氯米帕明
氯米帕明是一種**三環類抗憂鬱藥 (TCA)**，主要用於獸醫行為醫學。 * **犬**：獲 FDA 核准用於治療**強迫症**（儀式性刻板行為）和分離焦慮。也常標示外用於支配性攻擊和噪音恐懼症。 * **貓**：標示外用於行為問題，如噴尿、心因性脫毛和強迫性理毛。 * **鳥類**：用於治療啄羽行為。 **臨床提示**：與大多數 TCA 和 SSRI 一樣，氯米帕明需要較長的治療時間（通常為 4-8 週）才能觀察到最大的臨床療效。理想情況下，它應作為全面**行為矯正計畫**的輔助手段，而非單一療法。
作用機制: The exact mechanism of action of tricyclic antidepressants involves the blockade of monoamine reuptake in the central nervous system. * **Primary Action**: Clomipramine predominantly inhibits the presynaptic reuptake of **serotonin (5-HT)** via the **serotonin transporter (SERT)** → increasing synaptic serotonin concentrations. * **Active Metabolite**: Its primary active metabolite, **desmethylclomipramine**, primarily inhibits the reuptake of **norepinephrine (NE)** via the **norepinephrine transporter (NET)**. * **Receptor Downregulation**: The chronic elevation of these neurotransmitters leads to the gradual down-regulation of post-synaptic receptors, which correlates with the delayed onset of clinical behavioral effects (taking several weeks). * **Off-target Effects**: TCAs also exhibit antagonism at **muscarinic (cholinergic)**, **histamine (H1)**, and **alpha-1 adrenergic** receptors, which are responsible for many of their adverse effects (e.g., dry mouth, sedation, hypotension).
各物種劑量
- Urine marking/spraying; inter-cat aggression; redirected aggression; compulsive grooming/wool sucking · 0.5 mg/kg · PO · once daily
- Behavioral disorders · 0.3-0.5 mg/kg · PO · q24h
- Behavioral disorders · 0.5-1 mg/kg · PO · once daily
- Urine marking · 0.3-0.5 mg/kg PO q24h (2.5-5 mg per cat q24h) · PO · q24h
- Anxiety-related disorders, compulsive behaviours, urine spraying · 0.25-1 mg/kg · PO · q24h · Monitor for urinary retention.
- Adjunctive treatment of feather picking · 0.5-9 mg/kg · PO · q12-24h
- Label directions (Clomicalm) · 2-4 mg/kg · PO · once daily or divided twice daily
- Behavioral disorders · 3 mg/kg · PO · q12h · start at a low dose (e.g., 1 mg/kg for 2 weeks, then 2 mg/kg for 2 weeks, then 3 mg/kg)
- Male dimorphic behaviors, fearful/fear aggression, noise phobias, obsessive/compulsive behaviors · 1 mg/kg PO every 12 hours for 2 weeks; then 2 mg/kg PO q12h for 2 weeks, then 3 mg/kg PO q12h for 4 weeks and maintain · PO · q12h · Maintain after 8 weeks · May take 4-6 weeks to see apparent improvement.
給藥途徑
禁忌症
- Prior hypersensitivity to clomipramine or other tricyclic antidepressants
- Concomitant use with monoamine oxidase inhibitors (MAOIs) within 14 days
- Concurrent ingestion of aged cheeses (high tyramine content)
- Known sensitivity to tricyclic antidepressants (TCAs) or selective serotonin reuptake inhibitors (SSRIs)
- Concurrent use of Monoamine Oxidase Inhibitors (MAOIs) or within 2 weeks of their use
- Male breeding animals (due to risk of testicular hypoplasia)
不良反應
- Emesis
- Diarrhea
- Sedation, lethargy, and depression
- Anticholinergic effects (dry mouth, tachycardia, urinary retention)
- Elevation of liver enzymes
- Pancreatitis (rarely reported in dogs)
- Birds: Ataxia, drowsiness, regurgitation
- Sporadic vomiting
- Changes in appetite
- Lethargy
- Urinary retention (especially in cats)
- Testicular hypoplasia (in male breeding animals)
藥物相互作用
- Anticholinergic agents · Additive anticholinergic effects; use cautiously
- Butyrophenone antipsychotics (e.g., haloperidol) · Risk of extrapyramidal side effects (reported in a macaw)
- Cimetidine · May inhibit tricyclic antidepressant metabolism and increase the risk of toxicity · moderate
- Cisapride · Increased risk for prolonged QT interval
- Clonidine · May cause increased blood pressure
- CNS Depressants · Additive CNS depression; use cautiously
- Meperidine, Pentazocine, Dextromethorphan · Increased risk for serotonin syndrome
- Quinidine · Increased risk for QTc interval prolongation and tricyclic adverse effects
- Rifampin · May decrease tricyclic blood levels
- SSRIs (e.g., fluoxetine, paroxetine, sertraline) · Increased risk for serotonin syndrome
- Sympathomimetic agents · May increase the risk of cardiac effects (arrhythmias, hypertension, hyperpyrexia)
- Monoamine Oxidase Inhibitors (MAOIs, e.g., amitraz, selegiline) · Concomitant use is generally contraindicated due to high risk of fatal serotonin syndrome
- Selegiline (MAOIs) · Risk of fatal serotonin syndrome; do not use concurrently or within 2 weeks of each other · major
監測
- Clinical efficacy (behavioral improvement)
- Baseline and annual liver function tests
- EKG (especially in patients with cardiac risks or hyperthyroidism)
- Clinical efficacy (reduction in anxiety/compulsive behaviors)
- Signs of serotonin syndrome (agitation, tremors, hyperthermia, tachycardia) if used with other serotonergic drugs
- Urinary output and frequency, particularly in cats
- Appetite and gastrointestinal tolerance
過量
Clomipramine has a **narrow margin of safety**. Significant clinical signs can be seen at or slightly above the therapeutic range (2-3 mg/kg). * **Lethal Dose**: In dogs, lethal doses are approximately 50-100 mg/kg/day PO (12.5-25X recommended dose). * **Clinical Signs (Dogs)**: Lethargy, tachycardia, ataxia, depression, vocalization, and vomiting. * **Clinical Signs (Cats)**: Lethargy, mydriasis, tachypnea, ataxia, depression, and tachycardia. * **Severe Toxicity**: Overdosage with TCAs can be life-threatening, leading to severe arrhythmias, seizures, and cardiorespiratory collapse. > **Action**: Because toxicities and therapies are complicated and controversial, contact an animal poison control center immediately in any potential overdose situation.
VetSheet 藥物參考供持牌獸醫專業人員作臨床決策輔助之用,不能取代專業判斷或廠方最新藥品說明書。