ANTIFUNGAL AGENTS

(flip) vidwatch: https://www.youtube.com/watch?v=uU_OeL40E-E

Fungal Infections
http://courses.washington.edu/medch401/pdf_text/401_06_VI_Antifungal.pdf

Fungal infections are caused by microscopic organisms that can invade the epithelial tissue.
The fungal kingdom includes yeasts, molds, rusts and mushrooms. Most fungi are beneficial
and are involved in biodegradation, however, a few can cause opportunistic infections if they
are introduced into the skin through wounds, or into the lungs and nasal passages if inhaled.

Diseases caused by fungi include superficial infections of the skin by dermatophytes in the
Microsporum, Trichophyton or Epidermophyton genera. These dermophytic infections are
named for the site of infection rather than the causative organism. Systemic infections are
caused by the inhalation of spores and cause fungal pneumonia. This pneumonia cannot be
transmitted from human to human. These infections can occur in otherwise healthy individuals.
Many of the organisms that cause systemic fungal infections are confined to specific geographic
locations due to favorable climates for their proliferation.

Organisms that cause opportunistic infections will not gain a foothold in healthy individuals, but
in the immunocompromised they can cause serious, sometimes life-threatening infections.
Patients especially susceptible to these infections include individuals with leukemia and other
blood diseases, cancer, HIV and other immunodeficiencies, and diabetes.

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Antifungal Agents

1. AMPHOTERICIN B Class of Antifungal: Polyene

Mechanism of Action: Binds to ergosterol in fungal membrane causing membrane to become
leaky.
Products
a. Fungizone (Bristol Myers Squibb) 50 mg/vial with 41mg of sodium deoxycholate.
Several months of therapy is usually needed.
b. Abelcet (Liposome Co.) 1:1 mixture of amphotericin and lipid complex, 100 mg/20 ml.
Rationale for this lipid preparation is that amphotericin B should have a greater affinity
for the lipid vehicle than for cholesterol in cell membranes, thus lower toxicity
c. Aphotec (Sequus Pharmaceuticals) cholesterol colloidal dispersion, 50 or 100 mg/20 ml.
Supplied in variety of topical forms including a 3% cream, lotion or ointment and
100mg/mL oral suspension to treat cutaneous and mucocutaneous mycoses caused by
Candida albicans
d. AmBiosome (Fujisawa) liposomal, 50mg/vial.

2. NYSTATIN Class of Antifungal: Polyene

Mechanism of Action: Binds to ergosterol in fungal membrane causing membrane to
become leaky
Indications: Nystatin was originally isolated from Streptomyces noursei in 1951. A
conjugated tetraene, it was the first clinically useful polyene antifungal antibiotic.
Products
a. Mycostatin ® and other generic products.

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3. NATAMYCIN (Pimaricin, Natacyn) Class of Antifungal: Polyene
Mechanism of Action: Binds to ergosterol in fungal membrane causing membrane to
become leaky
Indications: Natamycin was first isolated from cultures of Streptomyces natalensis
suspension intended for the treatment of fungal conjunctivitis, blepharitis and keratitis.
Products
Natamycin is supplied as a 5% ophthalmic suspension intended for the treatment of fungal
conjunctivitis, blepharitis and keratitis.
Adverse Effects: Eye irritation, redness and swelling not present prior to use.

4. Azoles and Triazole Antifungal Agents: Ergosterol Biosynthesis Inhibitors

Azole antifungal agents are the largest class of synthetic antimycotics. About 20 agents on
the market today. Some used topically to treat superficial dermatophytic and yeast
infections. Others used systemically to treat severe fungal infections. Antifungal activity
stems from the presence of an aromatic five member heterocyclic, either an imidazole or a
triazole. The first members of the class were highly substituted imidazoles (clotrimazole,
miconazole) were not absorbed orally. Ketoconazole introduced in 1984 was the first
effective oral therapy for Candida.

