Download Thyroid hormones and antithyroid drugs

Thyroid hormones and
antithyroid drugs
Dept of Pharmacology
Shi-Hong Zhang (张世红)
[email protected]
Thyroid gland
Front view
Thyroid hormones
1. Uptake of iodide
2. Oxidation of iodide (peroxidase) and iodination and
coupling of tyrosine
3. Formation of thyroxine (T4) and triiodothyronine (T3)
from iodotyrosine
4. Secretion of thyroid hormones (proteolytic enzymes)
5. Regulation by thyroid stimulating hormone (TSH), T4,
T3
Hyperthyroidism
颤抖
甲状腺肿大，突眼，情绪激动
腱反射亢进
心慌，心脏肥大
多食、腹泻、消瘦
Hypothyroidism
cretinism (呆小症)
simple goiter
(单纯性甲状腺肿)
瘿
Therapeutic drugs on thyroid
dysfunction
• Hyperthyroidism:
– antithyroid drugs:
thiourea derivatives 硫脲类
iodine and iodides 碘和碘化物
 receptor antagonists
Radioiodines 放射性碘:
• Hypothyroidism:
– thyroid hormones
– iodine and iodides
131I
Antithyroid drugs
Thiourea
derivatives
丙硫氧嘧啶
甲巯咪唑
卡比马唑
Antithyroid drugs
Thiourea derivatives
1. Pharmacological effects
(1) Inhibiting the formation of thyroid hormones by
interfering with iodination: inhibiting peroxidation, then
the iodination and coupling
Symptom relieving: 2-3 weeks
Basic metabolic rate returning: 1-2 months
(2) Inhibiting peripheral deiodination of T4: T4  T3 
(propylthiouracil 丙硫氧嘧啶)
Antithyroid drugs
Thiourea derivatives
1. Pharmacological effects
(3) Inhibiting glucose metabolism by downregulating βreceptor
(4) Immunosuppression: TSI↓
Mechanism of inhibition of thyroid hormone
synthesis by thioureas: Thioureas are oxidized by
oxidized thyroid peroxidase (TPO)
Thiourea derivatives
2. Clinical uses
(1) Non-operative therapy of hyperthyroidism: latent period
(2) Preoperative therapy of hyperthyroidism: combined with
iodide
(3) Thyrotoxic crisis: combined with larger dose of iodide,
propylthiouracil
3. Adverse effects
(1) Agranulocytosis (0.2%)
(2) Hypersensitivity
(3) GI reactions
(5) Goitrogenic action (goiter): TSH↑
Antithyroid drugs
Iodine and iodides
1. Pharmacological effects
(1) Small doses: simple goiter
(2) Larger doses: inhibiting the release of
thyroid hormones (proteolysis ) and
synthesis
After iodide use, the thyroid vascularity is
reduced, and the gland becomes much firmer,
the cells become smaller.
Mechanism of iodides
Antithyroid drugs
2. Clinical uses
(1) Simple goiter
(2) Preoperative therapy of hyperthyroidism:
combined with thiourea derivatives
(2) Thyrotoxic crisis: combined with
thiourea derivatives (propylthiouracil)
Lugol’s solution 卢戈氏液: 5% iodine and
10% potassium iodide
Antithyroid drugs
3. Adverse effects
(1) Acute effects: hypersensitivity, angioedema,
swelling of the larynx
(2) Chronic intoxication (iodism)
(3) Thyroid dysfunction: exacerbation of
hyperthyroidism, goiter
Antithyroid drugs
Radioiodines
• 131I, 125I, 123I
• Destroying thyroid tissue: βray
• Careful use for hyperthyroidism and
differentiated thyroid carcinoma
• Radioactive iodine uptake test
Antithyroid drugs
 receptor antagonists
1. Pharmacological effects
(1) Heart: 1 block
(2) CNS: relieving anxiety
(3) Presynaptic 2 receptor: NE release 
2. Clinical uses
Adjuvant therapeutic drug
Pancreatic hormones &
antidiabetic drugs
胰高血糖素
胰岛素
生长抑素
Overview of Glucose Regulation by insulin
Glucose
absorption
lipolysis
Insulin secretion
lipogenesis
Persistent
Hepatic Glucose
Output
Glucose
disposal
Glycogenesis
Amended from Dinneen SF. Diabetes Med. 1997;14(suppl 3):S19-24.
