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Review Article Pharmacological Overview of Galactogogues Hindawi Publishing Corporation Veterinary Medicine International Volume 2014, Article ID 602894, 20 pages http://dx.doi.org/10.1155/2014/602894 Review Article Pharmacological Overview of Galactogogues Felipe Penagos Tabares, Juliana V. Bedoya Jaramillo, and Zulma Tatiana Ruiz-Cortés Biogenesis Research Group, Agrarian Sciences Faculty, University of Antioquia, Medellin, Colombia Correspondence should be addressed to Felipe Penagos Tabares; [email protected] and Zulma Tatiana Ruiz-Cortes;´ [email protected] Received 6 June 2014; Accepted 31 July 2014; Published 31 August 2014 Academic Editor: William Ravis Copyright © 2014 Felipe Penagos Tabares et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Galactogogues are substances used to induce, maintain, and increase milk production, both in human clinical conditions (like noninfectious agalactias and hypogalactias) and in massification of production in the animal dairy industry. This paper aims to report the state of the art on the possible mechanisms of action, effectiveness, and side effects of galactogogues, including potential uses in veterinary and human medicine. The knowledge gaps in veterinary clinical practice use of galactogogues, especially in the standardization of the lactogenic dose in some pure drugs and herbal preparations, are reviewed. 1. Introduction facial seborrhea, and hyperhidrosis, and even sudden death. In infants that ingested milk from treated mothers symptoms Milkproductionisessentialforoptimalfeedingofinfantsand include intestinal discomfort, lethargy, and sedation [2]. The has a direct impact on growth, development, and health in main galactogogue used in cattle is rBST which has reported neonatal period [1]. Breastfeeding is influenced by nutritional adverse health effects that directly affect animal welfare [4, 5]. and nonnutritional factors (associated with endocrinology, Plants with galactogogues components include fenugreek health, climate, and management) that affect milk synthesis (Trigonella graecum foecum), fennel (Foeniculum vulgare), and secretion. These factors modulate physiological actions goat’s rue (Galega officinalis), asparagus (Asparagus racemo- that regulate situations such as noninfectious agalactias sus), anise (Pimpinella anisum), and milk thistle (Silybum and hypogalactias, the latest being the main problem of marianum)[6, 7](Table 2). Nowadays, herbal preparations breastfeeding women [2]. Galactogogues are synthetic or are known to increase significantly milk production in plants molecules used to induce, maintain, and increase milk women, goats, cows, and other species. This research area production [3], which mediate complex processes involv- is very important for human breastfeeding medicine and in ing interaction between physical and physiological factors. veterinary dairy industry [7–11]. Among the most important factors are hormones such as There are numerous references about herbal medicine prolactin (PRL). However, somatotropine, cortisol, insulin, and breastfeeding. However, they are mainly based on leptin, estrogen, progesterone and medroxyprogesterone [2], empirical traditions and on human studies. This informa- oxytocin, recombinant bovine somatotropin (rBST), and tion could be deficient in systematization, is unstructured, thyrotropin releasing hormone (TRH) also play important heterogeneous, and thus has nonverifiable quality. From role as galactogogues (Table 1). previously mentioned plants classified as galactogogues, there Most common galactogogues for human use are meto- are currently available studies for efficacy and safety, but their clopramide, domperidone, chlorpromazine, and sulpiride mechanisms of action have not been elucidated yet [3, 12]. (Table 1); their remarkable side effects in mothers are xeros- Publications generally focus on the effects with no emphasis tomia (dry mouth syndrome or hyposalivation), gastroin- on the mechanism by which milk production stimulation testinal disorders, cardiac arrhythmia, lethargy, sedation, is achieved. The increased use of herbal medicine is also extrapyramidal symptoms such as hypertension, tremor, tic, encouraged by a trend towards organic production, mainly 2 Veterinary Medicine International ]. ]. ]. ]. 43 67 ]. ]. ]. ]. 93 ]. ]. 66 ]. 51 ]. 53 ]. 62 119 36 30 63 109 61 ]. 65 , 64 ]. 29 Equine: 6.8 minutes [ Swine: 127 seconds [ Rat: 1.46 minutes [ Bovine: 7–9 minutes and 25 minutes [ Rat: 4.16 minutes [ Goat: 22 minutes [ Humans: 272 seconds [ Dogs: 1.6–3.4 hours [ Humans: 7.15 hours [ Bovine: 54.8 minutes [ Dogs: 90 minutes [ Humans: 156.7 minutes [ Humans: 16–30 hours [ Humans: 7.5 hours [ ], ]. 94 30 ]. In high ], clinical 26 95 ]. 