Chapter 16: BIOLOGICS

Biologics
-

also refer to immunizing agents

a substance produced by a living
source
includes antibiotics, hormones, and
vitamins, among others

Natural immunity
-

The Advisory Committee on

Immunization Practices (ACIP)

refers to immunizing agents as

immunobiologics

According to the Code of Federal

Regulations

a biologic product is any virus,

therapeutic serum, toxin, antitoxin,
or analogous product employed for:
- prevention, treatment, or
cure of disease in humans.

help develop immunity in the person

receiving them.

defined as natural or acquired

resistance to disease

provision of immunity through the

use of a biologic.

Vaccination

more commonly used term

refers to the use of biologic product
(a vaccine) to develop active
immunity in the immunity

gonorrhea, typhoid fever,

influenza, measles, mumps,
and poliomyelitis.

Racial Immunity

aform of naturalimmunityshared by
most of themembers of a
geneticallyrelatedpopulation.

Factors that determine racial immunity:

TYPES OF IMMUNITY

anthrax ( in cattle, sheep,

horses)
- plagues (in rodents)
- rabies (in cats, dogs, bats,
and others)
correspondingly, many human
disease do not naturally occur in
animals.

Example:

Immunization

a form of naturalimmunityshared by
allmembers of a species
however, a number of infections that
occur primarily in animals can be
transmitted to human.

Example:

Immunity

natural, innate, or native

immunity depends on factors
that are in born.
classified as: species
immunity, racial immunity,
and individual immunity.

Species Immunity

Purpose of the products:

two main categories of

immunity: natural and
acquired

- elusive and not well known

racial immunity should not be used
synonymously or confused with
environmental immunity.

Environmental Immunity
-

results of resistance to
infection among individuals
in a community resulting
from the degree of acquired
immunity and other factors.

Acquired Immunity
-

Examples:
-

tuberculosis
smallpox that wreaked
havoc among the Eskimos
and American Indians, when
first to exposed to them.

Individual Immunity
-

an immunity of individuals
vary to ability to resist
common microbiologic
disease.
some individuals have a little
capacity to resist skin disorders, the
common cold, and other familiar
diseases.
Natural resistance of the same
individual may vary from time to
time.
Good health demonstrated by
healthy body tissues, skin, and
mucous membrane:
- Leukocytes provides
adequate barriers to
bacterial infiltration.
- Resident bacteria in gastro
intestinal and upper
respiratory tract provides
resistance to infection.
- Stomach acid has a capable
to destroy ingested
bacteria.
- Intestinal enzymes provide
secondary defense
mechanism.

It is a specific immunity that may be

active or passive
T Lymphocytes it regulates
cell-mediated immunity and are
responsible for controlling certain
bacteria and viral infections.
B Lymphocyte Are primarily
involved with humoral immunity
and antibody production.
Immunoglobulins - attach to the
invading antigen and cause its
destruction by phagocytes and
the complete system.

Active Immunity
-

Develops in response to antigenic

substances in the body.
Naturally acquired active
immunity occurs by natural
means
Artificially acquired active
immunity may develop in
response to administration of
a specific vaccine or toxoid.
Vaccine administered primarily for
prophylactic action
- may contain living
attenuated (weakened) or killed
microorganism or fractions of these
microorganisms
Toxiods Bacterial toxins modified
and detoxified with moderate heat
and chemical treatment so that the
antigenic properties remain while the
substance is rendered nontoxic.

Advantage: exposure of
immunocompetent persons
may result in antibody
production that will protect

the person against disease

caused by the natural toxin
Disadvantage: They produce
inadequate immunologic
responses when
administered alone.

Inactivated Vaccine A vaccine

composed of killed whole bacteria or
viruses or substructures

Public Health Service Act (58 Stat.

682)
- Approved on July 1, 1944
- License to produce biologics by
manufacturers

Center for Biologics Evaluation

and Research of the FDA
- Administering specified
standards for each product

Advantage: attenuated
vaccines typically have more
antigenicity so are more
likely to confer permanent
immunity
Disadvantage: inactivated
vaccines must be
administered again over
time.

