Chapter 14 - Glucocorticoid Therapy
第十四章 - 糖皮質激素治療

Glucocorticoid activities can roughly be divided into genomic and nongenomic effects. The classical genomic effect is mediated by a cytoplasmic glucocorticoid receptor (GR) that belongs to the nuclear receptor superfamily, which includes all of the steroid receptors. GRs are widely distributed throughout the body: every cell appears to have GRs (Boothe and Mealey, 2012). The GRs consist of three domains with different functions: a poorly conserved N-terminal domain, a highly conserved DNA-binding domain, and a well-conserved C-terminal glucocorticoid-binding domain. Several splice variants of the GR exist, of which GRα is the most widely expressed and is the variant exerting most of the glucocorticoid actions.
糖皮質激素的活性大致可分為基因組效應和非基因組效應。經典的基因組效應由細胞質中的糖皮質激素受體（GR）介導，該受體屬於核受體超家族，其中包括所有類固醇受體。GRs 在全身廣泛分佈：每個細胞似乎都具有 GRs（Boothe 和 Mealey，2012 年）。GRs 由三個功能不同的結構域組成：一個保守性較低的 N 端結構域、一個高度保守的 DNA 結合結構域，以及一個保守性良好的 C 端糖皮質激素結合結構域。GR 存在多種剪接變體，其中 GRα 表達最為廣泛，也是發揮大部分糖皮質激素作用的變體。
The variant GRβ is unable to bind glucocorticoids, but it may act as an inhibitor of GRα. The β variant may play a role in glucocorticoid resistance and possibly in autoimmune and inflammatory disorders (Ferguson et al., 2009, Nixon et al., 2013). In the resting (ligand-free) state, GR is located in the cytoplasm, where it exists as a multiprotein complex containing several heat-shock proteins (Hsp90, Hsp70, Hsp56, Hsp40); there is also interaction with other molecules, such as immunophilins and several additional factors (Stahn et al., 2007, Vandevyver et al., 2013). The GR is inactive until bound to a glucocorticoid ligand. Glucocorticoids enter the cell by passive diffusion through the cell membrane, although there may also be an active transport mechanism. After binding of the glucocorticoid, the heat shock proteins dissociate from the GR, resulting in conformational changes that unmask nuclear localization sequences.
變異體 GRβ無法與糖皮質激素結合，但它可能作為 GRα的抑制劑。β變異體可能在糖皮質激素抗性以及可能在自體免疫和炎症性疾病中扮演角色（Ferguson 等人，2009 年；Nixon 等人，2013 年）。在靜止（無配體）狀態下，GR 位於細胞質中，以一個包含多種熱休克蛋白（Hsp90、Hsp70、Hsp56、Hsp40）的多蛋白複合體形式存在；同時也與其他分子如免疫親和素及多種附加因子相互作用（Stahn 等人，2007 年；Vandevyver 等人，2013 年）。GR 在未與糖皮質激素配體結合前處於非活性狀態。糖皮質激素通過細胞膜的被動擴散進入細胞，儘管也可能存在主動運輸機制。糖皮質激素結合後，熱休克蛋白從 GR 上解離，導致構象變化，從而暴露出核定位序列。
Thereafter, the GR/glucocorticoid complex is translocated into the nucleus, where it activates or represses target gene transcription (Nixon et al, 2013). Although the main actions of glucocorticoids are mediated through the GR, some effects are also mediated through another nuclear receptor, the mineralocorticoid receptor (MR). The MR has a high affinity for endogenous glucocorticoids, which are generally present in much higher concentrations than mineralocorticoids.
隨後，GR/糖皮質激素複合物被轉運至細胞核內，在此激活或抑制目標基因的轉錄（Nixon 等，2013）。雖然糖皮質激素的主要作用通過 GR 介導，但部分效應也透過另一種核受體——礦物皮質激素受體（MR）實現。MR 對內源性糖皮質激素具有高親和力，而這些激素的濃度通常遠高於礦物皮質激素。
One of the major mechanism by which the body limits the access of endogenous glucocorticoids to the MR is through the activity of the enzyme 11β-HSD type 2 that converts cortisol to inactive cortisone.
身體限制內源性糖皮質激素接觸 MR 的主要機制之一，是透過 11β-HSD 類型 2 酶的活性，將皮質醇轉化為無活性的皮質酮。
Therefore, when the MR is co-expressed with 11β-HSD type 2, its activation results in mineralocorticoid activity; in the absence of 11β-HSD type 2, the MR is a high-affinity GR (Nixon et al, 2013). The best characterized mechanism of transcriptional activation is the binding of the GR/glucocorticoid complex to specific DNA binding-sites (glucocorticoid response elements [GREs]) in the promoter regions of target genes after entering the nucleus (Vandevyver et al, 2013). Binding to positive GRE induces synthesis of anti-inflammatory proteins as well as regulator proteins that are important for metabolism (e.g., enzymes involved in gluconeogenesis). The process mediated through positive GRE is also called transactivation and is considered to be responsible for numerous side effects of glucocorticoids.
因此，當 MR 與 11β-HSD type 2 共同表達時，其活化會導致礦物皮質素活性；而在缺乏 11β-HSD type 2 的情況下，MR 則是一種高親和力的 GR（Nixon 等人，2013 年）。最為人所知的轉錄活化機制是 GR/糖皮質素複合體進入細胞核後，與目標基因啟動子區域中的特定 DNA 結合位點（糖皮質素反應元件[GREs]）結合（Vandevyver 等人，2013 年）。與正向 GRE 結合會誘導抗發炎蛋白質及對代謝重要的調節蛋白質（例如參與糖質新生的酶）的合成。透過正向 GRE 介導的過程亦稱為轉活化，被認為是糖皮質素眾多副作用的原因。
Binding to negative GRE leads to inhibition of gene transcription (transrepression) of the pro-opiomelanocortin (the precursor of adrenocorticotropic hormone—ACTH), α-fetoprotein, and prolactin gene, as well as suppression of inflammatory genes, such as interleukin-1β (IL-1β) and interleukin-2 (IL-2) Löwenberg et al., 2007, Stahn et al., 2007). Besides binding to GRE, other mechanisms for the upregulation and downregulation of genes exist. For instance, suppressed target gene expression can be achieved through direct protein-protein interaction with pro-inflammatory transcription factors, such as activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nuclear factor of activated T-cells (NFAT), or signal transducers and activator of transcription (STAT; Löwenberg et al, 2007). It takes approximately 30 minutes for the activation of the GR, nuclear transportation of the GR/glucocorticoid complex, binding to promoter regions, and initiation of transcription and translation. Hours to days are required until changes on cellular, tissue or organism level become obvious (Stahn et al, 2007). For many years, it was thought that the undesirable side effects of glucocorticoid therapy are due to dimer-mediated transactivation, whereas its beneficial anti-inflammatory activity is mainly caused by monomer-mediated transrepressive effects.
與負向糖皮質激素反應元件（GRE）結合會抑制前阿片黑皮素（促腎上腺皮質激素—ACTH 的前體）、α-胎兒蛋白及催乳素基因的轉錄（轉錄抑制），並壓制發炎基因如白細胞介素-1β（IL-1β）和白細胞介素-2（IL-2）（Löwenberg 等人，2007；Stahn 等人，2007）。除了與 GRE 結合外，還存在其他調控基因上調與下調的機制。例如，可通過與促炎轉錄因子如激活蛋白-1（AP-1）、核因子κB（NF-κB）、活化 T 細胞核因子（NFAT）或信號轉導及轉錄激活因子（STAT）直接蛋白質相互作用來抑制目標基因表達（Löwenberg 等人，2007）。糖皮質激素受體（GR）的激活、GR/糖皮質激素複合物的核轉運、與啟動子區域的結合及轉錄與轉譯的啟動大約需要 30 分鐘。直到細胞、組織或生物體層面的變化顯現，則需數小時至數天（Stahn 等人，2007）。 多年來，人們認為糖皮質激素治療的不良副作用是由二聚體介導的轉錄激活所引起，而其有益的抗炎活性則主要由單體介導的轉錄抑制效應所導致。
Research was therefore focused on the development of dissociated compounds that only exhibit those actions of glucocorticoids that are monomer-dependent. The dimer/monomer dogma has recently been challenged, because it was demonstrated that the GR dimer-dependent transactivation is essential for the anti-inflammatory actions (Nixon et al., 2013, Vandevyver et al., 2013).
因此，研究重點轉向開發僅表現糖皮質激素單體依賴性作用的解離化合物。然而，二聚體/單體教條最近受到挑戰，因為研究表明 GR 二聚體依賴的轉錄激活對於抗炎作用至關重要（Nixon 等，2013；Vandevyver 等，2013）。

In addition to the classic genomic mode of action, glucocorticoids may exert effects through nongenomic mechanisms. It has been recognized that some of the immunosuppressive, anti-inflammatory, anti-allergic effects, and effects when used during shock occur too fast to be regulated via transcription.
除了經典的基因組作用模式外，糖皮質激素還可能通過非基因組機制發揮效應。已認識到某些免疫抑制、抗炎、抗過敏作用以及在休克期間使用時的效果發生過快，無法通過轉錄調控來解釋。
Rapid clinical effects may be seen when glucocorticoids are administered intravenously or intra-articularly at high doses.
當高劑量的糖皮質激素通過靜脈或關節內給藥時，可能會觀察到快速的臨床效果。
Various underlying mechanisms for the nongenomic effects have been described, such as nonspecific interactions of glucocorticoids with cellular membranes, nongenomic effects that are mediated by the cytosolic GR, and specific interactions with a membrane-bound GR (Löwenberg et al., 2007, Stahn et al., 2007).
已描述多種非基因組效應的潛在機制，例如糖皮質激素與細胞膜的非特異性相互作用、由胞質糖皮質激素受體（GR）介導的非基因組效應，以及與膜結合 GR 的特異性相互作用（Löwenberg 等人，2007；Stahn 等人，2007）。

The physiological effects of glucocorticoids in the fed state are small; however, during fasting, they contribute to the maintenance of blood glucose levels by increasing hepatic gluconeogenesis and decreasing uptake of glucose in peripheral tissues (muscle, fat). These effects protect glucose-dependent organs (e.g., brain and heart) from starvation.
糖皮質激素在進食狀態下的生理效應較小；但在禁食期間，它們通過增加肝臟糖質新生作用及減少周邊組織（如肌肉、脂肪）對葡萄糖的攝取，有助於維持血糖水平。這些效應保護了依賴葡萄糖的器官（如大腦和心臟）免受飢餓影響。
Glucocorticoids stimulate glycogen deposition and inhibit glycogen-mobilizing enzymes. This allows other hormones (e.g., glucagon and epinephrine) to mobilize glucose when needed (e.g., between meals).
糖皮質激素刺激肝醣沉積並抑制肝醣動員酶。這使得其他激素（如升糖素和腎上腺素）能在需要時（例如兩餐之間）動員葡萄糖。
Glucocorticoids exert catabolic effects on muscle (i.e., decreased glucose uptake and metabolism), decreased protein synthesis, and increased release of amino acids, providing precursors for gluconeogenesis in the liver.
糖皮質激素對肌肉產生分解代謝效應（即降低葡萄糖攝取與代謝）、減少蛋白質合成，並增加胺基酸的釋放，為肝臟中的糖質新生提供前驅物質。
In adipose tissue, glucocorticoids stimulate lipolysis, which generates free fatty acids and glycerol, thereby providing energy and substrate for gluconeogenesis (Carroll et al., 2011, Hall, 2011).
在脂肪組織中，糖皮質激素刺激脂肪分解，產生游離脂肪酸和甘油，從而為糖質新生提供能量和基質（Carroll 等人，2011；Hall，2011）。

In healthy individuals, the increase in blood glucose is counterbalanced by an increase in insulin secretion. High levels of glucocorticoids (endogenous or exogenous) reduce the sensibility of many tissues, in particular muscle and fat, to the stimulatory effects of insulin on glucose uptake and utilization (i.e., lead to insulin resistance).
在健康個體中，血糖的上升會透過胰島素分泌的增加來平衡。高水平的糖皮質激素（內源性或外源性）會降低許多組織，特別是肌肉和脂肪，對胰島素促進葡萄糖攝取與利用的刺激效應的敏感性（即導致胰島素阻抗）。
In this way, glucocorticoids may induce glucose intolerance and diabetes mellitus or worsen glycemic control in an individual with pre-existing diabetes. Glucocorticoid excess also leads to increased breakdown of protein, clinically seen as muscle wasting, thinning of the skin, and delayed wound healing (Boothe and Mealey, 2012). Although glucocorticoids stimulate lipolysis, increased fat deposition is a common clinical sign. The paradox has been explained by steroid-induced stimulation of appetite and the lipogenic effect of hyperinsulinemia. The reason for the abnormal fat distribution is unknown (Carroll et al, 2011).
如此一來，糖皮質激素可能誘發葡萄糖耐受不良與糖尿病，或使既有糖尿病患者的血糖控制惡化。糖皮質激素過量還會導致蛋白質分解增加，臨床上表現為肌肉萎縮、皮膚變薄及傷口癒合延遲（Boothe 與 Mealey，2012 年）。雖然糖皮質激素會刺激脂肪分解，但脂肪堆積增加仍是常見的臨床徵兆。此矛盾現象可歸因於類固醇誘發的食慾刺激及高胰島素血症的促脂肪生成作用。異常脂肪分佈的原因尚屬未知（Carroll 等人，2011 年）。