97 , 96 ], and phototoxic ]. 30 2 ], decreased hemoglobin 5 ]. Human: 40–60 hrs [ ]. Feline: in high doses tremors, 121 40 , 2 ], and mastitis [ ]. ]. 98 ]. 108 30 46 ]. , , 2 45 106 ]. ]. Result of using the drug in inappropriate 50 , 2 30 Human: hyperthyroidism and brief episodes of sweating [ Humans: headache, fatigue, extrapyramidal symptoms, acute dystonic reactions, and endocrine[ disruption When used appropriately atoxytocin reasonable rarely causes dosages, significant adverse reactions [ Bovine: low pregnancy rates, increased openincrease days incidences [ of retained placenta [ Human: amenorrhea [ individuals (adequate physical exam and monitoringpatient of are essential) or at too high doses [ and hematocrit [ doses they may cause discomfort, uterinehazardous cramping, of uterine rupture, and fetuses-placental compromise. [ and subclinical, reduced food intake, allergiclaminitis reactions, digestive disorders [ Humans: several gastrointestinal disorders, insomnia severe depression, and seizures and inconsume infants milk that from treated mothers causingdiscomfort intestinal [ Humans: xerostomia, gastrointestinal disorders, cardiac arrhythmia, and sudden death [ reactions [ Equine: ataxic reactions, excitation, panic reactionsviolent and consequences, sedation [ Humans: extrapyramidal symptoms in mothers and lethargy in infants [ shivering, rigidity, and loss of thelethargy, righting, diarrhea, reflexes, and loss of anal sphincter tone [ ] ]. 54 ]. ]. ]. ]. 105 49 42 31 37 ]. Equine: ]. ]. ]. 72 38 41 73 ]. ]. ]. Swine: 0.025 and 122 32 71 ]. 5 ]. Equine: 1.1 mg/kg PO BID ]. Sheep and goat: 1–5 ]. ]. Bovine: 20 IU SC EM 32 70 36 38 IU EM [ Equine: 1.1 mg/kg PO BID [ or 0.5 BID IM [ Canine and feline: 0.5–2.0 IU/kg dose SC EM [ [ Bovine: 500 mg SC every 14 days [ 0.05 IU IV EM [ 20 UI IM EM [ Humans: 150 mg IM every 3 months [ Human: 10 mg PO TID [ Canine/feline: 0.1-0.2 mg/kg, SC TID [ Human: 10 mg PO TID [ Canine/feline: 2.2 mg/kg SC, every 12 hours for 4–6 days [ Human: 25 mg PO TID [ Human: 50 mg PO TID [ [ Rat: 15 mg/kg [ ]. ]. Humans: 20 mg PO TID [ 92 Table 1: Pharmacological overview of some galactogogues synthetic drugs. 102 ]. ]. ]. ]. ]. 2 2 2 2 28 D2R antagonist, increase PRL secretion [ D2R antagonist, increase PRL secretion [ D2R antagonist, increase PRL secretion [ D2R antagonist, increase PRL secretion [ Induce milk ejection and this promotes milk synthesis by FIL decrease [ Increase basal metabolic rate and nutrients bioavailability, in mammary gland Increase MEC proliferation, survival and milk synthesis [ Increase PRL blood levels [ Galactogogue drugMetoclopramide Proposed mechanismDomperidone Doses and dosage form Adverse effectsChlorpromazine Sulpiride Oxytocin Half-life Recombinant bovine somatotropin (rBST) Thyrotropin releasing hormone (TRH) Medroxyprogesterone Not reported Abbreviations: BID, twice daily; TID, three times daily; PO, oral administration; SC, subcutaneous; IM, intramuscular; EM, every milking. Veterinary Medicine International 3 ]. 30 6hours[ Not reported. half-life average Human: silymarin elimination ]. Not reported. 161 eritoneal. ]. 30 plant family (including ragweed, ]. 171 Not reported.Human: gastrointestinal disturbances have been reported: nausea and diarrhea.allergies Patients to other who members have of the Asteraceae/Compositae marigolds, daisies, etc.) may exhibit allergicMilk reactions Thistle to derivatives [ Not reported. Sheep: doses over 5 g/kg were toxic [ Rat: methanol roots extract in dosefor of 60 100 days mg/Kg/day showed teratological disordersresorption as increased of fetuses, gross malformationsin legs, as and swelling intrauterine growth retardationplacental with size a small [ ] Not reported. Not reported. 127 ]. ]. ]. Rat: Plant 167 158 166 ] 156 ]. 176 Rat: ethanolic and aqueous extract 1g/kgIP[ Sheep: Plant (dry), 2 g/kg body weight in diet daily [ Bovine: plant (dry), 10 g PO[ SID Human: concentrated root extract, 60 mg/kg PO SID [ (dry), 2% of the diet [ Table 2: Pharmacological overview of some botanical galactogogues. Estrogenic action? Estrogenic action? Estrogenic action? Estrogenic action?Estrogenic Goat: action? dry plant 10 g SID [ Not reported Not reported. Not reported. Estrogenic action? ) ) ) ) ) ) Trigonella graecum foenum Foeniculum vulgare Pimpinella anisum Galega officinalis Asparagus racemosus Silybum marianum Herbal galactogogueFenugreek ( Fennel ( Proposed mechanismAnise ( Common doses and dosage formGoat’s rue ( Adverse EffectsAsparagus ( Milk thistle ( Half-life Abbreviations: SID, once daily; BID, twice daily; TID, three times daily; PO, oral administration; SC, subcutaneous; IM, intramuscular; IP, intrap 4 Veterinary Medicine International
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