Introduction to pharmacology

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  • Testing in Humans


  • 1. Pharmacology
  • 2. Introduction
    • What is pharmacology?
    • Why do we need to take pharmacology?
    • Significance of pharmacology to Dentistry
  • 3. History of Pharmacology
    • A history of pharmacology
    • Ancient Times A series of scattered facts exists that speak of the early history of humankind's efforts to harness the healing properties of natural compounds. However, what we know for certain is that ancient peoples made extensive use of plant, animal and mineral sources for this purpose.
  • 4. History of Pharmacology
    • The Ebers papyrus, written in Egypt in the 16 th century B.C., lists the extensive pharmacopia of that civilization. Included in this are: beer, turpentine, myrrh, , junipe r
    berries., poppy, lead, salt and crushed precious stones. Also included were products derived from animals, including lizard's blood, swine teeth, goose grease, ass hooves and the excreta from various animals. The effects of many of these drugs on patients of antiquity can only be imagined.
  • 5. History of Pharmacology
    • From ancient China comes evidence of that culture's extensive efforts to heal through the use of natural products. The Pen Tsao , or Great Herbal, comprised forty volumes describing several thousands of prescriptions .
  • 6. History of Pharmacology
    • Interestingly, the eastern herb Artemisia annua L. (wormwood), used in China since antiquity to treat fevers, is the source of the modern drug qinghaosu , which shows great promise as a modern anti-malarial compound.
  • 7. History of Pharmacology
    • Antiquity to the modern era The ancients considered disease a consequence of demonic possession, or the wrath of god. Thus, in ancient times, the treatment of illness with natural products was invariably accompanied by religious rituals deemed essential to the healing process.
  • 8. History of Pharmacology
    • With time, the thoughts returned to the appreciation that the natural products themselves held the power to cure.
    Although, traditional remedies still generally consisted of complex mixtures of distinct herbs and minerals, perhaps only one of which possessed any activity. Many poisonous mixtures were made.
  • 9. History of Pharmacology
    • For example, the purple foxglove, Digitalis purpurea , was one of twenty herbs used in a folk remedy to treat dropsy in 18 th century England. From the leaves of this plant was isolated the cardiac glycoside digitalis , a drug still used today to treat heart failure.
  • 10. History of Pharmacology
    • Over time, as a more sophisticated view of illness evolved, an increasingly scientific approach to the isolation of drugs from natural products was taken. In the early 19 th century,
    morphine was isolated from the opium poppy ( Papaver somniferum ) and the anti-malarial compound quinine from the bark of the cinchona tree ( Cinchona officinalis ).
  • 11. History of Pharmacology
    • Materia Medica
    • The ancient discipline of Materia Medica was born, devoted to understanding the origin, preparation and therapeutic applications of medicinal compounds.
    • It postulated that:
    • Each disease has a unique cause for which there is a specific remedy.
    • Each remedy has an identifiable nature or essence that is extracted from the natural product by chemical extraction.
    • The administration of a remedy is based on testing the amount of drug needed to achieve an effect (dose-response).
  • 12. History of Pharmacology
    • In 1897, Felix Hoffman, a research chemist employed by the "Farbenfabrikin vorm. Freidr. Bayer and Co." synthesized acetylsalicylic acid. On February 1, 1899, Aspirin® was registered as a trademark. On March 6 th of the same year, this drug was registered with the Imperial Patent Office in Berlin. Aspirin quickly become popular
    worldwide, and remains an important drug today. (Interestingly, it was not until 1971 that Sir John Vane discovered the mechanism of action of aspirin, a feat that earned him the 1981 Nobel Prize for Medicine.)
  • 13. History of Pharmacology Paul Ehrlich described drug-receptor binding: “ Corpora non agunt nisi fixate”. P. Ehrlich (1908)   ( “ Agents do not act unless they are bound”) In the United States, transformation was marked by the creation of the American Society for Pharmacology and Experimental Therapeutics (ASPET) in 1908.