Immunization during pregnancy

live attenuated vaccines should be
avoided for pregnant patients
because of the danger of
transmission of the microorganisms
to the fetus.

Passive Immunity
-

Occurs by introduction of the

immunoglobulin produced in another
individual (human or animal) into the
host, who is not involved in the
production.
Naturally Acquired Passive
Immunity occurs by placental
transmission of immunoglobulin
gamma (IgG) from the mother to
the fetus.

Acquired Passive Immunity immunoglobulins is not long lasting,

usually 1 to 2 weeks
PRODUCTION OF BIOLOGICS

Licensing includes:
Approval of a
specific series of
production steps
In-process control
tests
End product
specifications that
must be met lot by
lot

Each lot must pass rigid control

requirements before it may be
distributed for general use
Provisions applicable to biologic
products includes tests for
(POTENCY, GENERAL
SAFETY, STERILITY, PURITY,
WATER, PYROGENS,
IDENTITY, and CONSTITUENT
MATERIALS)
Constituent materials
(PRESERVATIVES, DILUENTS,
ADJUVANTS) should meet
compendial standards
Extraneous protein in cellcultured vaccines and antibiotics
compendial monographs on
antibiotics and antibiotic
substances are available
Biologics to be administered by
injection are packaged and

labeled in the same manner as

injections
Label of a biological
product must include:
Proper name
(name under
which the product
is licensed under
the Public Health
Service Act)
Name, address,
and license of the
manufacturer
Lot number and
expiration date
Recommended
individual dose for
multiple dose
containers
o Packaged label
Preservative and
its amount
Number of
containers if more
than one
Amount of product
in the container
Recommended
storage
temperature
Statement that
freezing is to be
avoided (if
necessary)
Most biologics are stored in a
refrigerator (2oC to 8oC or 35oF to
46oF); freezing is avoided
Container may be broken due to
expansion of an aqueous vehicle
resulting in loss of product
o

Most biologic products have an

expiration date of a year or

longer after the date of

manufacture or issue
Stated date on each
lotdetermines the dating period
o Dating period
Begins on the date of
manufacture and
beyond which the
product cannot be
expected to retain the
required safety, purity,
and potency
May be compromised
of an in-house
storage period (lot is
held under prescribed
conditions followed by
a period after issue)
Individual monographs
indicates both: after-issue time
frame for use and permissible inhouse storage period

STORAGE, HANDLING, AND SHIPPING

OF BIOLOGICS
-

Biologics are sensitive to

extreme temperatures and
exposure to heat or freezing =
decreases potency and
reduces effectiveness
Inventory of vaccines and other
immunologic products can
amount to tens of thousands of
dollars or more
If damaged product is
administered: person may not be
able to build up immunity and
may result in an infection or
inadequate protection from
disease
PHARMACIST: maintain the cold
chain; can be assured that the

quality of product will not be

diminished
o

Separate refrigerator is
preferable to minimize the times
the refrigerator is opened
WHO (World Health
Organization) recommends that
the door not be opened more
frequently than 4 times a day
o

Standard refrigeratorfreezers
For small-volume
biologics
Frost-free freezers
Used because ice
buildup interferes with
the freezers ability to
maintain very low
temperatures

Door shelving
Can be used to store
diluents or bottles of
water
Helps provide
insulation and a
thermal reserve

If a vaccine must be kept out of a

refrigerator for a few mins = put
product in an insulated container
with coolant packs (THERMAL
PACKS, BLUE ICE PACKS,
CHEMICAL PACKS)
o

Coolant packs
Should be kept in
the freezer and
ready for use in
shipping
Provide extra
insulation and
cooling power in
the freezer in

case of an
interruption of
electric power or
outage
THAT CONTAINS
WATER: as much
cooling capacity
as ethylene glycol
packs.

