrotoxicity, infertility

Treatment Considerations

• Depends on: cancer type/stage, animal's health, finances, access

• Dosing based on body surface area

• Must have a confident IV catheter – extravasation causes tissue necrosis

Common Protocol: CHOP-19 (19 weeks)

• Cyclophosphamide (CCNS)

• Hydroxydaunorubicin (doxorubicin – CCNS)

• Oncovin (vincristine – CCS)

• Prednisone (CCNS)

Chemotherapy Safety (CRITICAL!)

• Cytotoxic, teratogenic, mutagenic, carcinogenic

• Do not handle if pregnant

• PPE: Gown (closed front), goggles, mask, two pairs of latex gloves (not PVC)

• Prepare drugs in Type II biosafety cabinet or vertical laminar flow hood

• Vent the vial, use Luer-Lok syringes

• No eating/drinking, post signs

• Flush, flush, flush lines

• Chemo spill kit on hand

• Dispose in designated chemo bag → sharps bin for incineration

• Client instruction: Wear gloves when cleaning vomit/urine/feces for 48 hours to 7 days post-treatment

Pain Control in Cancer

• Use pain charts, assess appetite/activity/attitude/vitals/elimination/palpation

• Options: NSAIDs, opioids, steroids, local anesthetics

Case Study: Chazzberry (Rottweiler/Shepherd Mix)

Part 1 – Diagnostics (Behavior)

• Weight: 30 kg

• PVP Protocol: Chill Protocol

• Drugs & Doses:

  • Gabapentin: 20–25 mg/kg → 600 mg (25 mg/kg × 30 kg = 750 mg; closest option 600 or 1200? Likely 600 if conservative)

  • Melatonin: Large dog → 5 mg

  • Acepromazine: 0.025–0.05 mg/kg → 0.75–1.5 mg (closest option 1 mg)

  • Trazodone: 5 mg/kg → 150 mg

• Additional sedation if needed:

  • Hydromorphone (full mu agonist): 0.05 mg/kg, concentration 10 mg/mL → (0.05 × 30 = 1.5 mg → 1.5/10 = 0.15 mL)

  • Medetomidine (alpha-2 agonist): 3 µg/kg = 0.003 mg/kg, concentration 1 mg/mL → (0.003 × 30 = 0.09 mg → 0.09/1 = 0.09 mL)

Part 2 – Chemotherapy (Lymphoma)

• Protocol: CHOP Protocol

• Safety measures:

  • Vertical laminar flow hood

  • Two pairs of latex gloves

  • Wear goggles and particulate masks

  • Gown with closed front

  • Use Luer-Lok syringes

  • Chemo waste disposal + spill kit

  • Client wears gloves for 7 days post-treatment cleaning up excreta

Key Drug-Drug & Drug-Animal Cautions (Review List)

• NSAIDs + corticosteroids (e.g., prednisone) → GI ulceration

• NSAIDs + other NSAIDs → increased adverse effects

• Calcium-containing IV fluids (LRS) + blood products → clotting

• Tetracycline + calcium/milk → reduced absorption

• Sucralfate + enrofloxacin → reduced absorption (separate by 1–2 hours)

• Normasol-R + IV enrofloxacin → precipitates

• Serotonin syndrome risk: SSRI + SARI + MAOI + TCA + tramadol

• Butorphanol (kappa agonist, mu antagonist) → reverses mu opioids

• Diazepam: light-sensitive, absorbs into plastic

• Anticholinergics + alpha-2 agonists → contraindicated (hypertension, arrhythmias)

• Meloxicam: injectable concentration differs in large (20 mg/mL) vs small animal (5 mg/mL)

• Enrofloxacin in cats → retinal toxicity (blindness); in growing animals → joint damage

• Sulfa drugs → keratoconjunctivitis sicca (dry eye)

• Diazepam oral in cats with liver disease → caution

• KCl → must be diluted, CRI only

• Corticosteroids → common side effect: PU/PD

• Xylazine → species-specific; bovines very sensitive

• Chloramphenicol → rare aplastic anemia in humans

• Progestins & misoprostol → abortifacient in pregnant women

• Carfentanil → extremely potent, life-threatening in minute amounts

"What Drug Am I?" Quick Review Table