PHARMACOLOGY UNIT ONE

Warde

Drug Development and Nomenclature

Sources of drugs
Plants
Animals
Synthetic chemicals
Genetically engineered chemicals

Drug Development and Nomenclature

Plants
Date to primitive times
Classified according to their physical and chemical

properties

Alkaloids
Glycosides
Gums
Oils
Resins

Drug Development and Nomenclature

Animals
Traditionally, drugs from animal sources
eg.insulin

Today, genetically engineered hormones are rapidly

replacing animal-based drugs

Drug Development and Nomenclature

What is the advantage of genetically engineered

drugs over those made from animals?

Drug Development and Nomenclature

What is the advantage of genetically engineered

drugs over those made from animals?

Genetically engineered drugs are considered purer,

causing less adverse drug reactions

Drug Development and Nomenclature

Synthetic Chemicals
Most drugs today are synthetic chemical compounds
partial or total
Partially synthetic agent
derivative of a natural substance + a pure chemical.
An advantage of totally synthetic drugs
pure chemicals

Drug Development and Nomenclature

Genetically engineered Chemicals
Developed using DNA technologies
Insulin Recombinant DNA technology
Genomics
Study & identification of genes & gene function
Enabled researchers to manipulate chemical
formulas to produce more specifically targeted drugs
with fewer adverse effects
Proteomics
Study of protein structure and function
Technology essential in biomarker discovery

Drug Development and Nomenclature

Genetically engineered Chemicals

(cont.)

Transcriptomics
Study of the transcriptome
Aids in understanding the development and
differentiation of a cell
Metabonomics
Study of metabolic responses to drugs, environmental

changes, and diseases

Can possibly predict an individual patients response to
drug treatment

Drug Development and Nomenclature

Drug development process
First step: discovery of a potential new drug
molecule.
Preclinical trials
Designed to provide basic safety, bioavailability,

pharmacokinetic, and initial efficacy data about the

drug
Clinical trials
Performed on humans in several phases.
Only about 10% of new drugs that begin clinical

trials are approved.

Question
In this phase of clinical trials, the majority of the risks
associated with the new drug therapy are identified.
A. Phase I
B. Phase II
C. Phase III
D. Phase IV

Answer and Rationale

In this phase of clinical trials, the majority of the risks associated
with the new drug therapy are identified.
C. Phase III
In phase III of drug trials, 1,000 to 3,000 patient volunteers are
enrolled in double-blind studies and crossover design studies.
These studies are monitored closely to evaluate the safety and
effectiveness of the drug.

Drug Development
Critical Thinking Scenario
Page 23

Drug Development and Nomenclature

Nomenclature
Chemical name
Precisely describes the drugs atomic and molecular structure
Generic name
Nonproprietary name; identifies the drugs active ingredient
Trade name
Brand or proprietary name

Legislation
Legislation to Promote Truth In Advertising
1912
1938 first labeling requirements
Federal Trade Commission regulates the advertisement of
medications aimed at the general public
Standards for Drug Purity and Content
Pure Food and Drug Acts
Federal Food, Drug, and Cosmetics Act of 1938
Kefauver-Harris Amendment

Controlled Substances Legistation

Harrison Narcotic Law of 1914
Regulation of manufacture and distribution of certain drugs

The 1970 Comprehensive Drug Abuse Prevention and

Control Act
Established Drug Enforcement Agency (DEA)
Five categories, known as schedules, were established
Scale of I V; I has greatest potential for abuse and no accepted

medical use
Designed to alleviate problem of drug abuse
Drugs categorized & controlled based on abuse potential & medical
usefulness
Special rules for prescribing, dispensing & storing

Nursing Management of Controlled Substances

Prescribing, dispensing, & storing of controlled

substances is subject to governmental control

Procedures are precisely defined by law for every step,
from manufacture to administration to wasting or
discarding
Many hospitals use an automated system to
electronically track the use of stock drugs.

Legislation Regarding Drug Distribution

The Durham-Humphrey amendments (1952)
Nonprescription drugs (over-the-counter drugs [OTC])
Legend (prescription) drugs
Labeled properly
Procedures for the distribution of legend drugs

Patient Education A Safety Net

Patient learning needs
Teaching
Focus
Content
Evaluation & Documentation educational outcomes
Consumer info

Patient Education A Safety Net

Consumer info
Online Pharmacies
Increased usage
Average saving of 24%
Not all are regulated
The Ryan Haight Internet Pharmacy Consumer Protection Act of

2005
Nongovernmental Institutional Controls
Individual institutions & accrediting agencies
Safeguards in Drug Development, Manufacture, & Distribution in

Canada
Similar to US

Importance of Nursing Management of Drug

Therapy
Nurses
Legally responsible for the drugs they administer
Safe drug administration
Requires a thorough understanding of therapeutic drug actions and

adverse drug reactions.

