Basic Intravenous Therapy 2: Pharmacology, Rational Therapy, Pharmacodynamics, and Pharmacokinetics


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Lecture Presentation in Basic Intravenous Therapy Seminar talks on Basic Pharmacology, the pharmacodynamics and pharmacokinetics, the common IV medications used, precautions and interactions of medications

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Basic Intravenous Therapy 2: Pharmacology, Rational Therapy, Pharmacodynamics, and Pharmacokinetics

  1. 1. BASIC INTRAVENOUS THERAPY TRAINING PROGRAM CLINICAL PHARMACOLOGY Rational Therapeutics Pharmacokinetics Pharmacodynamics
  2. 2. ?
  3. 3. Rational Therapeutics <ul><li>Medicine </li></ul><ul><li>is an ever changing science </li></ul><ul><li>to broaden knowledge requires the need for a new research and clinical experience </li></ul><ul><li>including the changes in the treatment and drug therapy </li></ul>
  4. 4. Pharmacology <ul><li>Pharmacology is the study of interactions between chemicals and living tissue and provides the rational basis for therapeutics </li></ul><ul><li>To deliver the appropriate amount of drug for a reasonable length of time to achieve desired beneficial effects while minimizing adverse effects , it is useful to consider the relationship between the drug's pharmacodynamic and pharmacokinetic properties </li></ul>
  5. 5. Clinical Pharmacology <ul><li>Improvement in THERAPEUTIC DECISIONS: </li></ul><ul><ul><li>Personal impression </li></ul></ul><ul><ul><li>Tradition </li></ul></ul><ul><ul><li>Sentiment </li></ul></ul><ul><ul><li>Uncritical acceptance of advertisement claims </li></ul></ul>
  6. 6. Clinical Pharmacology <ul><li>1903 … </li></ul><ul><li>… the day has come when something more is demanded of a practitioner or physician-consultant than a diagnosis </li></ul><ul><li>… the what ; the how much ; the when ; and, in what form , and under what precautions , must be fully stated </li></ul>
  7. 7. Clinical Pharmacology <ul><li>RATIONAL THERAPEUTICS : </li></ul><ul><ul><li>Better understandings depend on systemic studies of use and patterns and effects of marketed drugs </li></ul></ul><ul><ul><li>Means, prescribing drugs to maximize the chances of efficacy and to minimize drug-induced illnesses </li></ul></ul><ul><ul><li>Individualize the therapeutic plans to match the needs of a particular patient by following the scientific principles of medicine and pharmacology </li></ul></ul>
  8. 8. Clinical Pharmacology <ul><li>APPROACH TO RATIONAL THERAPEUTICS: Principles </li></ul><ul><li>Set the legitimately expected results of therapy before beginning </li></ul><ul><li>A logical approach to therapy results in rational prescribing of even the most common medications – Rational Therapy </li></ul>
  9. 9. Clinical Pharmacology <ul><li>APPROACH TO RATIONAL THERAPEUTICS: Principles </li></ul><ul><li>3. Dose-response curve to approximate the first dose </li></ul><ul><li>4. Therapeutic index is not constant </li></ul><ul><li>5. Individualized qualitative and quantitative therapeutic decisions </li></ul>
  10. 10. Clinical Pharmacology <ul><li>Requirements of a Rational Therapy : </li></ul><ul><li>Certainty of the diagnosis </li></ul><ul><li>Understanding of the pathophysiology of the disease </li></ul><ul><li>Understanding the pharmacology of the drugs that could be use </li></ul>
  11. 11. Clinical Pharmacology <ul><li>Requirements of a Rational Therapy : </li></ul><ul><li>4. Choose the drug and dose that is optimal for the patient </li></ul><ul><li>5. Know end points of efficacy and toxicity </li></ul><ul><li>6. Develop a contract or alliance with the patient </li></ul>
