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pharmacodynamics for II MBBS CBME satya 2021

This interesting ppt contains Pharmacodynamics illustrated with pictures and diagrams for II MBBS CBME students.

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pharmacodynamics for II MBBS CBME satya 2021

  1. 1. PH 1.5 PHARMACODYNAMICS DR. V. SATHYANARAYANAN M.B.B.S., M.D., ACME PROFESSOR OF PHARMACOLOGY SRM MCH & RC
  2. 2. COMPETENCY ACHIEVEMENT • PH 1.5 DESCRIBE GENERAL PRINCIPLES OF MECHANISM OF DRUG ACTION
  3. 3. SPECIFIC LEARNING OBJECTIVES AT THE END OF THIS SESSION ALL THE PARTICIPANTS SHALL BE ABLE TO Define pharmacodynamics Enumerate and explain different types of drug action Enumerate and explain different sites of drug action Classify receptor families Explain signal transduction mechanisms State the clinical implications of upregulation and downregulation with examples Define potency and efficacy with examples Discuss drug synergism and antagonism with examples Enumerate the factors that modify drug effects
  4. 4. CONTENTS • DEFINITION • HISTORY • TYPES OF DRUG ACTION • SITES OF DRUG ACTION • MECHANISM OF ACTION OF DRUGS • DRUG AFFINTY AND EFFICACY • SOME DEFINITION OF TERMS • RECEPTOR FAMILIES • SIGNAL TRANSDUCTION MECHANISMS • RECEPTOR REGULATION AND ITS IMPLICATIONS • DOSE RESPONSE RELATIONSHIP • DRUG SYNERGISM AND ANTAGONISM WITH EXAMPLES • FACTORS THAT MODIFY THE EFFECTS OF DRUGS
  5. 5. DEFINITION Pharmacon = Drug Dynamics = Action/Power It covers all the aspects relating to “What a drug does to the body” (Mechanism of action)
  6. 6. Site of Action Dosage Effects Plasma Concen. Pharmacokinetics Pharmacodynamics
  7. 7. HISTORY • Molecular pharmacology is concerned with studies of basic mechanisms of drug actions on biological systems. • The idea that drugs act upon specific sites (receptive substance) began with John New Port Langley (1852-1926) of Cambridge. • However the word ‘receptor’ is given by Paul Ehrlich (1854- 19 15). • The receptor concept which forms a key note in the development of molecular pharmacology became firmly established by the quantitative work of Alfred Joseph Clark (1885-1941), a professor of pharmacology at Kings College London.
  8. 8. DRUG ACTION VS DRUG EFFECT •Action: How and Where the effect is produced is called as Action. •Effect: The type of response produced by drug.
  9. 9. TYPES OF DRUG ACTION EFFECT (Type of responses):- 1.Stimulation 2.Inhibition/Depression 3.Replacement 4.Irritation 5.Cytotoxic 6. Modification of immune status
  10. 10. STIMULATION • Some drugs act by increasing the activity of specialized cells. Ex: Catecholamines stimulate the heart and Heart rate, Force of contraction
  11. 11. INHIBITION • Some drug act by decreasing the activity of specialized cells. Ex: Alcohol, Barbiturates, General anesthetic these drug depress the CNS system. Atropine inhibits Ach action.
  12. 12. REPLACEMENT • When there is a deficiency of endogenous substances, they can be replaced by drugs. Ex: Insulin in Diabetes mellitus Throxine in cretinism and myxedema
  13. 13. IRRITATION • Certain drugs on topical application cause irritation of the skin and adjacent tissues. • These drugs are used for counterirritant purpose. Ex: Eucalyptus oil, methyl salicylates (Used in sprains, joint pain, myalgia.