Mechanism of Action: These imidazoles and triazoles inhibit CYP P450 14 α- demethylase in
fungi. This enzyme is involved in the conversion of lanosterol to ergosterol.
Five azole antifungals, miconazole, econazole, oxiconazole, sulconazole and tioconazole
are used in topical application only.
a. MICONAZOLE (developed by Janssen Pharmaceutica) is used for skin infections such as
tinea pedis, tinea cruris and vulvovaginitis. It comes in cream, lotion, powder, spray liquid
and spray powder, and also in suppository form for vaginal use. Miconazole is used once
or twice a day for one month for tinea pedis or two weeks for other skin infections. For
vaginal infections it is used once a day at bedtime for three or seven days.
Adverse effects include: increased burning, itching or irritation of the skin or vagina,
stomach pain, fever or foul-smelling vaginal discharge.
Products: Micatin, Monistat-3, Monistat-7, Monistat-Derm, Monistat Dual-Pak.

b. ECONAZOLE (developed by Janssen Pharmaceutica) is a topical cream applied to the skin

to treat fungal infections including: tinea corporis, tinea pedis, tinea cruris, and
superficial candidiasis.
Adverse effects include: Burning, itching, stinging, redness and skin rash.
Products: Spectrazole, Ecostatin

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c. OXICONAZOLE (developed by F. Hoffmann-LaRoche and Siegfried AG) is a cream or lotion
applied to the skin in the treatment of tinea corporis, tinea pedis and tinea cruris.
Adverse effects include: Burning, itching, blistering, crusting, dryness or flaking of the
skin, scaling, severe redness, soreness, swelling and pain in hairy areas with pus at the
root of hair.
Products: Oxistat, Oxizole

d. SULCONAZOLE (developed by Syntex Research) is a topical cream or solution to treat

tinea corporis, tinea pedis and tinea cruris.
Adverse effects include: Burning, stinging, itching and redness of the skin.
Products: Exelderm

e. TIOCONAZOLE (developed by Pfizer U.K.) is a cream to treat tinea corporis, tinea pedis,
tinea cruris and cutaneous candidiasis.
Adverse effects include: Burning, itching, redness, skin rash and swelling.
Products: Trosyd AF, Trosyd J

f. KETOCONAZOLE is supplied as a cream or in shampoos at one- or two-percent, for the

treatment of tinea pedis, tinea corporis, tinea cruris and cutaneous candidiasis.
Adverse effects include: itching, stinging, skin rash, dry skin, and dry or oily scalp.
Products: Nizoral Cream, Nizoral A-D Shampoo (1%), Nizoral Shampoo (2%)

g. ITRACONAZOLE is taken orally in capsule form to treat fungal infections that start in the
lungs and spread throughout the body. Itraconazole can also be used to treat fungal
infections of the nails, although it is important to point out that treatment of nail fungal
infections does not result in healthier looking nails. Normal nail appearance will occur
only with new growth, which can take up to six months for full nail growth. Oral solutions
of this antifungal agent can be used to treat oral candidiasis.
Drug Interactions: Patients on proton pump inhibitors should take itraconazole with a
cola soft drink to aid in bioavailability.
Adverse effects include: diarrhea, constipation, gas, stomach pain, heartburn, sore or
bleeding gums, sores in and around the mouth, headache, dizziness, sweating, muscle
pain, decreased sexual desire or ability, nervousness, depression and runny nose. More
severe side effects can include: excessive tiredness, loss of appetite, upset stomach,
vomiting, tingling or numbness in the extremities, fever, chills, rash, hives and difficulty
breathing or swallowing. HEPATOXICITY: yellowing of the eyes or skin, dark urine or pale
stools.
Product: Sporanox

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h. FLUCONAZOLE is a one-a-day tablet or suspension to treat yeast infections of the vagina,
mouth, throat, esophagus, abdomen, lungs, blood and other organs. Fluconazole is also
used to treat meningitis and can prevent yeast infections in patients who are likely to
become infected due to chemotherapy or radiation therapy before a bone marrow
transplant.
Adverse effects include: headache, dizziness, diarrhea, stomach pain, heartburn and
changes in the ability to taste food. More severe side effects can include: excessive
tiredness, loss of appetite, upset stomach, vomiting, tingling or numbness in the
extremities, fever, chills, rash, hives and difficulty breathing or swallowing.
HEPATOXICITY: yellowing of the eyes or skin, dark urine or pale stools.
Product: Diflucan

i. VORICONAZOLE is formulated in an oral suspension, tablets or parenteral injection. It is