NIP (National
Immunization Program)
Recommends
twice daily temp.
monitoring and
recording
Logs should be
kept 3 years

Refrigerator temperature range:

2oC and 8oC
Freezer: below 0oC (optimal
temp = -15oC/5oF
Store containers of same
vaccine together
Separate products to avoid
selecting wrong product (ex:
pediatric and adult dosage e.g.,
tetanus toxoids
o

Centers for Disease

Control and Prevention
(CDC)
where online
publication
describing storage
and handling
requirements for
currently
recommended
vaccines is
available

INCLUDES:

shipping and storage

recommendations for specific
vaccines
how to reconstitute them
information about vaccines shelf
life before and after
reconstitution
special handling instructions

Biologics for Active Immunity

Bacterial Vaccines
Vaccine suspension of attenuated (live) or
inactivated (killed) microorganisms or
fractions
- administered to induce immunity and
prevent disease
- originally, the organism is grown in a
suitable broth medium in a controlled
environment of temperature, pH, and
oxygen tension
Two Steps in Processing the Culture
1. Treated with phenol or
formaldehyde
- Used when the vaccine is to be
inactivated microorganisms
NOTE:
A live attenuated vaccine can also be
produced by genetic alteration of the
pathogenic organisms.
- allows the organism to survive and
multiply but not produce the disease.
- Organism is incapable of reverting to its
more pathogenic form
2. To employ purified antigen
subunits produced with use of
recombinant DNA.
Subunit vaccines the genes that code for
desired antigen are introduced into the
nonpathogenic organisms.

- no potential to harm the patient

- lower incidence of side effects
Example: Hepatitis B vaccine produced
through recombinant DNA technology by
common bakers yeast, into which the gene
for the hepatitis B surface antigen
(HBsAg) has been inserted.
Subunit vaccines had limited clinical
utility because of inability to produce a
sufficient, specific immune response.
Alternative biotechnology strategies
employed to produce subunit vaccine
immunogens and adjuvant-active
compounds that can be added to enhance
the immune response
MMR vaccine single product with three
immunogens for three viral diseases.
Mixed biologic may contain a vaccine
and a toxoid in the same product
Example: diphtheria, tetanus, and
pertussis (DTP).
Example: combination vaccine Pediatrix
(diphtheria and tetanus toxoids and acellular
pertussis adsorbed, hepatitis B
[recombinant], and inactivated poliovirus
vaccine [IVP] introduced in late 2002.
Strength of vaccine may be expressed in
the following:
-

Total number of organism

Total protective units per milliliter of
dose
- Micrograms of immunogen in each
milliliter or in each dose of vaccine
Viral Vaccines
Viruses cannot be grown on inanimate
media employed to grow bacteria
- propagated on one of several types of
animate media

Examples of animate media: embryonic

egg, cell cultures of chick embryo, human
diploid cell culture, monkey cell culture, skin
of living calves, and intact of mice
Purification steps taken to reduce the
incidence of hypersensitivity reactions to
animate media or host cells, most notably
embryonic egg
Influenza virus vaccine the virus is
prepared yearly with 3 virus strains.
3 virus strains since 1977 are:
-

Influenza A (H1N1)
Influenza A (H3N2)
Influenza B

The 2008-2009 trivalent vaccine strains

are:
-

A / Brisbane / 59 / 2007 like (H1N1)

A / Brisbane / 10 / 2007 like (H3N2)
B / Florida / 4 / 2006 like viruses

NOTE:
91% of influenza A (H1N1) viruses are
similar to
A / Solomon Islands / 3 / 2006- the
influenza A (H1N1) component of the 2007
2008 influenza vaccine.
Influenza A (H3N2) and influenza B
provide partial protection against related
strains and reduce the risk for influenzarelated complications and deaths.
Aluminum phosphate to prolong
stimulation of antibodies, the virion may be
adsorbed to this
Example: rabies vaccine (adsorbed)
Viral vaccines are available as:
-

Lyophilized (freeze-dried) products

require reconstitution prior to
administration with the provided
diluent.