  12. 12. Clinical Pharmacology <ul><li>PRINCIPLES OF DRUG THERAPY </li></ul><ul><li>Quantitative determinants of DRUG ACTION: </li></ul><ul><li>I. Plasma levels after single dose </li></ul><ul><ul><li>Distribution phase </li></ul></ul><ul><ul><li>Equilibrium phase </li></ul></ul>
  13. 13. Clinical Pharmacology <ul><li>PRINCIPLES OF DRUG THERAPY </li></ul><ul><li>Quantitative determinants of DRUG ACTION: </li></ul><ul><li>II. Drug accumulation </li></ul><ul><li>A. Loading dose </li></ul><ul><li>B. Maintenance dose </li></ul>
  14. 14. Clinical Pharmacology <ul><li>PRINCIPLES OF DRUG THERAPY </li></ul><ul><li>Quantitative determinants of DRUG ACTION: </li></ul><ul><li>III. Determinants of plasma levels during equilibrium </li></ul><ul><li>A. Extent of drug distribution outside plasma compartment </li></ul><ul><li>B. Extent to which the drug is bound to plasma proteins </li></ul>
  15. 15. Clinical Pharmacology <ul><li>PRINCIPLES OF DRUG THERAPY </li></ul><ul><li>Quantitative determinants of DRUG ACTION: </li></ul><ul><li>IV. Steady state </li></ul><ul><li>- drug’s availability </li></ul><ul><li>- “first pass effect” </li></ul>
  16. 16. Clinical Pharmacology <ul><li>PRINCIPLES OF DRUG THERAPY </li></ul><ul><li>Quantitative determinants of DRUG ACTION: </li></ul><ul><li>V. Drug elimination, not “first-order” </li></ul><ul><li>- dose-dependent elimination </li></ul>
  17. 17. Clinical Pharmacology <ul><li>Individualization of DRUG THERAPY </li></ul><ul><ul><li>Renal disease </li></ul></ul><ul><ul><li>Liver disease </li></ul></ul><ul><ul><li>Circulatory insufficiency: </li></ul></ul><ul><ul><ul><li>Cardiac failure </li></ul></ul></ul><ul><ul><ul><li>Shock </li></ul></ul></ul><ul><ul><li>Disease-induced changes in plasma binding </li></ul></ul><ul><ul><li>Drug use: </li></ul></ul><ul><ul><ul><li>Elderly </li></ul></ul></ul><ul><ul><ul><li>Pediatrics </li></ul></ul></ul><ul><li>Drug Interactions and Reactions </li></ul>
  18. 18. Clinical Pharmacology <ul><li>Pharmacological concepts apply to the characterization, evaluation, and comparison of all drugs </li></ul><ul><li>The relationship between the dose of a drug given to a patient and the utility of that drug in treatment is described in two basic areas in Pharmacology: Pharmacokinetics and Pharmacodynamics </li></ul>
  19. 19. Clinical Pharmacology <ul><li>Pharmacokinetics </li></ul><ul><ul><li>deals with absorption, distribution, biotransformation, and excretion of drugs </li></ul></ul><ul><li>Pharmacodynamics </li></ul><ul><ul><li>deals with the biochemical and physiological effects of drugs and their mechanisms of action </li></ul></ul>
  20. 20. <ul><li>General concept of pharmacokinetic/pharmacodynamic (PK/PD) modeling </li></ul><ul><li>PK/PD modeling combines a PK model component that describes the time course of drug in plasma and a PD model component that relates the plasma concentration to the drug effect in order to describe the time course of the effect intensity resulting from the administration of a certain dosage regimen </li></ul>
  21. 21. Clinical Pharmacology <ul><li>PHARMACOKINETICS </li></ul><ul><li>Branch of Pharmacology that deals with “what the body does to the drug” </li></ul><ul><li>The time course of the drug concentration in plasma or tissue fluid </li></ul>
