Veterinary Psychopharmacology (Part I)

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- neurotransmitters
- receptors
- signal transducing proteins
- cellular second messengers
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Terms in this set (56)
- neurotransmitters
- receptors
- signal transducing proteins
- cellular second messengers
Four major classes of molecules that are of particular interest: __________________________________________________________
- Drugs that act at any of these sites may modify behavior.
- acetylcholine
- dopamine
- norepinephrine
- serotonin
- glutamate
- GABA
Important neurotransmitters in behavior therapy are:
Receptors
_____________ recognize specific molecules, which results in signal transduction. Many of the clinically useful psychoactive drugs have their activity because of their interaction with the ____________
Signal transducing proteins
These produce changes in concentrations of specific ions or molecules across cell membranes.
Cellular second messengers
Integrate the information conveyed by a variety of neurotransmitters.
Receptor --> Signal transducing protein --> Cellular second messenger
Information pathway: Neurotransmitter -->
psychoactive medications
- Medications that produce changes in behavior and/or motivation
- Some have potential for human abuse
extra-label
Most use of psychoactive medications in veterinary medicine is
- client/veterinarian/patient
- Veterinarian
Animal Medicinal Drug Use Clarification Act (AMDUCA 1994):
- Valid _________ relationship
- Behavioral history MUST be taken
- __________ has established a diagnosis and the need for treatment
- Must be a specific rationale, and its use is accepted under current medical conditions.
Extra-label usage
- extra-label
- Inform client of the ____________ status of the drug.
- Inform the client of known side-effects.
- Signed informed consent statement.
- side-effect - toxicities - cure- Drugs labeled for human psychiatric problems may have different ___________ profiles and _________ in companion animals. - Psychoactive medications are usually most effective when used as an adjunct to behavior modification and environmental management. It is rare for a pill to provide a "______".- Antipsychotics - Antidepressants - Anxiolytics - Mood stabilizersPSYCHOACTIVE MEDICATIONS: Classification in Human Psychiatry:- HUMANSPSYCHOACTIVE MEDICATIONS: Classification in Human Psychiatry: - Based on distinguishing behavioral effects IN _________ - Even in humans is an oversimplification of behavioral actions - May or may not apply for behavioral effect in companion animals - e.g. Clomipramine is classified as an antidepressant, but functions and is used as an anxiolytic in dogs. It also has analgesic properties in humans.- function - chemical actionTypes of Classifications: By ___________: - Antidepressant - Anxiolytic - Analgesic - Anticompulsive By ____________: - Selective Serotonin Reuptake Inhibitor - NMDA Antagonist - Serotonin and Norepinephrine Reuptake Inhibitor- liver - urine or urine and feces - kidneys and liver - elimination - placentaGeneral Characteristics of Psychoactive drugs: 1. Metabolized in the _______ 2. Excreted in the _______ 3. Since long term use is common when treating behavioral problems, ensure that _______ and _______ are functioning adequately 4. Tests for liver and kidney function are not because it is common for the drugs to damage these organs, but because these organs must be functioning correctly for ___________ to occur at a normal rate 5. Most psychoactive drugs pass through the __________ and enter the milkAntipsychotics - Tranquilizers- Used to treat psychosis, including schizophrenia, in humans - Drugs differ in their potential side effectsAntipsychotics - Tranquilizers- Wide spectrum of physiological actions - High affinity for DA receptors - Blocking of D2 receptor subtype - traditional ones - 5-HT and DA receptor antagonists - newer, atypical onesAntipsychotics - Tranquilizers- reduced response to various stimuli - reduced exploratory behavior - reduced feeding behavior - conditioned avoidance responses are lostAntipsychotics - Tranquilizers- Restraint/Decrease behavioral arousal - Control of intractable animals - Decrease motor activity in cases of intense fear - Stereotypic behavior - Antiemetic / motion sickness - Most suitable in animals as short-term or intermittent medicationAntipsychotics and Anxiety- No specific anxiolytic effects - Overused and inappropriately used in the treatment of fears and phobiasPhenothiazine NeurolepticsAction: Decreases motor activity by blocking post-synaptic dopamine receptors in the CNS. May also inhibit the release of, and increase the turnover rate of dopaminePhenothiazine NeurolepticsSide Effects: - Sedation - Ataxia - Transient hypotension - Anticholinergic effects - Antiemetic - Antispasmodic - Antipyretic - Decrease basal metabolic rate - Antihistaminic effects - Antiserotonergic effects - Extrapyramidal motor effects including muscle tremors and akathisia (restlessness, pacing, agitation)Phenothiazine Neuroleptics- Produces general behavioral quieting, but does not have a specific anxiolytic effect. Useful for temporarily decreasing motor activity. - Not indicated for long-term treatment of thunderphobia, separation anxiety or other fear-related disorders - Anecdotal evidence that chronic use may result in exacerbation of noise-related phobiasAcepromazine maleateMost widely used phenothiazine neuroleptic in