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Basic Principles in      Pharmacology                  By        M.H.Farjoo M.D. , Ph.D.Shahid Beheshti University of Medi...
Basic Principles in Pharmacology   Introduction   Drug Size   Drug-receptor Bonds   Drug Shape   Drug-Body Interactio...
Introduction            Pharmacology: the study of substances that             activate or inhibit normal body processes....
Introduction (Cont,d)            Drug: a substance that changes biologic function             through its chemical action...
Introduction (Cont,d)            A receptor must be selective for drug;             and it must change its function upon ...
Introduction (Cont,d)            A drug must be capable of moving from its             site of entry to its site of actio...
Introduction (Cont,d)            Poison: a drug that has almost exclusively harmful             effects.            Toxi...
Introduction (Cont,d)            Pharmacogenomics (or pharmacogenetics): the             relation of the genetic makeup t...
Introduction (Cont,d)            Homozygous knockout mice have complete             suppression of the function.        ...
Introduction (Cont,d)            Big pharma: the multibillion-dollar companies             in drug discovery and developm...
Drug Size            The molecular size of drugs varies from very small             (lithium ion, MW 7) to very large (al...
Drug-receptor Bonds            Drugs interact with receptors by three types of chemical             forces: covalent, ele...
Drug-receptor Bonds (Cont,d)            Electrostatic bonds are weaker but much more             common than covalent bon...
Drug-receptor Bonds (Cont,d)            Hydrophobic bonds are important in the             interactions of lipid-soluble ...
Drug Shape            More than half of all useful drugs are chiral             molecules (stereoisomer), and exist as en...
Drug Shape (Cont,d)            One drug enantiomer is more susceptible to             drug-metabolizing enzymes.        ...
Drug-Body Interactions            The interactions between a drug and the body             are:                Pharmacod...
Drug-receptor Interactions            Agonist: drugs that bind to and activate the             receptor.            Anta...
Drug-receptor Interactions (Cont,d)            Partial agonists produce a lower response, than             do full agonis...
Duration of Drug Action            The effect may last as long as the drug             occupies the receptor.           ...
Weak Acids & Weak Bases            Weak acids and weak bases gain or lose protons             depending on the pH.      ...
Weak Acids & Weak Bases (Cont,d)            A large number of drugs are weak bases. Most             of these bases are a...
Weak Acids & Weak Bases (Cont,d)            The protonated form of a weak acid is the             neutral, more lipid-sol...
Weak Acids & Weak Bases (Cont,d)                                            Total Fluid:      Total Fluid:                ...
Summary In English
40 Km.Picture from earth as art website by NASA
Thank you Any question?
Basic principles in pharmacology
Basic principles in pharmacology
Basic principles in pharmacology
Basic principles in pharmacology
Basic principles in pharmacology
Basic principles in pharmacology
Basic principles in pharmacology
Basic principles in pharmacology
Basic principles in pharmacology
Basic principles in pharmacology
Basic principles in pharmacology
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Basic principles in pharmacology

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Transcript of "Basic principles in pharmacology"

  1. 1. Basic Principles in Pharmacology By M.H.Farjoo M.D. , Ph.D.Shahid Beheshti University of Medical Science
  2. 2. Basic Principles in Pharmacology Introduction Drug Size Drug-receptor Bonds Drug Shape Drug-Body Interactions Drug-receptor Interactions Duration of Drug Action Weak Acids & Weak Bases
  3. 3. Introduction  Pharmacology: the study of substances that activate or inhibit normal body processes.  Medical pharmacology: the science of substances used to prevent, diagnose, and treat disease.  Toxicology: deals with the undesirable effects of chemicals on living systems.M.H.Farjoo
  4. 4. Introduction (Cont,d)  Drug: a substance that changes biologic function through its chemical actions.  Prodrug: a chemical that is converted to the active drug inside the body.  A drug often interacts with a specific protein molecule, a receptor.  Orphan receptors: receptors for which no ligand has been discovered.M.H.Farjoo
  5. 5. Introduction (Cont,d)  A receptor must be selective for drug; and it must change its function upon binding.  To interact with its receptor, a drug must have the appropriate size, electrical charge and atomic composition.M.H.Farjoo
  6. 6. Introduction (Cont,d)  A drug must be capable of moving from its site of entry to its site of action.  A drug should be inactivated or excreted from the body at a reasonable rate.  Many drugs bind to albumin which is a nonregulatory protein and an inert binding site.M.H.Farjoo
  7. 7. Introduction (Cont,d)  Poison: a drug that has almost exclusively harmful effects.  Toxin : a poison of biologic origin, synthesized by plants or animals.  All substances can under certain circumstances be toxic.  Dietary supplements and health-enhancing chemicals should prove their efficacy and safety.M.H.Farjoo
