allisonbeale pharmacology203lecturer - laulima · iupac= international unionofpureand ......

Introduction

Allison Beale Pharmacology 203 Lecturer

Announcements

Face-‐‑to-‐‑Face (F2F): •  Please silence phones •  Late, leave early, or get up during class –  Equivalent to absent

•  Absent –  w/o accepted excuse, 10% off final grade

Both F2F and online: •  NO late work •  NO make ups or retakes of quizzes

EVERYONE! It is your responsibility to

check Laulima for postings, to familiarize yourself with due dates and deadlines, and to be

ready for class.

A Beale PHRM 203 Introduction 2

WWW Resources

•  Food and Drug Administration (FDA) –  www.fda.gov

•  Drugs @ FDA •  Medwatch •  Recalls, labels, safety

•  National Institutes of Health (NIH) –  hXp://dailymed.nlm.nih.gov •  Labels from FDA, but incomplete

–  www.clinicaltrials.gov/ •  Info about clinical trials

•  Drug Enforcement Administration (DEA) –  www.justice.gov/dea/pubs/scheduling.html •  The lists of controlled drugs

•  General –  www.drugs.com

•  Commercial cooperator with FDA

–  www.drugbank.ca/ •  David Wishart at the University of Alberta


Syllabus Overview •  Office = 118 Hale Imiloa, WCC •  Hours –  TBA

•  Phone – use email •  Emphasis of PHRM 203 –  Pharmacokinetics •  Absorption, distribution, metabolism, excretion

–  Pharmacodynamics •  Sites & mechanisms of action •  Toxicity vs therapeutic value •  Interactions between drugs

•  The Student Learning Outcomes (SLOs) for PHRM 203:

–  Describe the basic mechanisms of action –  Demonstrate knowledge of pharm.

terminology and concepts. –  Describe variables that affect drug

action including individual differences –  Define pharmacokinetics for specific

drugs –  Describe significant drug interactions –  Use pharmacokinetics to determine

dosing schedules and routes of administration

–  List the therapeutic uses for each drug class

–  Identify frequent complications & side effects associated of major drug classes


The SLOs for this course have been used to create questions to see if you have

mastered the material.

•  Course contents: –  Principles of PHRM –  Anatomy & PHRM of the major organ systems including the: •  Nervous system, heart, lungs, kidneys, gastrointestinal tract and blood.

–  Pain & Inflammation –  Chemotherapy of cancer and bacterial, protozoal, helminthic and viral diseases

–  Vitamins, minerals, supplements and herbals

•  Instructional methods –  Lecture –  Self-‐‑study –  Research –  Discussion –  Quizzes and exams

–  Reading

Syllabus Overview: content


•  Quizzes –  10-‐‑20 points each –  Matching –  No make up or retest

•  Midterm –  One worth 200-‐‑300 pts –  Multiple choice –  75% from SLO review ?’s

•  Final Exam –  Comprehensive –  Worth at least 500 points –  Multiple choice –  75% from review ?’s

•  Make up exams –  By arrangement at Library Resources CTR

–  WILL NOT be same exam as given in class

Syllabus Overview: exams

NO RETESTS ON ANY EXAM or QUIZ


•  Extra credit –  A number of opportunities

1.  Placebos 2.  Viper venom (as medication) 3.  Navigating the PHRM website 4.  Hallucinations 5.  From lab to pharmacy 6.  Improving healthcare 7.  Lab tests 8.  CombaXing depression 9.  Fat chance (about weight loss) 10.  Nightmare bacteria 11.  Omega-‐‑3 fish oil 12.  E-‐‑café survey

–  Worth 10 points each –  No make up or LATE work accepted –  No emailed copies for face-‐‑to-‐‑face

section –  Most require completing a worksheet

and answering questions in Tests, Tasks and Surveys in Laulima

•  AXendance to face-‐‑to-‐‑face section –  Required –  Late, leave early, get up during

class without prior arrangement •  Even if you return •  Equivalent to absent

–  Absent •  10% off final grade FOR EVERY

UNEXCUSED ABSENCE! •  Unless valid excuse (e.g., doctor’s

note) –  Don’t expect to be reminded.

