Overview and Clinical Importance
Central Nervous System (CNS) drugs represent a cornerstone of veterinary practice, spanning sedation, anesthesia, analgesia, seizure management, and behavioral therapy. These medications act on specific neurotransmitter systems to produce dose-dependent effects ranging from mild anxiolysis to complete unconsciousness. Understanding their mechanisms, species differences, and clinical applications is essential for the BCSE and daily veterinary practice.
This domain tests your ability to select appropriate drugs based on patient status, recognize adverse effects, understand drug interactions, and apply pharmacokinetic principles across species. CNS pharmacology questions frequently appear as clinical vignettes requiring integration of multiple concepts.
High-YieldCNS drugs comprise a significant portion of Domain 2 questions. Master the receptor mechanisms, species differences in metabolism, and reversal agents for exam success.
| Property |
Details |
| Mechanism |
Dopamine D2 antagonist; also blocks alpha-1, muscarinic, and histamine receptors |
| Primary Effects |
Tranquilization without analgesia; antiemetic; reduces anesthetic requirements by 20-30% |
| Cardiovascular |
Hypotension due to alpha-1 blockade and vasodilation; use with caution in hypovolemic patients |
| Duration |
4-6 hours in dogs; half-life approximately 2.5 hours in horses |
| Dogs |
0.01-0.05 mg/kg IV, IM, SQ; commonly used preanesthetic |
| Cats |
0.01-0.05 mg/kg; similar effects to dogs |
| Horses |
0.02-0.1 mg/kg IV; CAUTION: penile prolapse (paraphimosis) risk in stallions/geldings |
| Contraindications |
Hypovolemia, shock, severe cardiac disease, breeding stallions (penile prolapse) |
| Key Clinical Pearl |
No reversal agent available; effects must wear off naturally |
| Drug |
Alpha-2:Alpha-1 Ratio |
Species |
Key Features |
Reversal |
| Xylazine |
160:1 |
Horses, cattle, small animals |
Emetic in dogs/cats; vomiting common; used widely in horses/cattle |
Yohimbine, Atipamezole |
| Medetomidine |
1620:1 |
Dogs, cats |
Racemic mixture; more selective than xylazine; available in combination with ketamine |
Atipamezole |
| Dexmedetomidine |
1620:1 |
Dogs, cats |
Active enantiomer of medetomidine; twice as potent; OTM gel (Sileo) for noise aversion |
Atipamezole |
| Detomidine |
260:1 |
Horses primarily |
Prolonged sedation and analgesia in horses; OTM gel available |
Atipamezole |
| Romifidine |
340:1 |
Horses |
Less ataxia than xylazine; longer duration; good for standing sedation |
Atipamezole |
Section 1: Sedatives and Tranquilizers
Sedatives and tranquilizers reduce anxiety and produce dose-dependent CNS depression. The key distinction: tranquilizers decrease anxiety without drowsiness, while sedatives produce drowsiness and hypnosis. Increased doses of tranquilizers cause side effects without loss of consciousness, whereas increased sedative doses can produce anesthesia-like states.
[Include Image: Figure 1. Sedative Drug Classes and Their CNS Targets]
Phenothiazines
Phenothiazines, exemplified by acepromazine, are neuroleptic tranquilizers that work primarily through dopamine D2 receptor antagonism in the CNS. They also block alpha-1 adrenergic receptors (causing vasodilation), muscarinic receptors, and histamine receptors.
Acepromazine (ACE)
High-YieldAcepromazine does NOT provide analgesia. Horses may still kick even when heavily sedated. In stallions and geldings, can cause persistent penile prolapse (paraphimosis).
MEMORY AID - ACE Effects
ACE = Anti-emetic, Calming, Episodic hypotension (alpha block). Remember: 'ACE has no analgesia - Absence of pain Control Expected.'
Alpha-2 Adrenergic Agonists
Alpha-2 agonists revolutionized veterinary sedation by providing reliable sedation, analgesia, AND muscle relaxation. They act on presynaptic alpha-2 receptors in the CNS to decrease norepinephrine release from the locus coeruleus, producing profound sedation. Critically, they are REVERSIBLE with alpha-2 antagonists.
[Include Image: Figure 2. Alpha-2 Agonist Mechanism at Presynaptic Terminal]
Alpha-2 Agonist Effects - The Complete Picture
Cardiovascular: Biphasic blood pressure response - initial hypertension (peripheral vasoconstriction) followed by hypotension. Reflex bradycardia is common and expected. Arrhythmias including AV blocks may occur.