  22. 22. Clinical Pharmacology <ul><li>PHARMACOKINETICS </li></ul><ul><li>First, the drug must be liberated from its solvent and/or excipients to free the active component </li></ul><ul><li>Then, it has to be absorbed , if taken orally </li></ul><ul><li>Upon reaching the blood stream, its fate depend on several factors which includes: distribution, metabolism, and excretion or elimination </li></ul>
  23. 23. Clinical Pharmacology <ul><li>Parameters of Pharmacokinetics : </li></ul><ul><li>Volume of Distribution </li></ul><ul><li>Clearance ( Cl ) </li></ul><ul><li>Half-life ( t ½) </li></ul><ul><li>Bioavailability </li></ul><ul><li>Area Under the Curve ( AUC ) </li></ul><ul><li>Protein binding </li></ul>
  24. 24. Concentration over Time C ½
  25. 25. Clinical Pharmacology <ul><li>Volume of Distribution (Vd) </li></ul><ul><li>Oral medications given involves dissolution prior to absorption </li></ul><ul><li>The rate of dissolution depends on the following physical properties : </li></ul><ul><ul><li>Formulation of the drug, ie tablet, capsule or liquid form </li></ul></ul><ul><ul><li>pH, ie the acidity or alkalinity of the surrounding environment </li></ul></ul><ul><ul><li>Solubility, ie the capacity of the drug to be dissolved </li></ul></ul>
  26. 26. Clinical Pharmacology <ul><li>The drug will liberate the active form or pro-drug form and enters the circulation </li></ul><ul><li>Factors that affect absorption </li></ul><ul><li>The drug would act best if they were delivered to the body compartment where they would be most effective </li></ul>
  27. 27. Clinical Pharmacology <ul><li>Volume of Distribution (Vd) </li></ul><ul><li>= amount of drug in the body/concentration in blood </li></ul><ul><li>Will determine whether the drug will stay or leave the circulation </li></ul><ul><li>Small Vd – have high initial blood levels and not readily distribute </li></ul><ul><li>Large Vd – low initial blood levels and significant uptake by many tissues </li></ul>
  28. 28. Clinical Pharmacology <ul><li>The drug distributed in the body compartments will undergo transformation </li></ul><ul><li>“ First-Pass Effect” - </li></ul><ul><li>Drugs active by themselves or converted into active form/s will subsequently metabolize by conversion in the liver, kidneys, lungs, and other body sites – degraded into metabolites </li></ul>
  29. 29. Time to Peak Concentration
  30. 30. Clinical Pharmacology <ul><li>Drug Absorption and Bioavailability </li></ul><ul><li>Routes: </li></ul><ul><ul><li>Oral </li></ul></ul><ul><ul><li>Transdermal </li></ul></ul><ul><ul><li>Intravenous </li></ul></ul><ul><ul><li>Intraarterial </li></ul></ul><ul><ul><li>Intramuscular </li></ul></ul><ul><ul><li>Rectal </li></ul></ul><ul><ul><li>Local administration: </li></ul></ul><ul><ul><ul><li>Eyedrops </li></ul></ul></ul><ul><ul><ul><li>Nasal spray </li></ul></ul></ul><ul><ul><ul><li>Inhalants </li></ul></ul></ul><ul><ul><ul><li>topicals </li></ul></ul></ul>
  31. 31. Clinical Pharmacology <ul><li>Absorption of Drug , depends on: </li></ul><ul><ul><li>Properties of drug </li></ul></ul><ul><ul><li>Vehicle of administration </li></ul></ul><ul><ul><li>Condition at the site of administration </li></ul></ul><ul><ul><li>Rate of absorption: </li></ul></ul><ul><ul><ul><li>Tmax </li></ul></ul></ul><ul><ul><ul><li>Cmax </li></ul></ul></ul>
  32. 32. Clinical Pharmacology <ul><li>Bioavailability </li></ul><ul><li>This is the fraction of the administered dose that reaches the systemic circulation </li></ul><ul><li>The amount of drug delivered to the general circulation and the rate to which this occurs </li></ul><ul><li>Intravenous drugs is at once completely bioavailable </li></ul>