•  Absenteeism may require withdrawal

•  AXendance online section –  Required to access PHRM 203

website at least three times/week. •  This is tracked by Laulima

Syllabus Overview


Syllabus Overview

Evaluation Item Worth in Points Examinations 850 -‐‑ 950 points Extra credit assignments Up to 140 points AXendance issues subtract from total Potentially 10% off final grade for

EACH unexcused absence. Total points used to calculate grade Up to 1000 points

All values are approximate Grade will be based on a straight percentage of points accrued Keep track of your points in Laulima by using the score sheet provided.


Pharmacology

Physiology

Anatomy

Chemistry

Pharmacology requires an understanding of concepts from: •  Anatomy

•  The structure of organs, tissues, cells and subcellular parts

•  Physiology •  How organs, tissues

and cells function •  Chemistry

•  Properties of endogenous chemicals

•  Properties of pharmaceuticals


Pharmacology Overview Pharmcokinetics – what the body does to the drug

Kinetics

Distribution

Metabolism

Excretion

Absorption

Pharmcodynamics -‐‑ what the drug does to the body

Stimulate

Inhibit


Most Prescribed Drug CLASSES

1.  Antidepressants 2.  Antihypertensives 3.  Antihyperlipidemics 4.  Antiarthritics 5.  Bronchodilators 6.  Non-‐‑narcotic analgesics 7.  Antipyretics 8.  Acid reducers 9.  NSAIDs 10.  Blood glucose regulators

11.  Vitamins/minerals 12.  Antihistamines 13.  Beta blockers 14.  Vaccines or antisera 15.  ACE inhibitors 16.  Diuretics 17.  Narcotic analgesics 18.  Calcium channel blockers 19.  Adrenal corticosteroids 20.  Thyroid/antithyroid


From a 2007 study: www.cdc.gov/nchs/data/ad/ad387.pdf

Most Prescribed DRUGs Trade Name Generic Name Use/Class Lipitor Atorvastatin Statin to reduce cholesterol

Generic HYCD/APAP Generic hydrocodone with acetaminophen for analgesia

Toprol-‐‑XL Metoprolol β1-blocker for angina & hypertension

Norvasc Amlodipine Calcium channel blocker (CCB) for HT

Generic Amoxicillin β-‐‑lactam antibiotic

Generic HYCD/APAP Another generic narcotic analgesic

Synthroid Levothyroxine Synthetic thyroid hormone replacement

Nexium Esomeprazole Proton pump inhibitor for GERD

Lexapro Escitalopram Selective Serotonin Reuptake Inhibitor (SSRI) (antidepressant)

Generic Albuterol β Adrenergic agonist for asthma


Adapted from: www.pharmacytimes.com/issures/articles/2007-‐‑05_4629.asp

Drug Names

•  Chemical name (Systematic, IUPAC) –  (2S)-‐‑1-‐‑[(2S)-‐‑2-‐‑methyl-‐‑3sulfonylpropanoly]pyrrolidine-‐‑2-‐‑carboxylic acid

•  Generic name – Captopril

•  Nonproprietary •  US Adopted Names (USAN)

– May contain “stem” (e.g., “pril”)

•  Trade name – Capoten

•  Proprietary/Registered Trade Mark


IUPAC = International

Union of Pure and Applied Chemists

Stems •  β-‐‑blockers

–  Propranolol (Inderal) –  Metoprolol (Lopressor,

Toprol) •  Combined α & β blockers

–  Sotalol (Betapace) –  Labetalol (Normodyne)

•  Penicillin β-‐‑lactams –  Ampicillin –  Amoxicillin

•  Local anesthetics –  Lidocaine (Xylocaine) –  Benzocaine (Solarcaine)

•  ACE inhibitors –  Captopril (Capoten) –  Enalapril (Vasotec)

•  ARBs –  Valsartan (Diovan) –  Irbesartan (Avapro)

•  Diazepam-‐‑type antianxiety drugs –  Lorazepam (Ativan)

•  Leukotriene receptor antagonists –  Montelukast (Singulair) –  Zafirlukast (Accolate)


Ingredients

•  Active ingredient •  Inert or Inactive ingredients –  Fillers

•  Sugar, wax, varnish –  Lubricants –  Adhesives –  Disintegrants –  Enteric coatings