Respiratory: Decreased respiratory rate and tidal volume; mild decrease in PaO2.
GI: Vomiting in dogs and cats (central alpha-2 activation); decreased GI motility.
Metabolic: Decreased insulin release leading to hyperglycemia and glycosuria; increased urine production.
Uterine: Increases uterine tone - xylazine CONTRAINDICATED in late pregnancy in cattle (may induce abortion).
High-YieldAlpha-2 agonists cause splenic sequestration of RBCs in horses and dogs, resulting in temporary decrease in PCV/Hematocrit. Do NOT interpret this as blood loss!
MEMORY AID - Alpha-2 Triad
Alpha-2 agonists provide the 'SAM' triad: Sedation, Analgesia, Muscle relaxation. Remember: 'SAM is reversible' - use atipamezole!
MEMORY AID - Alpha-2 Selectivity
X-ray MeDia Room (Xylazine less than Medetomidine/Dexmedetomidine less than Romifidine). Higher selectivity = fewer alpha-1 side effects.
Alpha-2 Antagonists (Reversal Agents)
High-YieldWhen reversing alpha-2 agonists, analgesia is ALSO reversed. Ensure adequate alternative analgesia is provided before reversal!
Benzodiazepines
Benzodiazepines enhance the inhibitory effects of GABA at GABA-A receptors by increasing chloride channel opening frequency. They provide anxiolysis, muscle relaxation, and anticonvulsant effects with minimal cardiovascular depression. Important: They do NOT reliably sedate healthy adult dogs and cats - may paradoxically cause excitement!
Reversal: Flumazenil is a competitive benzodiazepine antagonist. Duration is shorter than most benzodiazepines, so re-sedation may occur.
High-YieldDiazepam should NEVER be mixed with lactated Ringers solution - calcium causes precipitation. Use saline if giving as CRI.
MEMORY AID - Benzodiazepine Best Patients
Benzodiazepines work best in 'YOS' patients: Young, Old, or Sick. Healthy adults may become excited!
| Drug |
Selectivity |
Clinical Use |
| Atipamezole |
Highly alpha-2 selective (8526:1) |
Preferred reversal for medetomidine/dexmedetomidine; dose = equal volume to agonist |
| Yohimbine |
Moderately alpha-2 selective (40:1) |
Used for xylazine reversal; less commonly used now |
| Tolazoline |
Non-selective alpha blocker |
Used in horses for xylazine reversal; can cause significant hypotension |
| Drug |
Water Soluble? |
Key Feature |
Clinical Use |
| Diazepam |
No (propylene glycol carrier) |
Adsorbs to plastic; painful IM; highly protein bound |
Anticonvulsant; co-induction with ketamine; appetite stimulant in cats |
| Midazolam |
Yes |
Can be given IM without pain; mixes well with opioids |
Preferred for premedication protocols; combined with opioids |
| Zolazepam |
Yes (in Telazol) |
Combined with tiletamine in Telazol/Zoletil |
Field immobilization; short procedures |
Section 2: General Anesthetics
Injectable Anesthetics
[Include Image: Figure 3. GABA-A Receptor with Anesthetic Binding Sites]
Propofol
High-YieldPropofol provides NO analgesia. It is safe for repeat dosing in dogs but historically caused prolonged recoveries and oxidative injury (Heinz bodies) in cats with older formulations.
Alfaxalone
MEMORY AID - Alfaxalone vs Propofol
ALFA = A Lipid-Free Alternative. Alfaxalone is safe for cats and repeat dosing, works IM, great for exotic species.
Ketamine (Dissociative Anesthetic)
High-YieldKetamine is the ONLY common IV anesthetic that provides significant analgesia. It increases intracranial and intraocular pressure - avoid in head trauma and glaucoma.
MEMORY AID - Ketamine Cardiovascular Effects
Ketamine KICKS up cardiovascular parameters (increases HR, BP, CO). Unlike other IV anesthetics that depress! Think 'K for Kicks.'
