1 / 48

Pharmacodynamics

Pharmacodynamics. Department of pharmacology Yang Fangju( 杨芳矩） 2010.3.

alvarezm
Download Presentation

Pharmacodynamics

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Pharmacodynamics Department of pharmacology Yang Fangju(杨芳矩） 2010.3

  2. 1. Drug action and pharmacological effects(1) pharmacological action: The action of the drug does the body. That is original action between the drug and the cells of the body. The action of the drug does the body. That is original action between the drug and the cells of the body.

  3. (2) pharmacological effects: The functional change of the organs or tissue in the body that is produced by the original drug action. • (3) excitation and exciter • (4) inhibition and inhibitor • (5) selectivity of pharmacological effect

  4. drugs are only selective--rather than specific--in their actions, because they bind to one or a few types of receptor more tightly than to others and because these receptors control discrete processes that result in distinct effects. • In drug development and in clinical medicine, selectivity is usually considered by separating effects into two categgries: beneficial or therapeutic effects versus toxic effects.

  5. It is only because of their selectivity that drugs are useful in clinical medicine. Thus, it is important, both in the management of patients and in the development and evaluation of new drugs, to analyze ways in which beneficial and toxic effects of drugs may be related, in order to increase selectivity and usefulness of drug therapy.

  6. Therapeutic Effects and Adverse Drug Reaction • 1. Therapeutic effect • The action is accord with using drug aim and propitious to prevention or treatment disease. • (1) etiological treatment • (2) symptomatic treatment • (3) supplement therapy

  7. 2. Adverse Drug Reaction (ADR) • The action is not accord with using drug aim and bring ailment or harm to the patients. (1) side reaction • This term is used to describe therapeutically undesirable but unavoidable effects of drugs. • Characteristics: ① it occurs in the treatment dose, ② the symptoms are light, ③ it can be predicated, ④ and it is avoidable or lighten by combing with other drugs, but unavoidable when using alone.

  8. (2) toxic reaction: • These may be arise from a single large dose or by accumulation after repeated dose and are usually shown as an exaggerated form of the pharmacological actions typical of the drugs. • Characteristics: ① it occurs in overdosage, ② the symptoms are severe,③ it can be predicated, ④ and it is avoidable.

  9. Toxic effects of drugs may be classified as pharmacological, pathological change, or special toxicity (alteration of DNA, such as carcinogenesis, mutagenesis and teratogenesis). • Toxic effects of drugs may also be classified as acute and chronic toxic effects. • The acute toxicity mainly affects the circulation system, CNS, or blood system. • The chronic toxicity mainly induces pathological change of tissue or special toxicity of cells.

  10. (3) Allergic Reactions: • These are mediated by an antigen-antibody reaction and usually involve previous exposure and sensitization to the drugs. • Characteristics: • ① the occurrence of the symptoms is not concerned with dose, • ② the symptoms can be light or serve, • ③ it can not be predicated, • ④ and it is unavoidable in a tiny minority condition.

  11. (4) Residual (after) Effect: • the residual biological effects when the drug concentration in blood is decreased under the minimum effective concentration (threshold concentration).

  12. (5) Withdrawal Reaction: • it is induced after withdrawal drug administration. (6) Idiosyncrasy: • it is used to describe a qualitatively abnormal reaction to a drug. An example is the hemolytic anemia that occurs in some patients after taking the antimalarial drug primaquine

  13. dose effect relationship Dose effect relationship: • the regular variation between the dose and the effects that the effects increase following the dose increase in some range. 1.Dose effect curve: • the curve is obtained from intensity of effect for the ordinate and dose or concentration for the abscissa.

  14. (1) Quantitative dose response curve: • the quantity for the ordinate expresses the intensity of effects. Such as heart rate, blood pressure, volume of Na+ excretion .

  15. (2) Qualitative dose response curve: • A cumulative frequency distribution of individuals achieving the defined effect as a function of drug concentration is qualitative dose response curve. • ( the concentration-percent curve or the quantal concentration effect curve). • the effect of a drug is recorded as an “ all or none event ” ( positive, negative response) for the ordinate of effects, e.g. death or survival, convulsion or unconvulsion, anaesthetization or unanaethetization.

  16. This curve resemble the sigmoid shape of the graded concentration-effect curve.

  17. Both above curves are plotted rectangular hyperbolic relationship. • these curves become symmetrical S-shaped(sigmoidal) if a ogarithmic dose axis is used.

  18. 2. Dose effects relationship • (1) dose: the share of drug administered. • ① minimal effective dose( minimal effective concentration), it is also called threshold dose or concentration. • ② maximum effective dose • ③ treatment dose • ④median effective dose ( ED50):the dose of drug that produces 50 percent effectivity in a group of animals. • ⑤median lethal dose(LD50): the dose of drug that produces 50 percent mortality in a group of animals.