•  Typical tablet –  5-‐‑10 % active drug –  80% fillers –  10% other ingredients added to ensure proper disintegration •  Time and place


Example: Captopril (Capoten) tablet contains captopril, microcrystalline cellulose, corn

starch, lactose, and stearic acid

Pharmaceutical Preparations

•  Drugs for two markets –  Prescription

•  Dentists •  Physicians •  Veterinarians

–  Over the counter •  The general public

•  Products supplied in various forms: –  Tablets/capsules/lozenges

–  Popsicles –  Solutions/suspensions –  Patches (skin) –  Aerosols –  Ointments, creams, gels, lotions

–  Suppositories –  Powders


See Introduction Board Notes Handout

Routes of Administration

Enteral •  Orally

–  Sublingual (technically parenteral, but some is swallowed)

–  Buccal –  Simply swallow the thing –  Enteric tube

•  Rectally

Parenteral •  Injection

–  IV –  IM –  SC –  Also, IA, epidural,

intrathecal, intra-‐‑articular, etc.

•  Transdermal •  Topical •  Inhalation


See Intro Board Notes

Drug Discovery

Discovery •  Collection of field

samples –  Biological

•  Animal, plant, fungal… –  Mineral

•  Characterization and screening –  High-‐‑throughput screening

•  Large computer databases

•  Synthesis

At end of discovery process •  Drug is believed to have

activity against a particular –  Receptor (or target molecule) –  Disease organism

•  There are many unknowns –  Safety –  Toxicity –  Kinetics

•  Dosage and scheduling –  Dynamics


Drug Development Experimental Studies 1.  In Vitro

–  Cell culture –  Test tube

2.  In Vivo –  In animals

1.  Major organ toxicity 2.  Type of toxicity

–  Acute, Sub-‐‑acute –  Chronic –  Teratogenic –  Mutagenic/carcinogenic

Where do drugs come from? •  Plants

–  Naturally occurring •  Artemisia annua extract

–  Processed •  Morphine from opium poppy

–  Recombinant DNA technology •  Bovine pancreatic trypsin inhibitor gene

(Aprotinin) spliced into corn •  Tissue plasminogen activator (tPA) gene

spliced into yeast •  Microbes

–  Bacteria and fungi •  Antibiotics

•  Animals –  Glandular extracts

•  Insulin, thyroid, growth hormone, adrenal extract

•  “Spit” from leaches (bivalirudin), snakes (eptifibatide, captopril) or lizards (exenatide)

•  Minerals –  Lithium, calcium, iron, potassium

•  Purely synthetic –  Usually based on a drug originally obtained

from a plant, animal, microbe or mineral. For instance, fentanyl.


Drug Development

Proposing Clinical Trials •  Once the experimental

studies are completed –  Company submits

application to FDA •  Investigational New Drug (IND) application

•  Reports on current findings

•  Proposes clinical trial(s) •  IND allows interstate transport and use of drug

Phase 1 Clinical Trials •  Usually designed to

determine HUMAN pharmacokinetics (ADME) –  Healthy, paid, “volunteers” –  Young, white males mostly

•  Also looking for: –  Biological effects –  Interactions –  Safety


Find clinical trial info: www.clinicaltrials.gov/

Phase 2 Clinical Trials •  Usually testing efficacy

–  Sick volunteers •  Often no other treatment alternative (very sick)

•  More than Phase 1 –  No placebos usually, but

may have various dosage regimens

•  Looking to understand: –  Therapeutic efficacy –  Dose ranges

Phase 3 Clinical Trials •  Usually testing potency

and safety –  Many more sick volunteers –  Often many locations –  Placebos in double blind or

cross-‐‑over studies

•  Looking to understand: –  Safety, efficacy and potency

in the target population


Drug Development

Phase 4 Clinical Trials •  Usually post-‐‑marketing trials for approved drugs –  Seeking new label

indication, regimen, combination or other new use

–  Placebos used in double blind or cross-‐‑over studies

•  Looking to understand: –  If additional indications are

warranted –  Adverse reactions –  PaXerns of drug use –  Possible combinations

Post-‐‑Marketing Surveillance •  MedWatch

–  www.fda.gov/medwatch/ –  Monitoring of safety after the drug is released for sale

–  ADR reports are solicited via voluntary reporting

–  Very important for •  Ideosyncratic reactions •  Rare reactions


Drug Development

Average drug is tested in <1500 people prior to marketing; rare effects may require 10,000’s of

exposures before showing up!