  14. 14. CYTOTOXIC • Treatment of infectious disease/cancer with drugs that are selectively toxic for infecting organism/cancer cells Ex: Anticancer drugs All Antibiotics
  15. 15. MODIFICATION OF IMMUNE STATUS • Vaccines and sera  improve our immunity • Immunosuppressants  depress immunity
  16. 16. SITE OF DRUG ACTION • Where: 1. Extra cellular 2. Cellular 3. Intracellular
  17. 17. EXTRA CELLULAR SITE OF ACTION 1.ANTACIDS NEUTRALIZING GASTRIC ACIDITY. 2.CHELATING AGENTS FORMING COMPLEXES WITH HEAVY METALS. 3.MGSO4 ACTING AS PURGATIVE BY RETAINING THE FLUID INSIDE THE LUMEN OF INTESTINE.
  18. 18. CELLULAR SITE OF ACTION 1.Ach on Nicotinic receptors of motor end plate, leading to contraction of skeletal muscle. 2.Effect of sympathomimetics on heart muscle and blood vessels.
  19. 19. INTRACELLULAR SITE OF ACTION - EXAMPLES -Folic acid synthesis inhibitors. Folic acid which is intracellular component essential for synthesis of proteins. Trimethoprim and sulfa drug interfere with synthesis.
  20. 20. MECHANISM OF ACTION OF DRUGS Drug act either by receptor or by non receptor or by targeting specific genetic changes. Majority of drugs acts by receptor mechanism Receptor mediated Non receptor mediated
  21. 21. FUNDAMENTAL MECHANISMS OF DRUG ACTION THROUGH 1. Receptors 2. Enzymes and pumps 3. Ion channels 4. Transporters and symporters 5. By Physical action 6. By chemical action 7. By altering metabolic processes
  22. 22. RECEPTOR MEDIATED ACTION Drugs produce their effect through interacting with some chemical component of living organism eg Receptor. Receptors are macromolecules Most are proteins Present either on the cell surface, cytoplasm or in the nucleus
  23. 23. Receptor Functions : Two essential functions • 1. Recognition of specific ligand molecule (Ligand binding domain) and binding • 2. Transduction of signal into response (Effector domain) Ligand binding domain Transduction of signal into response
  24. 24. Drug(D) +Receptor® Drug receptor complex Response 1. Selectivity:- Degree of complimentary correlation between drug and receptor. Ex:- Adrenaline Selectivity for α, ß Receptor 2. Affinity:- Ability of drug to bind to a receptor. 3. Intrinsic activity (IA) or Efficacy:- Ability of a drug to produce a pharmacological response after making the drug receptor complex. Drug receptor interaction
  25. 25. DRUGS ARE DESCRIBED BASED ON THE MAGNITUDE OF TWO PROPERTIES: 1. Affinity for the receptor. Affinity is related to potency. 2. Efficacy once bound to the receptor. Efficacy refers to the maximal effect the drug can elicit.
  26. 26. DRUG CLASSIFICATION (ON THE BASIS OF AFFINITY & EFFICACY)
  27. 27. AGONISTS AND ANTAGONISTS AGONIST - Has affinity for receptor and intrinsic activity/efficacy. ANTAGONIST - Has affinity but no efficacy. Competitive Antagonist Noncompetitive Antagonist Partial Agonist or Agonist- Antagonist Has affinity but lower efficacy than full agonist.
  28. 28. Response No response
  29. 29. • Partial agonist :These drug have full affinity to receptor but with low intrinsic activity (IA=0 to 1). • These are only partly as effective as agonist (Affinity is lesser when comparison to agonist) Ex: Pindolol, Pentazocine
  30. 30. INVERSE AGONIST These have full affinity towards the receptor but intrinsic activity is zero to -1 i.e., produces effect is just opposite to that of agonist. Ex:- ß-Carboline is inverse agonist for Benzodiazepine receptors.
