Transcript Introduction to Pharmacology

Introduction to Pharmacology
September 5, 2007
•Frank F. Vincenzi E-419, HSB
•206-543-1993
•[email protected]
•*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/OR
Final examination
(if a quiz is not taken, or if the percentage score
is less than the percentage on the Final Examination,
then the quiz is simply dropped)
• One take home quiz
• One quiz mainly on peripheral NS
• One quiz on CV and chemotherapy
100 points
100 points
100 points
• Final Examination (comprehensive)
300 points
Example of overall course average calculation
for a hypothetical student
• Quiz # 1 (take home)
• Quiz # 2 (ANS)
• Quiz # 3 (CV and chemo) (Autumn flu)
• Final examination - comprehensive (68%)
• (quiz 2 and quiz 3 dropped (< 68%)
• (90 + 204)/400 = 0.735, (i.e., 73.5% … pass)
points
90/100
60/100
-204/300
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
PDA
ePocrates
CP on Hand
Physician’s Drug Handbook,
Your Local Pharmacist !!
Internet……
PDR
Learning objectives for this session
Introductory understanding of:
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Pharmacology
Drug
Receptor
Agonist
Antagonist
Pharmacodynamics
Pharmacokinetics
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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
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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)
Human genomic proteins as receptors
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 (halfmaximal effects at nanomolar
concentrations)
– Simplest interpretation is that L-epinephrine
makes a three point contact with its receptors
Drugs: molecular weight considerations
Biological Systems: Interactions Through
Differentiated Aspects of the Whole
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Society
Community
Organism
Organ system
Organ
Tissue
Cell
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Subcellular organelles
Molecular systems
Molecules
Functional groups
Atoms
Subatomic particles
Quarks
Molecules are a LOT smaller than cells
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)
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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.)
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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...
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‘…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
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lanoxin, Dixogin®
ciprofloxacin hydrochloride, Cipro®
fluticasone propionate, Flonase®
ipratropium bromide, Atrovent®
nifedipine, Adalat®, Procardia®
Generic and trade names:
combination drugs
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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
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...(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.