Different forms of diabetes mellitus
prediabetic metabolic
“Beta-cell failure”
syndrome
Complications of diabetes mellitus
• Acute complications
– Diabetic ketoacidosis (酮症酸中毒)
– Hyperosmotic nonketotic coma(高渗性非酮症性昏迷）
• Chronic complications
–
–
–
–
–
–
–
Cardiovascular diseases
Renal damage
Retinal damage
Nerve degeneration
Infection
Myopathy
etc.
Pharmacological therapy
 Insulin
 Oral hypoglycemic drugs
Insulin secretagogues (促胰岛素分泌药):
Sulfonylureas 磺酰脲类
Meglitinides (Non-SU) 格列奈类
GLP-1 agonists and DPP-4 inhibitors
Insulin sensitizers 胰岛素增敏剂:
Thiazolidinediones (TDs，噻唑烷二酮类)
Biguanides 双胍类
α-glucosidase inhibitors α-葡萄糖苷酶抑制剂
 Amylin analogue 胰淀粉样多肽类似物
 Aldose reductase inhibitor 醛糖还原酶
A. Insulin
Frederick Sanger (1918- )
A. Insulin
1. Pharmacological effects
(1) Carbohydrate metabolism: reducing blood glucose levels
by glycogenolysis , glycogen synthesis , gluconeogenesis 
(ketone bodies ), glucose transport .
(2) lipid metabolism: fat synthesis , lipolysis , plasma free
fatty acids 
(3) Protein metabolism: active transport of amino acids ,
incorporation of amino acids into protein , protein catabolism

(4) Mechanism of insulin actions
Interacting with insulin receptor
A. Insulin
2. Clinical uses
(1) Insulin-dependent patients with diabetes
mellitus (type 1 diabetes mellitus)
(2) Insulin-independent patients: failure to other drugs
(3) Diabetic complications: diabetic ketoacidosis (酮症
酸中毒), hyperosmotic nonketotic coma（高渗性非酮症性昏迷）
(4) Critical situations of diabetic patients: fever,
severe infection, pregnancy, trauma, operation
(5) Others: promotion of K+ uptake into the cells
A. Insulin
3. Preparations
Fast-acting insulin
Regular insulin 正规胰岛素
Monocomponent insulin 单组分胰岛素
• Start working 0.5-1h after injection, reach peak 2-4h,
and last 5-7h.
A. Insulin
3. Preparations
Intermediate-acting insulin
Neurtral protamine hagedorn (NPH) 中性精蛋白锌胰岛素
Isophane insulin 低精蛋白锌胰岛素
Globin zinc insulin 珠蛋白锌胰岛素
• Start working 1-1.5h after injection, reach peak 8-12h,
and last 24h.
A. Insulin
3. Preparations
Long-acting insulin
Protamine zinc insulin(PZI) 鱼精蛋白锌胰岛素
• Start working 4-8h after injection, reach peak 14-20h,
and last 24-36h.
A. Insulin
3. Preparations
Mixed insulin
Human insulin isophane 低精蛋白锌胰岛素+
Human insulin 人胰岛素
• Start working 0.5h after injection, reach peak 2-12h,
and last 16-24h.
A. Insulin
3. Preparations
Fast-acting insulin analogs
Insulin aspart 门冬胰岛素
Insulin lispro 赖脯胰岛素
• Start working 5-15 minutes after injection, reach peak
at 1h, and last ~4 hours.
A. Insulin
3. Preparations
Super-long acting insulin analogs
Insulin glargine 甘精胰岛素
• Onsets 1-2 h after injection and continues to work for
as long as 24 hours.
• Used to treat type 1 or type 2 diabetes mellitus.