  31. 31. RECEPTOR LIGAND TYPES
  32. 32. RECEPTOR FAMILIES Four types of receptors families 2. ion channel receptors (ionotropic receptor) 1.G-protein-coupled receptors (Metabotropic receptor) 3. Enzymatic receptors (kinase-linked receptor) 4.Receptor regulating gene expression (transcription factors/ Steroid )
  33. 33. CHARACTERISTICS OF RECEPTOR FAMILIES Ligand gated G-protein coupled Enzymatic Nuclear Location Membrane Membrane Membrane Intracellular Effector Ion channel Ion Channel or enzyme Enzyme Gene coupling Direct G-protein Direct Via DNA Example Nicotinic Muscarinic Insulin Steroid Hormone
  34. 34. RECEPTOR FAMILIES • 5. Transmembrane non-enzymes ( cytokine and TLR )
  35. 35. SIGNAL TRANSDUCTION MECHANISMS
  36. 36. SIGNAL TRANSDUCTION MECHANISMS • Ion channel receptors:- proteins localized on cell membrane and coupled directly to an ion channel. Receptor Agonist Hyperpolarization or depolarization Receptor Blocker Permeation of ion is blocked Cellular effect No cellular effect Ion Na+2
  37. 37. • Ex: Nicotinic cholinergic receptor
  38. 38. ION CHANNELS • SODIUM CHANNEL • CALCIUM CHANNEL • POTASSIUM CHANNEL • CHLORIDE CHANNEL
  39. 39. G-PROTEIN COUPLED RECEPTORS • Membrane bound, which are coupled to effector system through GTP binding proteins called as G-proteins Bound to inner face of plasma membrane (2nd messenger)
  40. 40. R + E G G - + - Ions Second messengers Change in excitability Ca2+ release Protein phosphorylation other Cell effects G protein coupled receptors
  41. 41. VARIETIES OF G-PROTEIN G-protein Receptor for Signaling pathway/ Effector Gs ß adrenegic, H,5HT,Glucagon AC— cAMP Gi1,2,3 α2 adrenergic, Ach, AC— cAMP, Open K+ Gq Ach Phospholipase-C, IP3’cytoplasmic Ca+2 Go Neurotransmitters in brain Not yet clear
  42. 42. G-PROTEIN EFFECTOR SYSTEMS 1.Adenylase cyclase : cAMP system 2.Phospholipase –C: Inositol phosphate system 3. Ion channels
  43. 43. CAMP SYSTEM
  44. 44. • Phospholipase-C / IP3-DAG Pathway system
  45. 45. E Cam E* Gq PLC PIP2 DAG S Agonist Hydrolysis Activation IP3 PKC ATP ADP Product Ca+2 Cam Water soluble release Response Phospholipase-C system Hydrolysis PLC= Phospholipase-C PIP2 =Phosphotiydl inositol 4,5 di phosphate IP3 =Inositol tri phosphate DAG = Diacylglycerol E= Ezyme PKC = Phosphokinase -C
  46. 46. GS/GI or FC of heart muscle Lipolysis Glycogen Glycogen breakdown synthesis to glucose G protein + - Effector AC cAMP ATP Protein kinase Active Ca+2 release Phosphorylation
  47. 47. ION CHANNEL REGULATION • G-protein coupled receptors can control the functioning of ion channel by don't involving any second messenger • Ex:- In cardiac muscle
  48. 48. ENZYMATIC RECEPTORS • These receptor are directly linked tyrosine kinase. • Receptor binding domain present in extra cellular site. • Intracellular domain produce conformational changes • Ex:- Insulin receptors
  49. 49. ENZYMATIC RECEPTORS Extra cellular receptor binding domain Intra cellular changes
  50. 50. R/E Protein phosphorylation Gene transcription Protein synthesis Cellular effects Kinase linked receptors
  51. 51. RECEPTOR REGULATING GENE EXPRESSION (TRANSCRIPTION FACTORS) Unfolds the receptor and expose normally masked DNA binding site Increase RNA polymerase activity
  52. 52. R Nucleus Gene transcription Protein synthesis Cellular effects Nuclear receptors
  53. 53. JAK-STAT BINDING RECEPTOR
  54. 54. RECEPTOR REGULATION THEORY Receptors are in dynamic state. The affinity of the response to drugs is not fixed. It alters according to situation. Receptor down regulation: Prolonged use of agonist Receptor number and sensitivity Drug effect Ex: Chronic use of salbutamol down regulates ß2 adrenergic receptors.
  55. 55. RECEPTOR UPREGULATION Prolonged use of antagonist Receptor number and sensitivity Drug effect • Ex:- propranolol is stopped after prolonged use, produce withdrawal symptoms. Rise BP, induce of angina.
