Basic Principles in Pharmacology for

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Basic Principles in Pharmacology for
School of Biomedical Engineering, Drexel
University
Prof. Philip Lazarovici, Ph.D., M.Sc.,
B.Sc. Department of Pharmacology and Experimental
Therapeutics School of Pharmacy, Faculty of
Medicine, Hebrew University,
Jerusalem, Israel
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History of Pharmacology
THE IMPETUS
THE IDEA
CLAUDIUS GALEN (129-200
A.D.) The empiricists say that all is found by
experience. We, however, maintain that it is
found in part by experience, in part by theory.
Neither experience nor theory alone is apt to
discover all.
THEOPHRASTUS von HOHENHEIM (1493-1541) -
PARCELSUS - If you want to explain any poison
properly, what then isnt a poison? All things
are poison the dose alone causes a thing not to
be poison.
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History of Pharmacology
CONSOLIDATION
EARLY BEGINNINGS
FOUNDATION

• OSWALD SCHMIEDEBERG
  (1838-1921)
• Helped to establish the high reputation of
  pharmacology.
• Helped to establish fundamental concepts (such as
  structure-activity relationship, drug
  receptor).
• Founded the first journal of pharmacology.

• JOHANN JAKOB WEPFER (1620-1695)
• Was the first to verify by animal experimentation
  assertions about pharmacological or toxicological
  actions.

• RUDOLF BUCHHEIM
  (1820-1879)
• Founded the first institute of pharmacology at
  the University of Dorpat (Estonia).
• Strove to explain the chemical properties of
  drugs and their effects.

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Status Quo 1920 to
date

• After 1920, pharmacological laboratories sprang
  up in the pharmaceutical industry, outside
  established university institutes.
• After 1960, additional departments of clinical
  pharmacology were set up at many universities and
  in industry.

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Pharmacology
Greek - pharmakon drug or poison
logos word or discourse

• Pharmacology Disciplines
• Medicinal Chemistry The science of isolation and
  synthesis of drugs.
• Pharmacy The science of drug preparation and
  formulation.
• Pharmacology / Pharmacogenetics The science
  investigating mechanisms
  of drugs actions / the effect of gene expression
  on drug action.
• Toxicology The science investigating the
  toxicity of drugs and xenobiotics.

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The Placebo Effect

• The placebo effect is a therapeutic result
  arising from psychological factors.
• Can be observed in conditions involving the
  nervous or endocrine system.
• It is a result of a belief of the patient that
  the drug is efficatious (even it is an inert
  substance).
• The placebo effect is not predictable, but may
  occur in as many as 35 of patiens.

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Definitions

• Pharmacology the study of drugs observable
  interaction between drug and body constituent.
• a) pharmacodynamics the effect of the drug on
  the body on intact animals, tissue, cellular and
  molecular level.
• b) pharmacokinetics the effect of the body on
  the drug.
• ADME - Absorbtion
• - Distribution
• - Metabolism
• - Elimination

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The Basic Principles of Pharmacology

• The molecular basis of selective drug and toxin
  action
• 2. The entry, distribution and elimination the
  time coures of drug action
• 3. Drug metabolism and pharmacogenetics
• 4. Pharmaceutical aspects of drug delivery
• 5. Chemical and biotechnological aspects of drug
  development
• 6. Drug tolerance and physical dependence
• 7. Drug resistance, chemical - mutagenesis,
  carcinogenesis, teratogenesis.

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Drugs and Active Principle (1)
Drug (from French drogue) dried herb.

• Source
• Isolation
• Partial purification
• Identification of active principle

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Drugs and Active Principle (2)

• Drug a chemical which upon introduction
  (penetration into the body) changes the
  physiological function. This change may be
  exploited to alter a disease process or may cause
  toxicity.
• Vitamin C in orange juice is a food but ascorbic
  acid injected in high concentrations is a drug.
• Hydrocortizone secreted by the adrenal cortex is
  a hormone but injected in high concentrations is
  useful to treat an inflammatory process.

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Drug Classifications (1)
1. Classification Based on Origin a. Natural
Preparations or Galenicals e.g. digitalis leaf,
tincture of belladonna or opium b. Pure
Compounds e.g. morphine, atropine. c.
Semi-synthetic Substances e.g. diacetylmorphine
heroine, hydrocortisone fluor atom
fludrocortisone, penicillin side chain
oxacillin. d. Purely Synthetic Compounds
e.g. isoprenaline. 2. Classification Based on
Use Classification according to the
physiological systems upon which they exert their
most prominent actions, e.g. antibiotics,
diuretic/antidiuretic, neurological drugs,
hypnotic, antiarrhythmic.
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Drug Classifications (2)

• 3. Operational Classification
• Drugs for Emergencies (to be known perfectly by
  the physician) e.g. morphine, adrenaline.
• Drugs for Frequent Use (to be known in main
  outline), specific in the area of practice.
• Drugs Used Occasionally (after checking details)
  category including new drugs.
• Drugs to be Used Only by Experts, after special
  training and repeated practice.