  • 14. History of Pharmacology
    • The modern era These, and additional advances in the fields of chemistry and physiology, lead to the birth of modern pharmacology in the latter half of the 19 th century. Thus, Materia Medica evolved into the
    experimental science of pharmacology, which is devoted to understanding the physiological action of these molecules.
  • 15. History of Pharmacology
    • The 20 th century has witnessed the discovery of a steady stream of important new drugs that have immeasurably improved the human condition.
    • Not very long ago, vast numbers of humans perished prematurely or suffered an existence filled with pain due to the effects of infection or disorders that are now successfully treated.
      • chemotherapy of cancer
      • microbial infections
      • diabetes
      • hypertension
      • depression
      • AIDS
  • 16. Pharmacology
    • Pharmacology is the study of how drugs exert their effects on living systems.
    • Pharmacologists work to identify drug targets in order to learn how drugs work. Pharmacologists also study the ways in which drugs are modified within organisms.
    • In most of the pharmacologic specialties, drugs are also used today as tools to gain insight into both normal and abnormal function.
  • 17. Pharmacology
    • Divisions of Pharmacology
    • Pharmacokinetics
    • Pharmacodynamics
    • Pharmacogenomics
  • 18. Pharmacokinetics
    • Is what the body does to the drug.
    • The magnitud of the pharmacological effect of a drug depends on its concentration at the site of action.
    • Absorption
    • Distribution
    • Metabolism
    • Elimination
  • 19. Pharmacodynamics
    • Is what the drug does to the body.
    • Interaction of drugs with cellular proteins, such as receptors or enzymes, to control changes in physiological function of particular organs.
    • Drug-Receptor Interactions
      • Binding
    • Dose-Response
      • Effect
    • Signal Transduction
      • Mechanism of action, Pathways
  • 20. Pharmacogenetics
    • Area of pharmacology concerned with unusual responses to drugs caused by genetic differences between individuals.
    • Responses that are not found in the general population, such as general toxic effects, allergies, or side effects, but due to an inherited trait that produces a diminished or enhanced response to a drug.
        • Differences in Enzyme Activity
          • Acetylation polymorphism
          • Butylcholinesterase alterations
          • Cytochrome P450 aberration
  • 21. Drugs
    • Drugs can be defined as chemical agents that uniquely interact with specific target molecules in the body, thereby producing a biological effect.
      HOWARD UNIVERSITY       Drugs can be stimulatory or inhibitory
  • 22. Drugs
    • Drugs, as well as hormones, neurotransmitter, autocoids and toxins can make possible the transfer of information to cells by interaction with specific receptive molecules called “receptors”. Receptor DRUG
  • 23. Drugs
    • Drugs interact with biological systems in ways that mimic, resemble or otherwise affect the natural chemicals of the body.
    • Drugs can produce effects by virtue of their acidic or basic properties (e.g. antacids, protamine), surfactant properties (amphotericin), ability to denature proteins (astringents), osmotic properties (laxatives, diuretics), or physicochemical interactions with membrane lipids (general and local anesthetics).
  • 24. Receptors
    • Most drugs combine ( bind ) with specific receptors
    • to produce a particular response. This association or binding takes place by precise physicochemical and steric interactions between specific groups of the drug and the receptor.