  56. 56. NON RECEPTOR MEDIATED ACTION • All drugs action are not mediated by receptors. Some of drugs may act through chemical action or physical action or other modes. • Chemical action • Physical action (Astringents, sucralfate) • False incorporation (PABA) • Being protoplasmic action (antiseptics) • Formation of antibody (Vaccines) • Targeting specific genetic changes.
  57. 57. CHEMICAL ACTION 1.Ion Exchanges:-Anticoagulant effect of heparin(-ve charge) antagonized by protamine (+ve charged) protein. 2.Neutralization:- Excessive gastric acid is neutralized by antacids. 3. Chelation:-These bind heavy metals. Ex:-EDTA, BAL.
  58. 58. PHYSICAL ACTION Adsorption: Kaolin adsorbs bacterial toxin and thus acts as antidiarrhoeal agent. Protectives:- Various dusting powders.
  59. 59. PHYSICAL ACTION • Osmosis:- MgSo4 acts as a purgative by exerting osmotic effect within lumen of the intestine. • Astringents:- They precipitate the surface proteins and protect the mucosa Ex: tannic acid in gum patients • Demulcent:- These drugs coat the inflamed mucus membrane and provide soothing effect. Ex: Menthol • Radioactivity – I131 • Radio-opacity – Barium sulphate
  60. 60. FALSE INCORPORATION Bacteria synthesis folic acid from PABA (Para Amino Benzoic Acid), for growth sand development. Sulfa drugs resemble PABA, therefore falsely enter into the synthesis process of PABA, cause nonfunctional production and no utility for bacterial growth.
  61. 61. PROTOPLASMIC POISON • Germicides and antiseptics like phenol and formaldehyde act as non specifically as protoplasmic poison causing the death of bacteria
  62. 62. THROUGH FORMATION OF ANTIBODIES Vaccines produce their effect by inducing the formation of antibodies and thus stimulate the defense mechanism of the body Ex:- Vaccines against small pox and cholera
  63. 63. TARGETING SPECIFIC GENETIC CHANGES. Anti cancer drugs that specifically target genetic changes. Inhibitors of specific tyrosine kinase that that block the activity of oncogenic kinases.
  64. 64. THROUGH ENZYMES AND PUMPS • Large number of drugs act by inhibition of various enzymes – eg ASPIRIN, ENALAPRIL • Some drugs act by inhibiting membrane pumps – eg OMEPRAZOLE, DIGOXIN
  65. 65. THROUGH TRANSPORTERS AND SYMPORTERS
  66. 66. PHARMACODYNAMICS • Drug-receptor affinity • Governed by stereochemical fit • Effects on brain determined by location of receptor types • The dose-response relationship • Dose • Potency • Efficacy or maximum effect • Slope
  67. 67. 0 20 40 60 80 100 120 Dose Response % • The dose-response curve relates the amount administered to the response. • Response may be measured as % responding or as intensity of response
  68. 68. DRUG EFFECTIVENESS • Dose-response (DR) curve • Depicts the relation between drug dose and magnitude of drug effect • Drugs can have more than one effect • Drugs vary in effectiveness • Different sites of action • Different affinities for receptors • The effectiveness of a drug is considered relative to its safety (therapeutic index)
  69. 69. Potency • Relative strength of response for a given dose – Effective concentration (EC50) is the concentration of an agonist needed to elicit half of the maximum biological response of the agonist – The potency of an agonist is inversely related to its EC50 value • D-R curve shifts left with greater potency
  70. 70. Efficacy • Maximum possible effect relative to other agents • Indicated by peak of D-R curve • Full agonist = 100% efficacy • Partial agonist = 50% efficacy • Antagonist = 0% efficacy • Inverse agonist = -100% efficacy