used to treat different kinds of serious fungal infections and may be used in patients who
have not responded to other antifungal agents.
Drug interactions: Xanax, Versed, Halcion, Agenernase, Viracept, Invirase, Hismanal,
barbiturates, cyclosporine, ergot alkaloids, HMG CoA reductase inhibitors and warfarin.
Adverse effects include: rash, bloating or swelling of face, arms, hands, lower legs or
feet, stomach pain, blurred vision, chills, convulsions, dizziness, dry mouth, headache and
muscle pain. HEPATOXICITY: dark urine or pale stools.
Product: VFEND

j. BUTOCONAZOLE is a cream suppository used to treat vulvovaginitis. It is used either

once or in a seven-day regimen at bedtime.
Adverse effects include: burning or irritation in the vagina when cream is inserted,
stomach pain,fever or foul-smelling vaginal discharge.
Product: Gynazole-1

k. TERCONAZOLE is supplied as a cream or suppository to treat vulvovaginitis. It is usually

used daily at bedtime for either three or seven days.
Adverse effects include: headache, missed menstrual periods, burning or irritation in
vagina when cream or suppository is inserted, stomach pain, fever, or foul-smelling
vaginal discharge.
Product: Terazol 3, Terazol 7.

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l. POSACONAZOLE (Schering-Plough) is a novel triazole in Phase II clinical trials to be used
as an oral suspension to treat invasive fungal infections caused by Candida and
aspergillus.

Antifungal Agents Targeting Squalene Epoxidase: Ergosterol Biosynthesis Inhibitors

The allylamines have a more limited spectrum of activity than the azoles and triazoles and
are only effective against dermatophytes. They are employed in the treatment of fungal
infections of the skin and nails.
Mechanism of Action: These antifungal agents are reversible, noncompetitive inhibitors of
the first step in ergosterol biosynthesis; the conversion of squalene to squalene-2,3- epoxide
by squalene epoxidase. The buildup of squalene in the cell membrane is toxic to the cell,
causing pH imbalances and malfunction of membrane bound proteins.

a. TERBINAFINE comes as a tablet to take orally or as a topical cream It is used to treat

fungal infections of the nails.
Drug interactions: warfarin, antidepressant drugs, beta-blockers, proton pump inhibitors
and drugs to suppress the immune system.
Adverse effects include: headache, dizziness, diarrhea, stomach pain, heartburn and
changes in the ability to taste food.
More severe side effects can include: excessive tiredness, loss of appetite, upset
stomach, vomiting, tingling or numbness in the extremities, fever, chills, rash, hives and
difficulty breathing or swallowing. HEPATOXICITY: yellowing of the eyes or skin, dark
urine or pale stools.
Product: Lamisil

b. TOLNAFTATE is a topical cream to treat tinea infections of the skin.

Mechanism of Action: The exact mechanism unknown; however, it has been reported to
distort the hyphae and to stunt mycelial growth in susceptible organisms. Inhibition of
squalene epoxidation has also been reported.
Adverse effects are rare. Skin irritation has been reported.
Products:Aftate, Tinactin, Ting, Breezee

Other Antifungals Affecting Cell Membrane Stability

CICLOPIROX is a topical solution used to treat fungal infections of the nails and hair. It is
a broad-spectrum antifungal medication that also has antibacterial and anti-
inflammatory properties.
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 Mechanism of Action: Its main mode of action is thought to be its high affinity for
trivalent cations, which inhibit essential co-factors in enzymes.
Adverse effects: redness, irritation, burning, blistering or swelling at the site of
application and discoloration of the nails or surrounding area. Treated nails may become
ingrown.
Product: Loprox, Penlac nail lacquer

Inhibitors of Cell Division

a. GRISEOFULVIN is an antifungal produced from Penicillium griseofulvin. Therapy must
continue until new tissue replaces old diseased tissue. When given orally, plasma-borne
griseofulvin becomes incorporated into keratin precursor cells and ultimately into
kearatin that cannot support fungal growth.
Mechanism of Action: Griseofulvin inhibits microtubule polymerization thus inhibiting
the formation of the mitotic spindle.
Adverse effects: Headache is a common adverse effect. May cause aplastic anemia.
Being gradually replaced by newer agents.
Products: Fulvicin-U/F, Grifulvin V, Gris-PEG

Cell Wall Inhibitors

a. UNDECYLENIC ACID is widely used topically as the zinc salt in OTC preparations for
topical treatment of infections by dermatophytes.
Mechanism of Action: This organic acid will interact non-specifically with components in
the cell membrane. It can be used in concentrations up to 10% in solution, powder and
emulsions. Traditionally used for athlete’s foot (tinea pedis) although cure rates are low.
Adverse effects are rare. Skin irritation has been reported.
Products: Desenex, Cruex, Decylenes Powder, Caldesene, Gordochom Solution