Some clinical settings allow nurses to modify drug

regimens
Application of the nursing process to the pharmacologic
aspects of patient care is especially important d/t longterm use of drug therapy
Necessary to control chronic disease processes

Nursing management of drug therapy

An applied science

UNIT 2
Pharmacotherapeutics,
Pharmacokinetics, and
Pharmacodynamics

Pharmacotherapeutics
Key role in nursing drug management
The study of desired therapeutic goal/effect from drug therapy
The clinical purpose/indicationfor giving a drug

Can be to induce a cure or prevent a problem

Symptom relief
Cure
Prevention
Misc.

Pharmacotherapeutics (cont.)
Nurses role in pharmacotherapeutics?
Need to question all orders
Does the intended pharmacotherapeutics of a drug

correlate with the patients reason for receiving drug

therapy?

Pharmacokinetics
Movement of the drug particles inside the

body.
Phases
Absorption
Distribution
Metabolism
Excretion

Pharmacokinetics: Process By Which Drugs Move

Through The Body
Drug molecules move during all phases of pharmacokinetics.
Drugs cross cell membranes in one of three ways:
1.Can pass between the spaces or channels between the molecules in
the membrane
2. Can pass through the membrane with the help of a transport system
(If Hydrophilic, helper proteins and enzymes, water soluble more
steps involved, more time)
3. Can penetrate the membrane directly
(If lipophilic, no helpers needed, lipid soluble, less time)
The chemistry of the drug particles also affects the movement of

particles throughout the body

Principles of Absorption
Movement of drug from site of administration into

bloodstream
Rate of absorption depends on:
Route of administration
Oral vs. Parenterally vs. IM
Food or other drugs may interfere

Speed of dissolving
Enteric coating

vs SQ

Principles of Absorption (cont.)

Surface area
Blood flow
Lipid solubility
Drug concentration
pH

Principles of Distribution
Movement of drug through bloodstream, into

tissues, and into cells

Distribution depends on:
Blood flow
Most drugs do not produce its effect while in blood
Drugs ability to leave blood

Protein binding
Blood brain barrier
Placental membrane
Drugs ability to enter cells

Principles of Distribution and Protein Binding of

Drugs
Affects the distribution of a drug
A drug bound to protein is unable to pass thought the capillary

walls (protein needed to distribute through the blood)

Bonds will dissolve in time
Drug molecules will become free and active

Dosages are calculated by the drug manufacturer based on

the protein-binding characteristics of the drug

Distribution of the drug is altered in a patient with a lower-thanexpected protein level

The Effects of Administering Protein-Bound Drugs

Question
What will be the result of administering a highly proteinbound drug to a patient with liver failure?
A. There will be no significant difference in the
distribution of the drug.
B. The drug will reach the target cells more quickly and
therefore will not be as effective.
C. The drug will reach the target cells more quickly,
which could result in a toxic effect.
D. The drug will take longer to reach the target cells,
delaying the onset of action.

Answer and Rationale

What will be the result of administering a highly proteinbound drug to a patient with liver failure?
C. The drug will reach the target cells more quickly, which
could result in a toxic effect.
Patients with liver failure have lower levels of protein

and albumin in their blood than patients without liver

failure; therefore, the drug will reach the target cells
more quickly, which could lead to a toxic effect.
Remember that all recommended drug dosages are
calculated based on a patient with normal protein
levels

BloodBrain Barrier
What & Why is it ?
The capillary bed that services the brain is different from

other capillary beds

The cells are packed tightly together
Instead of wide spaces between the cells in the capillary walls

This structure prevents drug molecules, and other

foreign substances, from passing through and entering

the brain.
The purpose of the bloodbrain barrier
Keep toxins and poisons from reaching the brain
At times, this mechanism will prevent treatment of a problem

Placental Membrane
What & Why is it ?
Separates the maternal circulation from

the fetal circulation

It is not a barrier like the bloodbrain
barrier
Any drug that can pass through a membrane

can pass through the placenta

In order to pass through the placenta, a drug
must be lipophilic, not ionized, and not protein
bound.

Principles of Metabolism
Conversion of drug into another substance(s)
Generally from substances that are lipophilic to hydrophyllic
Sites of drug metabolism

LiverPrimary site
GI tract
Lungs
Kidneys
Skin

Factors affecting metabolism

Liver function
Life span/gender
Lifestyle, diet, habits
Environment

Principles of Metabolism (Pharmacokinetics cont)

Biotransformation
Another term for metabolism
Metabolites
Products of metabolism (the chemical the drug

becomes)
Metabolized drugs are generally changed into an
inactive form (inactive metabolite leaves body)
Prodrugs are drugs that are inactive until metabolized
into an active form
An active metabolite may cause a different and
potentially harmful effect, can cause adverse effects
before leaves body

Principles of Metabolism (cont.)

Rates of metabolism and first pass effect
Occurs at different rates for different drugs
Percentage of drug that is metabolized each time the drug

circulates, or passes, through the liver is the same

The total number of drug molecules that are metabolized
will be different
Drugs that are highly metabolized lose much of their
effectiveness during this first pass through the liver
This loss of effectiveness is called the first-pass effect.
These drugs may need higher oral doses to achieve a therapeutic level of

circulating drug

Principles of Metabolism (cont.)

