Upload
moris-french
View
217
Download
3
Tags:
Embed Size (px)
Citation preview
Introduction to PharmacologySeptember 5, 2007
•Frank F. Vincenzi E-419, HSB
•206-543-1993
•*Assignment*: If you have not already done so, send me an email message in response to my email to you. If you did not get a message from me, pay special attention. YOUR EMAILS WILL BE USED TO CREATE THE UNIQUE CLASS & MAILING LIST. Please tell me a little bit about yourself and what you hope/expect to learn in pharmacology - whatever you are comfortable sharing.
Food for thought• The Food & Drug Administration (FDA) approves
about 30 new drugs/year
• Most MDs prescribe drugs that were not known when they graduated
• About 2/3 of all physician visits lead to a prescription
• More than half of drug advertising $$ goes to ‘detailing’ MDs (about $5000/yr/MD)
Objectives of HuBio 543
•Impart a specific body of knowledge
•Develop an ability to use the knowledge
•Develop a systematic approach to critically evaluate pharmacological information
•Develop motivation to add the knowledge base on a life-long basis
Roadmap for Autumn Quarter
• Basic Principles of Pharmacology
• Peripheral Nervous System (somatic & ANS)
• Cardiovascular
• Chemotherapy
• Disease, Syndrome & Patient-oriented Sessions
Evaluation
• Zero to three NO HARM quizzes AND/ORFinal examination
(if a quiz is not taken, or if the percentage scoreis less than the percentage on the Final
Examination,then the quiz is simply dropped)
• One take home quiz 100 points
• One quiz mainly on peripheral NS 100 points
• One quiz on CV and chemotherapy 100 points
• Final Examination (comprehensive) 300 points
Example of overall course average calculation for a hypothetical student
• Quiz # 1 (take home) 90/100• Quiz # 2 (ANS) 60/100• Quiz # 3 (CV and chemo) (Autumn flu) --
• Final examination - comprehensive (68%) 204/300
• (quiz 2 and quiz 3 dropped (< 68%)
• (90 + 204)/400 = 0.735, (i.e., 73.5% … pass)
points
EXAMINATION FORMATS & GRADING
• Multiple choice• Calculations• Short answer/essay
• >= 70% overall average, guaranteed pass• >=90% overall average, guaranteed honors
Sources of Information• Syllabus and Lectures & handouts• Textbook: Goodman & Gilman’s The Pharmacological Basis
of Therapeutics, printed or online (Now in its11th edition)• Course Web Site
https://courses.washington.edu/chat543/– Schedule, objectives, grading, etc.– Drug List– Web Site for CV & ANS Pharmacology
https://courses.washington.edu/chat543/cvans/index.html• Books & CD-ROMS, Internet resouces
Katzung, Brody’s Human Pharmacology Physician’s Desk Reference (PDR) (Lippincott’s Board Review)
Most common sources of drug information - clinically
PDR
PDAePocratesCP on HandPhysician’s Drug Handbook,Your Local Pharmacist !!Internet……
Learning objectives for this session
Introductory understanding of:
• Pharmacology• Drug• Receptor• Agonist• Antagonist• Pharmacodynamics• Pharmacokinetics
• Toxicology• Silent receptor• Drug action• Drug effect• Chirality• Why most drugs have
MWs >100 and < 1000
Pharmacology is the science of drug action• Related disciplines:
– Pharmacognosy - the study of drugs from natural sources– Toxicology - That branch of pharmacology which
systematically studies the adverse effects of drugs on living systems
• Related professions:– Pharmacy - the art and science of compounding and
dispensing - and, increasingly, drug information...– Clinical pharmacology - the art and science of evaluating
and optimizing the use of drugs in humans
Drug
• Noun– Any agent that, by virtue of its chemical properties,
alters the structure or function of biological systems (pharmacologist’s view).
– Any agent approved by the Food and Drug Administration for the treatment or prevention of disease (legal view).
– Any agent taken by some, but disapproved by others (societal view).
Receptor
• Noun– Those molecules (or parts of molecules) with
which a drug must interact in order to produce a given action in a biological system
Macromolecules (especially proteins) as receptors
• G Protein coupled receptors (GPCRs) (e.g., beta adrenoceptor)
• Ligand-gated ion channels (e.g., NAChR)
• Cytokine receptors (e.g., erythropoietin)
• Structural proteins (e.g., tubulin)
• Transmembrane enzymes
– ion pumps (Na/K pump ATPase)
– receptor tyrosine kinases (insulin receptor)
Silent Receptor
• Those molecules or parts of molecules with which a drug interacts without producing an action - a site of binding.