Glucocorticoids suppress inflammatory and immune-mediated responses of the body, and this fact has been the stimulus for the development of potent glucocorticoid preparations. The anti-inflammatory and immunosuppressive effects only occur when supraphysiological doses (i.e., pharmacological doses) are given.
糖皮質激素能抑制身體的發炎和免疫介導反應，這一事實促使了強效糖皮質激素製劑的開發。抗炎和免疫抑制效果僅在給予超生理劑量（即藥理劑量）時才會出現。
Both effects are closely related, and which of the two predominates in a clinical situation is a question of the dose given. Many hundreds of glucocorticoid response genes have been identified. Additional to the genomic effects, rapid actions of glucocorticoids on inflammation are mediated by nongenomic mechanisms (Rhen and Cidlowski, 2005). It is important to remember that the encompassing properties render glucocorticoid therapy dangerous, because it can mask severity and progression of the disease and serious side effects may occur.
這兩種效應密切相關，在臨床情況中哪一種效應占主導地位取決於給予的劑量。目前已識別出數百種糖皮質激素反應基因。除了基因組效應外，糖皮質激素對炎症的快速作用還通過非基因組機制介導（Rhen 和 Cidlowski，2005 年）。重要的是要記住，這些廣泛的特性使得糖皮質激素治療具有危險性，因為它可能掩蓋疾病的嚴重程度和進展，並可能出現嚴重的副作用。
Glucocorticoids limit early and late manifestations of inflammation, including edema formation, fibrin deposition, leukocyte migration, phagocytic activity, collagen deposition, and capillary and fibroblast proliferation.
糖皮質激素限制炎症的早期和晚期表現，包括水腫形成、纖維蛋白沉積、白細胞遷移、吞噬活性、膠原沉積以及毛細血管和纖維母細胞增殖。
Many of these processes involve lymphokines, and other soluble mediators of inflammation and glucocorticoids exert their anti-inflammatory effects through those mediators (Boothe and Mealey, 2012).
這些過程中有許多涉及淋巴因子和其他可溶性炎症介質，而糖皮質激素則透過這些介質發揮其抗炎作用（Boothe 和 Mealey，2012 年）。

Similar to NF-κB, the transcription factor AP-1 is one of the key mediators of the inflammatory response; AP-1 is inhibited by glucocorticoids as well (Busillo and Cidlowski, 2013). NF-κB also induces the transcription of cyclooxygenase 2 (COX2), an enzyme that is essential for prostaglandin production; glucocorticoids inhibit COX2 through inhibition of NF-κB. Other mechanisms by which glucocorticoids inhibit prostaglandin synthesis are mediated through induction and activation of annexin I (also called lipocortin-1) and through induction of mitogen-activated protein kinase (MAPK) phosphatase 1. Annexin I is an anti-inflammatory protein that inhibits phospholipase A₂α, thereby blocking the release of arachidonic acid and its subsequent conversion to eicosanoids. Phospholipase A₂α is also inhibited by MAPK phosphatase 1. MAPKs are pivotal in the regulation of immune responses; they are involved in the production of inflammatory mediators (e.g., TNFα, IL-1, IL-6, prostaglandin, NO, and inducible nitric-oxide synthase) and in T-cell development and function. Removal of the phosphatases (which is induced by glucocorticoids) renders MAPK inactive (Rhen and Cidlowski, 2005, Liu et al., 2007). Glucocorticoids reduce local inflammation by preventing the actions of histamine and plasminogen activators (Stewart and Krone, 2011). In summary, the anti-inflammatory and immunosuppressive effects of glucocorticoids are attributed to partial or complete suppression of an extremely complex interplay of cells and cell mediators. The potent effects of glucocorticoids on leukocytes are responsible for most of the anti-inflammatory activity.
與 NF-κB 相似，轉錄因子 AP-1 是炎症反應的關鍵介質之一；AP-1 同樣受到糖皮質激素的抑制（Busillo 與 Cidlowski，2013 年）。NF-κB 還會誘導環氧合酶 2（COX2）的轉錄，該酶對前列腺素的生成至關重要；糖皮質激素通過抑制 NF-κB 來抑制 COX2。糖皮質激素抑制前列腺素合成的其他機制，是通過誘導並激活膜聯蛋白 I（亦稱脂皮素-1）以及誘導絲裂原活化蛋白激酶（MAPK）磷酸酶 1 來實現的。膜聯蛋白 I 是一種抗炎蛋白，能抑制磷脂酶 A ₂ α，從而阻斷花生四烯酸的釋放及其後續轉化為類二十烷酸。磷脂酶 A ₂ α也受到 MAPK 磷酸酶 1 的抑制。MAPKs 在免疫反應的調節中起著核心作用；它們參與炎症介質（如 TNFα、IL-1、IL-6、前列腺素、NO 及誘導型一氧化氮合酶）的產生，並影響 T 細胞的發育與功能。 移除磷酸酶（這是由糖皮質激素誘導的）會使 MAPK 失去活性（Rhen 和 Cidlowski，2005 年；Liu 等人，2007 年）。糖皮質激素通過阻止組織胺和纖溶酶原激活劑的作用來減輕局部炎症（Stewart 和 Krone，2011 年）。總之，糖皮質激素的抗炎和免疫抑制效應歸因於對極其複雜的細胞和細胞介質相互作用的部份或完全抑制。糖皮質激素對白血球的強效作用是大多數抗炎活性的原因。
These effects are also immunosuppressive, which explains their efficacy in immune-mediated disease. It should be remembered, however, that glucocorticoids can lead to an increased susceptibility to infection (Papich and Davis, 1989).
這些效應也具有免疫抑制作用，這解釋了它們在免疫介導疾病中的有效性。然而，應該記住，糖皮質激素可能導致對感染的易感性增加（Papich 和 Davis，1989 年）。

A distinction has to be made between plasma half-life and biological half-life of glucocorticoids. Plasma half-life is the amount of time required for 50% of a drug’s concentration to disappear from plasma, whereas the biological half-life refers to the duration of effect.
必須區分糖皮質激素的血漿半衰期與生物半衰期。血漿半衰期是指藥物濃度從血漿中消失 50%所需的時間，而生物半衰期則是指其作用持續的時間。
The biologic half-life of glucocorticoids is disparate, because many of the biological effects are due to alterations in genetic regulation of protein production; biological effects are delayed and prolonged compared to the drug concentration in plasma (Cohn, 2010). It is the biological half-life that needs to be considered when a treatment protocol is established. Glucocorticoids are usually divided into three groups according to the duration of HPA axis suppression.
糖皮質激素的生物半衰期存在差異，因為許多生物效應是由於基因調控蛋白質生產的改變所致；與血漿中的藥物濃度相比，生物效應會延遲且持續時間更長（Cohn, 2010）。在制定治療方案時，需要考慮的是生物半衰期。根據對 HPA 軸抑制的持續時間，糖皮質激素通常被分為三組。
Cortisol (hydrocortisone) and cortisone are considered short-acting (biologic half-life < 12 hours); prednisolone, prednisone, methylprednisolone, and triamcinolone are intermediate-acting (biologic half-life 12 to 36 hours); and dexamethasone and betamethasone are long-acting drugs (biologic half-life 36 to 72 hours) (see Table 14-1). Duration of action is influenced by factors such as route of administration, the preparation used (e.g., soluble or insoluble steroid ester), and other variables, such as health of the patient and concurrent use of other drugs.
皮質醇（氫化可的松）和可的松被視為短效藥物（生物半衰期 < 12 小時）；潑尼松龍、潑尼松、甲基潑尼松龍和曲安西龍屬於中效藥物（生物半衰期 12 至 36 小時）；而地塞米松和倍他米松則是長效藥物（生物半衰期 36 至 72 小時）（參見表 14-1）。作用時間受多種因素影響，如給藥途徑、使用的製劑（例如可溶性或不溶性類固醇酯），以及其他變量，如患者的健康狀況和同時使用的其他藥物。

Glucocorticoids of varying potency are available in oral, parenteral, and topical formulations.
不同效力的糖皮質激素有口服、腸胃外和局部製劑可供選擇。

After absorption, cortisol and synthetic glucocorticoids are bound to corticosteroid binding protein (CBP, also called transcortin) and albumin. Only the unbound, free fraction of glucocorticoids is active and can enter cells. CBP is α-globulin secreted by the liver, which has a high affinity for glucocorticoids but a relatively low binding capacity. Albumin, on the other hand, has a low affinity but large binding capacity.
吸收後，皮質醇與合成糖皮質激素會與皮質類固醇結合蛋白（CBP，亦稱為轉皮質素）及白蛋白結合。僅未結合的游離態糖皮質激素具有活性並能進入細胞。CBP 是由肝臟分泌的α-球蛋白，對糖皮質激素具有高親和力但結合容量相對較低。另一方面，白蛋白的親和力低但結合容量大。
Glucocorticoids compete with one another for binding sites and will displace one another at high concentrations (Boothe and Mealey, 2012). Compared to cortisol, binding to CBP is less for synthetic glucocorticoids; they are mainly bound to albumin or circulate as free hormones, thereby diffusing more readily into tissues. Glucocorticoids distribute widely in all tissues of the body, and they pass the blood brain and placental barrier.
糖皮質激素會相互競爭結合位點，在高濃度下會彼此取代（Boothe 和 Mealey，2012 年）。與皮質醇相比，合成糖皮質激素與 CBP 的結合較少；它們主要與白蛋白結合或以游離激素形式循環，因此更容易擴散到組織中。糖皮質激素廣泛分佈於身體的所有組織，並且它們能夠通過血腦屏障和胎盤屏障。
Glucocorticoids are metabolized in the liver and to a lesser extent in the kidney; synthetic drugs are metabolized slower than cortisol. Metabolism is by oxidation or reduction followed by glucuronidation or sulfation, and excretion of the metabolites is mainly via the kidney. Only small amounts of glucocorticoids are excreted in the unmodified form.
糖皮質激素主要在肝臟代謝，腎臟代謝程度較低；合成藥物的代謝速度比皮質醇慢。代謝過程包括氧化或還原，隨後進行葡萄糖醛酸化或硫酸化，代謝產物主要通過腎臟排泄。僅有少量糖皮質激素以未改變的形式排出。
Biliary and fecal elimination do not appear to be significant; enterohepatic cycling takes place to a small extent (Ungemach, 2010, Boothe and Mealey, 2012).
膽汁和糞便排泄似乎不顯著；腸肝循環在一定程度上發生（Ungemach，2010 年，Boothe 和 Mealey，2012 年）。

The glucocorticoid activity is closely related to the anti-inflammatory activity, and the effective anti-inflammatory time usually equals the time of HPA axis suppression (Ferguson et al, 2009). The anti-inflammatory and mineralocorticoid activities of cortisol (hydrocortisone) are used as a baseline for comparison with the synthetic glucocorticoids and are arbitrarily assigned as being 1. Chemical modifications have generated glucocorticoids with greater glucocorticoid/anti-inflammatory activity and less mineralocorticoid activity.
糖皮質激素活性與抗炎活性密切相關，有效抗炎時間通常等同於下視丘-腦垂體-腎上腺軸(HPA 軸)抑制時間(Ferguson 等學者，2009)。以皮質醇(氫化可體松)的抗炎與礦物皮質酮活性作為基準，與合成糖皮質激素進行比較，並將其活性任意設定為 1。化學修飾已開發出具有更高糖皮質激素/抗炎活性及更低礦物皮質酮活性的糖皮質激素。
Some derivatives (e.g., triamcinolone, dexamethasone) have no or negligible mineralocorticoid effects even at high doses. Increased anti-inflammatory potency is also associated with longer duration of action. The latter can be prolonged substantially by esterification. See the Chemistry of Glucocorticoids and Structure-Activity Relationship section and Box 14-1 for more details; the effects of esterification are discussed later.
某些衍生物（如曲安西龍、地塞米松）即使在高劑量下也不具有或僅有可忽略的礦物皮質酮效應。抗炎效力的增強也與作用時間的延長相關。後者可以通過酯化作用顯著延長。詳情請參閱「糖皮質激素的化學結構與活性關係」章節及方框 14-1；酯化作用的影響將在後文討論。

