ํด๋ก๋ฏธํ๋ผ๋ฏผ
ํด๋ก๋ฏธํ๋ผ๋ฏผ์ ์ฃผ๋ก ์์ ํ๋ ์ํ์์ ์ฌ์ฉ๋๋ **์ผํ๊ณ ํญ์ฐ์ธ์ (TCA)**์ ๋๋ค. * **๊ฐ**: **๊ฐ๋ฐ ์ฅ์ **(์์์ ์ธ ์๋ ํ๋) ๋ฐ ๋ถ๋ฆฌ ๋ถ์ ์น๋ฃ์ ๋ก FDA ์น์ธ์ ๋ฐ์์ต๋๋ค. ์ฐ์์ฑ ๊ณต๊ฒฉ์ฑ ๋ฐ ์์ ๊ณตํฌ์ฆ์๋ ์คํ๋ผ๋ฒจ๋ก ์ฌ์ฉ๋ฉ๋๋ค. * **๊ณ ์์ด**: ์๋ณ ์คํ๋ ์ด, ์ฌ์ธ์ฑ ํ๋ชจ, ๊ฐ๋ฐ์ ๊ทธ๋ฃจ๋ฐ๊ณผ ๊ฐ์ ํ๋ ๋ฌธ์ ์ ์คํ๋ผ๋ฒจ๋ก ์ฌ์ฉ๋ฉ๋๋ค. * **์กฐ๋ฅ**: ๊นํธ ๋ฝ๊ธฐ ํ๋์ ์น๋ฃํ๋ ๋ฐ ์ฌ์ฉ๋ฉ๋๋ค. **์์ ํ**: ๋๋ถ๋ถ์ TCA ๋ฐ SSRI์ ๋ง์ฐฌ๊ฐ์ง๋ก ์ต๋์ ์์์ ํจ๊ณผ๋ฅผ ๊ด์ฐฐํ๊ธฐ ์ํด์๋ ์ฅ๊ธฐ๊ฐ(๋ณดํต 4~8์ฃผ)์ ์น๋ฃ๊ฐ ํ์ํฉ๋๋ค. ๋จ๋ ์น๋ฃ๋ณด๋ค๋ ํฌ๊ด์ ์ธ **ํ๋ ๊ต์ ๊ณํ**์ ๋ณด์กฐ ์๋จ์ผ๋ก ์ฌ์ฉํ๋ ๊ฒ์ด ์ด์์ ์ ๋๋ค.
์์ฉ ๊ธฐ์ : 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)** โ 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).
๋๋ฌผ ์ข ๋ณ ์ฉ๋
- Urine marking/spraying; inter-cat aggression; redirected aggression; compulsive grooming/wool sucking ยท 0.5 mg/kg ยท PO ยท once daily
- Behavioral disorders ยท 0.3-0.5 mg/kg ยท PO ยท q24h
- Behavioral disorders ยท 0.5-1 mg/kg ยท PO ยท once daily
- Urine marking ยท 0.3-0.5 mg/kg PO q24h (2.5-5 mg per cat q24h) ยท PO ยท q24h
- Anxiety-related disorders, compulsive behaviours, urine spraying ยท 0.25-1 mg/kg ยท PO ยท q24h ยท Monitor for urinary retention.
- Adjunctive treatment of feather picking ยท 0.5-9 mg/kg ยท PO ยท q12-24h
- Label directions (Clomicalm) ยท 2-4 mg/kg ยท PO ยท once daily or divided twice daily
- Behavioral disorders ยท 3 mg/kg ยท PO ยท q12h ยท 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 ยท 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 ยท PO ยท q12h ยท Maintain after 8 weeks ยท May take 4-6 weeks to see apparent improvement.
ํฌ์ฌ ๊ฒฝ๋ก
๊ธ๊ธฐ
- 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)
์ด์๋ฐ์
- 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)
์ฝ๋ฌผ ์ํธ์์ฉ
- Anticholinergic agents ยท Additive anticholinergic effects; use cautiously
- Butyrophenone antipsychotics (e.g., haloperidol) ยท Risk of extrapyramidal side effects (reported in a macaw)
- Cimetidine ยท May inhibit tricyclic antidepressant metabolism and increase the risk of toxicity ยท moderate
- Cisapride ยท Increased risk for prolonged QT interval
- Clonidine ยท May cause increased blood pressure
- CNS Depressants ยท Additive CNS depression; use cautiously
- Meperidine, Pentazocine, Dextromethorphan ยท Increased risk for serotonin syndrome
- Quinidine ยท Increased risk for QTc interval prolongation and tricyclic adverse effects
- Rifampin ยท May decrease tricyclic blood levels
- SSRIs (e.g., fluoxetine, paroxetine, sertraline) ยท Increased risk for serotonin syndrome
- Sympathomimetic agents ยท May increase the risk of cardiac effects (arrhythmias, hypertension, hyperpyrexia)
- Monoamine Oxidase Inhibitors (MAOIs, e.g., amitraz, selegiline) ยท Concomitant use is generally contraindicated due to high risk of fatal serotonin syndrome
- Selegiline (MAOIs) ยท Risk of fatal serotonin syndrome; do not use concurrently or within 2 weeks of each other ยท major
๋ชจ๋ํฐ๋ง
- 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
๊ณผ์ฉ๋
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 ์ฝ๋ฌผ ๋ ํผ๋ฐ์ค๋ ๋ฉดํ ์์ ์ ๋ฌธ๊ฐ๋ฅผ ์ํ ์์ ์์ฌ๊ฒฐ์ ๋ณด์กฐ ๋๊ตฌ์ด๋ฉฐ, ์ ๋ฌธ์ ํ๋จ์ด๋ ์ ์กฐ์ฌ์ ์ต์ ๋ผ๋ฒจ์ ๋์ ํ์ง ์์ต๋๋ค.