– e.g., warfarin binding to serum albumin
Chirality of drugs (stereoisomerism)
• D-epinephrine is essentially inactive
• L-epinephrine is extremely potent (half-maximal effects at nanomolar concentrations)
– Simplest interpretation is that L-epinephrine makes a three point contact with its receptors
Biological Systems: Interactions Through Differentiated Aspects of the Whole
• Society
• Community
• Organism
• Organ system
• Organ
• Tissue
• Cell
• Subcellular organelles
• Molecular systems
• Molecules
• Functional groups
• Atoms
• Subatomic particles
• Quarks
Two equally and clinically important aspects of pharmacology
• Pharmacodynamics– Systematic study of the effects of drugs on
living systems
• Pharmacokinetics– Systematic study of the effects of living
systems on drugs
Agonist
• Noun– A drug molecule which, when it interacts with a
given receptor, produces a stimulus which results in a change in the biological system beyond the level of that receptor
• e.g., epinephrine
Partial Agonist
• Noun– A drug molecule which, when it interacts with a
given receptor, produces a stimulus for change beyond the level of that receptor, but the stimulus is less than the maximum characteristic of that receptor
• e.g., buprenorphine
Competitive Antagonist
• Noun– A drug molecule which, when it interacts with a
given receptor, does not directly produce a stimulus for change beyond the level of that receptor
• e.g., atropine
Sources of Drugs
• Natural sources (mainly plants)– Atropa belladonna (deadly nightshade), Ginkgo biloba
(Ginkgo), Hypericum perforatum (St. John’s Wort), etc.
• Pure compounds derived from plants, molds, etc.– digoxin, vinblastine, penicillin G
• Synthetic chemistry– Sulfanilamide, acetaminophen, zafirlukast
• Biotechnology– Smallpox vaccine, rhGH, ...
Alkaloids(basic nitrogenous compounds of plant origin
that are pharmacologically active)
• morphine (Papaver somniferum)
• quinine (Cinchona succirubra)
• atropine (Atropa belladonna)
• cocaine (Erythroxylum coca)
• colchicine (Colchicum autumnale)
• papaverine (Papaver somniferum)
• ephedrine (Ephedra sinensis)
• strychnine (Strychnos nux vomica)
• tubocurarine (Chondodendron tomentosum)
Alkaloids (cont.)
• nicotine (Nicotiana tabacum)
• reserpine (Rauwolfia serpentina)
• vinblastine (Cantharanthus roseus)
• physostigmine (Physostigma venenosum)
• ergonovine (Claviceps purpurea)
• pilocarpine (Pilocarpus jaborandi)
• mescaline (Lophophora williamsii)
• caffeine (Coffea arabica)
• theophylline (Camellia sinensis)
Non-alkaloid plant substances as drugs
• salicin (Salix purpurea and related species.)
• tetrahydrocannabinol (Cannabis sativa)
• digoxin (Digitalis lanata)
Drug Nomenclature• The endings...
– ‘…ine’ often (but not always) signifies an alkaloid– ‘…olol’; beta-blockers– ‘…opril’; ACE inhibitors– ‘…dipine’; dihydropyridine Ca channel blockers– ‘…cillin’; penicillins– ‘…tidine’; chemically related histamine antagonists– ‘…sartan; antagonists of aldosterone– ‘…statin; inhibitors of HMG CoA reductase
Drug names: a hint to identity
• Dihydropyridines: (one class of Ca channel blockers)
– nifedipine, nisoldipine, niludipine,nimodipine
• Local anesthetics– cocaine, procaine, bupivacaine, lidocaine, benzocaine
• ACE inhibitors– captopril, enalapril, fosinopril
• Beta blockers:– propranolol, metoprolol, nadolol, timolol, atenolol
Drug names: a hint to identity (cont)
• Penicillins– penicillin G, methicillin, amoxicillin, ticarcillin
• Cephalosporins– cephalothin, cefaclor, cefotaxime, cefepime
• Macrolide antibiotics– erythromycin, clarithromycin, azithromycin
• Antifungals– ketoconazole, itraconazole, fluconazole, clotrimazole
Generic and Trade names: Rx drugs
• lanoxin, Dixogin®
• ciprofloxacin hydrochloride, Cipro®
• fluticasone propionate, Flonase®
• ipratropium bromide, Atrovent®
• nifedipine, Adalat®, Procardia®
Generic and trade names: combination drugs
• fluticasone propionate-salmeterol (Advair®)• imipenem-cilastin sodium, Primaxin®• losartan potassium-hydrochlorothiazide, Hyzaar®• trimethoprim-sulfamethoxazole, Bactrim®, Septra®
• lidocaine hydrochloride-epinephrine, Xylocaine® with epinephrine
What to learn about drugs on the ‘drug list’
• Generic name (Trade name only if it helps recognition)
• Site of action• Mechanism of action•
...(and for clinically used drugs)
• Indications and contraindications• Major effects, limitations and adverse reactions• Major interactions
NOTE: Drug list items in the last chapter of the syllabus:‘Simplified Table of Pharmacokinetic Values’
Questions? (& reminder)
• Assignment: If you have not already done so, confirm your UW email address to [email protected].
• Your confirmations are used to build the unique mailing list for the course.
• Please add some personal background and expectations/hopes for the course - whatever you are comfortable sharing.
• Thank you.