Drug Development Activity Duration Preclinical Testing

Test tube/petri dish Animal short/long term tests

1-‐‑5 years AVERAGE = 2.6 years

Company applies for IND: FDA Safety Review 30 days Clinical Trials

Phase 1 Phase 2 Phase 3

2-‐‑10 years AVERAGE = 5.6 years

Company submits clinical trial results and proposed label to FDA. NDA process averages 1 year

Post marketing studies and surveillance

Ongoing


Regulations FDA

•  www.fda.gov/ –  Information, definitions –  Regulations

•  Pure Food & Drug Act 1906 •  Food Drugs & Cosmetic Act 1938 –  Orphan Drugs –  Accelerated Drug

approval

DEA •  www.justice.gov/dea/pubs/csa.html

•  Harrison Narcotics Act •  Comprehensive Drug

Abuse Prevention & Control Act –  Prescription limits –  Dispensing controls


In Hawaii, the Narcotics Enforcement Division of the Department of Public Safety enforces the Uniform Controlled Substances Act (Chp 329 of the Hawaii Revised Statutes)

Controlled Substances

Schedule 1 criteria •  High potential for abuse •  No currently accepted therapeutic use (in the US)

•  Lack of safety, even when used under medical supervision –  No Rx’s

•  Except medical marijuana •  Production set by DEA

Schedule 1 examples •  γ-‐‑hydroxybutyric acid (GHB) •  Ibogaine •  Cannabis & hashish •  Potent psychodelics

–  Dimethyltryptamine –  Psilocybin, peyote & mescaline –  LSD

•  Heroin & certain other opioids •  3,4 methylenedioxymeth-‐‑

amphetamine (MDMA, ecstasy)

•  Federal Analog Act materials


Schedule 2 Criteria •  High potential for abuse •  Currently accepted therapeutic use

•  Abuse may lead to severe psychological or physical dependence –  Available by Rx –  Distribution controlled by

DEA

Schedule 2 Examples •  Cocaine •  Methylphenidate (Ritalin)

and dexmethylphenidate (Focalin)

•  Opium •  Most Opioids

–  Methadone, oxycodone, fentanyl, pure codeine and hydrocodone (including combination products)

•  Some barbiturates –  Secobarbital & pentobarbital



Schedule 3 Criteria •  Potential for abuse is

lower than 1 or 2 •  Currently accepted therapeutic use

•  Abuse may lead to moderate or low physical or high psychological dependence –  Only available by Rx –  Distribution controlled by

DEA

Schedule 3 Examples •  Anabolic steroids

–  Testosterone, Oxandrolone •  Some barbiturates •  A few Opioids

–  Buprenorphine •  Dronabinol (synthetic THC) •  Ketamine •  “Xyrem”

–  GBH used to treat narcolepsy – only dual listed drug



Schedule 4 Criteria •  Low abuse potential •  Currently accepted therapeutic use

•  Abuse may lead to limited physical or psychological dependence –  Only available by Rx –  Distribution controlled by

DEA

Schedule 4 Examples •  Benzodiazepines and

relatives •  Long-‐‑acting barbiturates

(phenobarbital) •  Tramadol •  Diet drugs

–  Phentermine, sibutramine…

•  Chloral hydrate



Schedule 5 Criteria •  Low abuse potential •  Therapeutic use •  Limited physical or psychological dependence –  Available only by Rx

Schedule 5 Examples •  Certain Antidiarrheals

–  Opium preparations –  Diphenoxylate

preparations

•  Pregabalin (Lyrica) •  Pyrovalerone (an appetite

suppressant)



GREEK LETTERS to knowCapitol leXer Lower case leXer “Name”

Α α Alpha Β β Beta Γ γ Gamma Δ δ Delta Ε ε Epsilon Κ κ Kappa Λ λ Lambda Μ µ Mu Π π Pi Σ σ Sigma Τ τ Tau Ω ω Omega


allisonbeale pharmacology203lecturer - laulima · iupac= international unionofpureand ......

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