Tiletamine-Zolazepam (Telazol/Zoletil)
Fixed 1:1 combination of tiletamine (dissociative, similar to ketamine) and zolazepam (benzodiazepine). Provides chemical restraint with single IM injection. In dogs, tiletamine outlasts zolazepam (rough recoveries); in cats, zolazepam outlasts tiletamine (smoother recoveries). Recovery in dogs can be improved by adding diazepam. Commonly used for field immobilization in wildlife.
Etomidate
Imidazole derivative that enhances GABA-A activity. Key advantage: minimal cardiovascular depression, making it ideal for critically ill or cardiac patients. Provides no analgesia. Major concern: suppresses adrenocortical function (inhibits 11-beta-hydroxylase) for 2-6 hours even after single dose. Can cause myoclonus, pain on injection, nausea, and vomiting. Not commonly used in equine practice.
High-YieldEtomidate is the induction agent of choice for patients with severe cardiovascular compromise. Remember: adrenal suppression limits repeat dosing.
Inhalant Anesthetics
[Include Image: Figure 4. Anesthetic Machine with Vaporizer Components]
Inhalant anesthetics are the mainstay for maintenance of general anesthesia. They work through multiple mechanisms including enhancement of GABA-A receptors, glycine receptors, and two-pore potassium channels, plus inhibition of NMDA receptors. Potency is measured by MAC (Minimum Alveolar Concentration) - the concentration at which 50% of patients will not respond to a painful stimulus.
Factors That DECREASE MAC (Less Anesthetic Needed)
Concurrent drugs: Opioids, alpha-2 agonists, benzodiazepines, lidocaine CRI all reduce MAC. Hypothermia, hypotension, hypoxia, hypercapnia, metabolic acidosis, increasing age, and pregnancy also decrease MAC.
Factors That INCREASE MAC (More Anesthetic Needed)
Hyperthermia, hyperthyroidism, young age (pediatric patients), chronic alcohol exposure, and CNS stimulant drugs all increase MAC.
High-YieldLower blood:gas coefficient = faster equilibration = faster changes in anesthetic depth. Sevoflurane's low solubility makes it ideal for mask inductions and rapid recoveries.
MEMORY AID - MAC Decreasing Factors
OLD HIPPIE = Old age, Low temperature, Drugs (sedatives/analgesics), Hypotension, Hypoxia, Pregnancy, Increased CO2, Endocrine (hypothyroid).
| Property |
Details |
| Mechanism |
GABA-A receptor agonist; prolongs chloride channel opening; also some NMDA antagonism |
| Onset/Duration |
Rapid onset (less than 1 minute IV); short duration (5-10 minutes single bolus); highly lipophilic |
| Metabolism |
Hepatic and extrahepatic metabolism; rapid redistribution from CNS |
| Dogs |
4-6 mg/kg IV to effect for induction; safe for repeated doses or CRI maintenance |
| Cats |
4-8 mg/kg IV; repeated dosing may cause Heinz body formation and prolonged recovery (less concern with newer formulations) |
| Cardiovascular |
Dose-dependent hypotension and respiratory depression; apnea common if given rapidly |
| Special Notes |
Formulations contain lipid emulsion or cyclodextrin; no analgesic properties; supports bacterial growth - discard within 6-24 hours of opening |
| Property |
Details |
| Mechanism |
Neuroactive steroid; positive modulation of GABA-A receptors; different binding site than benzodiazepines |
| Onset/Duration |
Rapid onset; duration 15-20 minutes; smooth recovery |
| Dogs |
2-3 mg/kg IV for induction (premedicated); can be given IM in cats |
| Cats |
2-5 mg/kg IV or IM; excellent choice for cats; minimal accumulation with repeat dosing |
| Exotic Species |
Widely used in rabbits, ferrets, reptiles, and birds |
| Advantages |
Wide safety margin; can give IM; smooth recovery; suitable for repeat dosing |
Section 3: Local Anesthetics
Local anesthetics reversibly block voltage-gated sodium channels, preventing nerve impulse propagation. They exist in equilibrium between ionized (charged) and un-ionized (uncharged) forms. The un-ionized form crosses the nerve membrane, but the ionized form blocks the sodium channel from inside the cell.
[Include Image: Figure 5. Local Anesthetic Mechanism of Action at Sodium Channel]
Classification
Esters: Procaine, tetracaine, benzocaine. Metabolized by plasma esterases. Higher allergenic potential.
Amides: Lidocaine, mepivacaine, bupivacaine, ropivacaine. Metabolized by hepatic enzymes. Lower allergenic potential. Most commonly used in veterinary medicine.