Summary of drug–drug interactions for systemic antifungal agents

 Amphotericin B has few significant drug–drug interactions. The main concerns
arise from drugs with the potential for additive nephrotoxicity.
 Absorption of 2 triazole formulations—the itraconazole oral capsules and the
posaconazole oral solution—is affected by gastric acidity. Medications that alter
gastric pH, such as proton pump inhibitors and histamine-2 blockers, should be
avoided.
 The azole drugs act as substrates and inhibitors of the CYP450 enzymes (CYP3A4,
CYP2C19, CYP 2C9) and the affinities for each enzyme vary significantly by
individual drug.

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 Given the hundreds of potential drug–drug interactions for azoles, a patient’s
medication list should be carefully examined with initiation and discontinuation
of azoles.
 Some of the common drug–drug interactions for azoles include antiarrhythmics,
antipsychotics, immunosuppressants, migraine medications, antibiotics,
anticoagulants, antidepressants, antiepileptics, antiretrovirals
chemotherapeutics, antihypertensives, lipidlowering agents, narcotics, sedatives,
hormonal therapies, and medications for diabetes.

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ANTIVIRAL AGENTS
(Flip) Vid watch:
https://www.youtube.com/watch?v=DLTbpTXox08
https://www.youtube.com/watch?v=s8jhJXgC-bk

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CORONAVIRUS infection and test
(Flip) vidwatch
https://www.youtube.com/watch?v=j4Xiow30bGo
https://www.youtube.com/watch?v=akiXEfWW-V0

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HIV/AIDS infection and REPLICATION
(Flip ) Vidwatch:
https://www.youtube.com/watch?v=ng22Ucr33aw
https://www.youtube.com/watch?v=hdgNnXLY8LU

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ANTI HIV DRUGS
Vidwatch https://www.youtube.com/watch?v=VLEe5A74evo

HIV treatment involves taking medicines that slow the progression of the virus in your body.
HIV is a type of virus called a retrovirus, and the combination of drugs used to treat it is called
antiretroviral therapy (ART).
Retroviruses are a type of virus in the viral family called Retroviridae. They use RNA as their
genetic material and are named for a special enzyme that's a vital part of their life cycle —
reverse transcriptase.

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Page 20 of 26
 Antiparasitic Agents: Antiprotozoals, Anthelmintics and Others
https://www2.med.wayne.edu/elab/lectures/mic01web/lecture/kerns/antpar.pdf

Protozoa are single celled organisms. They come in many different shapes and sizes ranging
from an Amoeba which can change its shape to Paramecium with its fixed shape and complex
structure. They live in a wide variety of moist habitats including fresh water, marine
environments and the soil.

Some are parasitic, which means they live in other plants and animals including humans, where
they cause disease. Plasmodium, for example, causes malaria.
They are motile and can move by:
Cilia - tiny hair like structures that cover the outside of the microbe. They beat in a regular
continuous pattern like flexible oars.
Flagella - long thread-like structures that extend from the cell surface. The flagella move in a
whip-like motion that produces waves that propel the microbe around.
Amoeboid movement - the organism moves by sending out pseudopodia, temporary
protrusions that fill with cytoplasm that flows from the body of the cell.

I. Antiprotozoal Agents
Protozoa are one-celled eukaryotes which typically afford disease as a consequence of
replicating in large numbers in the host

A. Antimalarial Agents
 Malaria is caused by a class of red blood cell parasites (protozoa) called Plasmodium
(falciparum, Pmalariae, P. vivax, P. ovale, >100 other minor strains). P. falciparum most .
common and severe.
 Mosquitoes pass sporozoites to humans where they enter the blood stream and travel
to the liver where hepatocytes are infected (we will not discuss life cycle and
replication)
 Resistance to antimalarial agents, particularly Chloroquine, is a problem

1. Quinine and 4-Quinoline Methanols

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 Quinine original from Cinchona bark (used by Inca's pre 16th century)
Quinidine gluconate and sulfate salts given IV and may be used alone or in
combination with other agents where chloroquine resistance occurs.
a. Mefloquine approved in 1989: is a synthetic analog of quinine
 Kills Plasmodia at 'blood stage' of life cycle
 Not prescribed to patients with history of depression, psychosis, convulsions.
 Used for Prophylaxis where chloroquine resistance to P. falciparum occurs.