Note:
Some inactivated vaccines are available in
suspensions for injection
Otitis media recognized complication of
influenza in children, and the influenza virus
has been isolated from middle ear fluid in
children with influenza and middle ear
effusion.
Influenza vaccinestrongly recommended
annually for children aged 6 months or more
with certain risk factors, including but not
limited to asthma, cardiac disease, sickle
cell disease, HIV, and diabetes
FluMist, Wyeth; MedImmune live
intranasal influenza virus vaccine was
approved for active immunization against
influenza A and B viruses in healthy children
aged 5 to 17 and adults 18 49 years of
age (June, 2003)
- 1st vaccine approved in the United States
for administration as a nasal mist
- implication to help overcome barriers to
immunization
NOTE: The strength of viral vaccines can be
provided in tissue culture infectious doses,
the quantity of virus estimated to infect 50%
of inoculated cultures. Also, micrograms of
immunogen, international units, D-antigen
units, and plaque-forming units for yellow
fever vaccines are employed for these
products.
Cancer Vaccines
Cancer Vaccines in development are
intended to increase recognition of cancer
cells by the immune system
- preventing cancer in patients at high risk
because of familial diseases

- increase antigen awareness of the

immune cells
- increasecostimulatory signals that induce
an immune response
T cells, lymphokinetic-activated killer
cells, and natural killer cells
- have antitumor activity
Tumor vaccine development to
stimulate these immune cells instead of
antibody producing cells, the operational
model used to protect one from an infection.
Tumor-associated antigens (TAAs)
have peptide fragments that appear on the
cell surface either by the cancer cell or
taken up by a phagocytic cell.
TAAs categories:
-

Patient specific
Tumor specific
Shared

Patient specific antigens unique to a

specific patient
Example: an antigen expressed on the
surface of a B-cell malignancy
Tumor specific TAA unique to a
particular tumor
Example: prostate specific antigen, found in
prostate tumors
Shared TAAs created by tumor cells with
a common histology.
Example: carcinoembryonic antigen on
adenocarcinoma cells found in colon,
ovarian, and lung tumors
4 types of cancer vaccines:
-

Autologous tumor vaccines

Allogenic tumor vaccines
Anti-idiotypic vaccines
Gene therapy

Autologous tumor vaccines developed

from antigenic material procured from the
tumor of the patient
- combined with adjuvant, such as bacilli
Calmetter- Guerin (BCG) or C. parvum.
Major problem: the work and cost
associated with the production of vaccine
for the individual patient. Also some tumors
escape the immune system because their
antigens are not expressed on the tumor
surface
Allogenic tumor vaccines use the
concept of shared or tumor-specific
antigens
- produced from cell lines that express
tumor-specific or shared TAAs
- it can be used in a wide population of
patients
Anti-idiotypic vaccines 3D immunogenic
regions on the antibody that binds antigen
- used to induce immune responses
(cellular, antibody-antigen) to a given
antigen
Gene therapy allows a DNA template to
be placed within a cell, transcribed into
messenger RNA, and expressed as a
costimulatory protein
Human papillomavirus (HPV) (Types 6,
11, 16, 18) recombinant vaccine (Gardasil
by Merck) 1stquadrivalent approved by
FDA on June 2006
Types 16 and 18 caused the 70% of
cervical cancer by infection with HPV
Types 6 and 11 caused the 90% of
genital warts
- this vaccine is only indicated for women
9 to 26 years of age
- prevent vulvar and vaginal cancers

 Toxoids
Exotoxin the toxin formed in the filtrate of
cultured bacteria

Toxoid the detoxified toxin using

formaldehyde
- may be plain or contain an adjuvant (e.g.,
alum, aluminum hydroxide, aluminum
sulfate)
- may contain single, multiple, or mixed
immunogens (e.g., tetanus and diphtheria
toxoids adsorbed for adult use, which
contains 2 toxoids for active immunication
against different toxins)