• Less soluble than native human insulin at physiological
pH, and precipitates in skin following subcutaneous
injection, resulting in delayed absorption.
• For patients who eat meals out, may consider
use of an insulin pen.
• Most insulins now available as pen
Insulin Pump and Glucose Monitoring
Insulin Pump – “Open Loop”
Patient sets basal infusion rate
and superimposed
boluses
Continuous Glucose Monitor
“Closed Loop” insulin pump system is ultimate goal:
infusion rate adjusted based on input from continuous
glucose monitor.
A. Insulin
4. Adverse effects
(1) Hypersensitivity: treated with H1 receptor antagonist,
glucocorticoids
(2) Hypoglycemia: adrenaline secretion (sweating,
hunger, weakness, tachycardia, blurred vision, headache,
etc.), treated with 50% glucose
(3) Insulin resistance: acute, chronic
(4) Lipoatrophy and lipohypertrophy
(5) Weight gain
(6) Refractive errors
(7) Edema
B. Oral hypoglycemic drugs
Insulin secretagogues （促胰岛素分泌药）:
Sulfonylureas 磺酰脲类
Meglitinides (Non-SU) 格列奈类(苯丙胺酸衍生物)
GLP-1 agonists and DPP-4 inhibitors
Insulin sensitizers 胰岛素增敏剂:
Thiazolidinediones (TDs，噻唑烷二酮类)
Biguanides 双胍类
α-glucosidase inhibitors α-葡萄糖苷酶抑制剂
 Amylin analogue 胰淀粉样多肽类似物
 Aldose reductase inhibitor 醛糖还原酶
B. Oral hypoglycemic drugs
Sulfonylureas（磺酰脲类）
Tolbutamide (D860) 甲苯磺丁脲
Chlorpropamide 氯磺丙脲
Glibenclamide 格列本脲 (优降糖)
Glipizide 格列吡嗪（美吡达）
Gliclazide 格列齐特 (达美康)
Sulfonylureas
1. Pharmacological effects
1) Increase insulin release: blocking ATP sensitive
K+ channel, Ca2+ inflow 
Sulfonylureas
1. Pharmacological effects
2) Increase receptor affinity to insulin (longterm use)
3) Promote glucose uses
4) Increase sensitivity of cells to glucose
5) Anti-uretic effect (Chlorpropamide 氯磺丙脲)
6) Anti-platelet effect (Gliclazide格列齐特)
Sulfonylureas
2. Clinical uses
(1) Insulin-independent diabetic patients
(type 2): alone or combined with insulin
(2) Diabetes insipidus (尿崩症):
Chlorpropamide (氯磺丙脲): anti-uretic hormone
(ADH) 
Sulfonylureas
3. Adverse effects
(1) GI reactions
(2) CNS reactions
(3) Hypoglycemia: especially in elderly, hepatic or
renal insufficiencies
(4) Others: leukopenia ( 白 细 胞 减 少 ), cholestatic
jaundice (胆汁郁积性黄疸), hepatic damage
Sulfonylureas
4. Drug interactions
(1) Potentiation of hypoglycemic effects
replacement in plasma protein binding: salicylic acid,
sulfates, indomethacin, penicillin, warfarin, etc.
inhibition of hepatic microsomal enzymes:
chloramphenicol, warfarin
(2) Attenuation of hypoglycemic effects
induction of hepatic microsomal enzymes: phenytoin,
phenobarbital, etc.
interactions in pharmacodynamics: glucagon,
thiazides, etc.
Non-SU Insulin Secretagogues
• Act by binding to SUR1 on beta cells to promote insulin
secretion.
• Repaglinide (瑞格列奈) and Nateglinide (那格列奈) are
current agents in class.
• Major advantage is rapid onset and offset
– Can dose just prior to meals with better post-prandial
control
– Fewer overnight lows
– Ability to skip the dose if skip the meal.
• Efficacy for repaglinide appears to be similar to SU’s
Non-SU Insulin Secretagogues
• Hepatic metabolism permits use in patients with
impaired renal function.