  19. lethal effect toxic action Acted intensity effective Tolerance dose inaction ineffective dose Effective dose minimal effective dose Minimal toxic dose Minimal fatal dose Lethal dose Toxic dose

  20. (2) Effect • ① maximal effect( efficacy, Emax) • The maximal effect can be produced by a drug. It is determined principally by the properties of the drug and its receptor-effecter system and is reflected in the plateau of the concentration-effect curve. • ②potency

  21. The location of the concentration-effect curve along the concentration axis is an expression of the potency of a drug. • Potency refers to the concentration (EC50) or dose (ED50) of a drug required to produce 50% of that drug's maximal effect.

  22. volume of Na+ excretion . • （ mmol ） 200 ? 堵米 furosemide 150 ? 戊 ?? cyclopenthiazide ???? ??? 100 50 0.l 0.3 1 3 10 30 100 300 1000 dose （ mg ） The potency and Emax Comparison of Various diuretics

  23. (3) assessment of drug safety • ① therapeutic index: • the ratio which is the ratio of the dose which kills 50 percent of a group of animals, the median lethal dose(LD50), and which produces a desired pharmacological effect in 50 percent of a group of animals, the median effective dose(ED50).

  24. Therapeutic index = • ② margin of safety: • the ratio of the dose which kills 5 percent of a group of animals(LD5), and the dose which produces a desired pharmacological effect in 95 percent in a group animals(ED95). • Margin safety =

  25. ③ reliable safety coefficient: • the ratio of the dose which kills 1 percent of a group of animals(LD1), and the dose which produces a desired pharmacological effect in 99 percent in a group animals(ED99). • reliable safety coefficient = LD1 /ED99

  26. (4) individual variability • The concentration of a drug that produces a special effect in a single patient is termed the individual effective concentration. • This is quantal response, since the defined effect is either present or absent. • Individual effective concentration usually are lognormally distributed, which means that a normal variation curve is the result of plotting the logarithms of the concentration against the frequency of patients achieving the defined effect.

  27. mechanisms of drug action • 1 enzyme • 2 ion channel • 3 nucleic acid • 4 carrier • 5 immunity system • 6 gene therapy and gene engineering drug • 7 others: receptor action of drugs; physic and chemical action; complementarity action.

  28. receptors 1.concept of receptors • Drug receptors are proteins that serve as receptors for endogenous regulatory • ligands. Many drugs act on such physiological receptors and are often particularly selective.

  29. 2. interaction theory of drug and receptor • (1) occupation theory • (2) rate theory • (3) two model theory • 3. response dynamics of receptor and drug • (1) basic formula of response kinetics of receptor and drug

  30. A + R AR E • A: drug, R: receptor, • AR: complex of receptor and drug; • E: effect • KD =k2/k1 = ① ( KD: ionized constant), • [AR] = ① • ∵RT=[ R]+[ AR] ② , • (RT is total amount of receptor) • [R]=RT - [AR] [AR]=RT - [R]

  31. From ② to ① : • KD = • KD[AR] =[A]([RT]-[AR])=[A][RT]-[A][AR] • KD[AR]+[A][AR]=[A][RT] • [AR](KD+[A])=[A][RT] • ∴

  32. When binding ratio of receptor and drug arrives 100%, the effect arrives 100%. • ∴ • If: (r is binding percent of • drugs and receptor) • the binding receptor holds in r of total receptors, the effect arrives in corresponding • fraction E/Emax, then r = • When r increase far off exceed KD, r→1, that arrives in Emax.

  33. ∵ , • Transposition: • ∴ • When r→1,

  34. When r=50%, • That is drug dose when Emax arrives in the half (it means 50% of receptors hold). • PD2: -logKD of KD. That is direct ratio with affinity of A and R.

  35. 3. agonist and antagonist (1) agonist • ① affinity: The binding ability of the drug with receptor. • ② intrinsic activity: The ability of the drug excites receptor. It can be expressed asа. • ③ full agonist: it has intense affinity and intrinsic activity(а= 1) • ④ partial agonist: it has intense affinity, but weak intrinsic activity(а< 1) • ⑤ inverse agonist or negative antagonist ligand.

  36. (2) antagonist: • it has intense affinity, but has no intrinsic activity(а= 0) • ① competitive antagonist • affinity of competitive antagonist expresses as PA2. It is negative logarithmic • value of mol concentration of competitive antagonist added in reacted system of agonist that makes the effect of agonist in 2 times concentration equal to the effect of agonist in 1 time concentration.

  37. ② non-competitive antagonist • affinity parameter of non-competitive antagonist expresses as PA2’. It points negative logarithmic value of mol concentration of non-competitive antagonist during it makes Emax of agonist descend to half.

  38. transmembrane signaling and intracellular messenger • 1. classification of drug receptors according to mechanism of transmembrane signaling • (1) G protein-coupled receptor • (2) ligand gate ion channel receptor • (3) Tyrosine kinases receptor • (4)cell nuclear hormone receptor • (5)cytokine receptor • (6) other enzyme receptor

  39. 2. intracellular signal transductant • (1)first messengers: hormones, neurotransmitters, cytokines(interleukins, growth factor ). • (2) Second messengers • ① cAMP • ② cGMP • ③ phosphatidylinositol，DG, IP3 • ④ calcium ion, it participates in protein medium, such as PKC, calomodulin, etc. 3. signal transduced system of receptor and intracellular

More Related