  71. 71. THE DOSE-RESPONSE CURVE: EFFECTIVENESS AND SAFETY 0 20 40 60 80 100 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Dose Intensity of response, % Efficacy Slope Potency
  72. 72. Drug Concentration SEMILOG DOSE-RESPONSE CURVE Effect or
  73. 73. Drug Concentration SEMILOG DOSE-RESPONSE CURVE ED50 50% Effect Maximal Effect Effect or
  74. 74. SEMILOG DOSE-RESPONSE CURVE POTENCY EFFICACY ED50 Maximal Effect Log [Dose]
  75. 75. SEMILOG DOSE-RESPONSE CURVE RANK ORDER OF POTENCY: A > B > C > D A B C D Log [Dose]
  76. 76. SEMILOG DOSE-RESPONSE CURVE RANK ORDER OF POTENCY: A > B > C > D RANK ORDER OF EFFICACY: A = C > B > D A B C D ED50
  77. 77. THERAPEUTIC INDEX • Margin of safety • Depend upon factor of dose producing desirable effect  dose eliciting toxic effect. • TI should be more than one 50 50 ED LD index c Therapeuti 
  78. 78. THERAPEUTIC WINDOW • Optimal therapeutic range of plasma concentrations at which most o the patients experience the desired effect. • Therapeutic range Therapeutic window Sub optimal optimal
  79. 79. THERAPEUTIC WINDOW OF SOME DRUGS Cyclosporine – 100-400ng/ml Carbamazapine- 4-10µg/ml Digoxin- 0.8-2ng/ml Lithium- 0.8-1.4 mEq/L Phenytoin – 10-20µg/ml Quinidine- 2-6µg/ml
  80. 80. COMBINED EFFECT OF DRUGS
  81. 81. • Additive: combined effect of two drugs acting by same mechanism ( 1+1 =2 ) Ibuprofen and Paracetamol
  82. 82. SYNERGISM (SUPRA- ADDITIVE EFFECT) (1+1=3 OR 5) The combined effects of two drugs are greater than the sum of their independent effects. 1.Sulfamethaxazole+ Trimethoprim 2. Levodopa + Carbidopa.
  83. 83. TYPES OF ANTAGONISM Antagonism: Effect of two drugs is less than sum of the effects of the individual drugs. Chemical antagonism •Ex: -heparin(-ve) protamine +ve, Chelating agents Physiological /Functional antagonism Ex histamine and adrenaline Pharmacokinetic antagonism Pharmacodynamic antagonism •Competitive ( Reversible) •Non competitive (Irreversible)
  84. 84. PHYSIOLOGICAL ANTAGONISM • Two antagonists, acting at different sites, counter balance each other by producing opposite effect on same physiological system. • Histamine – bronchospasm • Adrenaline/epinephrine – bronchodilatation
  85. 85. PHARMACOKINETIC ANTAGONISM One drug affects the absorption, metabolism or excretion of other drug and reduce their effect. Ex:-Warfarin in presence of phenobarbitone, warfarin metabolism is increased, its effect is reduced.
  86. 86. PHARMACODYNAMIC ANTAGONISM • Pharmacodynamic antagonism between two drugs acting at same receptors. •1.Reversible(Competitive) •2.Irreversible •3. Non-Competitive
  87. 87. REVERSIBLE ANTAGONISM (COMPETITIVE ANTAGONISM) Ex:- Atropine is a competitive antagonist of Ach. These type inhibition can be overcome by increasing the concentration of agonist These inhibition is commonly observed with antagonists that bind reversibly to the same receptor site as that of an agonist.
  88. 88. IRREVERSIBLE ANTAGONISM It occurs when the antagonist dissociates very slow or not at all from the receptors resulting that no change when the agonist is administered . Antagonist effect cannot be overcome even after increasing the concentration of agonist
  89. 89. FACTORS THAT MODIFY THE EFFECTS OF DRUGS
  90. 90. • Individuals differ both in the degree and the characteristic of the response that a drug may elicit • Variation in response to the same dose of a drug between different patients and even in the same patient on different occasions.