MEMORY AID - Ester vs Amide
Amides have TWO letter i's in the name (lidocaine, bupivacaine, mepivacaine, ropivacaine). Esters have ONE i (procaine, tetracaine, benzocaine).
Local Anesthetic Toxicity
CNS Signs (first): Restlessness, tremors, seizures (paradoxical - CNS excitation from blockade of inhibitory neurons).
Cardiovascular Signs: Hypotension, bradycardia, arrhythmias, cardiovascular collapse. Bupivacaine is especially cardiotoxic - difficult to resuscitate!
Treatment: Lipid rescue therapy (20% IV lipid emulsion 1-4 mL/kg over 30 minutes) - creates lipid 'sink' to sequester local anesthetic away from tissues. Also: benzodiazepines for seizures, supportive care, oxygen.
High-YieldLidocaine is safer than bupivacaine for cardiotoxicity. Remember: 'B for Bupivacaine, B for Bad for the heart.' Lipid rescue can be life-saving!
MEMORY AID - Onset Speed
Lower pKa = Faster onset. Lidocaine (7.9) is faster than bupivacaine (8.1). More drug exists in un-ionized form at physiologic pH (7.4) when pKa is closer to pH.
| Property |
Details |
| Mechanism |
NMDA receptor antagonist; dissociates thalamocortical and limbic systems; also affects opioid, monoamine, and muscarinic receptors |
| Unique Features |
Provides dissociative anesthesia with profound somatic analgesia; eyes remain open with intact reflexes; cataleptic state |
| Cardiovascular |
Indirect sympathomimetic - increases HR, BP, and cardiac output (unlike other IV anesthetics); direct myocardial depressant but masked by sympathetic stimulation |
| Dogs/Cats |
5-10 mg/kg IV or IM; MUST combine with benzodiazepine or alpha-2 to prevent muscle rigidity and emergence delirium |
| Horses |
2.2 mg/kg IV after sedation; duration approximately 15 minutes; must heavily sedate first to prevent excitation |
| Contraindications |
Head trauma (increases ICP), open globe injuries (increases IOP), hypertrophic cardiomyopathy, hyperthyroidism |
| Metabolism |
Hepatic in most species; cats have prolonged elimination |
| Agent |
MAC Dog (%) |
MAC Cat (%) |
Blood:Gas Coefficient |
Key Features |
| Isoflurane |
1.28 |
1.63 |
1.4 (low - fast changes) |
Most commonly used; dose-dependent cardiovascular depression; maintains cardiac output better than halothane |
| Sevoflurane |
2.1 |
2.58 |
0.69 (very low - very fast) |
Rapid induction/recovery; less pungent; metabolized to inorganic fluoride; can be used for mask/chamber induction |
| Desflurane |
7.2 |
9.8 |
0.42 (lowest - fastest) |
Requires heated vaporizer; very rapid changes; airway irritant - not for induction; rarely used in veterinary |
Section 4: Analgesics
Opioid Analgesics
Opioids are the most effective systemic analgesics available and work by binding to opioid receptors (mu, kappa, delta) in the CNS and periphery. They are classified by receptor activity: full agonists, partial agonists, and agonist-antagonists. The mu receptor is primarily responsible for analgesia, sedation, and respiratory depression.
[Include Image: Figure 6. Opioid Receptor Types and Effects]
High-YieldOpioids produce MIOSIS in dogs and horses but MYDRIASIS in cats. Morphine causes excitement in horses, cattle, and pigs. Cats have prolonged opioid effects due to slower glucuronidation.
Opioid Reversal - Naloxone
Naloxone is a pure opioid antagonist at all receptor types. Onset within 1-2 minutes IV. Duration is shorter (30-90 minutes) than most opioids - may need repeat dosing or CRI. Complete reversal eliminates all analgesia. Partial reversal (titrate to effect with diluted doses) can maintain some analgesia while reversing respiratory depression. Buprenorphine has high receptor affinity and may not be completely reversed by naloxone.
MEMORY AID - Opioid Eye Effects by Species
D-M-H = Dogs get Miosis, Horses get Miosis. Cats are CONTRARY - they get mydriasis!
MEMORY AID - Full vs Partial Agonists
Full agonists (Morphine, Hydromorphone, Fentanyl, Methadone) = MHFM = 'My Horse Feels Marvelous.' Partial/Agonist-Antagonists have ceiling effects.