2. Aminoquinolines
a. Chloroquine is the most versatile (oral) used to treat acute attacks and prophylactic
where resistance not reported.
b. Primaquine used to prevent relapse (more adverse effects)
"Other agents developed/used because of resistance to chloroquine"

3. 9-Methanthrene Methanols (Halofantrine)

 FDA approved in 1992
 Contraindicated in heart disease and for use with mefloquine

4. Mechanism of Action for the Quinoline-Based Antimalarials

 Exact mechanism is not known: A number of molecular mechanisms are proposed
for how these agents act and whether they have 'identicle' or just similar
mechanisms of action. Generally, the following is accepted.
 These agents are weak bases which are uncharged at neutral pH. When the agents
enter the protozoa and subsequently the lysosomes, a more acidic environment, the
agents are converted to their 'charged' salt form and trapped in the lysosome. Thus,
high concentration of drug are accumulated in the protozoa food vacuoles
(lysosomes). It is then believed that when the parasite feeds on hemoglobin in red
blood cells the digestion of protein results in an insoluble precipitate in the
lysosome. (eg. Chloroquine complexes with these protein digest products (heme)) In
the end, degradation of hemoglobin by the malaria parasite is adversely effected by
these agents and the ultimate result is their death. Exactly how this happens is still
debated.
 This general mechanism also explains why resistance to these agents is associated
with impaired uptake of the drug by the malarial protozoa and that cross-resistance
has been observed among these agents.
5. Diaminopyrimidine/Dihydrotriazine Antimalaria Agents

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 (Inhibitors of folate metabolism, DHFR)

 These agents inhibit dihydrofolate reductase, which interferes with folic acid synthesis,
and thus ultimately as a folic acid antagonist results in interference of nucleotide
synthesis. High affinity for Plasmodia DHFR and low affinity for human DHFR.

6. Other Agents with Antimalarial Activity

 sulfa drugs as shown above for combination therapy with DHFR inhibitors (synergistic)
 Artemisinin
 tetracycline, chloramphenicol

B. Other Antiprotozoal Agents

 There are many other agents with a variety of mechanisms of action to treat protozoal
infections such as trypanosomiasis, leishmaniasis, amebiasis, giardiasis, trichomoniasis
and others.

1. Metronidazole
 Metronidazole is metabolically reduced to reactive metabolites in the protozoa. These
reactive metabolites bind DNA of the protozoa affording a lethal effect.
 Generally low toxicity in humans.
 widely used for variety of protozoal infections in North America
 Adverse Effects: nausea, dry mouth, metalic taste, disulfuram-like reaction with alcohol

2. Other agents typically used in North America

a. Paromycin (aminoglycoside)
b. Combinations of sulfa drugs (sulfamethazole) and DHFR inhibitor
(trimethoprim/pyrimethamine)
c. Tetracycline

3. Other agents available from CDC (for Leishmaniasis, Trypanosomiasis and other
protozoal infections not common in North America)
a. Pentamidine,
b. Suramin,
c. Sodium Stibogluconate,
d. melarsoprol,
e. nifurtimox

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II. Anthelminthic Agents
Helminths (worms) are multicellular animals that are much larger than protozoa. Many
types of worms (tapeworms, roundworms and flatworms (flukes))

1. The Benzimidazoles
a. Mebendazole (Vermox) used in the U.S.
 Cimetidine may inhibit liver metabolism of Mebendazole (roundworms and
tapeworms)
Mechanism of Action:
The benzimidazoles bind to beta-tubulin which results in the inhibition of microtubule
assembly involved in cell division. Therefore, cell division processes are arrested.
Glucose uptake is also depleted. The benzimidazoles have high affinity for beta-tubulin
in the parasite (worm) but low affinity for mammalian betatubulin affording 'selective
toxicity'.