      • Proteins
          • Carriers
          • Receptors
            • G protein-linked
            • Ligand gated channels
            • Intracellular
          • Enzymes
      • DNA
  • 25. Endogenous compounds act on their Receptors Neurotransmitter Neuropeptides Hormones Ions
  • 26. Receptor
    • Pharmacological
    • Mediator (i.e. Insulin, Norepinephrine, estrogen)
    • Biophysical and Biophysical
    • Second messenger system (i,.e. cAMP, PLC, PLA)
    • Molecular or Structural
    • Subunit composition (i.e. 5HT1A )
    • Anatomical
    • Tissue (i.e muscle vs ganglionic nAChRs)
    • Cellular (i.e. Membrane bound vs Intracellular)
    Classification of Receptors
  • 27. Types of Receptors
    • G-Protein-linked receptors
      • Serotonin, Muscarinic, Dopaminergic, Noradrenergic
    • Enzyme receptors
      • Tyrosine kinase
    • Ligand-gated ion channel receptors
      • Nicotinic, GABA, glutamate
    • Hormone receptors
    • Autocoid receptors
    • Growth factors receptors
    • Insulin receptors
  • 28. G Protein–linked Receptors
  • 29. Enzyme-like Receptors
  • 30. Ligand-gated Ion-Channel Receptors
  • 31. Nuclear Receptors
  • 32. Drug-Receptor Interactions
    • 1)        Lipophilic
    • 2)      Hydrophilic
    • 3)      Ionic
    • 4)      Hydrogen bonds
    • 5)      Steric (stereospecificity) effects
    • 6)      Electronic effect
    • 7)      pK effects
    Physicochemical and steric interactions
  • 33. Drug-Receptor Interactions Chemical Bonds Van der Waals Interactions Hydrophobic Interactions
  • 34. Drug-Receptor Interactions
    • Drug-receptor interactions serve as signals to trigger a cascade of events. This cascade or signaling pathway, is a collection of many cellular responses which serve to amplify the signal and produce a final effect.
    • Effectors are thus the molecules that translate the drug-receptor interaction into changes in cellular activity.
    •    +          EFFECT
    SIGNALLING PATHWAY www.freelivedoctor.comz
  • 35. Receptor Signaling Pathways
    • Second Messengers:
    • Ions (Ca 2+ , Na + , K + , Cl - )
    • cAMP, cGMP, IP3, Diacylglycerol
    • DNA binding – Transcriptional regulation.
    • Phosphorylated proteins and enzymes via tyrosine kinase receptors.
    • Third Messengers:
    • Enzymes (PKC, PKA)
    • Ions (Ca 2+ , K + )
  • 36. Receptor Signaling Pathways
    • Adenylate Cyclase (AC)
    • Guadenylyl Cyclase (GC)
    • Phospholipase C (PLC)
    • Phospholipase A (PLA 2 )
    • Nitric oxide Synthase
    • Ions
    cAMP cGMP DAG and IP3 Arachidonic acid NO and CO Na + , Ca 2+ , K + , Cl - EFFECTORS SECOND MESSENGER
  • 37. Receptor Signaling Pathways R R R R
  • 38. Receptor Signaling Pathways
  • 39. Drug-Receptor Interactions
    • Theory and assumptions of drug-receptor interactions.
    • Drug Receptor interaction follows simple mass-action relationships, i.e. only one drug molecule occupies each receptor and binding is reversible (We know now there are some exceptions).
    • For a given drug the magnitud of the response is proportional to the fraction of total receptor sites occupied by drug molecules.
    • Combination or binding to receptor causes some event which leads to a response .
    • Response to a drug is graded or dose-dependent.
  • 40. Law of Mass Action
    • When a drug (D) combines with a receptor (R), it does so at a rate which is dependent on the concentration of the drug and the concentration of the receptor.
    • D = drug
    • R = receptor
    • DR = drug-receptor complex
    • k 1 = rate for association
    • k 2 = rate for dissociation
    • K D = Dissociation Constant
    • K A = Affinity Constant
    •   Read the Appendix at the back of lecture 1B
    • k 1
    • [D] + [R]  [DR]
    • k 2
        • k 2 = K D = [D][R]
        • k 1 [DR]
    • 1 = K A = k 1 = [DR]
    • K D k 2 [D] [R]
  • 41. Key Topics
    • How are drugs described and referenced?
    • What are the relevant drug laws and regulations?
    • What are the factors affecting how drugs are given?
    • What are some of the key terms?