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)
NSAIDs inhibit cyclooxygenase (COX) enzymes, blocking prostaglandin synthesis. COX-1 is constitutive ('housekeeping') - maintains GI mucosal integrity and renal perfusion. COX-2 is inducible at sites of inflammation. COX-2 preferential drugs aim to reduce inflammation while sparing protective prostaglandins.
[Include Image: Figure 7. COX Pathway and NSAID Mechanism]
High-YieldNEVER combine NSAIDs with corticosteroids - dramatically increases GI ulceration risk. Wait 5-7 days washout period when switching between NSAIDs or from corticosteroids.
NSAID Adverse Effects and Contraindications
GI: Ulceration, vomiting, diarrhea, melena (COX-1 inhibition reduces protective prostaglandins).
Renal: Decreased renal blood flow in dehydrated or hypotensive patients; papillary necrosis with chronic use.
Hepatic: Idiosyncratic hepatotoxicity (not dose-dependent); monitor liver enzymes.
Platelets: Decreased aggregation (COX-1); COX-2 selective drugs have less platelet effect.
Cats: Deficient glucuronidation means longer half-lives and increased toxicity risk. NEVER give acetaminophen to cats (causes methemoglobinemia and Heinz body anemia).
High-YieldAcetaminophen is TOXIC to cats - causes methemoglobinemia and hepatic necrosis. Treatment: N-acetylcysteine. Dogs can receive acetaminophen but it has weak anti-inflammatory activity.
MEMORY AID - NSAID Contraindications
CRASH = Coagulopathy, Renal disease, Aspirin/other NSAIDs recently, Steroids concurrent, Hypovolemia/hypotension. Never use NSAIDs in CRASH patients!
| Drug |
pKa |
Onset |
Duration |
Clinical Notes |
| Lidocaine |
7.9 |
Fast (3-5 min) |
60-90 min (up to 2 hr with epi) |
Most versatile; can use IV as CRI for analgesia and antiarrhythmic; toxic dose: 6-10 mg/kg dog; 2-4 mg/kg cat |
| Mepivacaine |
7.6 |
Fast (10 min) |
2-3 hours |
Less tissue irritation; preferred for intra-articular use; common in equine practice |
| Bupivacaine |
8.1 |
Slow (15-20 min) |
4-8 hours |
Long duration ideal for post-op analgesia; MORE CARDIOTOXIC than lidocaine; toxic dose: 2-4 mg/kg |
| Ropivacaine |
8.1 |
Slow |
4-6 hours |
Less cardiotoxic than bupivacaine; less motor blockade; often used for epidurals |
| Drug |
Classification |
Potency vs Morphine |
Duration |
DEA Schedule |
Key Features |
| Morphine |
Full mu agonist |
1x (reference) |
4-6 hr |
II |
Gold standard; histamine release if given IV rapidly; causes defecation in dogs |
| Hydromorphone |
Full mu agonist |
5-7x |
2-6 hr |
II |
Less histamine release than morphine; excellent for perioperative use |
| Fentanyl |
Full mu agonist |
100x |
20-30 min IV; 72 hr patch |
II |
Very potent; short duration requires CRI; patches available for chronic pain |
| Methadone |
Full mu agonist + NMDA antagonist |
1-2x |
4-6 hr |
II |
Dual mechanism; useful for neuropathic pain; less GI side effects |
| Buprenorphine |
Partial mu agonist |
25-40x |
6-12 hr |
III |
Ceiling effect for analgesia and resp depression; excellent in cats; OTM effective |
| Butorphanol |
Mu antagonist/ Kappa agonist |
3-5x |
1-2 hr |
IV |
Short duration; antitussive; can antagonize mu agonists; good for visceral pain |
| Tramadol |
Weak mu agonist + SNRI |
0.1x |
4-6 hr |
IV |
Oral bioavailability varies; limited efficacy data in dogs; risk of serotonin syndrome |
Section 5: Anticonvulsants
Anticonvulsants are used for long-term seizure management in dogs and cats. The goal is to reduce seizure frequency and severity with acceptable side effects. Generally initiated when seizures occur more than once monthly, last longer than 5 minutes, or cluster. Single-drug therapy is preferred before adding agents.