• Major side effect is hypoglycemia.
• Many drug interactions. Most concerning is
gemfibrozil (吉非罗齐) which increases repaglinide (瑞
格列奈) concentration and may result in prolonged
effect.
• Cost may be an issue (1 or 2 mg tabs: $122.09/month
at drugstore.com)
GLP-1 agonists and DPP-4 inhibitors
• Exenatide (依可那肽): only available as
injection
• Sitagliptin (西他列汀)
B. Oral hypoglycemic drugs
Insulin sensitizers
Thiazolidinediones (TZDs) 噻唑烷酮类化合物
Rosiglitazone 罗格列酮
Pioglitazone 吡格列酮
Biguanides （双胍类）
Metformin 二甲双胍
Thiazolidinediones
1. Pharmacological effects
Selective agonists for nuclear peroxisome
proliferator activated receptor- (PPAR , 过氧化物酶
增殖体激活受体), increasing glucose transport into
muscle and adipose tissue.
(1) Lowering insulin resistance
(2) Lipid metabolism regulation: TG, free fatty acid 
(3) Preventive effects on diabetic complications
(4) Improve  cell function
Thiazolidinediones
2. Clinical uses
Used for treatment of insulin-resistant diabetic
patients or type 2 patients;
Delayed onset of action – takes 8-12 weeks to achieve
maximal effect;
Absence of hypoglycemia when used as monotherapy;
No reliance on renal excretion
Thiazolidinediones
3. Adverse effects
Edema: at higher doses and used with insulin, in older
patients, patients with multiple medical problems, patients
with underlying CAD or CHF
Headache
Myalgia (肌痛)
GI reactions
Hepatic damage (troglitazone).
Contraindicated with Class III or IV heart failure or significant
liver disease.
Biguanides
1. Pharmacological effects
Increasing glucose uptake in fat tissues and anaerobic
glycolysis in skeletal muscles
Decreasing glucose absorption in gut and glucagon release
2. Clinical uses
Mild insulin-independent patients with obesity
Major advantages: Lack of weight gain; Absence of
hypoglycemia; Low cost with generic prep.
3. Adverse effects
Severe lactic acidosis, malabsorption of vitamin B12 and
folic acid
B. Oral hypoglycemic drugs
Alpha-Glucosidase inhibitors
Acarbose-Precose 阿卡波糖
Miglitol-Glyset 米格列醇
Voglibose 伏格列波糖
Alpha-Glucosidase inhibitors
• Acarbose is an oligosaccharide, whereas miglitol
resembles a monosaccharide.
• Miglitol is fairly well-absorbed by the body, as opposed to
acarbose.
• Reducing intestinal absorption of starch (淀粉), dextrin
(糊精), and disaccharides (二糖) by inhibiting the action
of intestinal brush border -glucosidase.
• Acarbose also blocks pancreatic alpha-amylase (淀粉酶).
• Used for diabetes mellitus type 2, particularly with regard
to postprandial hyperglycemia.
Alpha-Glucosidase inhibitors
• Must be taken at the start of main meals to have maximal
effect.
• Efficacy will depend on the amount of complex
carbohydrates in the meal.
• Absence of hypoglycemia when used as monotherapy.
• Side effects: gastrointestinal side effects such as flatulence
and diarrhea; voglibose, in contrast to acarbose, has less of
GI side effects and more economical.
B. Oral hypoglycemic drugs
Amylin analogues
• Mechanism of action:
– Inhibits postprandial glucagon secretion, thereby reducing hepatic
glucose production
– Slows gastric emptying
– Promotes satiety reduces caloric intake
• Pramlintide (Symlin普兰林肽) is the only amylin analog on
the market
• As adjunct therapy for patients with type 1 or 2 diabetes to
control postprandial glucose
• Increases the risk of severe hypoglycemia
• Main side effect is nausea.
Riddle and Drucker. Diabetes Care 2006; 29:435-49.
B. Oral hypoglycemic drugs
Alsose reductase
– Aldose reductase activity increases in those
tissues that are not insulin sensitive, including
lenses, peripheral nerves and glomerulus.