veterinary medicineAcepromazine maleateContraindications: History of seizures Use caution: - Hepatic dysfunction - Renal impairment - Cardiac disease - Young or debilitated animals - Geriatric patients - Pregnant females - Giant breeds, greyhounds, boxersAcepromazine maleateSide Effects: • Ataxia • Sedation • Aggression • Hypotension • Bradycardia (vagal) • Reflex tachycardia • HypothermiaOther antipsychoticsButyrophenones - HaloperidolHaloperidolUsed in Psittacine birds - 0.2 mg/kg PO bid - Increase by 0.02 mg increments q2d to effect - Maximum dose 0.4 mg/kg bid - 0.1-0.2 mg/kg PO q12-24h (Welle)HaloperidolSide Effects: Birds: - Sedation - Incoordination - Vomiting - Agitation - Severe depression - Anorexia Discontinue if: - Anorexia - Ataxia - VomitingAntidepressants- Used extensively in the treatment of behavior problems in small animals - Heterogeneous range of behavioral effects - Wide range of effects on central neurotransmitters - Wide range of side-effectsTricyclic Antidepressants (TCAs)Action: Block the reuptake of serotonin and norepinephrine, resulting in increased serotonin and norepinephrine in the synaptic cleft and subsequent down-regulation of the post-synaptic receptorsNorepinephrine- ↓General arousal - ↑Attention - ↓Mood reactivity - Stress response modulationSerotonin- Regulate mood states: ↓ Fear responses - Feeding behavior - ↓ Stress response - ↓ Impulsive behaviorEffects of a-Adrenergic antagonists- Sedation - Orthostatic hypotension -- Dizziness -- Syncope - Vasoconstriction - Smooth muscle contractionEffects of anticholinergics- Urinary retention - Dry mouth -- Dental pathology -- Stomatitis - Mydriasis - ↓ Tear production - Impaired visual accommodation -- Blurred vision - BronchodilationEffects of antihistaminic- Anti-pruritic effect - Sedation - Weight gainTricyclic Antidepressants (TCAs)Uses in DOGS: - Anxiolytic effect - Aggression - Compulsive Disorder - Urine markingTricyclic Antidepressants (TCAs)Uses in CATS: - Anxiolytic effect - Aggression - Compulsive Disorder - Urine spraying - Hypervocalizationextra-label- Use of any drug for the treatment of aggression is, and will probably always be, ______________. - High risk for pharmaceutical industry to have a general label. - Lack of discrete diagnosis - Lack of ability to supervise and monitor that appropriate supervision and behavior modification occursTricyclic Antidepressants (TCAs)Side effects: - Sedating - Emesis and other GI upset - Lowers seizure threshold - Hypotensive - May cause cardiac arrhythmias in humans.Tricyclic Antidepressants (TCAs)- Bitter taste - May require 3-4 weeks or longer to take full effect - Pre-medication cardiac assessment is recommended in humans.Tricyclic Antidepressants (TCAs)**10 day supply for pet may be fatal to adult human; no antidote**!!!Tricyclic Antidepressants (TCAs)Contraindications: - Seizure disorders - Decreased GI motility - Increased intraocular pressure - Urinary retention - Do not give with MAOIs!!! ******* - Give cautiously with SSRIs - Cardiac arrhythmiasClomipraminebest for Serotonin Re-uptake InhibitionDesipraminebest for Norepinephrine re-uptake inhibitionAmitriptylinebest a-1 antagonistAmitriptylinebest antihistaminicAmitriptylinebest anticholinergicAmitriptylineTricyclic Antidepressant: ________________ HCl (Elavil® & generic) - Cheap but not very serotonin specific - More side-effects than the more serotonin-specific clomipramine - DOGS: 0.25-1.5 mg/kg q12-24h PO - CATS: 2.5-10 mg/cat q24h POClarification of Clomipramine dosewe use a higher dose range for this drug than is recommended by the FDA because multiple healthy adult patients need a higher dose to show adequate improvement - The lowest dose is most appropriately used as a starting dose and for geriatric dogs, or other dogs with compromised metabolism, e.g. liver diseaseClomipramineTricyclic Antidepressant: ____________________ HCl (Anafranil®, Clomicalmä) - DOGS: 1.0-3.0 mg/kg q12h PO - CATS: 0.25-1.0 mg/kg q24h POClomicalm (clomipramine)- The most serotonin-selective tricyclic antidepressant commercially available - per se inhibits the reuptake of Serotonin - Major metabolite is desmethylclomipramine, which inhibits reuptake of Norepinephrine. - Serotonin and Norepinephrine concentrations in CNS increase - Approval is for use WITH behavior modificationClomicalm (clomipramine)Administration: - Single or divided dose: Half-life about 24 hours allows for once a day dosing - 2-4 mg/kg (total daily dose)LABEL DOSE, NOT THE DOSE WE ACTUALLY USE - With or without food (administration with food may reduce incidence of emesis)Clomicalm (clomipramine)- Well tolerated at the recommended label dose - In a 6-month safety study: - Beagle dogs were dosed at 5x-10x the recommended daily dose (20 mg/kg/day) This much of an overdose would be fatal to a human - Emesis and decreased activity was seen, but there were no treatment-related changes observed (body weight, EKG, blood chemistries)Clomicalm (clomipramine)- Most common side effect is emesis. Decrease this by dividing daily dose for twice a day dosing. Also give with food. - Not severely cardiotoxic in dogs as is in humans - Testicular hypoplasia (do not use in breeding males)ImipramineTricyclic Antidepressant: - _______________ HCl (Tofranil® & generic) - Used to treat nocturnal enuresis in children - DOGS: 2.2-4.4 mg/kg q12-24h PO - Anti-enuretic effect - Canine submissive urination - Canine excitement-induced urination - Urinary incontinence (dogs and cats)