[Include Image: Figure 8. Sites of Action of Anticonvulsant Drugs]
High-YieldPotassium bromide is CONTRAINDICATED in cats - causes severe respiratory disease (pneumonitis). Phenobarbital is first-line in cats.
Emergency Seizure Management
Status Epilepticus (seizure lasting greater than 5 minutes or multiple seizures without full recovery): First-line: Diazepam 0.5-2 mg/kg IV (can repeat x3) or rectal (per rectum). Midazolam can be given IM/IN. If refractory: Phenobarbital loading dose, propofol CRI, or levetiracetam IV.
MEMORY AID - Anticonvulsant Selection
PB for First = PhenoBarbital First-line in dogs AND cats. Bromide Breathes Bad in cats (pneumonitis). Levetiracetam = Least side effects.
MEMORY AID - Phenobarbital Side Effects
The 3 P's: Polyuria, Polydipsia, Polyphagia. Plus sedation and hepatotoxicity with chronic use.
| Drug |
COX Selectivity |
Species Approved |
Duration/Dosing |
Special Notes |
| Carprofen (Rimadyl) |
COX-2 preferential |
Dogs |
2.2 mg/kg q12h or 4.4 mg/kg q24h |
Rare idiosyncratic hepatotoxicity reported; Labrador Retrievers may be overrepresented |
| Meloxicam (Metacam) |
COX-2 preferential |
Dogs, cats (single injection) |
Dogs: 0.1 mg/kg q24h; Cats: 0.1 mg/kg once (not repeated in US) |
Oral liquid available; long-term use in cats controversial in US but approved elsewhere |
| Deracoxib (Deramaxx) |
COX-2 selective |
Dogs |
1-2 mg/kg q24h |
Coxib class; highly selective; chewable tablets |
| Firocoxib (Previcox) |
COX-2 selective |
Dogs, horses |
Dogs: 5 mg/kg q24h; Horses: 0.1 mg/kg q24h |
Coxib class; approved for equine osteoarthritis; not for cats |
| Robenacoxib (Onsior) |
Highly COX-2 selective |
Dogs, cats |
Dogs: 1-2 mg/kg q24h; Cats: 1-2.4 mg/kg up to 3 days |
Newest coxib; approved for short-term use in cats; rapid tissue distribution |
| Grapiprant (Galliprant) |
EP4 receptor antagonist (NOT a COX inhibitor) |
Dogs |
2 mg/kg q24h |
Novel mechanism; blocks PGE2 at receptor level; may be safer for GI and renal |
| Drug |
Mechanism |
Species/Use |
Monitoring |
Key Points |
| Phenobarbital |
Enhances GABA-A activity; also blocks sodium channels |
First-line in dogs and cats |
Serum levels (therapeutic: 20-40 mcg/mL); liver enzymes every 6-12 months |
Hepatic enzyme inducer; PU/PD, polyphagia, sedation initially; liver toxicity with long-term use; taper gradually - never stop abruptly |
| Potassium Bromide (KBr) |
Hyperpolarizes neurons by mimicking chloride |
Dogs only - CONTRAINDICATED in cats (causes pneumonitis) |
Serum levels (therapeutic: 1000-3000 mcg/mL); takes 3-4 months to reach steady state |
Not hepatically metabolized; good for dogs with liver disease; salt intake changes can alter levels; sedation, PU/PD, rear limb weakness |
| Levetiracetam (Keppra) |
Binds SV2A protein; modulates neurotransmitter release |
Dogs and cats; adjunctive or monotherapy |
Therapeutic monitoring not required (wide safety margin) |
Minimal side effects; renally excreted; short half-life requires TID dosing; extended-release formulations available; useful for cluster seizures and feline audiogenic reflex seizures |
| Zonisamide |
Blocks sodium and T-type calcium channels; weak carbonic anhydrase inhibitor |
Dogs (off-label in cats) |
Serum levels available but not routinely needed |
Fewer side effects than phenobarbital; can be used with phenobarbital (dose adjustment needed); sulfonamide - caution with KCS/hepatic issues |
| Imepitoin |
Partial GABA-A agonist (low-affinity benzodiazepine site) |
Dogs only |
Not routinely monitored |
Approved for noise phobias and idiopathic epilepsy in Europe; fewer sedative effects; newer option |
Section 6: Behavior-Modifying Drugs
Behavior-modifying drugs are essential adjuncts to behavioral modification therapy for anxiety disorders, phobias, and compulsive behaviors in companion animals. Most work by modulating serotonin, norepinephrine, or dopamine neurotransmission. Important: These medications take 4-6 weeks to reach full therapeutic effect and should never be discontinued abruptly.
