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1、Chapter3 Pharmacodynamics【Learning points】Section 1 The Basic Effects of Drugs 一、Drug effects and pharmacological effects Drug action refers to the initial action between the drug and the bodys cells,which is the motivation,and it has the specific characteristic.The pharmacological effect is the res
2、ult of the action of the drug and the manifestation of the bodys reaction.The pharmacological effect means a change in the original functional level of the bodys organs including function enhancement called excitation,and functional reduction called inhibition.Most drugs produce pharmacological effe
3、cts through chemical reactions.The specificity of this chemical reaction makes the drug specific.The substance basis of drug action specificity is the chemical structure of the drug.The role of the drug action also has its selectivity,refers to the various response when a certain dose of the drug ta
4、king effects on different tissues or organs.The basis of selectivity are:The differences in the distribution of drugs in vivo,the structure of tissues and cells in the body,and the differences in biochemical functions.The specificity and selectivity of drug action are not necessarily parallel.Sectio
5、n 2 The therapeutic effect Therapeutic effect,refers to the result of the action of the drug which is beneficial for the patients physiological,biochemical function or pathological process,then it can normalize the diseased body.According to the effect of the therapeutic effect,the therapeutic effec
6、t can be divided into:(1)Etiological treatment:The purpose of medication is to eliminate the original pathogenic factors and cure the disease completely.(2)Symptomatic treatment:The purpose of medication is to ameliorate symptoms,which called symptomatic treatment.The cause cannot be eradicated by s
7、ymptomatic treatment,but it is essential for diseases that cannot be cured temporarily for unknown reasons.In some critical illnesses such as shock,high fever,and severe pain,symptomatic treatment is more urgent than etiological treatment.Section 3 Adverse reactions The reactions that are not relate
8、d to the purpose of the medication and bring discomfort or pain to the patient are collectively referred as adverse reactions.Most adverse reactions are inherent effects of drugs,which are generally predictable,but not necessarily avoidable.A few of the serious adverse reactions are difficult to rec
9、over and are called drug-induced diseases,such as neurodegenerative deafness caused by gentamicin.A.Side reaction:Due to low selectivity,multiple organs are involved when drugs taking pharmacological effects.When an effect is used for therapeutic purposes,other effects become side effects.For exampl
10、e,when atropine is used to relieve gastrointestinal cramps,it can cause side effects such as dry mouth,palpitations,and constipation.Side effects occur at therapeutic doses and are inherent in the drug itself,most of which are mild and predictable.B.Toxic reaction:Toxic reaction refers to a hazardou
11、s reaction that occurs when the dose is too large or the drug accumulates in the body too much,which is generally serious.Toxic reactions are generally predictable and should be avoided.Acute toxicity often damages circulation,respiratory and nervous system functions,while chronic toxicity often dam
12、ages liver,kidney,bone marrow,endocrine and other functions.Carcinogenesis,teratogenesis and mutagenesis reactions also belong to the category of chronic toxicity.C.Residual effect:refers to the residual pharmacological effect when the blood drug concentration has dropped below the threshold concent
13、ration after drug withdrawal.D.Withdrawal reaction:refers to the aggravation of the original disease after sudden withdrawal,also known as rebound reaction.E.Allergic reaction:It is a type of immune reaction.The reaction that will occur when non-peptide drugs,as haptens,binding to body proteins as a
14、ntigens after a sensitization process about 10 days of contacting.It is also called hypersensitive reactions.It is common in patients with allergies.The nature of the reaction has nothing to do with the original effect of the drug,and pharmacological antagonists is ineffective for rescue.The severit
15、y of the response varies greatly,regardless of dose.The reaction gradually disappears after the drug is stopped,and may recur when used again.The sensitizer may be the drug itself,its metabolite,or it may be an impurity in the preparation.Although skin allergy tests are often done before clinical me
16、dication,there are still a few false positive or false negative reactions.F.Idiosyncratic reaction:This is a kind of reaction caused by congenital genetic abnormality,but it is basically consistent with the inherent pharmacological effect of the drug,the severity of the reaction is proportional to t
17、he dose,and the pharmacological antagonist treatment may be effective.This reaction is not an immune response,so no prior sensitization process is required.Section 4 Relationship between Drug Dose and Effect The pharmacological effect is proportional to the dose within a certain range,this is the do
18、se-effect relationship.The dose-effect curve is obtained by plotting the effect intensity as the ordinate,the drug dose or the drug concentration as the abscissa.The pharmacological effect can be divided into two cases:quantitative response and qualitative response according to the nature.The streng
19、th of the effect shows a continuous increase and decrease.The specific quantity or the percentage of the maximum response can be called a graded response.The following specific sites can be seen from the dose-effect curve of volume response:Minimum effective dose or minimum effective concentration:n
20、amely the minimum dose or minimum drug concentration that can just cause an effect,also known as threshold dose or threshold concentration.Maximum effect(Emax):As the dose or concentration increases,the effect also increases.When the effect increases to a certain degree,if the drug concentration or