P-450 system
Microsomal enzymes are called the cytochrome P450 system
Liver metabolism is predominantly achieved by
these specific liver enzymes
The enzyme CYP3A4 is the most common
Some drugs either induce or inhibit the P-450 system
A large quantity of one of these enzymes is present,
more metabolism can occur through this pathway
T his increase in metabolism rapidly decreases the
amount of circulating drug

Principles of Excretion
Excretion
Most common route for drug excretion through the urine
Routes of excretion
Urine
Bile
Exhaled from lungs
Breast milk
Sweat
Saliva

Principles of Excretion (cont.)

Factors affecting renal excretion
Glomerular filtration
Passive tubular reabsorption
Active tubular secretion
Diseases and pathophysiologic changes in the kidney decrease the
effectiveness of the kidney in drug excretion
Can be increased if the pH of the urine encourages the drug to
become an ion
Overuse of the active transport system
Some of the drug particles will remain in the blood until they can be

moved by the transport system

Two drugs can be given together to slow deliberately the rate of excretion
of one or both of the drugs

Question
What drug can be given with penicillin to slow the excretion
of the drug?
A. Birth control pill
B. Rifampin
C. Probenecid
D. Warfarin

Answer and Rationale

What drug can be given with penicillin to slow the excretion
of the drug?
C. Probenecid
Probenecid is a drug used to treat gout. In this situation, the

probenecid is used not for its normal pharmacotherapeutic effect

but solely to slow the rate of active transport and excretion of the
antibiotic

Principles of Excretion (cont.)

Factors affecting biliary excretion
Enterohepatic recirculation
Drug molecules that are in the bile are reabsorbed
This process lengthens the time the drug is present in the
bloodstream and can produce an effect

Misc Key Concepts

Half-life
Amount of time required to remove half (50%) of

the blood concentration of a drug

Metabolism + excretion are responsible for
elimination of a drug from the body
Varies w/drug d/t pharmacologic properties
In one half-life, a set percentage of the drug
molecules present in the blood is eliminated

Critical Thinking Scenario

Half-life and Drug Dosing (p. 48)

Misc Key Concepts

Steady state
The point at which the amount of drug being administered and
the amount being eliminated balance off are equal
Achieved @ four to five half-lives
Increasing the dose has no effect being achieved
Based on the amount of time required for four to five half-lives to
occur
Determines the full pharmacotherapeutic response of a
particular drug dose

Misc Key Concepts

Clearance
Rate at which drug molecules disappear from the

circulatory system
Major modes of clearance
Renal excretion
Hepatic metabolism

Gender of the patient can also alter the

clearance of some drugs

Pharmacodynamics
Biological, chemical, and physiological actions of a

particular drug within the body & the study of how

those actions occur.
Responsible for therapeutic effects and sometimes

adverse effects
Drugs cannot create new responses in the body
Can only turn on, turn off, promote, or block a response
that the body is inherently capable of producing

Pharmacodynamics (cont.)
Drug-Receptor Interactions
Most drugs create their effects in the body by attaching to
special sites, called receptors
At the receptor site, the drug is able to stimulate the cell to
act in a way that the cell is designed to act
Each type of receptor is responsible for producing a
particular effect in the cell
An agonist causes the cell to act
An antagonist or blocker prevents something else from
attaching to the cell blocking and action
If the drug is on the receptor, the other chemical cannot
also be on the receptor.

Pharmacodynamics (cont.)
Occupancy Theory
Single occupancy theory
The intensity of the bodys response to the drug is
directly related to the number of receptors occupied
by the drug
The maximum response occurs when all of the
receptors have drug molecules attached
Modified occupancy theory
Different drugs have different strengths of attractions,
or affinity, for receptor sites.
Once a drug is attached to a receptor, it has different
abilities to stimulate the receptor

Pharmacodynamics (cont.)
Occupancy Theory (cont.)
Receptor sensitivity changes
Not static
Continual stimulation from an agonist usually makes the drug

less effective
Continual blockage from an antagonist usually makes the drug
more likely to react

Nonrecepter responses
Drugs exert their effect by reacting physically or chemically
with other molecules in the body

Factors Influencing Drug Dose

Potency
Amount of a drug that must be given in order to produce

a particular response
Efficacy
The level of the drug and how well a drug produces its

desired effect
Minimum effective concentration

Factors Influencing Drug Dose

Maintenance
Daily dose
Dose that is given consistently over time

Loading doses
Larger than usual dose to reach an therapeutic effect
quicker
Is computed so that after some of the drug is eliminated,
the drug concentration in the body is still in the
therapeutic range

Factors Influencing Drug Dose

Therapeutic index
Difference between an effective dose and a toxic dose
Relation of ED50 to LD50
If the amount of a drug required to be the ED50 is similar to the

amount that is the LD50, the mathematical ratio of the two values
will equal a number close to one.
When the ED50 and the LD50 do not differ by much, the drug is
considered to have a narrow therapeutic index.

Factors Influencing Drug Dose

Drug Dosage and Blood Concentration
The higher the drug levels within the body, the s more likely the

patient will experience adverse effects from drug therapy

Monitor blood levels of the drug

Notify the caregiver if the level indicates that the blood levels are not in

the therapeutic range

The therapeutic range is an average
Varies with patient.