  33. 33. Clinical Pharmacology <ul><li>Distribution and Redistribution of Absorbed Drugs </li></ul><ul><ul><li>Plasma proteins </li></ul></ul><ul><ul><li>Drug’s molecular weight </li></ul></ul><ul><ul><li>Solubility: </li></ul></ul><ul><ul><ul><li>Lipophilic </li></ul></ul></ul><ul><ul><ul><li>Hydrophilic </li></ul></ul></ul>
  34. 34. Clinical Pharmacology <ul><li>Plasma Clearance (Cl ) </li></ul><ul><li>Drugs cleared by organs for elimination from plasma </li></ul><ul><li>2 important pumps and filter systems: </li></ul><ul><ul><li>Kidneys </li></ul></ul><ul><ul><li>Liver </li></ul></ul><ul><li>A drug with fast clearance will not stay around for long </li></ul>
  35. 35. Clinical Pharmacology <ul><li>Total clearance </li></ul><ul><li>General Rule : </li></ul><ul><ul><li>Most drugs are lipophilic and are not rapidly cleared by the kidneys, thus, are first biotransformed in the liver </li></ul></ul><ul><ul><li>Enzymatically mediated hepatic biotransformation: C P450 </li></ul></ul><ul><ul><li>Hepatic drug biotransformation via conjugation reaction: Metabolites </li></ul></ul><ul><li>The balance of hepatic and renal clearance must be understood in order to prescribe a drug wisely </li></ul>
  36. 36. <ul><li>Metabolism </li></ul><ul><li>Drugs and toxins are seen as foreign to patients bodies </li></ul><ul><li>Drugs can undergo metabolism in the lungs, blood, and liver </li></ul><ul><li>Body works to convert drugs to less active forms and increase water solubility to enhance elimination </li></ul>
  37. 37. <ul><li>Metabolism </li></ul><ul><li>Liver - primary route of drug metabolism </li></ul><ul><li>Liver may be used to convert pro-drugs (inactive) to an active state </li></ul><ul><li>Types of reactions </li></ul><ul><ul><li>Phase I (Cytochrome P450 system) </li></ul></ul><ul><ul><li>Phase II </li></ul></ul>
  38. 38. <ul><li>Phase I Reactions </li></ul><ul><li>Cytochrome P450 system </li></ul><ul><li>Located within the endoplasmic reticulum of hepatocytes </li></ul><ul><li>Through electron transport chain, a drug bound to the CYP450 system undergoes oxidation or reduction </li></ul><ul><li>Enzyme induction </li></ul><ul><li>Drug interactions </li></ul>
  39. 39. <ul><li>Phase I Reactions Types </li></ul><ul><li>Hydrolysis </li></ul><ul><li>Oxidation </li></ul><ul><li>Reduction </li></ul><ul><li>Demethylation </li></ul><ul><li>Methylation </li></ul><ul><li>Alcohol dehydrogenase metabolism </li></ul>
  40. 40. <ul><li>Phase II Reactions </li></ul><ul><li>Polar group is conjugated to the drug </li></ul><ul><li>Results in increased polarity of the drug </li></ul><ul><li>Types of reactions </li></ul><ul><ul><li>Glycine conjugation </li></ul></ul><ul><ul><li>Glucuronide conjugation </li></ul></ul><ul><ul><li>Sulfate conjugation </li></ul></ul>
  41. 41. Clinical Pharmacology <ul><li>Half-life (t ½) Elimination </li></ul><ul><li>The time it takes for the concentration to fall and eliminate the drug to half of its previous plasma concentration </li></ul><ul><li>It is only a consequence and determined by both clearance and volume of distribution </li></ul><ul><li>Larger volume of distribution has longer half-life </li></ul><ul><li>3 important concepts in half-life elimination: </li></ul><ul><ul><li>Use to determine time needed to have steady concentration </li></ul></ul><ul><ul><li>Use to determine the time drug concentration fall in plasma </li></ul></ul><ul><ul><li>Useful in designing dosing interval/s </li></ul></ul>