Mixed biologic has 2 toxoids and a

vaccine in a single-dosage form for active
immunization against different toxicities and
infection
- advantage: broad immunization
coverage and minimum number of injections
Example: diphtheria and tetanus toxoids
and pertussis vaccine adsorbed for pediatric
use
NOTE: These mixtures or types of biologics
differ from polyvalent products, which are
used for different strains of the same toxicity
or infection (e.g., influenza virus vaccine,
pneumococcal vaccine polyvalent)
Flocculating (Lf) units (e.g., tetanus
toxoid, 4 to 5 Lf U/0.5 mL dose) strength
of a toxoid
- smallest amount of toxin that flocculates
most rapidly one unit of standard antitoxin in
a series of mixtures containing fixed
amounts of anti-toxin and varying amounts
of toxin
Administration And Toxicity Associated
With Biologics Products.

Biologics

Biologics must be dispensed in the

original container to avoid
contamination and deterioration
They are sterile when packaged and
are injected by aseptic techniques.
Few administered in the mouth

Liposomal delivery

Decreased side effects while it

enhance the vaccines effectiveness

*
- The foremost adverse effect of concern
with immunization is hypersensitivity,
most notably anaphylaxis, ranging from
pruritus or urticarial to
bronchospasm, respiratory distress
laryngeal edema, circulatory
collapse, and death

- Life-threatening anaphylaxis is a
rarity but quite possible

Thimerosal

used in vaccines as a preservative

since 1930s.
effective for killing bacteria in
several vaccines
prevention from bacterial
contamination, especially in
opened multidose vials.

*-September 1999, American Academy of

Pediatrics (AAP)
Committee on Infectious Disease and
Comitte on Environmental Health urged the
government and pharmacist to help reduce
of childrens exposure from mercury (from
vaccines).

Gerber and Offit

- End of 2001, 98% less of childrens

exposure from mercury.

- Massive overdoses of thimerosalcontaining products have resulted in

toxicity expressed in the central nervous
system, kidneys, and immune system.

The FDA determined that infants

who would receive thimerosalcontaining vaccines at several visits
might be exposed to more mercury.

Discussed the genesis of each

theory and reviewed relevant
epidemiological evidence/
Neither Thimerosal nor MMR
causes autism.

IM injection

FDA Modernization Act of 1997

The scientists determined that the

risk of autistic disorders from the
vaccine is 8% less than those who
were not vaccinated.

Preferred route of administration

Vastus lateralis

Preferred site for injection for

infants

Deltoid muscle
Pichichero et al.
-

Demonstrated that mercury does not

accumulate in children who receive
thimerosal-caontaining vaccines

Madsen et al.

Identified more than 537,000

children in Denmark from 1991 to
1998, 82% whom had received the
MMR vaccine.

Preferred site for injection for

children older that 18 months

Influenza

major cause of morbidity and

mortality in the United States
- FluMist
o the first intranasal live
attenuated influenza
virus (LAIV) vaccine
approved for clinical
use in the US

originally
o restricted to healthy
children 5 to 17 y/o &
adults 18 to 49 y/o
LAIV
o is an acceptable
alternative to the IM
trivalent inactivated
influenza vaccine (TIV).
FDA's Vaccines and Related
Biological Products Advisory
Committee
o determined that the
vaccine was not safe
for patients under age 5
o increased rates of
asthma within 6 weeks
of vaccination.
FluMist and TIV were compared
in a randomized clinical trial
o Children aged 6 to 59
months
o FluMist
55% greater
efficacy compared
with TIV in
preventing culture
confirmed
influenza illness
ACIP
o recommended that
either the LAIV or TIV
can be used to
vaccinate healthy
nonpregnant persons
aged 2 to 49 years
Healthy persons
o defined as those who
do not have an
underlying medical
condition that
predisposes them to
influenza complications.
For patients 50 y/o and older