2. Pyrantel

Pyrantel pamoate acts on the nervous system of pinworm, roundworm and hookworm.
It is a depolarizing neuromuscular blocking agent that causes spastic paralysis in
susceptible helminths.
3. Niclosamide (a salicylanilide) –
 used for tapeworms
 kills on cantact by uncoupling oxidative phosphorylation (energy depletion)

4. Praziquantel
 Broad spectrum
 well tolerated
 Mechanism of Action: Appears to effect helminth membranes ultimately
stimulating the action of hosts antibodies. (expose/release antigen(s))

5. Other Antihelminths with various applications

a. Ivermectin
b. Diethylcarbamazine
c. Piperazine

III. Pediculocides and Miticides (Lice and Scabies)

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1. Lindane (Kwell®)
 Effect on insects is similar to DDT but lower toxicity to humans
 Adverse effects: rash, conjunctivitis (rare: convulsions, aplastic anemia)
 Insecticidal against lice

2. Malathion - Another insecticide that has limited use for lice. (local irritation and foul
smelling)
3. Pyrethrins
 Pyrethrins are natural extracts from Chrysenthemum (A-200, RID, Pronto)
 Only major adverse effect is possible allergic reaction
 for lice (pyrethrin + piperonyl butoxide)

a. Permethrin is a synthetic pyrethrin which is chemically more stable

 Mechanism of Action: Disrupts sodium conductance of nerve cell membranes
of the parasite.
 Adverse Effects: burning, numbness, rash

i. (Eliminate®) 5% permethrin for scabies, alternative is 1% lindane or 10%

crotamilton
ii. (Nix®) 1% permethrin for lice

4. Crotamiton- Scabicide (Eurax®)

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---END OF MODULE 4---

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 NOTRE DAME OF DADIANGAS UNIVERSTY (NDDU)
College of Pharmacy
COURSE TITLE PHARMACOLOGY II COURSE CODE Pharm36
rd st
Course Placement 3 yr, 1 SEM CONTACT HOURS 3 hours/week, 54 hours/sem
Date for this topic 2020 Oct 12 SME: Melba M. Roma, RPh, MSPh
MODULE 6: SPECIAL TOPICS (Vaccines and Nutritional Supplements)
Reading Assignment: Katzung , B.G., Basic Clinical Pharmacology, 14th ed.
Online resources: https://www.who.int/vaccine_safety/initiative/tech_support/Part-2.pdf?ua=1

Content Demonstrate knowledge with biologic products like vaccines and nutritional
Standards supplements.
Functional Discuss biologic products including vaccines, immunoglobulins, etc.
Knowledge Discuss different types of vaccines based on their indication on specific age
group

Module outcomes
By the end of this module you should be able to:
1. Explain the modes of action of live attenuated vaccines, conjugate vaccines, subunit
vaccines, and toxoid vaccines,
2. List types of vaccine components, including adjuvants and preservatives, and explain
their functions,
3. Explain the difference between live attenuated and inactivated vaccines,
4. Identify the contraindications for vaccination that may present an additional risk.

NOTE: PPhA Advocacy on immunization must be integrated under this unit.

VACCINES

The word “vaccine” originates from the Latin Variolae vaccinae (cowpox), which Edward Jenner
demonstrated in 1798 could prevent smallpox in humans. Today the term ‘vaccine’ applies to
all biological preparations, produced from living organisms, that enhance immunity against
disease and either prevent (prophylactic vaccines) or, in some cases, treat disease (therapeutic
vaccines). Vaccines are administered in liquid form, either by injection, by oral, or by intranasal
routes.

(Flip) vidwatch: https://www.youtube.com/watch?v=34UWTlxK6Ks

Types of vaccine

Page 1 of 7
 1. Live attenuated Vaccine (LAV)

Available since the 1950s, live attenuated vaccines (LAV) are derived from disease- causing
pathogens (virus or bacteria) that have been weakened under laboratory conditions. They will
grow in a vaccinated individual, but because they are weak, they will cause no or very mild
disease.

 Live microorganisms provide continual antigenic stimulation, giving sufficient time for
memory cell production.
 Attenuated pathogens are capable of replicating within host cells.
 Excellent immune response
 Usually not given in pregnancy
 Less safe compared to inactivated vaccines
– Tuberculosis (BCG)
– Oral polio vaccine (OPV)
– Measles
– Rotavirus
– Yellow fever

2. Inactivated (killed antigen)

Inactivated vaccines are made from microorganisms (viruses, bacteria, other) that have been
killed through physical or chemical processes. These killed organisms cannot cause disease
 May not always induce an immune response at first dose.
 Response may not be long-lived, requiring several doses of vaccine
 Less strong immune response compared to live vaccines
 Safer and more stable than LAVs
 Excellent stability profile

– Whole-cell pertussis (wP)

– Inactivated polio virus (IPV)

3. Subunit (purified antigen) vaccines, can be further categorized into:

■ Protein-based subunit vaccines,

■ Polysaccharide vaccines,
■ Conjugate subunit vaccines.