  42. 42. t ½ C ½
  43. 43. Clinical Pharmacology <ul><li>All other routes of drug administration usually result in incomplete bioavailability due to: </li></ul><ul><ul><li>Incomplete absorption </li></ul></ul><ul><ul><li>Drug biotransformation </li></ul></ul><ul><ul><li>Both </li></ul></ul><ul><li>Biotransformation is a measure of the fraction of an administered dose that reaches the systemic circulation </li></ul>
  44. 44. Clinical Pharmacology <ul><li>Area Under the Curve (AUC) </li></ul><ul><li>AUC is a measurement of the amount of drug that has bee absorbed at a given time after administration (a measurement of the area underneath a plot of plasma concentration against time </li></ul><ul><li>Useful in assessing the total drug exposure </li></ul><ul><li>Peak concentration (Cmax) </li></ul><ul><li>Time of elimination </li></ul><ul><li>Half-life (t ½) </li></ul><ul><li>Therapeutic level </li></ul><ul><li>Trough level </li></ul><ul><li>Therapeutic window </li></ul>
  45. 45. Area Under the Curve (AUC)
  46. 46. <ul><li>DOSE-RESPONSE AND CONCENTRATION-RESPONSE DETRMINANTS </li></ul><ul><li>DOSE PRESCRIBED </li></ul><ul><li>1. compliance with prescription </li></ul><ul><li>2. drug cost </li></ul><ul><li>DOSE TAKEN </li></ul><ul><li>1. absorption/bioavailability </li></ul><ul><li>2. distribution/redistribution </li></ul><ul><li>3. clearance: biotransformation </li></ul><ul><li> elimination </li></ul><ul><li>4. half-life </li></ul><ul><li>DOSE CONCENTRATION IN PLASMA </li></ul><ul><li>1. unbound (free) fraction </li></ul><ul><li>2. tissue compartment distribution </li></ul><ul><li>3. concentration at site of action </li></ul><ul><li>4. patient factors </li></ul><ul><li>PHARMACOLOGIC RESPONSE </li></ul><ul><li>INTENDED RESPONSE UNINTENDED RESPONSE </li></ul><ul><li> (Therapeutic) (Toxic) </li></ul>DOSE-RESPONSE CONCENTRATION- RESPONSE
  47. 47. Clinical Pharmacology <ul><li>Increasing or decreasing dosage without knowing what the body does to the drug is dangerous </li></ul><ul><li>May result in: </li></ul><ul><ul><li>Not reach its target </li></ul></ul><ul><ul><li>Underdosed </li></ul></ul><ul><ul><li>Overdosed </li></ul></ul><ul><li>Impact on the effectivity or failure of the drug regimen in use </li></ul>
  48. 48. Pharmacokinetic Principles <ul><li>Steady State : the amount of drug administered is equal to the amount of drug eliminated within one dosing interval resulting in a plateau or constant serum drug level </li></ul><ul><li>Drugs with short half-life reach steady state rapidly; drugs with long half-life take days to weeks to reach steady state </li></ul>
  49. 49. Steady State Pharmacokinetics <ul><li>Half-life = time required for serum plasma concentrations to decrease by one-half (50%) </li></ul><ul><li>4-5 half-lives to reach steady state </li></ul>
  50. 50. Loading Doses <ul><li>Loading doses allow rapid achievement of therapeutic serum levels </li></ul><ul><li>Same loading dose used regardless of metabolism and elimination dysfunction </li></ul>
  51. 51. Linear Pharmacokinetics <ul><li>Linear = rate of elimination is proportional to amount of drug present </li></ul><ul><li>Dosage increases result in proportional increase in plasma drug levels </li></ul>
  52. 52. Nonlinear Pharmacokinetics <ul><li>Nonlinear = rate of elimination is constant regardless of amount of drug present </li></ul><ul><li>Dosage increases saturate binding sites and result in non- proportional increase/decrease in drug levels </li></ul>
