Introduction to PharmacologySeptember 5, 2007

•Frank F. Vincenzi E-419, HSB

•206-543-1993

•vincenzi@u.washington.edu

•*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)

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 (half-maximal 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

• Society

• Community

• Organism

• Organ system

• Organ

• Tissue

• Cell

• 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)

• 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 vincenzi@u.washington.edu.

• 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.