There is a general belief that there are no relevant qualitative differences between the various glucocorticoid preparations because they all bind to the GR. Equipotent amounts of any glucocorticoid exert similar effects, meaning that a higher dose of a less potent glucocorticoid can achieve the same effect as a lower dose of a more potent preparation (Cohn, 2010). When choosing a treatment protocol, the veterinarian has to be aware of the equivalent doses of glucocorticoids. Failure to make dose adjustments for different glucocorticoids will result in the administration of inadequate or excessive doses, leading to either inefficacy or dangerous overdose.
普遍認為各種糖皮質激素製劑之間並無顯著的質性差異，因為它們都與糖皮質激素受體（GR）結合。等效劑量的任何糖皮質激素都會產生相似的效果，這意味著較低效價的糖皮質激素可以通過提高劑量來達到與高效價製劑相同的作用（Cohn, 2010）。在選擇治療方案時，獸醫師必須了解不同糖皮質激素的等效劑量。若未能針對不同糖皮質激素調整劑量，將導致給藥不足或過量，造成治療無效或危險的過量反應。
For instance, a dose of 1 mg/kg prednisolone in a dog is a reasonable anti-inflammatory dose; the equivalent dose of dexamethasone is only approximately 0.14 mg/kg (Calvert and Cornelius, 1990a). Generally, the anti-inflammatory dose is considered to be approximately 10 times the physiological dose, and immunosuppressive doses are roughly twice the anti-inflammatory dose. In contrast to the aforementioned belief of equal effects, it is possible that there are indeed some qualitative differences between the various synthetic steroids.
例如，對狗而言，1 毫克/公斤的潑尼松龍劑量是一個合理的抗炎劑量；而等效的地塞米松劑量僅約為 0.14 毫克/公斤（Calvert 和 Cornelius，1990a）。一般來說，抗炎劑量被認為大約是生理劑量的 10 倍，而免疫抑制劑量則大約是抗炎劑量的兩倍。與前述認為效果相等的觀點相反，實際上各種合成類固醇之間可能存在一些質性差異。
In an in vitro model, it was shown that dexamethasone was more effective than prednisone and cortisol in inhibiting the clearance of immunoglobulin G (IgG)-coated cells by its effect on Fc receptors of splenic macrophages (Ruiz et al, 1991). In healthy cats, dexamethasone showed a greater diabetogenic effect than equipotent doses of prednisolone (Lowe et al, 2009).
在一項體外模型中顯示，地塞米松比潑尼松和皮質醇更有效地抑制免疫球蛋白 G（IgG）包被細胞的清除，這是通過其對脾巨噬細胞 Fc 受體的影響（Ruiz 等，1991）。在健康貓中，地塞米松顯示出比等效劑量的潑尼松龍更大的致糖尿病效應（Lowe 等，2009）。

For parenteral application, three galenic formulations are available.
對於腸胃外給藥，有三種製劑配方可供使用。

Combination products between glucocorticoids and other pharmaceutical products (e.g., antibiotics) are available. However, their use is associated with various problems, such as dose discrepancies and variable duration of effects of the constituent drugs.
市面上已有糖皮質激素與其他藥品（如抗生素）的複方製劑。然而，其使用伴隨著諸多問題，例如劑量差異及各成分藥物作用時間不一等。
Dose discrepancy means that administrations based on recommended dose for one of the drugs may result in underdosing or overdosing of the other drug in the product. The use of those drugs is discouraged.
劑量差異意指依據其中一種藥物的建議劑量給藥，可能導致複方製劑中另一種藥物的劑量不足或過量。此類藥物的使用應予以避免。

Except in case of physiological replacement, therapy with glucocorticoids is not directed at the inciting agent. Glucocorticoids are used to reduce the processes that are activated in response to a disease (Boothe and Mealey, 2012).
除生理性替代治療外，糖皮質激素治療並非針對誘發因子。糖皮質激素用於減緩疾病激活的反應過程（Boothe 和 Mealey，2012 年）。
Oftentimes, glucocorticoids are applied, although there is no indication or even a clear contraindication in higher than recommended doses and/or as depot preparations that lead to long-term suppression of the HPA axis. The goal is to bring the disease process under control with the lowest dose necessary. In serious conditions, initial IV application may be required. For this purpose, water-soluble ester preparations should be used. Thereafter, treatment should be continued with oral glucocorticoids (e.g., prednisolone).
通常情況下，糖皮質激素被應用於無明確適應症或甚至存在禁忌症的情況下，且劑量高於建議值及/或使用導致 HPA 軸長期抑制的長效製劑。目標是以最低必要劑量控制疾病進程。在嚴重情況下，可能需要初始靜脈注射。為此目的，應使用水溶性酯類製劑。之後，治療應以口服糖皮質激素（如潑尼松龍）繼續進行。
Parenteral use of depot preparations (insoluble steroid esters) should only be used in exceptional cases (i.e., if application of shorter acting steroids is not possible [fractious cats]). After achieving disease remission, the latter should be maintained with the lowest possible dose; alternate-day regimens using oral prednisolone should be used whenever indicated.
長效製劑（不溶性類固醇酯）的腸胃外使用僅應在特殊情況下（即無法使用短效類固醇時[如難控制的貓]）使用。達到疾病緩解後，應以最低可能劑量維持治療；只要適用，應採用隔日口服潑尼松龍的給藥方案。
Cats have fewer GRs than dogs and require higher doses. For the discussion on the preferred use of prednisolone over prednisone, see the Route of Administration section.
貓咪的糖皮質激素受體(GRs)數量較狗少，因此需要更高劑量。關於優先使用潑尼松龍而非潑尼松的討論，請參閱「給藥途徑」章節。

Generally, given dose ranges should be regarded as approximate guidelines, because glucocorticoid sensitivity differs between individuals. Frequent reevaluations of patients treated with glucocorticoids are of utmost importance. It is the predominant opinion that cats require higher doses of glucocorticoids than dogs.
一般而言，所列劑量範圍應視為近似指導原則，因為個體對糖皮質激素的敏感度存在差異。對接受糖皮質激素治療的病患進行頻繁重新評估至關重要。主流觀點認為貓咪需要比狗更高的糖皮質激素劑量。
This belief is supported by a study demonstrating that cats have approximately half the density of GRs in skin and liver as compared to dogs, and the receptors have lower binding affinity (van den Broek and Stafford, 1992, Lowe et al., 2008a). Physiological effects of glucocorticoids occur at much lower doses than do anti-inflammatory and immunosuppressive doses (see Dose Equivalents of Glucocorticoids). Before initiating glucocorticoid therapy, the clinician should identify the goal (e.g., physiological replacement, suppression of inflammation, suppression of the immune system, or other actions like in neurological or neoplastic disorders) (Cohn, 2010). Other questions that should be answered prior to glucocorticoid therapy are (Ferguson et al, 2009):
此觀點得到一項研究的支持，該研究表明貓咪皮膚和肝臟中的糖皮質激素受體(GRs)密度約為狗的一半，且受體結合親和力較低(van den Broek and Stafford, 1992, Lowe et al., 2008a)。糖皮質激素的生理效應發生在遠低於抗炎和免疫抑制劑量的情況下(參見《糖皮質激素劑量當量》)。在開始糖皮質激素治療前，臨床醫師應明確治療目標(例如：生理性替代、抑制炎症、抑制免疫系統，或用於神經系統或腫瘤疾病等其他作用)(Cohn, 2010)。在糖皮質激素治療前應回答的其他問題包括(Ferguson et al, 2009)：

• •
  Has an exact diagnosis been made and specific treatment been initiated?
  是否已確立精確診斷並開始特定治療？
• •
  Have other types of treatment been explored to minimize glucocorticoid dose and side effects?
  是否已探索其他治療方式以最小化糖皮質激素劑量及副作用？
• •
  Are there contraindications or known risk factors?
  是否存在禁忌症或已知風險因素？
• •
  How serious is the disease?
  這種疾病的嚴重程度如何？
• •
  What is the anticipated length of glucocorticoid therapy?
  糖皮質激素治療的預期療程是多久？

Animals with primary or secondary adrenocortical insufficiency require replacement of glucocorticoids. In case of primary disease (Addison's disease), the majority of patients also need mineralocorticoid replacement. Replacement means to provide glucocorticoids in amounts similar to those of the naturally produced glucocorticoids (mainly cortisol).
患有原發性或繼發性腎上腺皮質功能不全的動物需要進行糖皮質激素替代治療。在原發性疾病（艾迪生病）的情況下，大多數患者還需要礦物皮質激素替代。替代意味著提供與自然產生的糖皮質激素（主要是皮質醇）量相似的糖皮質激素。
Ideal replacement mimics the hormonal output of the adrenal gland under basal conditions, which is roughly 1 mg/kg cortisol per day in dogs and cats. Dose increase is needed in times of stress (Ferguson et al, 2009). A perfect replacement is difficult to reach because of the dynamic function of the adrenal gland with minute-to-minute adaption of cortisol secretion according to the actual requirement. Prednisolone is the glucocorticoid preparation most commonly used for replacement therapy in a dose of 0.1 to 0.25 mg/kg once daily.
理想的替代治療應模擬腎上腺在基礎狀態下的激素分泌量，犬貓每日約需 1 毫克/公斤體重的皮質醇。在壓力時期需增加劑量（Ferguson 等，2009 年）。由於腎上腺具有動態功能，能根據實際需求每分鐘調整皮質醇分泌，因此要達到完美替代相當困難。潑尼松龍是最常用於替代療法的糖皮質激素製劑，每日一次劑量為 0.1 至 0.25 毫克/公斤。
Glucocorticoid sensitivity varies widely between individuals, and therefore, replacement doses have to be curtailed to the patient's need. In some dogs in which the mineralocorticoid deficiency is replaced by fludrocortisone (which also has glucocorticoid activity), additional prednisolone may not be required under normal conditions.
個體對糖皮質激素的敏感度差異極大，因此替代劑量需根據患者需求調整。某些犬隻若已使用氟氫可的松（兼具糖皮質激素活性）替代礦物皮質酮缺乏症，在正常情況下可能無需額外補充潑尼松龍。
During times of stress, the need for glucocorticoid activity increases. As a rough guideline, the replacement dose should be increased two to five times in case of moderate stress, and five to twenty times in case of severe stress (e.g., surgery) (Ferguson et al, 2009). See Chapter 12 for more details.
處於壓力狀態時，對糖皮質激素活性的需求會增加。粗略準則為：中度壓力時替代劑量應增加 2 至 5 倍，重度壓力（如手術）時則需增加 5 至 20 倍（Ferguson 等，2009 年）。詳見第 12 章說明。

Inflammatory and allergic disorders are the most common reasons for the use of glucocorticoids. If no specific treatment can be initiated or is insufficient, glucocorticoids can help to combat the clinical signs. However, there is a great potential for misuse in this category.
炎症和過敏性疾病是使用糖皮質激素最常見的原因。如果無法開始特定治療或治療不足，糖皮質激素可以幫助對抗臨床症狀。然而，這一類藥物有很大的濫用潛力。
If an infectious disease goes unnoticed, the use of glucocorticoids may have deleterious effects because the disease can progress and the outcome can potentially be fatal.
如果未被發現的感染性疾病使用糖皮質激素，可能會產生有害影響，因為疾病可能進展，結果可能致命。
Due to the general effects of glucocorticoids (e.g., reduction of fever, stimulation of appetite, feeling of euphoria, and suppression of the clinical signs of inflammation), the clinician may have the impression of improvement, while in fact the disease is worsening (Cohn, 2010). Calvert and Cornelius (1990b) described this as, “When glucocorticoids are misused, the patient may walk all the way to the necropsy laboratory.” There are a few exceptions, as in some infectious diseases (e.g., bacterial or Malassezia-induced otitis externa or severe ehrlichiosis), the concurrent administration of glucocorticoids may have beneficial effects.
由於糖皮質激素的一般效果（例如，降低發燒、刺激食慾、產生欣快感以及抑制炎症的臨床症狀），臨床醫生可能會有改善的印象，而實際上疾病正在惡化（Cohn, 2010）。Calvert 和 Cornelius（1990b）將其描述為「當糖皮質激素被濫用時，患者可能會一路走到屍檢室。」有一些例外情況，如在某些感染性疾病（例如細菌或馬拉色菌引起的外耳炎或嚴重的艾利希體病）中，同時使用糖皮質激素可能有益。
It is understood that in the latter disease the application should be limited to a few days (2 to 7 days) (Cohn, 2003, Rougier et al., 2005, Bensignor and Grandemange, 2006). Generally, before using glucocorticoids for their anti-inflammatory effects, information regarding specific conditions should be reviewed.
據了解，在後者疾病中，糖皮質激素的應用應限制在幾天內（2 至 7 天）（Cohn，2003；Rougier 等人，2005；Bensignor 和 Grandemange，2006）。一般而言，在利用糖皮質激素的抗炎作用之前，應複習有關特定條件的資訊。