– Epalrestat (依帕司他) inhibits aldose reductase.
– Delay the progression of diabetic neuropathy
and ameliorate the associated symptoms of the
disease.
B. Oral hypoglycemic drugs
Mechanism of Action
Class of Agent
Indications for Use
Stimulators of insulin secretion
Sulfonylureas
Glinides
Primary
Insulin sensitizers
Thiazolidinediones
(PPAR agonists)
Primary or Secondary
Suppressors of hepatic glucose
production
Biguanides
Primary or Secondary
Reduces postprandial glucose
excursion
Alpha-glucosidase
Inhibitors
Glinides
Secondary
Enhance incretin/GLP1 action
GLP1 analogs
DPPIV inhibitors
Secondary
Type II Diabetic Medications
Medication
Site of
Action/Mechanism
Side-Effects
Sulfonylurea (eg.
glyburide)
Augments insulin
secretion, binds SUR
Hypoglycemia, caution
renal insufficiency, elderly
Thiazolidinediones (eg.
rosiglitazone)
PPARg receptor/increased
insulin sensitivity
Liver, LE edema,
congestive heart failure,
MI
Biguanide (metformin)
Reduced hepatic
gluconeogenesis
GI upset, Lactic acidosis
(very rare), only use if
creatinine<1.5 mg/dl
Glinides (repaglinide)
Bind SUR, short action
Hypoglycemia, caution in
renal insufficiency
Alpha-glucosidase
inhibitors (acarbose)
Inhibits brush border
enzyme/Reduce glucose
absorption
Flatulence, diarrhea
Incretins/GLP-1 (exenatide) Stimulates insulin, delays
gastric emptying, satiety
Nausea, vomiting (given
by injection)
DPP4 Inhibitors
(vildagliptin)
GI side effects
Inhibits GLP1 breakdown
Adrenocorticoids &
adrenocortical antagonists
Adrenocortical hormones
– Glucocorticoids
(Glucocorticosteroids)
– Mineralocorticoids
– Sex hormones
Zona
Faseciculata
Zona
Reticularis
Androgens
Adrenaline
Structure and function of adrenal cortex
‒
ACTH
Regulation of
glucocorticoids
A. Glucocorticoid drugs
Basic structure of glucocorticoid drugs
18
H
12
C 14
13
19
1
A
3
9
2
4
D 15
16
10
5
B
6
8
7
甾体结构
A. Glucocorticoid drugs
Structure
(1) 1位和2位碳之间改成不饱和的双键:
cortisone  prednisone;
hydrocortisone  prednisolone.
(2) 16引入羟基:
triamcinolone(曲安西龙).
(3) 6引入甲基:
6-methylprednisone
(6甲基泼尼松).
(4) 9引入氟原子:
fludrocortosone
(氟氢可的松).
基本结构
H
19
1213 18 16
C 14 D 15
2 1
10 9 8
A 5 B
3
4
6 7
Hydrocortisone
(氢化可的松,
Cortisol)
Cortisone
(可的松)
H
Prednisone
(泼尼松)
(地塞米松)
Prednisolone
(泼尼松龙)
Fluocinolone
(氟轻松)
A. Glucocorticoid drugs
2. ADME and properties of commonly
used drugs
Cortisone and prednisone are reduced and
transformed to hydrocortisone and
prednisolone (active forms) in the liver
Metabolism will be increased by hepatic
enzyme inductors (phenobarbital, phenytoin,
rifampine, etc.)