  8. 8. Introduction (Cont,d)  Pharmacogenomics (or pharmacogenetics): the relation of the genetic makeup to response to drugs.  Gene therapy: insertion of a "healthy" gene into somatic cells.  Knocked out gene: the gene for the receptor has been mutated so that the receptor is absent or nonfunctional.M.H.Farjoo
  9. 9. Introduction (Cont,d)  Homozygous knockout mice have complete suppression of the function.  Heterozygous knockout mice have partial suppression.  Knocked down genes: a gene with limited suppression of function.  Knockin mice: animals with overexpression of certain proteins of interest.M.H.Farjoo
  10. 10. Introduction (Cont,d)  Big pharma: the multibillion-dollar companies in drug discovery and development.  These companies translate basic findings into commercially successful therapeutics.  Profit margins for big pharma have exceeded all other industries by a significant factor.M.H.Farjoo
  11. 11. Drug Size  The molecular size of drugs varies from very small (lithium ion, MW 7) to very large (alteplase MW 59,050).  Most drugs have molecular weights between 100 and 1000.  The lower limit is required for specificity and good "fit" to a receptor.  The upper limit is required for drug movement from site of administration to site of action.M.H.Farjoo
  12. 12. Drug-receptor Bonds  Drugs interact with receptors by three types of chemical forces: covalent, electrostatic, and hydrophobic.  Because of covalent bond between aspirin and platelets, its effect is reversed by production of new platelets (7 days).  DNA-alkylating agents used in cancer chemotherapy also make covalent bonds .M.H.Farjoo
  13. 13. Drug-receptor Bonds (Cont,d)  Electrostatic bonds are weaker but much more common than covalent bonds.  Electrostatic bonds consist of:  Relatively strong ionic bonds  Weaker hydrogen bonds  Very weak van der waals forces.M.H.Farjoo
  14. 14. Drug-receptor Bonds (Cont,d)  Hydrophobic bonds are important in the interactions of lipid-soluble drugs with the lipids of cell membranes.  Drugs that bind through weak bonds are more selective than drugs that bind by very strong bonds.  To design a highly selective short-acting drug for a receptor, we avoid molecules that form covalent bonds.M.H.Farjoo
  15. 15. Drug Shape  More than half of all useful drugs are chiral molecules (stereoisomer), and exist as enantiomeric pairs.  Drugs with two asymmetric centers have four diastereomers.  In most cases, one of these enantiomers is much more potent than its mirror image.M.H.Farjoo
  16. 16. Drug Shape (Cont,d)  One drug enantiomer is more susceptible to drug-metabolizing enzymes.  45% of the chiral drugs are marketed as the active isomer, the rest are racemic mixtures.  Many patients receive drug doses of which 50% or more is less active, inactive, or actively toxic.M.H.Farjoo
  17. 17. Drug-Body Interactions  The interactions between a drug and the body are:  Pharmacodynamic processes: the actions of the drug on the body  Pharmacokinetic processes: the actions of the body on the drugM.H.Farjoo
  18. 18. Drug-receptor Interactions  Agonist: drugs that bind to and activate the receptor.  Antagonist: drugs whose binding to a receptor, prevent binding of other molecules.M.H.Farjoo
  19. 19. Drug-receptor Interactions (Cont,d)  Partial agonists produce a lower response, than do full agonists.  Partial agonists do not have decreased affinity for receptors.  Partial agonists competitively inhibit the responses produced by full agonists.M.H.Farjoo
  20. 20. Duration of Drug Action  The effect may last as long as the drug occupies the receptor.  The action may persist after the drug has dissociated. (Some coupling molecule is still active).  In covalent binding, the effect persists until new receptors or enzymes are synthesized.M.H.Farjoo
  21. 21. Weak Acids & Weak Bases  Weak acids and weak bases gain or lose protons depending on the pH.  Their movement between aqueous & lipid mediums varies with the pH.  Kidney filters drugs, by changing the urine pH the drug can be "trapped" in the urine (in overdose).  Weak acids are excreted faster in alkaline urine and vise versa.M.H.Farjoo
  22. 22. Weak Acids & Weak Bases (Cont,d)  A large number of drugs are weak bases. Most of these bases are amine-containing molecules.  Primary, secondary, and tertiary amines undergo reversible protonation.  They vary their lipid solubility with pH.  Quaternary amines are always in the poorly lipid-soluble charged form.M.H.Farjoo
  23. 23. Weak Acids & Weak Bases (Cont,d)  The protonated form of a weak acid is the neutral, more lipid-soluble form.  The unprotonated form of a weak base is the neutral form.  The uncharged form is more lipid-soluble.  A weak acid is more lipid-soluble at acid pH, and a basic drug is more lipid-soluble at alkaline pH.M.H.Farjoo
  24. 24. Weak Acids & Weak Bases (Cont,d) Total Fluid: Total Fluid: Blood Blood Concentration Concentration Body Fluid Range of pH Ratios for Ratios for Sulfadiazine Pyrimethamine (acid, pKa 6.5) (base, pKa 7.0) Urine 5.0-8.0 0.12-4.65 72.24-0.79 Breast milk 6.4-7.6 0.2-1.77 3.56-0.89 Jejunum, ileum 7.5-8.0 1.23-3.54 0.94-0.79 contents Stomach contents 1.92-2.59 0.11 85,993-18,386 Prostatic secretions 6.45-7.4 0.21 3.25-1.0 Vaginal secretions 3.4-4.2 0.11 2848-452M.H.Farjoo
  25. 25. Summary In English
  26. 26. 40 Km.Picture from earth as art website by NASA
  27. 27. Thank you Any question?
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