Except in emergency cases (e.g., acute bronchial disease) in which IV administration of sodium succinate or sodium phosphate esters of prednisolone or methylprednisolone is indicated, oral prednisolone is usually the treatment of choice. In dogs, the anti-inflammatory dose of prednisolone is 0.5 to 1.0 mg/kg per day.
除緊急情況（例如急性支氣管疾病）需要靜脈注射潑尼松龍或甲基潑尼松龍的琥珀酸鈉或磷酸鈉酯外，口服潑尼松龍通常是首選治療方法。對於犬類，潑尼松龍的抗炎劑量為每天每公斤體重 0.5 至 1.0 毫克。
In cats, it is usually recommended to give twice the dose of dogs (e.g., 1.0 to 2.0 mg/kg) (Lowe et al., 2008a, Cohn, 2010). As soon as clinical signs of inflammation are under control, the dose should be reduced to the lowest necessary concentration. The induction period usually ranges between 5 and 7 days (Behrend and Kemppainen, 1997). Prednisolone (or methylprednisolone) enables accurate dose titration and the possibility of withdrawal in case of adverse effect. It is also the glucocorticoid that can be most appropriately used every other day after remission is achieved, thereby allowing the HPA axis to recover to a certain extent (Boothe and Mealey, 2012). There is some controversy as to whether the daily dose of prednisolone should be given at once or divided twice daily. As studies supporting either frequency are lacking, once-daily dosing seems reasonable—in particular in animals that are difficult to medicate (Lowe et al, 2008a).
在貓咪中，通常建議給予狗隻兩倍的劑量（例如 1.0 至 2.0 毫克/公斤）（Lowe 等人，2008a；Cohn，2010）。一旦炎症的臨床症狀得到控制，劑量應降低至所需的最低濃度。誘導期通常介於 5 至 7 天之間（Behrend 和 Kemppainen，1997）。潑尼松龍（或甲基潑尼松龍）能夠進行精確的劑量滴定，並在出現不良反應時可撤藥。它也是達成緩解後最適合隔日使用的糖皮質激素，從而讓 HPA 軸得以某種程度恢復（Boothe 和 Mealey，2012）。關於潑尼松龍的每日劑量應一次給予還是分兩次給予存在一些爭議。由於缺乏支持任一頻率的研究，每日一次給藥似乎更為合理——特別是對於難以給藥的動物（Lowe 等人，2008a）。

Topical instead of systemic glucocorticoids may be useful in inflammatory conditions of the eye, skin, respiratory tract, gastrointestinal tract, and joints. Topical steroids reduce inflammation by their local activity while minimizing systemic effects.
對於眼睛、皮膚、呼吸道、胃腸道及關節的發炎狀況，局部使用而非全身性給予的糖皮質激素可能更為適用。局部類固醇透過其局部活性來減輕發炎，同時將全身性影響降至最低。
Newer generation glucocorticoids (also called “soft glucocorticoids”) were designed specifically for topical use in humans, and some of them have also been investigated in small animals. Inhalant glucocorticoids are used in nebulizers or metered dose inhaler (MDI) in patients with chronic inflammatory airway inflammation.
新一代糖皮質激素（亦稱為「軟性糖皮質激素」）專為人類局部使用而設計，其中部分已在小型動物中進行研究。吸入型糖皮質激素用於霧化器或定量吸入器（MDI）中，治療患有慢性發炎性氣道炎症的病患。
They have relatively low systemic bioavailability because of their poor absorption and extensive first-pass metabolism in the liver into inactive metabolites. Examples are fluticasone and budesonide; their local potencies are extremely high. In the case of budesonide, the potency compared to cortisol is 60, that of fluticasone is 540 (Viviano, 2013). Both have been successfully used as inhaled glucocorticoids in dogs and cats (Bexfield et al., 2006, Padrid, 2006, Cohn et al., 2010, Galler et al., 2013). Budesonide is also available as an oral drug and exerts its inflammatory action locally in the intestinal tract. It is mainly used to treat IBD in dogs (Dye et al., 2013, Pietra et al., 2013). Mometasone is a potent topical glucocorticoid with low systemic effects designed for use in dermatological diseases; it is 25 times more potent than cortisol (Mendelsohn, 2009).
由於吸收不良及在肝臟中經歷廣泛的首過代謝轉化為無活性代謝物，它們的全身生物利用度相對較低。例如氟替卡松和布地奈德；它們的局部效力極高。就布地奈德而言，其效力與皮質醇相比為 60 倍，氟替卡松則為 540 倍（Viviano，2013 年）。兩者均已成功用作犬貓的吸入性糖皮質激素（Bexfield 等人，2006 年；Padrid，2006 年；Cohn 等人，2010 年；Galler 等人，2013 年）。布地奈德也可作為口服藥物使用，並在腸道局部發揮其抗炎作用。主要用於治療犬的炎症性腸病（Dye 等人，2013 年；Pietra 等人，2013 年）。莫米松是一種強效外用糖皮質激素，全身性作用低，專為皮膚病設計使用；其效力是皮質醇的 25 倍（Mendelsohn，2009 年）。

Glucocorticoids are considered the initial first-line therapy in various immune-mediated diseases, including immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis, systemic lupus erythematosus, and pemphigus complex.
糖皮質激素被視為多種免疫介導疾病的首選初始治療，包括免疫介導性溶血性貧血、免疫介導性血小板減少症、免疫介導性多關節炎、系統性紅斑狼瘡及天疱瘡複合症。
They are also used to prevent organ rejection after transplantation and to reduce immunological reactions associated with some infectious diseases, such as feline infectious peritonitis (FIP) and ehrlichiosis (Cohn, 2003, Gregory et al., 2006, Case et al., 2007, Addie et al., 2009, Hopper et al., 2012). It should be noted, however, that treatment protocols for small animals are mostly empirical and adapted from human medicine. Rigorous evaluations by randomized double-blinded placebo-controlled trials have not been performed (Whitley and Day, 2011).
它們也被用於預防移植後的器官排斥，以及減少與某些傳染病相關的免疫反應，例如貓傳染性腹膜炎（FIP）和艾利希體症（Cohn, 2003; Gregory 等人, 2006; Case 等人, 2007; Addie 等人, 2009; Hopper 等人, 2012）。然而，應該注意的是，小動物的治療方案大多是經驗性的，並從人類醫學中改編而來。尚未進行隨機雙盲安慰劑對照試驗的嚴格評估（Whitley 和 Day, 2011）。

The goal of immune-suppressive therapy is to achieve disease remission quickly, which usually requires high doses; thereafter, the dose is tapered slowly to the lowest level that will maintain remission. Oral application of prednisolone is the preferred modality.
免疫抑制治療的目標是快速達到疾病緩解，這通常需要高劑量；之後，劑量會逐漸減少到能夠維持緩解的最低水平。口服潑尼松龍是首選的治療方式。
In acute or emergency situations, IV application of water-soluble esters of prednisolone or methylprednisolone may be indicated. Depot preparations do not allow dose adjustments and should not be used. The initial oral dose of prednisolone typically is 2 to 4 mg/kg in dogs and 2 to 8 mg/kg in cats per day (Cohn, 1997, Cohn, 2010, Lowe et al., 2008a). The dose is usually divided twice daily, based on the belief that this division will decrease gastrointestinal side effects. Generally, larger dogs should be treated with the lower end of the dose range (Cohn, 2010). In the opinion of the author, the high-end dose in cats should be used with great caution. The recommendation may in part be based on the frequent use of prednisone instead of prednisolone. As mentioned earlier, it is now known that only a small part of oral prednisone appears as prednisolone in the systemic circulation in cats (Graham-Mize and Rosser, 2004). Some clinicians prefer to use dexamethasone for the first few doses and thereafter switch to oral prednisolone. There are no controlled clinical studies to confirm any advantage of this approach. In one experimental study, dexamethasone was more effective than prednisone and cortisol in inhibiting the clearance of IgG-coated cells (Ruiz et al, 1991) (see Dose Equivalents of Glucocorticoids).
在急性或緊急情況下，可能需要靜脈注射水溶性潑尼松龍或甲基潑尼松龍酯類製劑。長效製劑無法調整劑量，因此不應使用。潑尼松龍的初始口服劑量通常為犬隻每日 2 至 4 毫克/公斤，貓咪每日 2 至 8 毫克/公斤（Cohn, 1997; Cohn, 2010; Lowe 等人, 2008a）。基於認為分次給藥可減少胃腸道副作用，通常將每日劑量分為兩次給予。一般而言，體型較大的犬隻應使用劑量範圍的下限（Cohn, 2010）。作者認為，貓咪的高劑量使用應極為謹慎。此建議可能部分基於經常使用潑尼松而非潑尼松龍的情況。如前所述，現已知貓咪口服潑尼松後僅有少量轉化為系統循環中的潑尼松龍（Graham-Mize 與 Rosser, 2004）。部分臨床醫師偏好在前幾劑使用地塞米松，之後再轉換為口服潑尼松龍。目前尚無對照臨床研究證實此方法的任何優勢。 在一項實驗研究中，地塞米松在抑制 IgG 包被細胞的清除方面比潑尼松和皮質醇更有效（Ruiz 等人，1991 年）（見糖皮質激素的劑量等效性）。

If dexamethasone is used, equipotent doses have to be calculated (e.g., 2 mg/kg prednisolone equals approximately 0.3 mg/kg dexamethasone). High doses of prednisolone are continued for several days after remission is achieved; usually, high doses are needed for 1 to 4 weeks.
如果使用地塞米松，則需計算等效劑量（例如，2 毫克/公斤的潑尼松龍大約等於 0.3 毫克/公斤的地塞米松）。在病情緩解後，仍需繼續使用高劑量的潑尼松龍數天；通常，高劑量需要持續 1 至 4 週。

Thereafter, the dose should be tapered slowly over many weeks to months (see Glucocorticoid Reduction Protocol). Adverse effects are commonly seen with immunosuppressive doses, and the owner has to be warned about them. The addition of other immunosuppressive agents may have steroid-sparing effects and may allow disease control at lower glucocorticoid doses and faster tapering of the dose (Cohn, 2010).
之後，劑量應在數週至數月內緩慢遞減（見糖皮質激素減量方案）。免疫抑制劑量常伴隨不良反應，需事先告知飼主。添加其他免疫抑制劑可能具有節省類固醇的效果，並可能在較低的糖皮質激素劑量下控制疾病，以及更快地減少劑量（Cohn，2010 年）。

Prednisolone is often included in combination chemotherapy protocols for their cytotoxic activity. Additional desired effects of prednisolone are reduction of edema and inflammation, appetite-stimulations, and decrease of nausea and vomiting.
潑尼松龍常被納入聯合化療方案中，因其具有細胞毒性活性。潑尼松龍的其他理想效果包括減輕水腫和炎症、刺激食慾，以及減少噁心和vomiting。
Oral prednisolone is also used for alleviation of chronic cancer pain; the recommended dose in dogs is 0.25 to 1.0 mg/kg, and for cats it is 0.5 to 1.0 mg/kg (Mealey et al., 2003, Lascelles, 2013). Interestingly, in dogs with multicentric lymphoma using a multidrug protocol, the benefit of prednisolone with regard to outcome was recently questioned (Zandvliet et al, 2013). In case of financial or other restrictions, prednisone/prednisolone (initial dose, 2 mg/kg) is sometimes used as a single agent in lymphoma cases with a possible tumor control of 1 to 2 months. Besides the short remission period, other disadvantages include serious side effects and the potential induction of multidrug resistance.
口服潑尼松龍也用於緩解慢性癌症疼痛；犬的推薦劑量為 0.25 至 1.0 毫克/公斤，貓則為 0.5 至 1.0 毫克/公斤（Mealey 等人，2003 年；Lascelles，2013 年）。有趣的是，最近有研究對潑尼松龍在多中心性淋巴瘤犬使用多藥方案中的療效提出了質疑（Zandvliet 等人，2013 年）。在經濟或其他限制條件下，潑尼松/潑尼松龍（初始劑量 2 毫克/公斤）有時會作為單一藥物用於淋巴瘤病例，可能控制腫瘤 1 至 2 個月。除了緩解期短外，其他缺點還包括嚴重的副作用和可能誘導多藥耐藥性。
The latter would limit the success of more aggressive drug therapy in case the owner changes his or her mind (Chun, 2009, Vail et al., 2013). Besides the potential risk of decreased response to later chemotherapy, glucocorticoids induce apoptosis of neoplastic lymphocytes and may interfere with the diagnosis; they should therefore only be used after the diagnosis has been made.
後者將限制在飼主改變心意時採取更積極藥物治療的成功率（Chun, 2009; Vail 等人, 2013）。除了可能降低對後續化療反應的風險外，糖皮質激素還會誘導腫瘤淋巴細胞凋亡，並可能干擾診斷；因此，它們應僅在確診後使用。

Glucocorticoids may also be used in patients with hypercalcemia of malignancy (see Chapter 15) and to increase blood glucose concentrations in cases with insulinoma (see Chapter 9).
糖皮質激素也可用於惡性腫瘤引起的高鈣血症患者（見第 15 章），以及在胰島素瘤病例中提高血糖濃度（見第 9 章）。