  91. 91. FACTORS MODIFYING THE EFFECTS OF DRUGS • One or more of the following categories of differences among individuals are responsible for the variations in drug response: • Individuals differ in pharmacokinetic handling of drugs • Variation in number or state of receptors, coupling proteins or other components of response • Variation in neurogenic/ hormonal tone or concentrations of specific constituents
  92. 92. FACTORS MODIFYING THE EFFECTS OF DRUGS a) Quantitatively • The plasma concentration and / or the drug action is increased or decreased b) Qualitatively • The type of response is altered, eg: drug allergy and idiosyncrasy
  93. 93. THE VARIOUS FACTORS ARE: 1. Body weight/size:  It influences the concentration of drug attained at the site of action  The average adult dose refers to individuals of medium built
  94. 94. FACTORS MODIFYING THE EFFECTS OF DRUGS – BODY WEIGHT • For exceptionally obese or lean individuals and for children dose may be calculated on body weight basis  BSA=BW(Kg)0.425 x Height(cm)0.725 x 0.007184 dose adult Average x 70 (kg) BW dose Individual  dose adult Average x 1.7 (m2) BSA dose Individual 
  95. 95. FACTORS MODIFYING THE EFFECTS OF DRUGS  However, infants and children have important physiological differences  Higher proportion of water  Lower plasma protein levels  More available drug  Immature liver/kidneys  Liver often metabolizes more slowly  Kidneys may excrete more slowly
  96. 96. 2. AGE Infants and Children: • The dose of drug for children often calculated from the adult dose formula) s Young' .........( dose adult x 12 Age Age dose Child   formula) s g' ...(Dillin dose...... adult x 20 Age dose Child 
  97. 97. FACTORS MODIFYING THE EFFECTS OF DRUGS Elders: •In elderly, renal function progressively declines (intact nephron loss) and drug doses have to be reduced Chronic disease states Decreased plasma protein binding Slower metabolism Slower excretion Dietary deficiencies Use of multiple medications Lack of compliance
  98. 98. FACTORS MODIFYING THE EFFECTS OF DRUGS 3. Sex: • Females have smaller body size, and so require doses of drugs on the lower side of the dose range • They should not be given uterine stimulants during menstruation, quinine during pregnancy and sedatives during lactation
  99. 99. FACTORS MODIFYING THE EFFECTS OF DRUGS 4. Pregnancy: • Profound physiological changes which may affect drug responses: • GI motility reduced –delayed absorption of orally administered drugs • Plasma and ECF volume expands • Albumin level falls • Renal blood flow increases markedly • Hepatic microsomal enzyme induction
  100. 100. FACTORS MODIFYING THE EFFECTS OF DRUGS 5. Food:  Delays gastric emptying, delays absorption (ampicillin)  Calcium in milk –interferes with absorption of tetracyclines and iron by chelation  Protein malnutrition  Loss of BW  Reduced hepatic metabolizing capacity  Hypoproteinemia
  101. 101. FACTORS MODIFYING THE EFFECTS OF DRUGS 6. Species and race: • Rabbits resistant to atropine • Rat & mice are resistant to digitalis • In humans: blacks require higher, Mongols require lower concentrations of atropine and ephedrine to dilate their pupil
  102. 102. FACTORS MODIFYING THE EFFECTS OF DRUGS 7. Route of drug administration:  I.V route dose smaller than oral route  Magnesium sulfate:  Orally –purgative  Parenterally –sedative  Locally –reduces inflammation
  103. 103. FACTORS MODIFYING THE EFFECTS OF DRUGS 8. Biorhythm: (Chronopharmacolgy) • Hypnotics –taken at night • Corticosteroid –taken at a single morning dose 9. Psychological state: • Efficacy of drugs can be effected by patients beliefs, attitudes and expectations • Particularly applicable to centrally acting drugs • In some patients inert drugs (placebo) may produce beneficial effects equivalent to the drug, and may induce sleep in insomnia
  104. 104. FACTORS MODIFYING THE EFFECTS OF DRUGS 10. Presence of diseases/pathological states:  Drug may aggravate underlying pathology  Hepatic disease may slow drug metabolism  Renal disease may slow drug elimination  Acid/base abnormalities may change drug absorption or elimination  Severe shock with vasoconstriction delays absorption of drugs from s.c. or i.m  Drug metabolism in:  Hyperthyroidism –enhanced  Hypothyroidism -diminished
  105. 105. FACTORS MODIFYING THE EFFECTS OF DRUGS 11. Cumulation: • Any drug will cumulate in the body if rate of administration is more than the rate of elimination • Eg: digitalis, heavy metals etc.