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Drugs and Society

• Our societys comes into contact with drugs in
  different ways
• Medical Prescription
• Over-the-counter sale (without prescription)
• Social use (alcohol, cannabis)
• Industrial use (artificial flavorings, colorings)
• Agricultural use (pesticides)
• Accident (accidental poisoning)

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Drugs Standards and References

1. HANDBOOKS
2. PHARMACOPOEIAS e.g. British Pharmacopoeia,
   U.S. Pharmacopoeia.
3. PEDIATRIC DOSAGE HANDBOOK
4. U.S. NATIONAL FORMULARY (N.F.) ISRAELI DRUG
   COMPENDIUM.
5. ACCEPTED DENTAL THERAPEUTICS (A.D.T.)
6. COMPENDIUM of PHARMACEUTICALS and SPECIALTIES
   (C.P.S.)
7. DRUG BENEFIT FORMULARY (PARCOST)
8. MEDIC.

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Journals

1. JPET Journal of Pharmacology and Experimental
   Therapeutic (ASPET)
2. Molecular Pharmacology (ASPET)
3. European Journal of Pharmacology
4. British Journal of Pharmacology
5. Pharmacology Reviews (ASPET)

Books

1. Pratt, W.B., Taylor, P. (1990) Principles of Drug
   Action The Basis of Pharmacology 3rd ed.,
   Churchill Livingstone, New York.
2. Rang, H.P., Dale, M.M., Ritter, J.M. (1999)
   Pharmacology 4th ed., Churchill Livingstone, New
   York.
3. Brody, M.T., Larner, J., Minneman, P.K. (1998)
   Human Pharmacology, Molecular to Clinical 3rd
   ed., Mosby, St.Louis.

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Useful Links and Software

• Lectures and self study questions
• a) www.pharmacology2000.com
• b) www.medfac.leidenuniv.nl/t
  rc/version_eng/
• Teaching Courses
• a) www.md.huji.ac.il/courses
  /pharmacology/learn.html

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Drug Nomenclature

• Chemical Name 1-methyl-4-phenyl-4-carbethoxy
  piperidine.
• Nonpropritary drug name generic name
  pethidine (B.P.), meperidine (U.S.P.),
  isonipecaine (I.P.).
• Official names (in pharmacopoeias)
• Approved names (not yet in
  pharmacopoeias), e.g. Canadian Proper Names,
  U.S. Adopted Name (USAN).
• Proprietary name manufacturers trade name
  Demerol, Dolantin, Dolantol, Eudolal.
• Common name pethidine.

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Drug Development

• Preclinical testing
• Clinical testing
• Phase I Healthy subjects side effects,
  toxicity, initial dose evaluation.
• Phase II Selection of sick patients
  therapeutic efficacy.
• Phase III Very large groups of patients
  dose response, therapeutic effect.
• Phase IV Post marketing surveillance.

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Drug Administration

• DOSAGE FORM
• Liquid preparation solution, suspension,
  emulsion.
• Eye and nose drops
  
• Solid dosage form tablets, coated tablets
  capsules.

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Oral Administration of Tablets

• Drug Release
• 2. Site of Absorption

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Other Dosage Forms

1. Parenteral injectable solutions intravenous,
   intramuscular, subcutaneous.
2. Inhalation aerosol form, onto the mucosa of the
   body cavities.
3. Rectal/Vaginal suppositories and vaginal tablets
   the latter effects mostly locally.
4. Percutaneous powders, ointments, pastes drugs
   or skin protection/care effects.

• These drugs must
• Penetrate the cutaneous barrier
• Be effective in small doses
• Posses wide therapeutic margin.

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Drug Administration by Inhalation

• Inhalation as an aerosol, a gas or a mist.
• The drug is applied to the bronchial mucosa and
  to the alveolar membranes
• Effect on bronchial smooth muscle and/or the
  bronchial mucous.
• The size of the aerosol particles determines the
  depth of the penetration into the respiratory
  tract (only particles smaller than 2 ?m reach the
  alveoli).
• Less than 10 of the drug inhaled reaches the
  respiratory tract.
• Mucociliary transport is affected by external
  factors, such as smoking, drugs.

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Drug Administration by Percutaneous
Administration (Dermatologic Agents)

• Skin protection
• a) dusting powders
• b) lipophilic ointment
• c) paste
• d) lipophilic (oily) cream
• e) hydrogel and water soluble ointment
• f) hydrophilic (aqueous) cream
• 2. Dermatologic agents as vesicles