[Include Image: Figure 9. Serotonergic Synapse and Drug Targets]
Selective Serotonin Reuptake Inhibitors (SSRIs)
Tricyclic Antidepressants (TCAs)
Other Behavior-Modifying Agents
High-YieldSerotonin syndrome can occur when combining serotonergic drugs (SSRIs + TCAs + trazodone + tramadol + MAOIs). Signs: agitation, hyperthermia, tremors, seizures. Can be fatal!
MEMORY AID - SSRI Onset
SSRIs and TCAs take 4-6 weeks ('a month and a half') for full effect. Trazodone and benzodiazepines work within hours for acute situations.
MEMORY AID - FDA-Approved Behavior Drugs
Fluoxetine (Reconcile) and Clomipramine (Clomicalm) are FDA-approved for separation anxiety in dogs. Sileo (dexmedetomidine OTM) is approved for noise aversion.
| Drug |
Dosing |
Indications |
Notes |
| Fluoxetine (Reconcile) |
Dogs: 1-2 mg/kg q24h; Cats: 0.5-1 mg/kg q24h |
Separation anxiety (FDA approved), aggression, compulsive disorders, urine marking |
Takes 4-6 weeks for full effect; appetite changes common; can cause restlessness initially |
| Sertraline (Zoloft) |
Dogs: 1-5 mg/kg q24h; Cats: 0.5-1.5 mg/kg q24h |
Anxiety disorders, fear-based behaviors |
Similar to fluoxetine; human formulation |
| Paroxetine (Paxil) |
Dogs: 0.5-2 mg/kg q24h; Cats: 0.5-1.5 mg/kg q24h |
Social anxiety, fear |
Most sedating SSRI; shorter half-life; potential for more withdrawal effects |
| Drug |
Dosing |
Indications |
Notes |
| Clomipramine (Clomicalm) |
Dogs: 1-3 mg/kg q12h; Cats: 0.25-0.5 mg/kg q24h |
Separation anxiety (FDA approved), compulsive disorders, urine marking in cats |
Most serotonin-selective TCA; scored tablets available; takes 2-4 weeks for effect |
| Amitriptyline |
Dogs: 1-4 mg/kg q12-24h; Cats: 0.5-2 mg/kg q12-24h |
Anxiety, pruritus (antihistamine effect), chronic pain |
Less serotonin-specific than clomipramine; more anticholinergic effects (dry mouth, urinary retention); useful adjunct for neuropathic pain |
| Drug |
Mechanism/Class |
Indications |
Key Points |
| Trazodone |
SARI (Serotonin Antagonist/Reuptake Inhibitor) |
Situational anxiety, adjunct to SSRIs/TCAs, hospitalized patients, post-surgical confinement |
Fast onset (1-2 hours); mildly sedating; can be used PRN; risk of serotonin syndrome if combined with other serotonergic drugs |
| Gabapentin |
Calcium channel modulator (also anticonvulsant/analgesic) |
Situational anxiety (vet visits), noise phobias, neuropathic pain |
Causes sedation; can use PRN before stressful events; oral liquid contains xylitol (toxic to dogs) - use capsules |
| Selegiline (Anipryl) |
MAO-B inhibitor |
Cognitive dysfunction syndrome (CDS), pituitary-dependent hyperadrenocorticism |
Increases dopamine; takes 4-6 weeks for effect; do NOT combine with SSRIs, TCAs, or opioids (serotonin syndrome risk) |
| Buspirone |
5-HT1A partial agonist (azapirone) |
Urine marking in cats, intercat aggression |
Minimal sedation; takes 2-4 weeks for effect; not effective for panic or phobias |
| Alprazolam |
Benzodiazepine |
Panic, noise phobias (thunderstorms), acute anxiety |
Fast-acting; can be given PRN before anticipated stressor; controlled substance (Schedule IV); paradoxical excitement possible |
| Sileo (Dexmedetomidine OTM) |
Alpha-2 agonist (oromucosal gel) |
Noise aversion in dogs (FDA approved) |
Given between cheek and gum 30-60 min before noise; do not swallow; can repeat q2h; avoid in cardiovascular disease |