safe and effective use

of FluMist has not been
established
o restricted from use in
this patient population
use of the LAIV in children 2 to 4
y/o
o health care providers
should consult the
medical record
o recurrent wheezing that
might indicate asthma
In the past 12 months, has a
health
care provider ever told you that
your child had wheezing or
asthma?
o if yes
should not receive
FluMist
o injective TIV should be
administered instead.
FluMist must be used cautiously
and
never administered parenterally.
Patients with a history of
anaphylactic reactions to eggs
o should not generally
receive this vaccine.
Children and adolescents
receiving
chronic aspirin therapy
o should not receive
FluMist
o risk of Reye syndrome
patients with a history of
Guillain-Barr syndrome
o should not receive
FluMist.
Pregnant women
o Should not receive
FluMist.
nasal vaccine
o epinephrine injection
should be available
o

anaphylactic
reaction.
FluMist most common adverse
effects
1. Nasal congestion
2. runny nose (45%)
3. sore throat (28%)
4. cough (14%)
5. chills (9%)
Serious adverse events occurred
at similar rates in healthy
children aged 60 to 71 months
receiving FluMist and those
receiving the placebo
3 other changes in the use of
FluMist and its 2007 to 2008
formulation
o amount of vaccine
administered
o temp at which FluMist
is shipped and stored
after delivery
o minimum interval
between doses have
changed compared with
the 2006 to 2007
influenza-season
formulation.
FluMist
o prefilled, single-use
sprayer
o 0.2 mL of vaccine
instead of the previous
0.5- mL dose.
1. spray 0.1 into the first
nostril while in the
upright position.
2. attached dose-divider
clip removed from
sprayer
3. second half
administered into the
second nostril
o Previously
shipped and
stored frozen.

It is now shipped at
35F to 46F (2C to
8C).
o recommended
interval from the first
to second dose
changed from a
min of 6 weeks to
a minimum of 4
weeks
the same interval
recommended for
TIV.
o live vaccine
IM inactivated
vaccine
preferred
for health
care
workers
and for
family
members
other close
contacts of
immunosu
ppressed
pt.
o Package insert
advisesFluMist
recipients to avoid
close contact to
immunocompromi
sed pt. for at least
21 days.
Children aged 6 to 23 months
o susceptible to the risk
of influenza-related
hospitalizations
aged 24 to 59 months
o increased risk of
influenza-related clinic
and emergency room
visits.
o

vaccination of children
in these age groups is
encouraged when
feasible.
annual influenza vaccine
o ACIP
recommended for
children aged 6 to
59 months as well
as their household
contacts and outof-home
caregivers
o CDC
children aged 6
months through
18 y/o.
Influenza vaccination
o Recommended
annually for children
over 6 months with
certain risk factors
Asthma
Cardiac
Disease
Sickle cell disease
HIV
Diabetes
Household
members in
groups at high risk
o can be administered to
all others wishing to
obtain immunity.
Children <12 years old should
receive vaccine in a dosage
appropriate for their age
o 0.25 mL
ages 6 to 35
months
o 0.5 mL
ages 3 years and
older
Children <9 years old receiving
influenza vaccine for the first
time
o

should receive two

doses separated by at
least 4 weeks.
Children <9 years old who were
vaccinated for the first time last
season and received only one
dose
o should receive two
doses separated by at
least 4 weeks.
o
new catch-up immunization
schedule by the CDC
o for children and
adolescents who start
vaccinations late or
who are more than 1
month behind has been
published by the CDC
o divided into two distinct
age groupings
4 mos-6 y/o
7-18 y/o
o

Toxins
-

Botulinum toxin type A (i.e.,

Botox)
o axillary hyperhidrosis
o cervical dystonia (CD)
decrease the
severity of
abnormal head
position and neck
pain associated
with CD
o strabismus and
blepharospasm
associated with
dystonia
Botulinum toxin type A (i.e.,
Botox Cosmetic)
o indicated for the
temporary improvement
in the appearance of
moderate to severe
glabellar lines