  53. 53. Michaelis-Menten Kinetics <ul><li>Follows linear kinetics until enzymes become saturated </li></ul><ul><li>Enzymes responsible for metabolism /elimination become saturated resulting in non-proportional increase in drug levels </li></ul>
  54. 54. Special Patient Populations <ul><li>Renal Disease : same hepatic metabolism, same/increased volume of distribution and prolonged elimination   dosing interval </li></ul><ul><li>Hepatic Disease : same renal elimination, same/increased volume of distribution, slower rate of enzyme metabolism   dosage,  dosing interval </li></ul><ul><li>Cystic Fibrosis Patients : increased metabolism/ elimination, and larger volume of distribution   dosage,  dosage interval </li></ul>
  55. 55. <ul><li>Applied Pharmacokinetics </li></ul><ul><ul><li>Loading dose </li></ul></ul><ul><ul><li>Maintenance dose: </li></ul></ul><ul><ul><ul><li>IV infusion </li></ul></ul></ul><ul><ul><ul><li>Repeated doses </li></ul></ul></ul><ul><li>Adverse Drug Reactions </li></ul>
  56. 56. Clinical Pharmacology <ul><li>PHARMACODYNAMICS </li></ul><ul><li>The study of the biochemical and physiological effects of drugs and their mechanism of action </li></ul><ul><li>The study of “what drugs do to the body” </li></ul><ul><li>Parameters: </li></ul><ul><ul><li>MIC </li></ul></ul><ul><ul><li>MBC </li></ul></ul>
  57. 57. t ½ Pharmacokinetic parameters describing a typical plasma concentration time profile after an oral administration. C max , maximum concentration; t max , time to C max ; t ½ , half-life; AUC , area under the curve; MEC , minimum effective concentration; MTC , maximum tolerated concentration.
  58. 58. Clinical Pharmacology <ul><li>Describes both the good ( therapeutic ) effects, as well as the bad (or toxic ) effects of the drug </li></ul><ul><li>The relationship of concentration vs. effect </li></ul><ul><li>Importance to all the drugs including the antibiotic use to optimize the treatment (better and faster cure with least side effects) </li></ul>
  59. 59. Clinical Pharmacology <ul><li>Drug’s effectivity </li></ul><ul><li>The activity of the drug, specifically antibiotics against specific microorganism was measured using: </li></ul><ul><ul><li>minimum inhibitory concentration (MIC) </li></ul></ul><ul><ul><li>minimum bactericidal concentration (MBC) </li></ul></ul>
  60. 60. Clinical Pharmacology <ul><li>MIC </li></ul><ul><li>Refers to the lowest antibiotic concentration required to completely inhibit visible growth of microorganism </li></ul><ul><ul><li>Low MIC means that the antibiotic has high antibiotic activity </li></ul></ul><ul><ul><li>High MIC means that the bacteria are less susceptible to the antibiotic, so higher concentrations are needed </li></ul></ul><ul><li>MIC 90 </li></ul><ul><ul><li>The concentration of antibiotic that inhibits 90% of bacteria </li></ul></ul>
  61. 61. Clinical Pharmacology <ul><li>MBC </li></ul><ul><li>The lowest concentration of the antibiotic required to kill bacteria </li></ul><ul><li>The measure of the drug’s bactericidal activity </li></ul><ul><li>Ideally, MBC would be the same as or only slightly higher than the MIC </li></ul>
  62. 62. Clinical Pharmacology <ul><li>MIC and MBC do not provide information on how fast they can eliminate the organism, and if the rate can be increase by increasing the concentration or amount of drug being given </li></ul><ul><li>They do not provide information on persistent effects of the antibiotics </li></ul><ul><li>Persistent effects </li></ul><ul><ul><li>Refers to the ability of antibiotics to inhibit the growth of the organism after exposure to the drug </li></ul></ul>