The use of high-dose glucocorticoid therapy for shock has fallen repeatedly in and out of favor (Cohn, 2010). Different from the past, high-dose glucocorticoids are nowadays mentioned only in the treatment protocols of anaphylactic shock. In humans, epinephrine is the first line treatment with a rapid onset of action; and although glucocorticoids are often used, their onset of action is considered quite slow (Lieberman, 2014). A systemic review of databases failed to identify adequately designed studies, and no relevant evidence for the use of glucocorticoids was found. The authors were therefore unable to make any recommendations for the use of glucocorticoids in the treatment of anaphylaxis in humans (Choo et al, 2013). Similarly, in dogs and cats, epinephrine is the drug of choice for treatment of anaphylaxis (Shmuel and Cortes, 2013). Glucocorticoids continue to be frequently used in small animals with anaphylaxis; however, as in humans, no studies support their benefit. Of note, glucocorticoids themselves may cause allergic reaction and even anaphylaxis. The application of methylprednisolone sodium succinate 30 mg/kg intravenously is commonly mentioned for cases with anaphylactic shock (Dowling, 2009).
高劑量糖皮質激素療法用於休克的治療，其受青睞程度時高時低（Cohn，2010 年）。與過去不同，現今高劑量糖皮質激素僅在過敏性休克的治療方案中被提及。在人類中，腎上腺素因其作用迅速而成為首選治療藥物；儘管糖皮質激素常被使用，但其作用起始被認為相當緩慢（Lieberman，2014 年）。一項系統性文獻回顧未能找到設計完善的研究，也未發現支持使用糖皮質激素的相關證據。因此，作者無法對糖皮質激素用於人類過敏性休克的治療提出任何建議（Choo 等人，2013 年）。同樣地，在犬貓中，腎上腺素是治療過敏性休克的首選藥物（Shmuel 和 Cortes，2013 年）。糖皮質激素在小動物過敏性休克的治療中仍頻繁使用；然而，如同在人類中一樣，沒有研究支持其益處。值得注意的是，糖皮質激素本身可能引起過敏反應甚至過敏性休克。 在過敏性休克病例中，靜脈注射 30 毫克/公斤的甲基強的松龍琥珀酸鈉是常見的處置方式（Dowling, 2009）。

In humans with septic shock, relative adrenal insufficiency may be present and low-dose glucocorticoid therapy for a few days appeared to be safe and may have some benefit for shock reversal and short-term survival (Annane et al., 2009, Sligl et al., 2009). Although relative adrenal insufficiency may also exist in dogs and cats, no clinical studies have investigated the use of low-dose glucocorticoid therapy in cases with septic shock. The results of one experimental study using low-dose corticosteroids showed beneficial effects in dogs with severe sepsis; however, results also pointed to reduced bacterial clearance even with short term treatment (Hicks et al, 2012). Therefore, no recommendation can be made for the application of glucocorticoids in septic shock. They should only be used at low doses, if at all, under close monitoring of the patient.
在人類的敗血性休克中，可能出現相對性腎上腺功能不全，而低劑量的糖皮質激素治療數天似乎是安全的，並可能對休克逆轉和短期生存有所助益（Annane 等人，2009；Sligl 等人，2009）。雖然犬貓也可能存在相對性腎上腺功能不全，但目前尚無臨床研究探討低劑量糖皮質激素治療在敗血性休克病例中的應用。一項使用低劑量皮質類固醇的實驗研究顯示，對患有嚴重敗血症的犬隻有積極效果；然而，結果也指出即使短期治療也會降低細菌清除率（Hicks 等人，2012）。因此，無法對糖皮質激素在敗血性休克中的應用提出建議。如果必須使用，應僅在低劑量下並密切監測病患狀況。

Previously, glucocorticoids were advocated for the treatment of traumatic brain injury on the basis that they decreased brain edema. However, in humans, high-dose methylprednisolone was associated with an increase in mortality. Their use in humans as well as in small animals with brain injury is no longer recommended (DiFazio and Fletcher, 2013). In acute spinal cord injury, methylprednisolone is considered to reveal free radical-scavenging effects, which other glucocorticoids are lacking. It is suggested that methylprednisolone has a positive effect if administered within 8 hours of the time of insult.
過去，糖皮質激素曾被提倡用於治療創傷性腦損傷，基於其能減少腦水腫的理論。然而，在人體中，高劑量的甲基強的松龍與死亡率上升相關。因此，無論是人類還是小動物，在腦損傷情況下使用此類藥物已不再被建議（DiFazio 與 Fletcher，2013 年）。在急性脊髓損傷中，甲基強的松龍被認為具有清除自由基的效果，這是其他糖皮質激素所缺乏的特性。建議若能在受傷後 8 小時內給予甲基強的松龍，可能產生積極效果。
Suggested initial dose of methylprednisolone sodium succinate is 30 mg/kg followed by repeated boluses of 15 mg/kg at 2 and 6 hours, then every 8 hours up to 48 hours after the trauma (Park et al, 2012). However, these doses are enormous and have the potential of serious side effects (e.g., gastrointestinal ulceration, immunosuppression, and impaired wound healing). Sound data to support the use of this protocol is lacking in small animals, and its use in acute spinal cord injury is currently controversial (Park et al, 2012).
甲基強的松龍琥珀酸鈉的建議初始劑量為 30 毫克/公斤，隨後於 2 小時和 6 小時重複推注 15 毫克/公斤，之後每 8 小時一次，持續至創傷後 48 小時（Park 等人，2012 年）。然而，這些劑量極大，可能導致嚴重副作用（例如胃腸道潰瘍、免疫抑制及傷口癒合受損）。目前缺乏有力數據支持此方案在小動物中的應用，且其在急性脊髓損傷中的使用仍具爭議性（Park 等人，2012 年）。

In a significant percentage of dogs with hyperadrenocorticism, the disease is in fact caused by exogenous glucocorticoids. Clinical signs and laboratory abnormalities of iatrogenic hyperadrenocorticism are identical to those of the endogenous form of the disease.
在相當比例的犬隻腎上腺皮質功能亢進症病例中，該疾病實際上是由外源性糖皮質激素引起。醫源性腎上腺皮質功能亢進症的臨床症狀和實驗室異常與內源性形式的疾病完全相同。
Polyuria, polydipsia, polyphagia, and panting usually manifest within the first 1 to 2 weeks of therapy in dogs (e.g., with oral prednisolone in anti-inflammatory or immunosuppressive doses). These signs may even occur within hours after the first dose. They dissipate as the dose is tapered or discontinued (Feldman and Nelson, 2004). More severe signs such as cutaneous lesions (thin hair coat, alopecia, hyperpigmentation, pyoderma, calcinosis cutis, and thin skin), poor wound healing, muscle weakness and atrophy, hepatomegaly due to steroid hepatopathy, pendulous abdomen, urinary tract infection, and myotonia usually require a longer time and develop within weeks to months (Behrend and Kemppainen, 1997, Huang et al., 1999, Feldman and Nelson, 2004). Lethargy may be seen either as a short- or long-term effect. Resolution of those signs takes considerably longer than cessation of polyuria, polydipsia, polyphagia, and panting. Improvement may be seen within a few weeks; however, depending on severity, resolution may take up to 6 months or longer.
多尿、多飲、多食及喘息等症狀通常於犬隻治療的頭 1 至 2 週內出現（例如，使用口服潑尼松龍的抗炎或免疫抑制劑量時）。這些徵兆甚至可能在首次給藥後數小時內發生。隨著劑量遞減或停藥，這些症狀會逐漸消退（Feldman 與 Nelson，2004 年）。更嚴重的症狀如皮膚病變（毛髮稀疏、脫毛、色素沉著過度、膿皮病、皮膚鈣質沉著及皮膚變薄）、傷口癒合不良、肌肉無力與萎縮、因類固醇肝病導致的肝腫大、腹部下垂、尿路感染及肌強直，通常需要較長時間才會顯現，並在數週至數月內發展（Behrend 與 Kemppainen，1997 年；Huang 等人，1999 年；Feldman 與 Nelson，2004 年）。嗜睡可能是短期或長期的副作用。這些症狀的消退時間遠比多尿、多飲、多食及喘息的停止來得長。改善可能在幾週內可見；然而，依嚴重程度而定，完全恢復可能需要長達 6 個月或更久。
Resolution may not always be complete; for instance, persistence of calcinosis cutis and of pulmonary mineralization has been reported, and there may be color change in new hair growth (Huang et al., 1999, Blois et al., 2009). Exogenous glucocorticoids lead to atrophy of the adrenal glands, which may be seen ultrasonographically as reduction in length and height of the cranial and caudal pole. The decrease in size is progressive during therapy and percentage change varies between dogs (Pey et al, 2012). Generally, there is a large individual variation with regard to glucocorticoid sensitivity. The same dose may be tolerated well in one dog, whereas substantial side effects are seen in another dog. Even low doses (e.g., suggested for physiological replacement) may induce side effects in sensitive dogs.
症狀的緩解可能並非總是徹底的；例如，已有報告指出皮膚鈣質沉著症和肺部礦化可能持續存在，且新生的毛髮可能出現顏色變化（Huang 等人，1999 年；Blois 等人，2009 年）。外源性糖皮質激素會導致腎上腺萎縮，這在超聲檢查中可表現為腎上腺頭尾極長度和高度的減少。這種尺寸的減小在治療過程中是漸進的，且不同犬隻之間的百分比變化各異（Pey 等人，2012 年）。一般而言，個體對糖皮質激素的敏感度存在很大差異。相同的劑量可能在一隻犬隻中耐受良好，而在另一隻犬隻中則可能出現顯著的副作用。即使是低劑量（例如建議用於生理性替代的劑量）也可能在敏感犬隻中誘發副作用。
In particular, large breed dogs may develop profound weakness and paraparesis when treated with high doses of glucocorticoids.
特別是大型犬種在接受高劑量糖皮質激素治療時，可能會出現嚴重的虛弱和後肢輕癱。

Cats are considered to be more resistant than dogs toward the development of iatrogenic hyperadrenocorticism. Associated signs occur most often after repeated injections of long-acting glucocorticoid preparations; however, occurrence of signs (e.g., polyphagia and weight gain) have also been reported after a single injection of methylprednisolone acetate (Ferasin, 2001). It is often assumed that polyuria and polydipsia do not occur in cats until diabetes mellitus is induced by exogenous glucocorticoids. Although this may be true for the majority of cases, polyuria and polydipsia have also been reported in cats without diabetes (Lien et al., 2006, Lowe et al., 2008a). Other signs of iatrogenic hyperadrenocorticism are similar to those seen in dogs. Unique to the cat is the development of spontaneous tearing and sloughing of the skin and, in rare cases, medial curling of the pinnae (Scott et al., 1982, Lowe et al., 2008a, Lowe et al., 2008b). Steroid hepatopathy does occur in cats, but is considered to be less common than in dogs (Schaer and Ginn, 1999). Of note, signs of iatrogenic hyperadrenocorticism may not only occur with oral or parenteral application but also with topical treatment. Exceptions are the newer generations of topical glucocorticoids (budesonide, fluticasone), which seem to have minimal side effects. There is no treatment for iatrogenic hyperadrenocorticism.
貓被認為比狗更能抵抗醫源性腎上腺皮質功能亢進症的發生。相關症狀最常在反覆注射長效型糖皮質激素製劑後出現；然而，也有報告指出，單次注射甲基強的松龍醋酸酯（Ferasin，2001 年）後會出現症狀（例如多食和體重增加）。通常認為，直到外源性糖皮質激素誘發糖尿病之前，貓不會出現多尿和多飲。雖然這在多數情況下可能是正確的，但也有報告指出，貓在沒有糖尿病的情況下也會出現多尿和多飲（Lien 等，2006 年；Lowe 等，2008a）。醫源性腎上腺皮質功能亢進症的其他症狀與狗所見相似。貓獨特的症狀包括自發性流淚和皮膚脫落，以及在極少數情況下耳廓內捲（Scott 等，1982 年；Lowe 等，2008a；Lowe 等，2008b）。類固醇性肝病確實會在貓身上發生，但被認為比狗少見（Schaer 和 Ginn，1999 年）。 值得注意的是，醫源性腎上腺皮質功能亢進的症狀不僅可能發生於口服或腸外給藥，也可能出現在局部治療中。例外的是新一代的局部性糖皮質激素（布地奈德、氟替卡松），它們似乎副作用極小。目前醫源性腎上腺皮質功能亢進尚無治療方法。
The only measure consists in cessation of glucocorticoid therapy. Because the HPA axis is usually suppressed, adrenocortical insufficiency may develop if therapy is abruptly stopped (see later and Glucocorticoid Reduction Protocol section).
唯一措施在於停止糖皮質激素治療。由於下丘腦-垂體-腎上腺軸通常受到抑制，若突然停藥可能導致腎上腺皮質功能不全（詳見後文及糖皮質激素減量方案部分）。