associated with
corrugators and/or
procerus muscle
activity
facial frown lines
adult patients 65
years
Botulinum toxin type A
o powder for injection in a
single-use vial
o Unopened vials are to
be stored in a
refrigerator (2C to 8C)
for up to 24 months
o administered within 4
hours of reconstitution
o reconstituted injection
is clear, colorless, and
without particulate
matter.
o Prior to injection
vacuum-dried
botulinum toxin
type A is
reconstituted with
sterile normal
saline without a
preservative
0.9 w/v sodium
chloride
injection
Recomme
nded
diluent.
for glabellar line injection
using Botox Cosmetic
o 21-gauge needle
o appropriately sized
syringe
o to draw up a total of 2.5
mL of 0.9% sterile
saline solution
without preservative
o at least 0.5 mL of the
properly reconstituted

toxin is drawn up into

the sterile syringe,
preferably a tuberculin
syringe, expelling air
bubbles in the syringe
barrel.
o 30-gauge needle is
attached
o concentration
4 U/0.1 mL
o total dose
20 U in 0.5 mL.
o duration of activity
3 to 4 months.
Botulinum toxin type A
o The safe and effective
use depends upon
proper product
storage
selection of the
correct dose
proper
reconstitution
proper
administration
o Physicians must have a
clear understanding
relevant
neuromuscular or
orbital anatomy of
the area
any alterations
caused by prior
surgical
procedures.
o must not be confused
with botulinum toxin
type B
Botulinum toxin type B
o preservative-free
injectable solution,
o 5,000 U/mL
o also indicated for CD
o clinical doses are not
interchangeable
between products

Responding to Bioterrorism
September 11, 2001 (9/11)
- awareness of the necessity for
vigilance to illness patterns and
diagnostic clues that might
indicate an unusual infectious
disease outbreak heightened
Pharmacists and allied health
professionals
- were asked to report any
indication of suspicious
symptoms to local and state
health departments.
Evidence of intentional release of biologic
agents includes infection in these groups
1. people in the same location
with symptoms that suggest
an infectious disease
outbreak
o unexplained febrile
illness
o associated with sepsis
o pneumonia
o respiratory failure
o rash
o botulism-like syndrome
with flaccid muscle
paralysis
2. age groups not normally
associated with the disease
in question
3. numerous cases of acute
flaccid paralysis with
prominent bulbar palsies that
suggest the release of
botulinum toxin.
Pharmacists
- also encouraged to participate in
their community's disaster
preparedness efforts
- can bring an important and
unique perspective to
determining and preparing for
health care needs during times

of natural disasters or manmade

crises.
American Pharmacists Association
- has attempted to assist involved
pharmacists by creating a
National Pharmacists
Response Team
o 10 teams will assist
communities with
chemoprophylaxis or
vaccinations during
times of need.
After 9/11
- the news media concentrated on
the threat of an anthrax outbreak
but there are other more
prominent diseases with greater
potential harm to the public.
- listed by the CDC as the biggest
biologic threats
o smallpox
o pneumonic plagu
- Other agents of concern
o Clostridium botulinum
toxin (botulism)
o Francisellatularensis(i.e
., tularemia)
o hemorrhagic fevers
Smallpox
caused by variola virus
- initial symptoms
o high fever
o fatigue
o headache
o backaches
These symptoms are followed
by a rash
- most patients recover
- up to 30% of cases result in
death.
spread by face-to-face contact.
- Routine vaccination ended in
1972
o Level of immunity
among persons

vaccinated up until this

time is unknown
o All individuals are
considered susceptible.
In
- adverse effects of the
smallpox vaccine
1. lymph node
swelling
2. rash
3. fever
4. scarring
5. severe skin
reactions
6. encephalitis
the ACIP concluded risks
outweighed the benefits
o recommended that the
general public not be
inoculated against
smallpox.
o Recommended
vaccinations to a total
of about 15,000 health
care workers around
the country
In an attempt to determine whether more
smallpox vaccines could be made
available
to the general population given
supply questions,
a recent study was conducted by the
- National Institute of Allergy
and Infectious
Disease (NIAID)
- Conducted a study to determine
whether more smallpox vaccines
could be made available to the
general population
- 680 adults <32 years of age
who were never vaccinated for
smallpox
o assigned to three
treatment groups.