– Acellular pertussis (aP),--> protein based

– Haemophilus in¬uenzae type b (Hib),--> conjugate

Page 2 of 7
 – Pneumococcal (PCV-7, PCV-10, PCV-13)--> conjugate
– Hepatitis B (HepB)- protein based
 Must determine which combination of antigenic properties will produce an effective
immune response with the correct pathway
 A response may be elicited, but with no guarantee that memory will form for future
response
 Less strong immunity response compared to LAVs
 Have no live components, no risk of inducing the disease
 Safer and more stable than LAVs
 Excellent stability profile

4. Toxoid (inactivated toxins)

– Tetanus toxoid (TT),
– Diphteria toxoid

 Toxoid vaccines are based on the toxin produced by certain bacteria (e.g. tetanus or
diphtheria).
 The toxin invades the bloodstream and is largely responsible for the symptoms of the
disease.
 The protein-based toxin is rendered harmless (toxoid) and used as the antigen in the
vaccine to elicit immunity.
 To increase the immune response, the toxoid is adsorbed to aluminium or calcium
salts, which serve as adjuvants.
 May require several doses and usually need an adjuvant
 Not highny immunogenic

Combination vaccines
Licensed combination vaccines undergo extensive testing before approval by national
regulatory authorities to assure that the products are safe, effective, and of acceptable quality.
Combination vaccines consist of two or more antigens in the same preparation. This approach
has been used for over 50 years in many vaccines such as DTwP and MMR. Combination
products simplify vaccine administration and allow for the introduction of new vaccines without
requiring additional health clinic visit and injections.

Potential advantages of combination vaccines include:

■ Reducing the cost of stocking and administering separate vaccines,

Page 3 of 7
■ Reducing the cost of extra health care visits,
■ Improving timeliness of vaccination
■ Facilitating the addition of new vaccines into immunization programmes

Components of a vaccine*
 Vaccines include a variety of ingredients including antigens, stabilizers, adjuvants,
antibiotics, and preservatives.
 They may also contain residual by-products from the production process.

1. Antigens
Antigens are the components derived from the structure of disease-causing organisms,
which are recognized as ‘foreign’ by the immune system and trigger a protective
immune response to the vaccine.

2. Stabilizers
Stabilizers are used to help the vaccine maintain its effectiveness during storage.
Vaccine stability is essential, particularly where the cold chain is unreliable. Instability
can cause loss of antigenicity and decreased infectivity of LAV. Factors affecting stability
are temperature and acidity or alkalinity of the vaccine (pH). Bacterial vaccines can
become unstable due to hydrolysis and aggregation of protein and carbohydrate
molecules. Stabilizing agents include MgCl2 (for OPV), MgSO4 (for measles), lactose-
sorbitol and sorbitol-gelatine.

3. Adjuvants
Adjuvants are added to vaccines to stimulate the production of antibodies against the
vaccine to make it more effective.
Adjuvants have been used for decades to improve the immune response to vaccine
antigens, most often in inactivated (killed) vaccines. In conventional vaccines, adding
adjuvants into vaccine formulations is aimed at enhancing, accelerating and prolonging
the specific immune response to vaccine antigens. Newly developed purified subunit or
synthetic vaccines using biosynthetic, recombinant, and other modern technology are
poor vaccine antigens and require adjuvants to provoke the desired immune response.
Chemically, adjuvants are a highly heterogeneous group of compounds with only one
thing in common: their ability to enhance the immune response.

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4. Antibiotics
Antibiotics (in trace amounts) are used during the manufacturing phase to prevent
bacterial contamination of the tissue culture cells in which the viruses are grown.
Usually only trace amounts appear in vaccines, for example, MMR vaccine and IPV each
contain less than 25 micrograms of neomycin per dose (less than 0.000025 g). Persons
who are known to be allergic to neomycin should be closely observed after vaccination
so that any allergic reaction can treated at once.

