オキシトシン
オキシトシンは、視床下部の室傍核および視索上核で合成され、下垂体後葉に貯蔵されるノナペプチドホルモンです。獣医学では主に子宮収縮薬として、分娩時の子宮収縮の誘発または増強、産後の胎盤停滞および子宮内膜炎の治療、子宮復古の促進、無乳症における乳汁分泌の促進に使用されます。 **臨床上のポイント：** * **ミニドーズの推奨：** 現代の獣医産科学では、従来の高用量ではなく「ミニドーズ」（例：犬で総量0.25〜4単位）が強く推奨されています。高用量は強直性で無効な子宮収縮を引き起こし、胎盤圧迫による胎児の酸素供給低下や子宮破裂のリスクを高めます。 * **カルシウム依存性：** オキシトシンの有効性は細胞外カルシウムに大きく依存します。投与前に低カルシウム血症や低血糖を補正する必要があります。カルシウムは収縮の「強さ」を増し、オキシトシンは「頻度」を増します。 * **子宮頸管の状態：** 子宮頸管が閉鎖している場合、または未矯正の閉塞性難産が存在する場合は、絶対に投与してはいけません。
作用機序: Oxytocin exerts its effects by binding to specific **G-protein coupled oxytocin receptors (OXTR)** on the cell membrane of uterine myofibrils and myoepithelial cells of the mammary gland. * **Uterine Contraction:** Binding to OXTR activates the **Gq/11 pathway** → stimulates **Phospholipase C (PLC)** → increases inositol triphosphate (**IP3**) and diacylglycerol (**DAG**) → triggers the release of intracellular calcium from the sarcoplasmic reticulum. Calcium binds to calmodulin, activating **Myosin Light Chain Kinase (MLCK)**, leading to smooth muscle contraction. The threshold for oxytocin-induced contraction is significantly lowered late in pregnancy due to upregulation of oxytocin receptors by high estrogen levels. * **Milk Let-down:** Oxytocin stimulates the contraction of myoepithelial cells surrounding the mammary alveoli, forcing milk into the larger ducts and cisterns. It does *not* have galactopoietic (milk-producing) properties.
動物種別の用量
- For retained placenta in patients with uterine atony · 10-20 Units oxytocin. · IM/IV · Once · Limited value after 48 hours postpartum. Note for CAMELIDS (NW): 5-10 Units IM at 10-minute intervals for retained placenta (Adams 2008).
- For mild to moderate cases of acute post-partum metritis · 5-10 Units IM 3-4 times a day for 2-3 days · IM · TID to QID · 2-3 days
- For retained placenta in patients with uterine atony · 10-20 Units oxytocin. · IM/IV · Once · Limited value after 48 hours postpartum.
- For mild to moderate cases of acute post-partum metritis · 5-10 Units IM 3-4 times a day for 2-3 days · IM · TID to QID · 2-3 days
- To control post-extraction cervical and uterine bleeding after internal manipulations · 10-20 Units IV, may repeat SC in 2 hours · IV/SC · Once, may repeat in 2h
- To promote uterine involution after uterine prolapse manual reduction · 0.5-5 Units IM OR 5-10 Units (total dose) IM · IM · Once · Extrapolated from dog doses.
- To treat primary uterine inertia · 0.25 Units (total dose) SC or IM to a maximum dose of 4 Units per queen. Generally not given more frequently than hourly. · SC/IM · q1h · Given 15 minutes after calcium gluconate.
- For adjunctive treatment of metritis · 0.5-5 Units IM · IM · Once · May be used if birth occurred less than 24 hours prior.
投与経路
禁忌
- Dystocia due to abnormal fetal presentation (unless corrected)
- Closed or unrelaxed cervix
- Known hypersensitivity to oxytocin
- Significant cephalopelvic disproportion
- Obstetrical emergencies where surgical intervention (C-section) is warranted
- Pregnancy (for nasally administered oxytocin)
有害事象
- Uterine cramping and discomfort
- Tetanic uterine contractions (at high doses)
- Uterine rupture
- Fetal compromise or death (due to placental compression)
- Water intoxication (with prolonged high-dose infusions)
- Hypersensitivity reactions (more common with non-synthetic products)
薬物相互作用
- Thiopental · May delay thiopental anesthesia (reported in humans; clinical significance in animals is not firmly established).
- Vasoconstrictors (Sympathomimetics) · Concurrent use post-partum may result in severe hypertension. Monitor closely.
モニタリング
- Uterine contractions (frequency, duration, and strength via tokodynamometry if available)
- Status of the cervix (must be dilated)
- Fetal monitoring (heart rate/distress)
- Maternal calcium and glucose levels
過量投与
Effects of overdosage on the uterus depend on the stage of the uterus and the position of the fetus(es). * **Uterine Effects:** Hypertonic or tetanic contractions can occur, leading to tumultuous labor, uterine rupture, fetal injury, or fetal death due to compromised placental blood flow. * **Water Intoxication:** Can occur if large doses are infused for a long period, especially with large volumes of electrolyte-free IV fluids. * *Early signs:* Listlessness, depression. * *Severe signs:* Coma, seizures, death. * *Treatment:* Stop oxytocin therapy, restrict water access. Severe cases may require osmotic diuretics (mannitol, urea, dextrose) with or without furosemide.
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