Tripelennamine
Tripelennamine is a **first-generation, ethylenediamine-derivative antihistamine** used primarily in large animal veterinary medicine. It is utilized to mitigate histamine-mediated allergic reactions and anaphylaxis. Interestingly, it is also employed off-label as a **CNS stimulant** in "Downer cow" syndrome when administered via slow IV. Because it is a first-generation antihistamine, it readily crosses the blood-brain barrier, which can cause significant central nervous system (CNS) effects ranging from sedation to paradoxical excitation (especially in horses). *Clinical Pearl*: While highly effective for acute allergic reactions, its use has declined in small animal medicine due to the availability of newer, less sedating antihistamines and the discontinuation of many oral tripelennamine formulations.
Mechanism: Tripelennamine acts as a **competitive antagonist at the H1-receptor**. * **Histamine Release** → Histamine binds to H1 receptors on smooth muscle, endothelium, and the CNS. * **Tripelennamine** → Competes for these receptor sites → Prevents histamine-induced bronchoconstriction, vasodilation, and increased capillary permeability. *Note*: Antihistamines do *not* inactivate histamine or prevent its degranulation/release from mast cells; they only block its downstream effects. Compared to other antihistamines, tripelennamine has **moderate sedative activity** and **minimal anticholinergic activity**.
Dosing by species
- General antihistamine · 1 mg/kg PO q12h · PO · q12h · Oral dosage forms may no longer be obtainable
- General antihistamine · 1 mg/kg IM · IM
- General antihistamine · 1.1 mg/kg (2.5 mL per 100 lbs body weight) IV (for more immediate effect) or IM q6-12h as needed · IV/IM · q6-12h · as needed
- Downer Cow Syndrome (Adjunctive treatment) · 0.5 mg/kg slow IV in conjunction with parenteral mineral treatment · IV · Used as a CNS stimulant
- General antihistamine · 1 mg/kg IV or IM · IV/IM
- General antihistamine · 1.1 mg/kg (2.5 mL per 100 lbs body weight) IM q6-12h as needed · IM · q6-12h · as needed · Do NOT give IV. ARCI UCGFS Class 3 Drug.
- General antihistamine · 1 mg/kg IM · IM · Do NOT give IV. ARCI UCGFS Class 3 Drug.
- General antihistamine · 1 mg/kg IV or IM · IV/IM
- General antihistamine · 1 mg/kg PO q12h · PO · q12h · Oral dosage forms may no longer be obtainable
Routes of administration
Contraindications
- Intravenous (IV) administration in horses is strictly contraindicated due to severe CNS stimulation
Adverse effects
- CNS stimulation (hyperexcitability, nervousness, muscle tremors) - especially in horses given IV
- CNS depression / Sedation
- Ataxia / Incoordination
- Gastrointestinal disturbances
Drug interactions
- CNS Depressants (e.g., barbiturates, opioids) · Increased sedation and CNS depression
- Heparin · May partially counteract the anticoagulation effects
- Warfarin · May partially counteract the anticoagulation effects
Monitoring
- Clinical efficacy (resolution of allergic signs)
- Adverse effects (CNS stimulation, sedation, ataxia)
Overdose
Overdosage of tripelennamine can cause **CNS excitation, seizures, and ataxia**. * **Treatment**: Treat symptomatically and supportively if clinical signs are severe. * **Seizure Management**: Phenytoin (IV) is recommended in the treatment of seizures caused by antihistamine overdose in humans. **Barbiturates and diazepam are generally avoided** as they may exacerbate post-excitatory CNS depression.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.