PHARMACOLOGY INTRODUCTION

DEFINITIONS

§    Pharmacology - The science of chemicals that effect a living process

§    Toxicology - Adverse effects of chemicals

§    Drug Therapy - “Management” of disease with a medication

§    Drug - Alters an effect already existing in a quantitative manner of changes

FEDERAL LEGISLATION

§    1938 Food and Drug Cosmetic Act

–  Must prove safety

§    1962 Kefaver-Harris Amendment

–  Must prove efficacy

–  Grandfather Clause

INVESTIGATIONAL NEW DRUG (IND) PROCEDURE

§    REQUIRED FOR:

–  Chemical or substance not previously used in humans

–  New combination not used in combination before

–  New use for a previously issued drug

–  New dosage form

 

INVESTIGATIONAL PHASES

§    Phase 1 - Determine safety and tolerated dose in a few “healthy” volunteers

§    Phase 2 - Determine safety, efficacy and pharmacokinetics in selected “diseased” individuals

§    Phase 3 - Determine safety and efficacy in widespread study

§    Phase 4 - Drug marketed with surveillance

TYPES OF STUDIES

§    DOUBLE BLIND

 

§    SINGLE BLIND

DEFINITIONS

§    GENERIC NAME - chemical name for a medication

§    TRADE NAME - a manufacture’s name for the generic product

§    OVER THE COUNTER - non-prescriptive agent

§    LEGEND DRUG - prescriptive agent

DEFINITIONS

§    CONTROLLED SUBSTANCE - prescriptive agent that has the potential for abuse

 

§    BIOAVAILABLE/BIOEQUIVALENT - generic medications that have been determined to be equivalent

CONTROLLED SUBSTANCES

§    1970 Comprehensive Drug Abuse and Prevention Act

§    Drugs of abuse are divided into 5 schedules

SCHEDULE I

§    High abuse potential, little medicinal benefit

§    Illegal Drug

§    Examples include:  heroin, LSD, PCP, marijuana, rock cocaine

SCHEDULE II

§    High abuse potential, medicinal benefit

§    Triplicate prescription required for ambulatory care prescriptions

§    Examples include:

–  Narcotics:  morphine, meperidine, methadone

–  Stimulants: dextroamphetamine, methylphenidate

–  Barbiturates: secobarbital, pentobarbital

SCHEDULE III

§    Lower Abuse Potential, medicinal benefit

§    Examples Include:

–  Combinations with Narcotics:  acetaminophen with codeine

–  Testosterones

SCHEDULE IV

§    Lower Abuse Potential, Medicinal Benefit

§    Examples Include:

–  Benzodiazepines - diazepam, alprazolam

–  Long acting barbiturate: phenobarbital

–  Propoxyphene

SCHEDULE V

§    Low Abuse Potential, medicinal benefit

§    Examples Include:

–  Cough Syrups with Narcotics

–  Diphenoxylate/atropine (antidiarrheal agent)

DRUG DOSAGE

§    DEGREE OF ABSORPTION

 

§    VOLUME OF DISTRIBUTION

 

§    RATE OF ELIMINATION

DEGREE OF ABSORPTION

§    Rate from 0 to 100%

§    Depends on route of administration

–  Intravenous is 100% absorbed

–  Some drugs not intended to be absorbed

§    Depends on dosage form

–  Suppositories are poorly absorbed

DISTRIBUTION

§    Ability to cross tissues

–  The more tissues crossed the higher the dose and the greater the potential for side effects

–  Many agents cannot cross blood brain barrier

§    Protein Binding

–  Higher the protein binding the greater the potential for drug/drug interactions

ELIMINATION

§    RENAL

–  Dependent on kidney function, disease and age

–  Determine creatinine clearance

§    HEPATIC

–  Dependent on disease and age

–  Drug interactions

 

 

ELIMINATION

§    HEPATIC (continued):

–  Enzyme induction

–  Enzyme inhibition

§    HALF LIFE

–  The time it takes medication blood levels to drop in half.

DEFINITIONS

§    ADDITIVE - Two medications given together produce an effect equal to the sum of the effects of each agent

§    SYNERGY - Two medications given together produce an effect much greater than the sum of the effects of each agent

DEFINITIONS

§    POTENTIATION - Two medications given together, but only one of the two agents  possess the required action, but that action is enhanced by the second agent

§    AGONIST -  An agent that stimulates a receptor

§    ANTAGONIST - An agent that blocks a receptor from being stimulated

FACTORS INFLUENCING DRUG EFFECTS

§    BODY WEIGHT

§    SURFACE AREA

§    AGE

§    SEX (renal function)

§    DISEASE STATES

§    GENETICS (metabolism)

§    IMMUNOLOGY (allergies)

UNTOWARD EFFECTS

§    Side Effect - Unavoidable effect at proper dose

§    Toxic Effect - Avoidable effect due to improper dose and drug/drug interaction

§    Poison - harmful effect even in small amounts

§    Adverse Effect - Unexpected effect, but may may happen, including allergies

ALLERGIES

§    Not dose related

§    Requires prior exposure

§    Reactions may be immediate to delayed for days

§    Reactions may be mild to life threatening