A. Glucocorticoid drugs
Commonly used drugs
Short-acting: hydrocortisone (cortisol) 氢化可的松
cortisone 可的松
Intermediate-acting: prednisone 泼尼松, 强的松
prednisolone 泼尼松龙, 强的松龙
Long-acting: dexamethasone 地塞米松
Topical:
fluocinolone 氟轻松
A. Glucocorticoid drugs
Mechanisms of glucocorticoid actions
binding to glucocorticoid receptor (GR)
nuclear translocation
binding to GRE or nGRE
regulating related gene transcription
biological effects (usually slow)
Genetic action mode of
glucocorticoid drugs
CBG: corticosteroid binding globulin
S: glucocorticoid steroids
GR: glucocorticoid receptor
HSP: heat shock protein
IP: immunophilin
GRE: glucocorticoid-response element
Dexamethasone
Nuclear
translocation of
glucocorticoid
receptors (GR)
Examples of glucocorticoid actions:
Inhibition of proinflammatory gene transcription (AP-1 and
NFB)
A. Glucocorticoid drugs
1. Pharmacological effects
(1) Effects on metabolism
(2) Permissive action
(3) Anti-inflammatory effects
(4) Effects on immune and allergy
(5) Anti-shock
(6) Other effects
antipyretic effects
effects on blood and blood-forming organs
skeletal system
CNS effects
A. Glucocorticoid drugs
(1) Effects on metabolism
①Glucose metabolism:
gluconeogenesis, glucose oxidation and utilization
 blood glucose.
②Protein metabolism:
synthesis, degradation.
③Lipid metabolism:
plasma cholesterol, fat redistribution (central
obesity: moon face, buffalo hump, etc.).
④Water and electrolytic metabolism:
Na+ excretion, K+ excretion, Ca2+ excretion and
absorption.
Weaker action of glucocorticoid drugs (cortisol
氢化可的松) on mineralocorticoid receptor
A. Glucocorticoid drugs
(2) Anti-inflammatory effects
1) Acute
a) Increasing anti-inflammatory proteins and enzymes
inducing lipocortin (脂皮素), inhibiting phospholipase A2 activity,
decreasing mediators: PGs, LTs, PAF
inducing vasocortin (血管内皮素), decreasing microvascular
permeability
inhibiting the expression of COX-2, inducible NOS, etc.
b) Inhibiting cytokines: decreasing the transcription and activities
of TNFα, IL-1, IL-2, IL-5, IL-6, IL-8, etc.
c) Inhibiting adhesion molecules
d) Inducing apoptosis of inflammatory cells
A. Glucocorticoid drugs
(2) Anti-inflammatory effects
Chronic: inhibiting fibroblast proliferation
deposition of collagen
cicatrization (瘢痕形成)
Inhibition of proinflammatory gene transcription (AP-1 and
NFB)
A. Glucocorticoid drugs
(3) Suppressive effects on immune and allergy
a) inducing apoptosis of T and B lymphocytes
b) inducing DNA degradation of T and B lymphocytes
c) Inhibiting DNA and protein synthesis of T and B
lymphocytes
d) inhibiting transcription factor activity (eg. AP-1, NF-B
e) Inhibiting mast cells (anti-allergic)
(4) Permissive action
Potentiating the effects of catecholamines and
glucagon
A. Glucocorticoid drugs
(5) anti-shock
a) improving cardiovascular functions
b) inhibiting the production of inflammatory
factors
c) stabilizing lysosome membrane:
decreasing the release of myocardial
depressant factor (MDF)
d) increasing the tolerance to endotoxin from
bacteria
A. Glucocorticoid drugs
(6) Other effects
a) antipyretic effects
b) effects on blood and blood-forming organs
red cell ; lymphocytes ; neutrophils  (function );
eosinophils ; platelets 
c) skeletal system: osteoporosis
d) CNS: increasing excitability (elevated mood, euphoria,
insomnia, restlessness, increased motor activity)
A. Glucocorticoid drugs
3. Clinical uses
(1) Immune diseases
a) autoimmune disorders: rheumatic fever, rheumatic
carditis, rheumatic arthritis, rheumatoid arthritis,
osteoarthritis, systemic lupus erythematosus,
polyarthritis nodosa, nephritic syndrome, etc.
b) rejection of organ transplantation
c) allergic diseases: urticaria (风疹), serum sickness,
contact dermatitis, drug allergic reactions, chronic
severe asthma, status asthmaticus, angioneurotic
edema, etc.