  • 42. Drug Descriptions
    • Names
    • Sources
    • Forms
    • Reference Materials
    • Components of Drug Profiles
  • 43. Drug Names
    • Chemical Name: 2-(diethylamino)-2’,6’-acetooxylid monohydrochloride monohydrate.
    Not Particularly Useful!
  • 44. Drug Names
    • Generic Name: lidocaine hydrochloride
    • Official Name: Lidocaine Hydrochloride, USP
    • Brand (Trade) Name: Xylocaine ®
    Much More Useful
  • 45. Drug References
    • USP
    • PDR
    • Drug Inserts
    • Nursing Drug References
    • Pocket Field Guides
    • Digital Guides
      • Jeff’s Pharmacology Review
  • 46. Components of a Drug Profile
    • Names
    • Classification (including prototype)
    • Mechanism of Action
    • Kinetics
    • Indications
    • Contraindications
    • Side Effects
    • Interactions
    • Routes of Administration
    • Dosage
    • How Supplied
    • Special Considerations
  • 47. Drug Laws
    • Pure Food and Drug Act of 1906
    • Harrison Narcotic Act of 1914
    • Federal Food, Drug and Cosmetic Act of 1938
      • Durham-Humphrey Amendments
    • Comprehensive Drug Abuse Prevention and Control Act of 1970
  • 48. Controlled Substances
  • 49. State and Local Laws
    • ‘ Scope of Practice’ Laws
    • Responsibility vs Authority of Medical Direction
  • 50. Drug Standardization
    • Assays
    • Bioequivalence
    • Bioassay
    • USP is the official standard
  • 51. Research and Development
    • Key points from FDA handout
      • Purpose?
      • What are controls?
      • What are the phases?
      • What is an IND? An NDA?
      • Why is skepticism important?
      • Handout Source:
  • 52. Six Rights of Medication Administration
    • Right Medication
    • Right Dose
    • Right Time
    • Right Route
    • Right Patient
    • Right Documentation
  • 53. Pregnancy Considerations
    • Increased maternal HR, CO and blood volume
      • May affect absorption, distribution, effectiveness
    • Drugs may cross placenta
    • Drugs may cross into breast milk
    • Tertatogens
  • 54. Pregnancy Categories
    • A: controlled studies in pregnancy (<1 %).
    • B: animal studies show no risk; Inadequate human data.
    • C: animal studies show risk, inadequate human data.
    • D: human data show risk, benefit may outweigh risk.
    • X: animal or human data positive for risk. Use unwarranted.
  • 55. Pediatric Considerations
    •  Oral absorption
    • Thinner skin (  topical absorption)
    •  Plasma protein concentration
      •  Free protein-bound drug availability
    •  Extracellular fluid in neonate
    • Altered metabolic rates
    •  Elimination/metabolism
    • BSA/weight based dosing important!
  • 56. Geriatric Considerations
    •  Oral absorption
    •  Plasma protein concentration
    •  Muscle mass,  body fat
    •  Liver/renal function
    • Multiple drugs
    • Multiple diseases
  • 57. Some Terminology
    • Receptor affinity
    • Efficacy
    • 1 ° vs. 2 nd messengers
    • Up vs. down receptor regulation
    • Agonist vs. antagonist
    • -lytic vs. -mimetic
    • Inhibition (antagonism)
      • Competitive vs. noncompetitive vs. irreversible
    • Allergic reaction
    • Idiosyncrasy
    • Tolerance
  • 58. More Terminology
    • Cross tolerance
    • Tachyphylaxis
    • Cumulative effect
    • Dependence
    • Drug interactions
    • Summation (1+1=2)
      • Additive effect
    • Synergism (1+1=3)
    • Potentiation
    • Interference
  • 59. Basics of Drug Classification
    • Knowledge grouping
    • Prototype drug
    • Predictive value
  • 60. Drug Classification
    • By chemistry
      • electrolytes
    • By mechanism
      • Beta blockers
      • benzodiazepines
    • By disease
      • antihypertensives
      • Antiemetics