21、dose continues to increase and the effect does not continue to increase,the limit of this pharmacological effect is called the maximum effect,also known as efficacy.Concentration for 50%of maximal effect(EC50):refers to the concentration that can cause 50%of maximum effect.Potency:refers to the rela
22、tive concentration or dose that can cause an equivalent response(generally using 50%effect amount),the smaller the value,the greater the intensity.The maximum effect of the drug is completely different from the potency strength,and the two are not parallel.If the pharmacological effect is not a cont
23、inuous quantity change with the increase or decrease of the drug dose or concentration,but a change in the nature of the reaction,it is called a qualitative response(quantal response or all-or-none response).The qualitative response is expressed in a positive or negative,all-or-nothing manner,such a
24、s death and survival,convulsions and non-convulsions.The following specific sites can be seen from the dose-effect curve of qualitative reaction:Median effective dose(ED50):the drug dose that can cause 50%of laboratory animals to have a positive reaction;if the effect is death,it is called median le
25、thal dose(LD50).Therapeutic index(TI):The ratio of the drugs LD50/ED50,used to indicate the safety of the drug.Drug safety evaluation index:drugs with large therapeutic index are safer than drugs with small therapeutic index.But it is not completely reliable.Because there is an overlap between the e
26、ffective dose and its lethal dose.For this reason,some people use the ratio of 1%lethal dose(LD1)to 99%effective dose(ED99)or the distance between 5%lethal dose(LD5)and 95%effective dose(ED50)to measure the safety of drugs.Section 5 Drugs and Receptors 1.The origin of receptor research 2.The concept
27、 and characteristics of the receptor Receptor:It is a type of functional protein(glycoprotein or lipoprotein)that exists in the cell membrane or cell and recognizes and binds specific biologically active molecules and transduces signals to cause corresponding biological effects.Ligand:refers to the
28、substance that can specifically bind to the receptor in the body,also known as the first messenger.The receptor has a very high recognition capacity for the corresponding ligand,and the receptor has corresponding endogenous ligands,such as neurotransmitters,hormones,and autologous substances(autacoi
29、d).2.The receptor has the following characteristics:sensitivity,specificity,saturability,reversibility,multiple-variation.3.Interaction between receptors and drugs(1)The classic theory of receptors-occupation The receptor can only be activated and produce an effect by binding to the drug,and the int
30、ensity of the effect is proportional to the number of occupied receptors.The greatest effect occurs when the receptors are all occupied.(2)Receptor and drug response kinetics The effect of the drug binding to the receptor requires not only affinity but also intrinsic activity.When the affinity of th
31、e two drugs is equal,the effect strength depends on the strength of the intrinsic activity,and when the intrinsic activity is equal,it depends on the magnitude of the affinity.4.Classification of drugs acting on receptors According to the difference between the effects of drugs and receptors,it is c
32、ustomary to classify drugs that act on receptors into agonists,partial agonists,and antagonists(blockers).(1)Agonist drugs:drugs that have both affinity and intrinsic activity,they can bind to the receptor and activate the receptor to produce an effect.According to its intrinsic activity,it can be d
33、ivided into full agonist and partial agonist.The former has strong affinity and strong intrinsic activity(=1);the latter has strong affinity,but the intrinsic activity is not strong(1).It can also antagonize some of the effects of agonist when used in combination with agonist.(2)Antagonists:drugs th
34、at can bind to receptors and have strong affinity without intrinsic activity(=0).Antagonists are classified into competitive antagonists and noncompetitive antagonists according to whether their binding to the receptor is reversible.Competitive antagonists can compete with agonists for the same rece
35、ptor,and their binding is reversible.By increasing the dose of the agonist drug and the competitive binding site of the antagonist drug,the dose-effect curve can be shifted to the right in parallel,but the maximum efficacy remains unchanged.5.Types of receptor According to the characteristics of the
36、 receptor protein structure,signal transduction process,effect properties,and receptor position,the receptor can be roughly divided into the following five categories:G protein-coupled receptor,ligand-gated ion channel receptor,tyrosine kinase Receptors,intracellular receptors,other enzyme receptors
37、.6.Intracellular signal transduction After the receptor recognizes and binds to the corresponding ligand,it needs the second intracellular messenger to obtain information enhancement,differentiation,integration,and transmission to the effector in order to exert its specific physiological function or
38、 pharmacological effect.The earliest discovered second messenger was cAMP,and now it is known that cAMP,cGMP,phosphatidylinositol,calcium and many other substances participate in intracellular signaling divert.7.Regulation of receptors The regulation of receptors is an important factor to maintain t
39、he stability of the environment in the body.There are two types of regulation methods:desensitization and sensitization.Receptor desensitization refers to a phenomenon in which the sensitivity or responsiveness of tissues or cells to agonists decreases after long-term use of an agonist.Receptor hype
40、rsensitization is a phenomenon opposite to receptor desensitization,which can be caused by decreased levels of receptor agonists or long-term use of antagonists.If receptor desensitization and sensitization only involve changes in receptor density,they are called down-regulation and up-regulation,respectively.