A. Glucocorticoid drugs
3. Clinical uses
(2) Severe infection and inflammation
a)
acute severe infections: merely suppressing
inflammatory manifestations but at times lifesaving
Caution: ①combination with effective anti-microbial drugs;
②Large dose; ③short term administration !
Usually be not used in viral and fungal infections except
for those with cerebral edema or severe systemic
symptoms
b) prevention of sequelae ( 后 遗 症 ) of some types of
inflammation, such as in brain, heart, eye, joint, etc.
A. Glucocorticoid drugs
3. Clinical uses
(3) Septic shock:
Caution: larger dose, short-term, and combined with
antimicrobial drugs.
(4) Hemological diseases: acute lymphocytic leukemia,
lymphomas, aplastic anemia ( 再 生 障 碍 性 贫 血 ),
hemolytic anemia, leukocytopenia, thrombocytopenia,
etc.
(5) Topical applications: skin, eye, respiratory tract,
joint (local injection)
(6) Some types of tumors: breast and prostatic cancers,
acute lymphocytic leukemia, etc.
A. Glucocorticoid drugs
4. Adverse effects
(1) Effects resulting from continued used of large
doses
a) Hypercorticism-like syndrome: central obesity
(moon face, buffalo hump,
glycosuria, hypokalemia; etc.
etc.);
hypertension;
b) Increasing susceptibility to infections:
Caution: specific antimicrobial drugs should be
administered with GCs
c) Ingestive system: peptic ulcers, etc.
A. Glucocorticoid drugs
4. Adverse effects
d) Cardiovascular system: hypertension,
arteriosclerosis
e)
Myopathy
and
osteoporosis:
compression fractures, spontaneous
especially in postmenopausal women
vertebral
fractures,
f) CNS: behavioral disturbances, induction of
epileptic seizures
g) Inhibition or arrest of growth in children
‒
ACTH
Suppression of
hypothalamicpituitary-adrenal
axis
and glucocorticoid drugs
A. Glucocorticoid drugs
4. Adverse effects
(2) Withdrawal syndrome
a) Suppression of hypothalamic-pituitary-adrenal axis
b) Exacerbation of the underlying diseases (rebound)
(3) Contraindications
psychiatric disorders; epilepsy; active peptic ulcers;
fractures; hypercorticism; severe hypertension;
diabetes mellitus; viral or fungal infections, etc.
Balance the ratio of benefit/risk
before the use of GCs !
A. Glucocorticoid drugs
5. Applications
(1) Replacement therapy: usually using hydrocortisone
(2) Prompt intensive treatment: i.v. gtt hydrocortisone,
dexamethasone
(3) Long-term therapy: oral prednisone or prednisolone
morning single dose
alternate-day therapy
Notes: for less severe and less sustained patients;
less suppression on hypothalamic-pituitaryadrenal (HPA) axis
(4) Typical applications: skin; eye; respiratory tract
Some indications for the use of glucocorticoids
B. Mineralocorticoid drugs
Aldosterone 醛固酮
• Roles:
Na+ excretion , K+ excretion 
edema
hypertension
hypokalemia, etc.
• Used for adrenocortical dysfunction with
imbalance of water and electrolytes
Action of aldosterone on mineralocorticoid receptor
AIP
Mineralocorticoid receptor signal transduction.
• MR: mineralocorticoid receptor;
• HRE: hormone responsive element.
• AIP: Aldosterone induced protein
C. Adrenocorticotropic hormone and
corticosteroid synthetase inhibitors
Adrenocorticotropic hormone (ACTH)
1. Used for diagnosis of adrenocortical function
2. inhibition of secretion of adrenocortical
hormones after long-term glucocorticoid
drug use
3. Easily inducing allergy to ACTH
C. Adrenocorticotropic hormone and
corticosteroid synthetase inhibitors
2. Corticosteroid synthetase inhibitors
Mitotane 米托坦
Metyrapone 美替拉酮
Aminoglutethimide 氨鲁米特
Used for adrenocortical tumors or
hypercorticism