  63. 63. Clinical Pharmacology <ul><li>Persistent Effects , divided into 3 parameters </li></ul><ul><ul><li>Post-antibiotic effect (PAE) </li></ul></ul><ul><ul><li>Post-antibiotic sub-MIC effect (PAE-SME) </li></ul></ul><ul><ul><li>Post-antibiotic leukocyte enhancement (PALE) </li></ul></ul>
  64. 64. Clinical Pharmacology <ul><li>PAE Post-Antibiotic Effect </li></ul><ul><ul><li>Refers to the persistent suppression of bactericidal growth after short exposure to an antibiotic </li></ul></ul><ul><li>PAS-SME Post-antibiotic Sub-MIC Effect </li></ul><ul><ul><li>Antibiotic concentration below MIC, although not enough to kill the organism, may slow down its growth </li></ul></ul><ul><li>PALE Post-antibiotic Leukocyte Enhancement </li></ul><ul><ul><li>The phenomenon when bacteria become more susceptible to killing or phagocytosis by the leukocytes after they have been exposed to the antibiotics </li></ul></ul>
  65. 65. Clinical Pharmacology <ul><li>Persistent effects of antibiotics enhance their killing power </li></ul><ul><li>The patterns of antimicrobial activity fall into 2 major patterns: </li></ul><ul><ul><li>Time-dependent killing </li></ul></ul><ul><ul><ul><li>Duration of exposure is important </li></ul></ul></ul><ul><ul><ul><li>eg. Beta-lactams, cephalosporins, flucytosine </li></ul></ul></ul><ul><ul><li>Time-dependent killing with prolonged PAE </li></ul></ul><ul><ul><ul><li>eg. Macrolides, tetracyclines, azithromycin, clindamycin, fluconazole </li></ul></ul></ul><ul><ul><li>Concentration-dependent killing </li></ul></ul><ul><ul><ul><li>Concentration or amount of drug is important </li></ul></ul></ul><ul><ul><ul><li>eg. Aminoglycosides, quinolones, amphotericin B </li></ul></ul></ul>
  66. 66. Drug Interactions <ul><li>Two Principal Types of Interactions between Drugs: </li></ul><ul><li>I.A PHARMACOKINETIC INTERACTIONS causing DECREASE drug delivery </li></ul><ul><li>A. Impaired GI absorption </li></ul><ul><li>B. Induction of hepatic metabolizing enzymes: Cyto-P450 </li></ul><ul><li>C. Inhibition of cellular uptake binding </li></ul>
  67. 67. Drug Interactions <ul><li>Two Principal Types of Interactions between Drugs: </li></ul><ul><li>I.B PHARMACOKINETIC INTERACTIONS causing INCREASE drug delivery </li></ul><ul><li>A. Inhibition of drug delivery </li></ul><ul><li>B. Inhibition of renal elimination </li></ul><ul><li>C. Inhibition of clearance by multiple mechanisms </li></ul>
  68. 68. Drug Interactions <ul><li>Two Principal Types of Interactions between Drugs: </li></ul><ul><li>II. PHARMACODYNAMIC INTERACTIONS and other interactions between drugs </li></ul><ul><li>ADVERSE DRUG REACTIONS </li></ul>
  69. 69. Drug Interaction Tables <ul><li>The table contains lists of drugs in columns under the designation of specific cytochrome P450 isoforms </li></ul><ul><li>A drug appears in a column if there is published evidence that it is metabolized, at least in part, via that isoform </li></ul><ul><li>It does not necessarily follow that the isoform is the principal metabolic pathway in vivo, or that alterations in the rate of the metabolic reaction catalyzed by that isoform will have large effects on the pharmacokinetics of the drug. </li></ul>Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed [date].
  70. 70. Drug Interactions Chart
  71. 72. Drug Interactions
  72. 73. Drug Interactions
  73. 74. Drug Interactions
  74. 76. Dr. Ronald Sanchez - Magbitang Thank You !