Closely related to the development of clinical signs of glucocorticoid excess is the suppression of the HPA axis. Of note, however, suppression of the HPA axis may be present without the animal displaying clinical signs of hyperadrenocorticism. All synthetic glucocorticoids suppress CRH and ACTH secretion, but their effects are not equivalent.
與糖皮質激素過量臨床症狀發展密切相關的是下丘腦-垂體-腎上腺軸的抑制。但需注意，即使動物未表現出腎上腺皮質功能亢進的臨床症狀，HPA 軸的抑制仍可能存在。所有合成糖皮質激素都會抑制 CRH 和 ACTH 的分泌，但它們的效果並不等同。
Generally, the greater the anti-inflammatory potency, the greater is the capacity to suppress the HPA axis. Over time, the glucocorticoid-producing cells of the two inner zones of the adrenal cortex atrophy and the responsiveness of the HPA axis decrease progressively (Behrend and Kemppainen, 1997). Animals with suppression of the HPA lack the ability to secrete cortisol sufficiently in response to stress and may develop signs of acute adrenocortical insufficiency. The zona glomerulosa and its function are preserved, and therefore, electrolyte abnormalities associated with mineralocorticoid deficiency are not seen.
一般而言，抗炎效力越強，抑制下視丘-腦下垂體-腎上腺軸（HPA 軸）的能力也越大。隨著時間推移，腎上腺皮質內兩層區域中負責生產糖皮質激素的細胞會萎縮，HPA 軸的反應性也會逐漸降低（Behrend 與 Kemppainen，1997 年）。HPA 軸受抑制的動物無法在壓力狀態下分泌足夠的皮質醇，可能出現急性腎上腺皮質功能不全的症狀。由於腎小球帶及其功能得以保留，因此不會出現與礦物皮質激素缺乏相關的電解質異常。
Suppression of the HPA axis may occur quite soon after the onset of glucocorticoid therapy.
HPA 軸的抑制可能在糖皮質激素治療開始後不久即發生。

Oral, parenteral, and topical administration all lead to HPA axis suppression, which is most serious and prolonged after repeated injection of long-acting preparations (water-insoluble esters).
口服、腸胃外及局部給藥均會導致 HPA 軸抑制，其中以反覆注射長效製劑（水不溶性酯類）後的情況最為嚴重且持續時間最長。
In experimental dogs, a single dose of methylprednisolone acetate (2.5 mg/kg IM) suppressed the HPA axis, as demonstrated by reduced response of cortisol after ACTH, for at least 5 weeks (Kemppainen et al, 1981). A dog that was treated for pruritus with a similar single dose of methylprednisolone acetate experienced HPA axis suppression for 7 weeks (Meyer, 1982). A single dose of triamcinolone acetonide (0.22 mg/kg IM) suppressed the HPA axis for 2 to 4 weeks (Kemppainen et al, 1982). Single IV doses of 0.01 mg/kg and 0.1 mg/kg dexamethasone (as free alcohol) resulted in reduced cortisol response after ACTH for 16 to 24 hours and 32 hours, respectively. Dexamethasone sodium phosphate was associated with a somewhat shorter suppression compared with the free alcohol with the 0.01 mg/kg dose (Kemppainen and Sartin, 1984). A single dose of prednisone (2.2 mg/kg IM) did not result in adrenocortical suppression (Kemppainen et al, 1982). However, even prednisone/prednisolone given at physiological doses can suppress the HPA axis when given for some time. Oral application of 0.22 mg/kg (physiological dose) or 0.55 mg/kg per day led to a significantly depressed cortisol after ACTH stimulation after 1 week.
在實驗犬中，單次劑量的甲基強的松龍醋酸酯（2.5 毫克/公斤肌肉注射）抑制了 HPA 軸，表現為對 ACTH 後皮質醇反應降低，持續至少 5 週（Kemppainen 等人，1981 年）。一隻因搔癢症接受類似單次甲基強的松龍醋酸酯治療的犬隻，其 HPA 軸抑制持續了 7 週（Meyer，1982 年）。單次劑量的曲安西龍丙酮酸酯（0.22 毫克/公斤肌肉注射）使 HPA 軸抑制持續 2 至 4 週（Kemppainen 等人，1982 年）。單次靜脈注射 0.01 毫克/公斤和 0.1 毫克/公斤的地塞米松（游離醇形式）分別導致對 ACTH 後皮質醇反應降低 16 至 24 小時和 32 小時。與游離醇相比，地塞米松磷酸鈉在 0.01 毫克/公斤劑量下的抑制作用稍短（Kemppainen 和 Sartin，1984 年）。單次劑量的強的松（2.2 毫克/公斤肌肉注射）未導致腎上腺皮質抑制（Kemppainen 等人，1982 年）。然而，即使是生理劑量的強的松/強的松龍，長期使用時也能抑制 HPA 軸。 口服給予 0.22 毫克/公斤（生理劑量）或每天 0.55 毫克/公斤的劑量，一週後會顯著抑制 ACTH 刺激後的皮質醇分泌。
Administration of 1 mg/kg prednisone daily resulted in HPA axis suppression within 2 weeks; administration of 1 mg/kg prednisolone every other day was associated with HPA axis suppression after 3 weeks (Chastain and Graham, 1979, Moore and Hoenig, 1992). Cats are more resistant to the development of clinical signs of iatrogenic hyperadrenocorticism; however, they experience HPA suppression similar to dogs (Behrend and Kemppainen, 1997). The application of a single dose of methylprednisolone acetate (20 mg IM) to healthy cats led to a reduced cortisol response after ACTH within 1 week (Scott et al, 1979). In a cat treated with subcutaneous (SC) methylprednisolone acetate (20 mg) weekly for 4 weeks, complete suppression of the HPA axis was still seen 1 month after the last injection (Ferasin, 2001). Daily oral administration of prednisolone (2 mg/kg) resulted in HPA axis suppression after 1 week and was more pronounced after 2 weeks of daily therapy (Middleton et al, 1987). Similarly, daily oral methylprednisolone (4 mg/kg) was associated with HPA axis suppression within 1 week (Crager et al, 1994).
每日給予 1 毫克/公斤的潑尼松在 2 週內導致 HPA 軸抑制；每隔一天給予 1 毫克/公斤的潑尼松龍則在 3 週後與 HPA 軸抑制相關（Chastain and Graham, 1979, Moore and Hoenig, 1992）。貓對於醫源性腎上腺皮質功能亢進的臨床症狀發展更具抵抗力；然而，它們經歷的 HPA 抑制與狗相似（Behrend and Kemppainen, 1997）。對健康貓單次應用甲基潑尼松龍醋酸酯（20 毫克肌肉注射）在 1 週內導致對 ACTH 的皮質醇反應降低（Scott et al, 1979）。在一隻每週皮下注射甲基潑尼松龍醋酸酯（20 毫克）連續 4 週的貓中，最後一次注射後 1 個月仍觀察到 HPA 軸的完全抑制（Ferasin, 2001）。每日口服潑尼松龍（2 毫克/公斤）在 1 週後導致 HPA 軸抑制，且在每日治療 2 週後更為明顯（Middleton et al, 1987）。同樣地，每日口服甲基潑尼松龍（4 毫克/公斤）在 1 週內與 HPA 軸抑制相關（Crager et al, 1994）。

Any topically applied glucocorticoid can suppress the HPA axis. Application of triamcinolone, fluocinonide, and betamethasone valerate on the skin of healthy dogs (once daily for 5 days) resulted in decreased cortisol after stimulation with ACTH within 5 days. The HPA axis remained suppressed for 3 to 4 weeks after the last treatment (Zenoble and Kemppainen, 1987). Ophthalmic instillation of 1% prednisolone acetate or 0.1% dexamethasone four times daily in both eyes resulted in HPA axis suppression within 2 weeks, intensifying throughout the treatment period (Roberts et al., 1984, Glaze et al., 1988). Ototopical administration of therapeutic doses of dexamethasone-containing ointment daily to healthy dogs resulted in HPA axis suppression within 11 days (Abraham et al, 2005). The new generation of topical steroids cause minimal signs of iatrogenic hyperadrenocorticism but are associated with HPA axis suppression. Oral budesonide in dogs with IBD resulted in significantly lower post-ACTH cortisol concentrations after 30 days of therapy (Tumulty et al, 2004). Inhalant budesonide in cats with chronic bronchial disease resulted in HPA axis suppression in three of 15 cases (Galler et al, 2013). Inhaled fluticasone in healthy dogs and inhaled flunisolide in healthy cats suppressed the HPA axis within 2 to 3 weeks (Reinero et al., 2006, Cohn et al., 2008).
任何局部應用的糖皮質激素都可能抑制 HPA 軸。在健康犬隻皮膚上每日一次連續 5 天應用曲安西龍、氟輕鬆和戊酸倍他米松後，5 天內 ACTH 刺激後的皮質醇水平下降。最後一次治療後，HPA 軸的抑制狀態持續了 3 至 4 週（Zenoble 和 Kemppainen，1987 年）。雙眼每日四次滴注 1%醋酸潑尼松龍或 0.1%地塞米松，兩週內即導致 HPA 軸抑制，且隨治療時間延長而加劇（Roberts 等，1984 年；Glaze 等，1988 年）。健康犬隻每日耳部局部應用含治療劑量地塞米松的軟膏，11 天內即出現 HPA 軸抑制（Abraham 等，2005 年）。新一代局部類固醇雖極少引發醫源性腎上腺皮質功能亢進的症狀，但仍與 HPA 軸抑制相關。口服布地奈德治療 IBD 犬隻 30 天後，其 ACTH 刺激後的皮質醇濃度顯著降低（Tumulty 等，2004 年）。 在患有慢性支氣管疾病的貓中，吸入型布地奈德導致 15 例中有 3 例出現 HPA 軸抑制（Galler 等人，2013 年）。健康犬吸入氟替卡松及健康貓吸入氟尼縮松均在 2 至 3 週內抑制了 HPA 軸（Reinero 等人，2006 年；Cohn 等人，2008 年）。

Diagnosis of HPA axis suppression is made by performing an ACTH stimulation test. Depending on the severity, post-ACTH cortisol concentrations can be below the detection limit of the cortisol assay, low (e.g., 2 to 5 μg/dL, 55 to 138 nmol/L) or low-normal.
HPA 軸抑制的診斷是通過進行 ACTH 刺激試驗來確定的。根據嚴重程度，ACTH 刺激後的皮質醇濃度可能低於皮質醇檢測的檢測限、偏低（例如 2 至 5 μg/dL，55 至 138 nmol/L）或處於正常低值。
Animals with undetectable or low concentrations are at risk for signs of adrenal insufficiency, in particular when encountering a stressful situation. Potentially lethal situations may arise. If clinical signs (e.g., lethargy, anorexia, or vomiting) develop after cessation of steroids, prednisolone administrations should be instituted.
皮質醇濃度無法檢測或偏低的動物面臨腎上腺功能不全症狀的風險，尤其是在遭遇壓力情境時。可能出現致命情況。若在停用類固醇後出現臨床症狀（如嗜睡、厭食或vomiting），應開始給予潑尼松龍治療。
The dose is somewhat arbitrary and depends on the clinical situation. If severity of signs and extent of stress are moderate, prednisolone doses between 0.5 to 1 mg/kg/day may be sufficient; doses up to 2 to 4 mg/kg/day may be needed temporarily in life-threatening situations. The prednisolone dose should then be tapered slowly. Generally, glucocorticoids should be reduced slowly after a longer period of glucocorticoid administration (e.g., > 2 weeks). Suppression of the HPA axis is usually reversible. The length of time required for full axis recovery depends on duration, dose, preparation, and frequency of application of the steroid.
劑量的選擇具有一定隨意性，需視臨床情況而定。若症狀嚴重程度與壓力程度中等，每日 0.5 至 1 毫克/公斤體重的潑尼松龍劑量可能已足夠；在危及生命的情況下，可能需要暫時提高至每日 2 至 4 毫克/公斤體重。隨後應緩慢遞減潑尼松龍劑量。一般而言，長期使用糖皮質激素（如超過兩週）後，應逐步緩慢減少用量。下視丘-腦垂體-腎上腺軸（HPA 軸）的抑制通常可逆，其完全恢復所需的時間取決於類固醇使用的持續時間、劑量、製劑類型及給藥頻率。
Single doses of triamcinolone acetonide or methylprednisolone acetate can suppress adrenal responsiveness for up to 5 weeks (see earlier). Multiple injections of long-acting preparations will aggravate the suppressive effect, and HPA axis malfunction may persist for months. Oral administration of shorter-acting or less-potent preparations may result in quicker normalization (Behrend and Kemppainen, 1997).
單次注射曲安奈德或醋酸甲基潑尼松龍可抑制腎上腺反應達五週之久（見前文）。多次注射長效製劑會加劇此抑制作用，導致 HPA 軸功能異常可能持續數月。口服短效或效力較低的製劑可能使功能更快恢復正常（Behrend 與 Kemppainen，1997 年）。

