中医中药药理学外文版 (34).pdf

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1、PWMCThyroid and anti-thyroid drugsoutlines(1)thyroid hormone synthesis and application(2)treatments of hyperthyroidismPWMCEffects of T4 and T3 physiological effects maintain growth and function nervous,skeletal,and reproductive tissues increase metabolism of carbohydrate,fats,proteins,and vitamin pa

2、thological effects Excess amounts thyrotoxicosis hypermetabolic states Inadequate hypothyroidism,cretinism,myxedma hypothyroidismPWMCThyroid hormone synthesisPWMCRegulation of secretionfeedbackHigh iodidePWMCThyroid hormoneshyperthyroidismmyxedemahypothyroidismThyroxine(T4)Triiodothyronine(T3)iodide

3、sThioamidessurgeryCretinism-hypometabolismental retardation PWMCTargets for drugsIodine uptakeactive iodinePeroxidasetyrosineMono-,Di-iodotyrosineT4 T3ReleaseTSHHypothalamus and pituitaryBiological effectsThioureasHighdose iodine receptor blockerPWMCAntithyroid agentsThioureas Inhibit peroxidase,iod

4、ine organification,coupling of iodotyrosines,deiodination of T4 Adverse effects Manulopapular,pruritic rash,fever Rare adverse effects Agranulocytosis(Most dangerous complication)Iodides Inhibit iodine organification,release,decrease the vascularity Adverse effects-Uncommon and reversibleRadioactive

5、 iodine and beta receptor blockersBlockade of hormone releasePWMCtreatment options for hyperthyroidismMethods Duration patientsdisadvantagesAntithyroid drug 1-2yearsSmall gland and mild diseaseReversible hypothyroidismThroidectomy6weeksLarge gland or multinodulargoitersIrreversiblehypothyroidismRadi

6、oactiveiodine6-12monthsPatients without heart disease,pregeancy and cant ultize above methodsIrreversible hypothyroidismAdjuncts to antithyroiddrugsthyrotoxicosisbackPharmacology Department of Wenzhou Medical UniversityPWMCPancreatic hormone and antidiabeticdrugs PWMCWhat are diabetes and their comp

7、lication?Diabetes Most factors:enviromental factor,drugs and lifestyle,especially diets,and diseases.Dysfunction of Pancreas Insulin secretion not enough Insulin resistance Diabetic retinopathy,nephropathy,diabetic foot,and so on.(all tissue)Im“sick tigger”PWMCFeatures of main diabetesPWMCHow do glu

8、cose initiate the injury of tissues and the targets Causes(1)insulin deficiency(2)inadequate(3)resistanceHigh Glucose AGEsInflammatory reactionEndothelial dysfunctionsSigals inetworkingRejectionReplacementimprovementBlockadecomplicationsStimulation PWMCinsulin and insulin receptorresistancePWMCsecre

9、tion,Degradation of insulin Liver clear Kidney clearPWMCEffects of insulin on its targets Effect on liver:Inhibits glycogenolysis Inhibits conversion of fatty acids and AA to keto acidsInhibits conversion of amino acids to glucose Promotes glucose storage as glycogen Decreases triglyceride and VLDL

10、formation Effect on muscle:Increases amino acid and glucose transport Increases ribosomal protein synthesis Induces glycogen synthase and inhibits phosphorylase Effect on adipose tissue Lipoprotein lipase activate and inhibit Intracellular lipase Malmstrm,Defective regulation of triglyceride metabol

11、ism by insulin in the liver in NIDDM Diabetologia.1997,40(4):454-62PWMCTreatment with insulin insulin-Dependent diabete Insulin-inpendent diabete Resistance to alimentary control and ORAL ANTIDIABETIC AGENTS Diabetes ketoacidosis,or nonketotic hyperosmolar coma diabetes with infection,fever,pregency

12、,trauma and surgery Intracelluar hypokalemiaPWMCadverse effects Hypoglycemia Most common complication Symptoms Hypoglycemic unawareness TreatmentsImmuopathology of insulin therapy Insulin allergy Immune insulin resistanceLipodystrophy at injection sitesPWMCinsulin preparation and treatmentsRapid-act

13、ing and short-acting insulin preparationsIntermediate-acting insulin(NPH)Long-acting insulin preparationsInsulin combinationsPWMCintensive and standard therapyMore dose,More pharmacological effectsmore adverse effects-Free GlucoseOral antidiabetic agents Mechanisms of oral antidiabetic agentsglucose

14、starchglycogenBlood glucoseamineglycogenProteinenergy(1)Sulfonylureas(5)Glucosidase inhibitorsInsulins(2)Glinides(3)Biguanides(4)ThiazolidinedionesSodiumglucose cotransporter 2 inhibitorsPWMCOral antidiabetic agents Sulfonylureas block ATP-K+-channel First generation Tolbutamide Chlorpropamide Tolaz

15、amide Second generation Glyburide Glipizide Glimepiride Secondary failure and tachyphylaxis to sulfonylureasPWMCOral antidiabetic agents Drugs mechanismClinical useSide effectsMeglitinidesPotassiumchannels:two binding sitesType 2 diabetic individuals with sulfonylureasallergyhypoglycemiaD-phenylalan

16、ine derivativePotassium channelsIsolatedpostprandial hyperglycemia,combinationhypoglycemiathiazolidinedionesPpar-receptorType 2 diabetes monotherapyWeight gain,fluid retention-glucosidaseinhibitorsIntestineglucosidaseType 2 diabetes,monotherapy and combinationGlatulence,diarrhea,painManagement of diabetesWhat treatment options are available for type 2 diabete?Dietary limited and excises Oral antidiabetic drugs Insulin injectionWhat are insulin clinical applications?