received vaccine that

was undiluted, diluted
1:5, or diluted 1:10
initial vaccination was successful
in 97.8% of all three groups.
second vaccination
o two dilutions were both
effective against
smallpox
1:10 dilution
o could protect 10 times
as many persons as
would be protected by
the administration of
the undiluted vaccine.
o

Botulism
- muscle-paralyzing disease
caused by the toxin produced by
C. botulinum
- Food-borne botulism
o public health
emergency
o contaminated food may
still be available to
other people.
o occurs when the
preformed toxin is
ingested in
contaminated food
o causes illness within 6
hours to 2 weeks
o Symptoms
1. double vision
2. blurred vision
3. drooping
4. eyelids
5. slurred speech
6. difficulty swallowing
7. dry mouth
8. muscle weakness
that leads to
paralysis of the
breathing muscles
- communicable from one person
to the next.
Pneumonic plague

Yersinia pestisinfects the lung

initial symptoms
1. fever
2. headache
3. weakness
4. cough with a bloody or
watery sputum.
- 2 to 4 days
- may cause septic shock
If treatment is not initiated, the
result is death.
communicable with face-to-face
contact
- Early treatment with antibiotics (e.g.,
tetracycline, streptomycin,
chloramphenicol) is imperative.
There is no vaccine against this
disease.
Anthrax
- three forms:
o cutaneous
skin surface is
exposed to
anthrax particles
skin lesions
develop
o gastrointestinal
particles are
ingested
o inhalation
often fatal
- Cutaneous anthrax
o the arms or hands as a
swelling of the skin
o develops into a central
area of ulceration or a
depression
o dark, blackish-brown
scab forms over the
area.
o can be painless
o fever may be present
- Gastrointestinal anthrax
o acute inflammation of
the intestines
o loss of appetite
o vomiting

o pain.
o abdominal pain
o vomiting of blood
o severe diarrhea
Inhalation anthrax
o Initial symptoms
common cold
progress to
severe respiratory
problems
shock.
cannot be transmitted from one
person to another
Treatment
o Antibiotics
Penicillin
Doxycycline
Fluoroquinolones
o only those exposed to
disease should be
treated
prescriptions for Cipro, a
fluoroquinolone
o increased as concerned
individuals were
stockpiling to protect
themselves and their
families from the threat
of anthrax.

Diagnostic Skin Antigens

Antigens in vivo as diagnostic tools
these are injected intradermally
- site inspected for development of
a hypersensitivity reaction
- positive reaction determined
by
o extent of induration (in
millimeters)
o degree of reaction, from
slight induration to
vesiculation
o necrosis.
- These signs demonstrate
o sensitivity to the
antigen

presence of antibodies
due to present or past
infection with the
particular organism.
FDA panel on Review of Skin Antigens
- questioned the reliability of skin
test antigens for trichinosis,
lymphogranuloma, venereum,
and mumps
- recommended that these be
withdrawn from the market and
not licensed
Candida albicansskin test antigen
- One of the more recent in vivo
diagnostic biologics
- useful in the assessment of
diminished cellular immunity in
persons infected with HIV.
- HIV infection
o can modify the delayedtype hypersensitivity
(DTH) response to
tuberculin
o skin test HIV-infected
patients at high risk for
tuberculosis with
antigens in addition to
tuberculin
assess their
competency to
react to
tuberculin.
Responses to DTH antigens
- also have prognostic value in
patients with cancer.
o

The Multiple Skin Test Antigens

(Multitest
CMI, Merieux)
- skin test for multiple antigens
- consists of
o disposable applicator
with eight sterile
heads preloaded
with seven
delayed
hypersensitivity
skin test antigens
o glycerin negative
control
for percutaneous
administration
- The seven antigens
1. tetanus toxoid
antigen
2. diphtheria toxoid
antigen
3. streptococcus
antigen
4. old tuberculin
5. Candida antigen
6. trichophyton
antigen
7. Proteus antigen.
The intent of this multiple test
- detectanergy through delayed
hypersensitivity skin testing.
- anergy
o lack of response to
antigens