Abrupt cessation of glucocorticoids may result in a so-called glucocorticoid withdrawal syndrome (Greco and Behrend, 1995). Several subgroups are known in humans; one of them is attributed to the sudden lack of the high concentration of steroids. In this situation, the body perceives the glucocorticoid withdrawal as a relative deficiency. The signs are vague and can easily be mistaken with those of true adrenal insufficiency. The syndrome has been poorly characterized in dogs and cats.
突然停止使用糖皮質激素可能導致所謂的糖皮質激素戒斷綜合症（Greco 和 Behrend，1995 年）。在人類中已知有幾個亞組；其中一個被歸因於突然缺乏高濃度的類固醇。在這種情況下，身體將糖皮質激素的戒斷視為相對缺乏。症狀模糊，容易與真正的腎上腺功能不全混淆。該綜合症在狗和貓中的特徵描述較少。
In questionable cases, an ACTH stimulation test should be performed to differentiate between absolute or relative adrenal insufficiency. Prednisolone administration may be needed in either situation.
在可疑情況下，應進行 ACTH 刺激試驗以區分絕對或相對腎上腺功能不全。無論哪種情況，都可能需要給予潑尼松龍。

Glucocorticoids may exert diabetogenic properties thereby inducing hyperglycemia in previously normoglycemic patients, as well as worsening glycemic control in patients already known to have diabetes mellitus.
糖皮質激素可能具有致糖尿病特性，從而在先前血糖正常的患者中誘發高血糖，並使已知患有糖尿病的患者的血糖控制惡化。
Glucocorticoids increase insulin resistance in peripheral tissues (muscle, fat) and increase hepatic glucose production, and they may also inhibit insulin release from the β cells. In humans, overt diabetes or impaired glucose tolerance is seen in 14% to 28% of individuals receiving long-term glucocorticoids.
糖皮質激素會增加周邊組織（肌肉、脂肪）的胰島素阻抗性，並增加肝臟的葡萄糖生成，它們也可能抑制β細胞釋放胰島素。在人類中，長期接受糖皮質激素治療的個體中有 14%至 28%會出現明顯的糖尿病或葡萄糖耐受不良。
Prevalence of diabetes induced by exogenous glucocorticoids has not been systematically studied in dogs and cats. It is well known that cats are more susceptible to the diabetogenic effects of glucocorticoids than dogs. Approximately 80% of cats with endogenous hyperadrenocorticism are diabetic, whereas in dogs, the prevalence is only about 10%.
外源性糖皮質激素誘發糖尿病的盛行率在狗和貓中尚未被系統性研究。眾所周知，貓比狗更容易受到糖皮質激素的致糖尿病效應影響。約有 80%患有內源性腎上腺皮質功能亢進的貓會發展成糖尿病，而在狗中，這一比例僅約 10%。
Steroid diabetes can occur after oral or parenteral, as well as after topical administration of any of the traditional glucocorticoids, but it has not been reported with the newer class of topical drugs (budesonide, fluticasone).
類固醇糖尿病可能發生於口服或非腸道給藥後，也可能在使用任何傳統糖皮質激素的局部給藥後出現，但尚未有報告指出新型局部藥物（布地奈德、氟替卡松）會引起此類情況。
Glucocorticoid sensitivity varies between individuals and therefore dose, duration, and frequency of application that will ultimately lead to hyperglycemia cannot be predicted. Experimental studies have shown that abnormalities may already become apparent after short-term therapy.
個體對糖皮質激素的敏感性存在差異，因此無法預測最終會導致高血糖的劑量、持續時間及用藥頻率。實驗研究顯示，短期治療後可能已經會出現異常情況。
Administration of 2 mg/kg prednisolone once daily for 8 days resulted in reduced glucose tolerance after an IV glucose load in all six cats, and three of the six cats developed hyperglycemia (Middleton and Watson, 1985). Weekly injections of 20 mg methylprednisolone subcutaneously lead to hyperglycemia within 4 weeks in the two cats studied (Scott et al, 1982). Within 1 month of daily administration of immunosuppressive doses of prednisolone or dexamethasone, 29% and 71% of cats developed glucosuria (Lowe et al, 2009). The later study points to a greater diabetogenic effect of dexamethasone than equipotent doses of prednisolone. Steroid-induced diabetes is also seen in dogs but with much lower frequency than in cats (Campbell and Latimer, 1984, Jeffers et al., 1991). Administration of anti-inflammatory/immunosuppressive doses of prednisone (1.1 mg/kg/day) or prednisolone (1 to 2 mg/kg/day) for 28 days to normal dogs has not produced hyperglycemia, glucose intolerance, or insulin resistance (Wolfsheimer et al., 1986, Moore and Hoenig, 1993, Moore et al., 1993).
每日一次給予 2 毫克/公斤的潑尼松龍，連續 8 天後，所有六隻貓在接受靜脈葡萄糖負荷後均顯示葡萄糖耐受性降低，其中三隻貓發展出高血糖（Middleton 和 Watson，1985 年）。在研究的兩隻貓中，每周皮下注射 20 毫克甲基潑尼松龍，4 週內導致高血糖（Scott 等人，1982 年）。每日給予免疫抑制劑量的潑尼松龍或地塞米松後 1 個月內，分別有 29%和 71%的貓出現糖尿（Lowe 等人，2009 年）。後續研究指出，地塞米松比等效劑量的潑尼松龍具有更強的致糖尿病效應。類固醇誘發的糖尿病在狗中也有發現，但發生率遠低於貓（Campbell 和 Latimer，1984 年；Jeffers 等人，1991 年）。對正常狗給予抗炎/免疫抑制劑量的潑尼松（1.1 毫克/公斤/天）或潑尼松龍（1 至 2 毫克/公斤/天）28 天，並未產生高血糖、葡萄糖不耐受或胰島素抵抗（Wolfsheimer 等人，1986 年；Moore 和 Hoenig，1993 年；Moore 等人，1993 年）。

Diagnosis of steroid-induced diabetes should result in cessation of glucocorticoid therapy whenever possible; depending on the disease, alternative drugs (e.g., cyclosporine) or topical use of the new generation of glucocorticoids should be considered.
診斷出類固醇誘發性糖尿病時，應盡可能停止糖皮質激素治療；根據疾病情況，可考慮使用替代藥物（如環孢素）或局部應用新一代糖皮質激素。
In cats, steroid-induced diabetes often goes into remission, provided that the glucocorticoid application is ceased immediately and insulin treatment is initiated. In dogs, diabetic remission has been seen; however, too few data have been published to make a general statement.
在貓咪中，若能立即停用糖皮質激素並開始胰島素治療，類固醇誘發性糖尿病通常會進入緩解期。在狗中雖也有糖尿病緩解的案例，但由於發表數據過少，尚無法做出普遍性結論。
In a dog or cat with known diabetes, glycemic control usually worsens when glucocorticoids are administered. Diabetes mellitus should not be regarded as an absolute contraindication for glucocorticoids, because in some diseases they may be life-saving. The glucocorticoid dose should be as low as possible to control the disease.
對於已知患有糖尿病的犬貓，給予糖皮質激素通常會使血糖控制惡化。糖尿病不應被視為糖皮質激素的絕對禁忌症，因為在某些疾病中它們可能具有救命效果。糖皮質激素的劑量應以能控制疾病的最低量為準。
In short-term glucocorticoid therapy (1 to 2 weeks), the insulin dose may be maintained while awaiting the withdrawal of the drug. If long-term glucocorticoid therapy is needed, an increase in the daily insulin doses is usually necessary to maintain control over the diabetic state. The amount of increase is variable and should follow the guidelines discussed in Chapters 6 and 7Chapter 6Chapter 7. Careful monitoring of blood glucose levels is important. After the effect of the glucocorticoid on insulin sensitivity wears off, the insulin requirement decreases, resulting in the need to also decrease the insulin dose. Remission may fail to appear if treatment is inadequate or if the cat has substantial islet pathology.
在短期糖皮質激素治療（1 至 2 週）期間，可維持胰島素劑量，等待藥物停用。若需長期糖皮質激素治療，通常需增加每日胰島素劑量以維持對糖尿病狀態的控制。增加的劑量因人而異，應遵循第 6 章和第 7 章討論的指導原則。密切監測血糖水平十分重要。當糖皮質激素對胰島素敏感性的影響消退後，胰島素需求會降低，因此也需要相應減少胰島素劑量。若治療不足或貓咪存在顯著的胰島病變，可能無法出現緩解。
If glucocorticoid therapy cannot be terminated and no alternative drug can be used, the insulin dose has to be adjusted based on the severity of the insulin resistance. In those cases, glycemic control oftentimes remains difficult.
若無法終止糖皮質激素治療且無替代藥物可用，則需根據胰島素抵抗的嚴重程度調整胰島素劑量。此類情況下，血糖控制往往仍具挑戰性。

In the physiological state, glucocorticoids exert protective effects for the gastrointestinal integrity by various mechanisms. The administration of glucocorticoids in pharmacological doses may alter mucosal defense mechanisms in many ways (e.g., by decreasing mucus production, altering the biochemical structure of mucus, decreasing mucosal cell turnover, increasing acid output, and impairing mucosal blood flow).
在生理狀態下，糖皮質激素通過多種機制對胃腸道完整性發揮保護作用。然而，以藥理劑量給予糖皮質激素可能從多方面改變黏膜防禦機制（例如：減少黏液分泌、改變黏液的生化結構、降低黏膜細胞更新率、增加胃酸分泌，以及損害黏膜血流）。
Other mechanisms are decreased healing rate and promotion of bacterial colonization of ulcers (Hanson et al., 1997, Rohrer et al., 1999a, Feldman and Nelson, 2004). In most situations, it is unlikely that glucocorticoids are the sole factor for gastrointestinal problems. The exception may be when extremely high doses of steroids are used.
其他機制包括降低潰瘍癒合速率及促進潰瘍處細菌定植（Hanson 等人，1997；Rohrer 等人，1999a；Feldman 與 Nelson，2004）。在多數情況下，糖皮質激素不太可能是導致胃腸道問題的唯一因素。例外情況可能發生在使用極高劑量類固醇時。
The application of methylprednisolone sodium succinate (30 mg/kg initially, and then 15 mg/kg 2 and 6 hours later and every 6 hours thereafter for 48 hours) was associated with gastric hemorrhage in all of the 10 dogs and was severe in nine of them (Rohrer et al, 1999a). Similarly, the application of extremely high doses of dexamethasone (4.4 mg/kg/day for 8 days) or prednisone (8.8 mg/kg/day for 7 days) to experimental dogs did result in endoscopic evidence of hemorrhage but not in ulcers (Sorjonen et al., 1983, Behrend and Kemppainen, 1997).
甲基強的松龍琥珀酸鈉的應用（初始劑量 30 毫克/公斤，隨後在 2 小時和 6 小時後以及之後每 6 小時給予 15 毫克/公斤，持續 48 小時）在 10 隻狗中均與胃出血相關，其中九隻情況嚴重（Rohrer 等人，1999a）。同樣，對實驗犬應用極高劑量的地塞米松（每天 4.4 毫克/公斤，持續 8 天）或強的松（每天 8.8 毫克/公斤，持續 7 天）確實導致了內窺鏡下的出血證據，但未形成潰瘍（Sorjonen 等人，1983；Behrend 和 Kemppainen，1997）。

In clinical patients, the most striking gastrointestinal side effects have been reported in dogs with neurological disease.
在臨床病患中，最顯著的胃腸道副作用被報告於患有神經系統疾病的狗隻中。
However, because a neurological problem can result in gastrointestinal lesions itself, it is difficult to say how much glucocorticoids contributed to the development of the problems. In one study, 23 of 155 dogs with intervertebral disk herniation had gastrointestinal problems, and 10 of them had not received glucocorticoids (Moore and Withrow, 1982). More than 75% of dogs with acute intervertebral disc disease treated with glucocorticoids had gastric mucosal lesions as detected by endoscopy. In 8% of dogs, gastric ulcers developed during the treatment period. Only 24% of the dogs had clinical signs such as vomiting or melena (Neiger et al, 2000). The most catastrophic of the gastrointestinal complications is colon perforation. Colonic perforation in 13 dogs treated with glucocorticoids was uniformly fatal (Toombs et al, 1986). Ten of the 13 dogs were neurosurgical patients, one was treated for head-trauma and non-ambulatory paresis, and two others had undergone major surgery for other reasons. Dexamethasone was the most frequently used steroid and was given in a mean cumulative dose of 6.4 mg/kg/day over a period of 5 days. The most common clinical signs were depression, anorexia, and vomiting.
然而，由於神經系統問題本身也可能導致胃腸道病變，因此難以斷定糖皮質激素在問題發展中扮演了多少角色。一項研究中，155 隻患有椎間盤突出的犬隻裡有 23 隻出現胃腸道問題，其中 10 隻並未接受糖皮質激素治療（Moore 與 Withrow，1982 年）。超過 75%接受糖皮質激素治療的急性椎間盤疾病犬隻，經內窺鏡檢查發現胃黏膜病變。8%的犬隻在治療期間發展出胃潰瘍，僅 24%表現出如vomiting或黑便等臨床症狀（Neiger 等人，2000 年）。胃腸道併發症中最嚴重者為結腸穿孔。13 隻接受糖皮質激素治療後發生結腸穿孔的犬隻全數死亡（Toombs 等人，1986 年）。這 13 隻犬隻中有 10 隻是神經外科病例，1 隻因頭部創傷及非行走性輕癱接受治療，另 2 隻則因其他原因接受重大手術。地塞米松是最常使用的類固醇，平均累積劑量為每日 6.4 毫克/公斤，持續 5 天。 最常見的臨床症狀包括抑鬱、食慾不振及vomiting。
Signs became evident 3 to 8 days after surgery and preceded death by an average of 22 hours (Toombs et al, 1986).
症狀在手術後 3 至 8 天內顯現，並在死亡前平均 22 小時出現（Toombs 等人，1986 年）。