5. Preservatives
Preservatives are added to multidose vaccines to prevent bacterial and fungal growth.
They include a variety of substances, for example Thiomersal, Formaldehyde, or Phenol
derivatives.
Thiomersal
■ Very commomly used preservative. Thiomersal is an ethyl mercury-containing
compound,
■ It is used in multidose vials and for single dose vials in many countries as it
helps reduce storage requirements/costs,
■ Thiomersal has been subjected to intense scrutiny, as it contains ethyl
mercury. The Global Advisory Committee on Vaccine Safety continuously review
the safety aspects of Thiomersal. So far, there is no evidence of toxicity when
exposed to Thiomersal in vaccines. Even trace amounts of thiomersal seem to
have no impact on the neurological development of infants.

Formaldehyde
■ Used to inactivate viruses (e.g. IPV) and to detoxify bacterial toxins, such as the
toxins used to make diphtheria and tetanus vaccines,
■ During production, a purification process removes almost all formaldehyde in
vaccines,
■ The amount of formaldehyde in vaccines is several hundred times lower than
the amount known to do harm to humans, even infants. E. g., DTP-HepB + Hib
“5-in-1” vaccine contains less than 0.02% formaldehyde per dose, or less than
200 parts per million.*

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 Route of administration
The route of administration is the path by which a vaccine (or drug) is brought
into contact with the body. This is a critical factor for success of the
immunization. Routes of administration vary to maximize effectiveness of
vaccine.
1. Intramuscular (IM) injection administers the vaccine into the muscle mass. Vaccines
containing adjuvants should be injected IM to reduce adverse local effects.
2. Subcutaneous (SC) injection administers the vaccine into the subcutaneous layer above
the muscle and below the skin.
3. Intradermal (ID) injection administers the vaccine in the topmost layer of the skin. BCG
is the only vaccine with this route of administration. Intradermal injection of BCG
vaccine reduces the risk of neurovascular injury. Health workers say that BCG is the
most difficult vaccine to administer due to the small size of newborns’ arms. A short
narrow needle (15 mm, 26 gauge) is needed for BCG vaccine. All other vaccines are
given with a longer, wider needle (commonly 25 mm, 23 gauge), either SC or IM.
4. Oral administration of vaccine makes immunization easier by eliminating the need for a
needle and syringe.
5. Intranasal spray application of a vaccine offers a needle free approach through the
nasal mucosa of the vaccinee.

Contraindications
The only contraindication applicable to all vaccines is a history of a severe allergic reaction
after a prior dose of vaccine or to a vaccine constituent.

Anaphylaxis
Anaphylaxis is a very rare allergic reaction (one in a million vaccinees), unexpected, and can be
fatal if not dealt with adequately. Vaccine antigens and components can cause this allergic
reaction. These reactions can be local or systemic and can include mild-to severe anaphylaxis or
anaphylactic-like responses (e.g. generalized urticaria or hives, wheezing, swelling of the mouth
and throat, breathing difficulties, hypotension and shock).

Using adrenaline to treat anaphylaxis

Adrenaline stimulates the heart and reverses the spasm in the blood vessels and the lung
passages, reduces oedema and urticaria, thus countering the anaphylaxis. But this very potent
agent can cause irregular heartbeat, heart failure, severe hypertension and tissue necrosis if
used inappropriately, although not when treating true anaphylaxis.
Active and passive immunization
(flip) vidwatch: https://www.pharmacytimes.com/interviews/immunizations-active-versus-passive

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 Herbal Supplement Claimed Health Benefit (Indication)

Black Cohosh menopausal symptoms

Cannabidiol chronic pain

Coenzyme Q10 chronic heart failure (HFrEF)

Cranberry urinary tract infections

DHEA menopause related hot flashes

Echinacea symptoms of colds, flu & other infections

Fish oil (Omega-3s)♥ prevention of cardiovascular disease

Garlic lower blood pressure & serum cholesterol

Ginkgo Biloba Alzheimer's dementia & cerebral insufficiency

Ginseng improved mental performance & immune system

Glucosamine/chondroitin joint health

Ma-huang (ephedra) diet suppressant, stimulant

Melatonin sleep disorders / jet lag

Milk Thistle improving liver health in liver disease

Peppermint Oil antispasmodic for irritable bowel syndrome

Probiotics (Lactobacillus) infectious or antibiotic-induced diarrhea

Saw Palmetto benign prostatic hyperplasia (BPH)

St John's wort depression

---END OF MODULE ---

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