  106. 106. FACTORS MODIFYING THE EFFECTS OF DRUGS 12. Genetic factors: • Lack of specific enzymes • Lower metabolic rate • Acetylation • Plasma cholinesterase (Atypical pseudo cholinesterase) • G-6PD • Glucuronide conjugation
  107. 107. FACTORS MODIFYING THE EFFECTS OF DRUGS 13. Tolerance:  It means requirement of a higher dose of the drug to produce an effect, which is ordinarily produced by normal therapeutic dose of the drug  Drug tolerance may be:  Natural  Acquired  Cross tolerance  Tachyphylaxis (ephedrine, tyramine, nicotine)  Drug resistance
  108. 108. TOLERANCE • Tolerance: Increased amount of drug required to produce initial pharmacological response. • Usually seen with alcohol, morphine, barbiturates, CNS active drugs • Reverse tolerance:- Same amount drug produces increased pharmacological response. • Cocaine, amphetamine  rats- increase motor activity
  109. 109. TYPES OF TOLERANCES • Innate tolerance: Genetically lack of sensitivity to a drug. Ex: • Rabbits tolerate to atropine large doses • Chinese Castor oil • Negros  Mydriatic action of sympathomimetics • Eskimos high fatty diets
  110. 110. ACQUIRED TOLERANCES Occurs due to repeated use of drug • Pharmacokinetic tolerances • Pharmacodynamic tolerance • Acute tolerance Pharmacokinetic tolerances:- Repetitive administration causes decrease in their absorption or increase in its own metabolism Ex: Alcohol  dec. absorption Barbiturates Inc. own metabolism
  111. 111. PHARMACODYNAMIC TOLERANCE Down regulation of receptors Impairment in signal transduction Ex: Morphine, caffeine, nicotine. Acute tolerance: Tachyphylaxis Acute development of tolerance after a rapid and repeated administration of a drug in shorter intervals Ex; Ephedrine, tyramine
  112. 112. FACTORS MODIFYING THE EFFECTS OF DRUGS 14. Other drugs:  By interactions in many ways
  113. 113. SUMMARY
  114. 114. SUMMARY What the drug does to the body is Pharmacodynamics Drugs act on extracellular or intracellular sites There are several types of drug action Most drugs act produce their effects by binding to specific target proteins Many drugs act by interacting with specific receptors There are 5 types of receptor families and they have specific signal transduction mechanisms Receptors are either upregulated or downregulated depending upon their number and sensitivity Clinical response to the increasing dose of the drug is defined by the shape of the dose response curve When two or more drugs are given concurrently, the effect may be additive, synergistic or antagonistic There are various factors modify the response to a drug
  115. 115. POST-TEST MCQS 1. What the drug does to the body is called as a) Pharmacokinetics b) Pharmacodynamics c) Pharmacotherapeutics d) Chronopharmacology 2. The upper limit of dose response curve is the index of a) Drug potency b) Drug efficacy c) Drug safety d) Drug toxicity
  116. 116. POST-TEST MCQS • 3. The transducer mechanism which is the FASTEST in its time course of action is a) G-protein coupled receptors (GPCR) b) Receptors with intrinsic ion channel c) Enzyme - linked receptors d) Receptors regulating gene expression
  117. 117. POST-TEST MCQS 4. All are second messengers EXCEPT a)Cyclic AMP b) G-Protein c) IP3 d) DAG 5. The therapeutic index of a drug is a measure of its a) Safety b) Potency c) Efficacy d) Dose variability
  118. 118. • The young physician starts life with 20 drugs for each disease, and the old physician ends life with one drug for 20 diseases Sir. William Osler 1849 - 1919
  119. 119. THANK YOU

This interesting ppt contains Pharmacodynamics illustrated with pictures and diagrams for II MBBS CBME students.

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