Because of the potential association between glucocorticoids and gastrointestinal side effects, certain precautions should be taken, in particular in patients with neurological disease. Non-ambulatory patients certainly have an increased risk (Behrend and Kemppainen, 1997).
由於糖皮質激素可能與胃腸道副作用有關，應採取特定預防措施，尤其是對神經系統疾病患者。非行動不便患者無疑具有更高的風險（Behrend 與 Kemppainen，1997 年）。
The following recommendations have been made: to use prednisolone or methylprednisolone instead of the more potent dexamethasone, limit treatment to the lowest possible dose and duration, avoid concurrent or successive use of other drugs with known ulcerogenic potential (in particular non-steroidal anti-inflammatory drugs), avoid urinary retention by closed urine drainage, and correct fecal retention problems prior to surgery (Toombs et al, 1986).
已提出以下建議：使用潑尼松龍或甲基潑尼松龍替代效力更強的地塞米松，將治療限制在最低有效劑量與最短持續時間，避免同時或連續使用其他已知具有致潰瘍潛力的藥物（特別是非類固醇抗炎藥），通過閉式尿液引流避免尿滯留，並在手術前解決糞便滯留問題（Toombs 等人，1986 年）。

Misoprostol, cimetidine, or sucralfate were evaluated for their potential preventative role for gastrointestinal hemorrhage but did not show any effect (Hanson et al., 1997, Rohrer et al., 1999b).
針對米索前列醇、西咪替丁或硫糖鋁在預防胃腸道出血方面的潛在作用進行了評估，但未顯示任何效果（Hanson 等人，1997 年；Rohrer 等人，1999b 年）。

The most common biochemical abnormalities in dogs receiving exogenous glucocorticoids are elevation of liver enzymes. Any glucocorticoid and any form of application (oral, parenteral, or topical) can lead to an increase of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT).
接受外源性糖皮質激素治療的犬隻最常見的生化異常是肝臟酶升高。任何糖皮質激素及任何給藥形式（口服、腸胃外或局部）都可能導致鹼性磷酸酶（ALP）、丙氨酸氨基轉移酶（ALT）和γ-谷氨酰轉移酶（GGT）的升高。
However, there is a tremendous amount of variation between individual dogs; in some, the elevation may reach several-fold of normal, whereas others only have minor increase or even no change. In part, the changes may be dose-related.
然而，個體犬隻之間存在極大的變異性；有些犬隻的酶值可能升高至正常值的數倍，而其他犬隻僅有輕微升高甚至無變化。部分變化可能與劑量相關。
The administration of 1.1 mg/kg/day prednisone by mouth for 35 days did not result in a significant increase of ALP and the glucocorticoid-induced ALP isoenzyme. Only five of the 18 healthy dogs had ALP activities above the reference range (Moore et al, 1992). A prednisone dose of 4.4 mg/kg/day IM for 14 days was associated with a significant increase in ALP activity within 2 days, in ALT activity within 3 days, and in GGT activity within 6 days. Six weeks after the end of the study, the enzyme activities were still slightly to moderately increased (Badylak and Van Vleet, 1981).
口服 1.1 毫克/公斤/天的潑尼松持續 35 天並未導致 ALP 及糖皮質激素誘導型 ALP 同工酶顯著上升。18 隻健康犬中僅有 5 隻的 ALP 活性超出參考範圍（Moore 等，1992 年）。肌肉注射 4.4 毫克/公斤/天的潑尼松連續 14 天，則在 2 天內顯著提升 ALP 活性、3 天內提升 ALT 活性、6 天內提升 GGT 活性。研究結束後六週，這些酶活性仍呈現輕度至中度升高（Badylak 與 Van Vleet，1981 年）。

The application of other glucocorticoids, such as dexamethasone, methylprednisolone (acetate), and triamcinolone, has similar effects. The contributory role of the glucocorticoid induced isoenzyme of ALP to the increase of total ALP activity seems to be inconsistent. In the study of Moore and colleagues (1992), it contributed only to a small extent to the total ALP activity. In a study by Solter and colleagues (1994), the initial increase of ALP was mainly due to the liver ALP isoenzyme, followed by the glucocorticoid and bone isoenzyme 7 and 10 days after initiating treatment with prednisone. Serum bile acids may also increase during glucocorticoid therapy, whereas ammonia tolerance test does not seem to be affected (Meyer, 1982, DeNovo and Prasse, 1983, Solter et al., 1994). For effects on blood glucose and lipase activity, see the Diabetes Mellitus section and the Pancreatitis section. Otic medications containing triamcinolone or dexamethasone were also associated with an increase in ALP, ALT, and GGT (Meyer et al., 1990, Abraham et al., 2005). Increase in liver enzyme activities may also be seen with the new generation of glucocorticoids. A short term (30 days) oral application of budesonide was associated with an increase in ALP activity in dogs, but the difference to pretreatment levels was not significant (Tumulty et al, 2004). Cats are generally considered more resistant to the effects of glucocorticoids and do not have a glucocorticoid induced isoenzyme. Increases in liver enzyme activities after administration of glucocorticoids do occur, and the most consistent increase is seen in ALT activity. The ALP activity may also increase; however, it often still remains within the normal range (Scott et al., 1982, Sharkey et al., 2007, Lowe et al., 2008b). As in dogs, glucocorticoid administration in cats may result in steroid (vacuolar) hepatopathy, although the frequency is lower (Schaer and Ginn, 1999). Increase in serum lipids (cholesterol, triglycerides) may be seen in both species.
其他糖皮質激素（如地塞米松、甲基強的松龍（醋酸酯）和曲安西龍）的應用具有相似效果。糖皮質激素誘導的 ALP 同工酶對總 ALP 活性增加的貢獻似乎不一致。在 Moore 及其同事（1992 年）的研究中，其對總 ALP 活性的貢獻僅占很小比例。Solter 及其同事（1994 年）的研究顯示，ALP 的初始升高主要歸因於肝臟 ALP 同工酶，隨後在使用強的松治療 7 天和 10 天後，糖皮質激素和骨骼同工酶才顯著增加。血清膽酸在糖皮質激素治療期間也可能升高，而氨耐受性測試似乎不受影響（Meyer, 1982 年; DeNovo 和 Prasse, 1983 年; Solter 等, 1994 年）。關於對血糖和脂肪酶活性的影響，請參閱「糖尿病」章節和「胰腺炎」章節。含有曲安西龍或地塞米松的耳科藥物也與 ALP、ALT 和 GGT 的升高相關（Meyer 等, 1990 年; Abraham 等, 2005 年）。新一代糖皮質激素也可能觀察到肝酶活性的增加。 短期（30 天）口服布地奈德與狗隻 ALP 活性上升有關，但與治療前水平相比差異並不顯著（Tumulty 等，2004 年）。貓通常被認為對糖皮質激素的作用更具抵抗力，且不具糖皮質激素誘導的同功酶。糖皮質激素給藥後確實會出現肝酶活性上升，其中最一致的上升見於 ALT 活性。ALP 活性也可能增加；然而，其數值往往仍維持在正常範圍內（Scott 等，1982 年；Sharkey 等，2007 年；Lowe 等，2008b 年）。與狗類似，貓隻給予糖皮質激素可能導致類固醇（空泡性）肝病變，儘管發生頻率較低（Schaer 與 Ginn，1999 年）。兩種物種均可能觀察到血清脂質（膽固醇、三酸甘油酯）上升。

Glucocorticoids also affect hematological parameters. In dogs with iatrogenic hyperadrenocorticism, eosinopenia was seen in 18 out of 28 dogs and was the most frequent finding. Other constituents of the “stress leukogram” were also found, but to a lesser extent (Huang et al, 1999). In 14 cats treated with glucocorticoids (4.4 mg/kg prednisolone or 0.55 mg/kg dexamethasone for 56 days), neutrophils were significantly higher, and lymphocytes and eosinophils were significantly lower after treatment (Lowe et al, 2008b). In this study, monocytes were also increased, which is usually considered not a typical finding in steroid-treated cats.
糖皮質激素也會影響血液學參數。在患有醫源性腎上腺皮質功能亢進的狗中，28 隻狗中有 18 隻出現嗜酸性粒細胞減少，這是最常見的發現。其他「壓力性白血球圖」的組成部分也有發現，但程度較輕（Huang 等，1999）。在 14 隻接受糖皮質激素治療的貓（每天 4.4 毫克/公斤的潑尼松龍或 0.55 毫克/公斤的地塞米松，持續 56 天）中，治療後中性粒細胞顯著增加，而淋巴細胞和嗜酸性粒細胞顯著減少（Lowe 等，2008b）。在這項研究中，單核細胞也有所增加，這通常不被認為是類固醇治療貓的典型發現。

More than 500 drugs have been reported to the World Health Organization (WHO) because they were suspected to induce pancreatitis in humans. In many of them, evidence of causality is weak, and for only 31 of those drugs a definitive causality has been established. Among them are steroids, but they do not belong to the group of high risk drugs (Nitsche et al, 2010). Previously, glucocorticoids were also assumed to cause pancreatitis in small animals. Much of the evidence regarding this association, however, is related to an increased viscosity of pancreatic secretion shown in rabbits.
世界衛生組織（WHO）已收到超過 500 種藥物的報告，這些藥物被懷疑會引發人類胰腺炎。其中許多藥物的因果關係證據薄弱，僅有 31 種藥物確立了明確的因果關係。類固醇雖列於其中，但不屬於高風險藥物群（Nitsche 等人，2010 年）。過去，糖皮質激素也被認為會導致小動物胰腺炎。然而，有關此關聯的大部分證據與兔子胰腺分泌物黏稠度增加有關。
In dogs, increased viscosity of pancreatic secretions has been shown only when isolated pancreases were perfused with a huge dose of methylprednisolone (400 mg); a lower dose (200 mg) did not change the viscosity (Kimura et al., 1979, Behrend and Kemppainen, 1997). Pancreatitis has also been seen in dogs treated with glucocorticoids. However, these were sporadic cases, and the dogs suffered from intervertebral disc disease, which may alone be a risk factor (Behrend and Kemppainen, 1997). The administration of dexamethasone to healthy dogs in various doses for up to 3 weeks did not cause pancreatitis. However, it increased lipase activity without any histological damage to the pancreas (Parent, 1982). In a more recent study, evaluating the canine pancreatic lipase immunoreactivity (cPLI), immunosuppressive doses of prednisone (2.2 mg/kg once daily) given for 6 weeks did not result in an increase in cPLI (Steiner et al, 2009).
在狗隻中，僅當以極高劑量的甲基強的松龍（400 毫克）灌注離體胰腺時，才會顯示胰腺分泌物黏度增加；較低劑量（200 毫克）則未改變黏度（Kimura 等人，1979 年；Behrend 與 Kemppainen，1997 年）。接受糖皮質激素治療的狗隻也曾出現胰腺炎。然而，這些均為零星案例，且這些狗隻本身患有椎間盤疾病，此病症本身可能就是一個風險因素（Behrend 與 Kemppainen，1997 年）。對健康狗隻給予不同劑量的地塞米松長達三週，並未引發胰腺炎。不過，它確實提高了脂肪酶活性，但未對胰腺造成任何組織學損傷（Parent，1982 年）。在一項較近期的研究中，評估犬胰腺脂肪酶免疫反應性（cPLI）時，給予免疫抑制劑量的強的松（每日一次，每公斤 2.2 毫克）持續六週，並未導致 cPLI 上升（Steiner 等人，2009 年）。

In dogs and cats, the early concerns that glucocorticoids could cause pancreatitis have now largely been dismissed. Steroids are no longer included in the list of drugs suspected of being associated with pancreatitis (Armstrong and Williams, 2012, Mansfield, 2012). It is possible, however, that glucocorticoids are a contributing factor in sick animals or that only a subset of patients is susceptible for steroid-induced pancreatitis.
在犬貓中，早期關於糖皮質激素可能引發胰臟炎的擔憂現已大致被排除。類固醇不再被列為與胰臟炎相關的懷疑藥物名單中（Armstrong 和 Williams，2012 年；Mansfield，2012 年）。然而，糖皮質激素可能對患病動物是一個促成因素，或者僅有特定患者群體對類固醇誘發的胰臟炎具有易感性。

Glucocorticoids may have numerous other adverse effects, including growth retardation in young animals, induction or worsening of hypertension, disposing the animal to infections due to immunosuppression (e.g., urinary tract infection), interference with fertility, induction of abortion, and behavior changes.
糖皮質激素可能具有多種其他不良影響，包括幼年動物的生長遲緩、誘發或加劇高血壓、因免疫抑制（例如泌尿道感染）而使動物易受感染、干擾生育能力、誘發流產以及行為改變。