Fungus Among Us:

Antifungal Agents
Catessa Howard, PharmD
Pharmacy Technician Lecture
February 26, 2018
Learning Objectives
§ Compare and contrast the mechanisms of action of various
classes of antifungal agents

§ Describe side effects commonly associated with each of the

antifungal classes

§ Describe the drug interaction potential for each class of

antifungals

§ List the formulations available for each antifungal agent 2

Key Terms
§ Aspergillus
§ Candida
§ Dermatophytes
§ Eukaryotic
§ Fungal
§ Fungicidal

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Key Terms, Contd.
§ Fungus
§ Immunocompromise
§ Mold
§ Opportunistic pathogen
§ Postantifungal effect (PAFE)
§ Yeast

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Introduction

Fungi

Mushrooms Yeasts Molds

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How fungi are different
§ Fungi vs. Human § Fungi vs. bacteria
§ Similar § Similar
⎻ Eukaryotic ⎻ Cell wall
§ Different § Different
⎻ Cell wall ⎻ Eukaryotic
⎻ Cell membrane composition ⎻ Cell wall composition
⎻ Enzymes/proteins

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Background/Epidemiology:
§ Fungal infections often occur in immunocompromised patients
§ Often thought of as opportunistic pathogens

§ Common fungi species:

§ Candida
§ Aspergillus

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Antifungal Agents - Polyenes
§ Mechanism of action
§ Binds to ergosterol à fungicidal

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 Antifungal Agents - Polyenes
§ Mechanism of action
§ Binds to ergosterol à fungicidal

§ Postantifungal Effect (PAFE)

Drug concentration

Concentration needed
PAFE to kill fungus

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Time after dose
 Antifungal Agents – Polyenes: Amphotericin
Generic Brand Name(s) Formulations Indications Side effects
Amphotericin B Fungizone® IV Invasive, serious Infusion reactions
desoxycholate fungal infections
Not all amphotericins are created Nephrotoxicity
Lipid complex Abelcet® equal!
These products are not Electrolyte
Liposomal AmBisome® interchangable. disturbances

Cholesteryl Amphotec®
sulfate

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 Antifungal Agents – Polyenes: Nystatin
Generic Brand Name(s) Formulations Indications Side effects
Nystatin Bio-Statin Powder Candida Nausea and
infections diarrhea
-- Shake containers
Vaginal well before use!
tablet
Nyamic,
Nystop, Pedi- Cream,
Dri ointment,
powder

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Antifungal Agents – Polyenes, contd.

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POP QUESTION!
What is a common side effect of amphotericin B?
A.  Stomach upset
B.  Confusion
C.  Increased potassium
D.  Renal toxicity

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 Antifungal Agents – Azoles
§ Mechanism of action:
§ Target enzyme that is used to produce ergosterol
⎻ Disrupts the equilibrium between inside and outside the cell
⎻ Increased level of ergosterol precursors à toxic

§ Potential to inhibit human enzymes as well

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 Antifungal Agents -Azoles
§ Mechanism of action

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Antifungal Agents – Azoles
Azoles

Imidazole Triazoles

Topical Systemic
treatment treatment

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Generic Brand Name(s) Formulations Indications Side effects
Fluconazole Diflucan® IV, PO Candida Increased liver
function tests (all
azoles)
Itraconazole Sporanox® PO Candida Phototoxicity
Aspergillus
Endemic fungi
Azoles have a LOT of drug
Voriconazole VFEND® PO Candida Renal toxicity (IV)
interactions!!
Aspergillus Visual disturbances
Endemic fungi Hallucinations
Mold Phototoxicity
Posaconazole Noxafil® PO Candida Increased liver function
Aspergillus tests (all azoles)
Endemic fungi
Molds
Isavuconazonium Cresemba® IV, PO Candida Increased liver function
Aspergillus tests (all azoles)
Endemic fungi 17

Molds
Antifungal Agents - Echinocandins
§ Mechanism of action:
§ Inhibit enzyme responsible for synthesis of glucan
⎻ Without glucan à loses ability of regulate water à cell death

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 Antifungal Agents - Echinocandins
Generic Brand Name(s) Formulations Indications Side effects
Micafungin Mycamine® Caspofungin
IV and Candida Increased LFTs
Caspofungin anidulafungin
Cancidas® IV ordered with aCandida
Few side effects
double dose for first Aspergillus
compared to
Anidulafungin Eraxis® administration
IV Candida other antifungals

Drug of choice of serious

Candida infections

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 Antifungal Agents – Miscellaneous
Generic/Brand Mechanism of Formulations Indications Side effects
Action
Terbinafine/ Blocks a different Creams Skin fungal Increased LFTs
Lamisil® enzyme for Powder infections
ergosterol Sprays
synthesis PO Onocomycosis
Flucytosine/ Antimetabolite PO Candida CNS
Ancobon® Aspergillus Bone marrow
Cryptococcus suppression
Dermatophytes Liver/kidney
toxicity
Griseofulvin/ Inhibits fungal PO Dermatophytes Few side effects
Grifulvin® cell mitosis
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POP QUESTION!

Which antifungal class has the most drug-drug interactions?

A.  Echinocandins
B.  Azoles
C.  Polyenes

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Topical Antifungals
§ Topical Azoles
§ Creams, suppositories, vaginal tablets

§ Nystatin
§ Cream and ointment

§ Many combinations with topical corticosteroid to help with itching and

inflammation

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 Fungal Infections: Candida
§ Candida
§ Candidasis à any infection caused by Candida
§ Varies in presentation and severity
⎻ Thrush
⎻ Vaginal Nystatin/Azoles

⎻ Skin infection
⎻ Bloodstream
⎻ Deep organ infections
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 Fungal Infections: Candida
§ Candida
§ Candidasis à any infection caused by Candida
§ Varies in presentation and severity
⎻ Thrush
⎻ Vaginal
⎻ Skin infection
⎻ Bloodstream Echinocandins
Azoles
⎻ Deep organ infections Amphotericin B
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 Fungal Infections: Aspergillus
§ Aspergillosis
§ A. fumigatus, A. niger, A. flavus
§ Inhalation of aspergillus spores
§ Allergic type reaction or severe disease if spread from lungs
§ Difficult to treat
§ Treatment:
⎻ Amphotericin B
⎻ Azoles: Posaconazole, voriconazole
⎻ Echinocandins 25
POP QUESTION!

1.  The following picture represents what type of fungal infection?

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POP QUESTION!

2. What would be the best agent to treat this patient?

A.  Amphotericin B
B.  Micafungin
C.  Fluconazole
D.  Terbinafine

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Endemic Fungal Infections
§ Refers to those infections that are commonly only among certain
populations or in certain regions

§ Transmitted through the inhalation of fungal spores

§ Typically cause pulmonary infections including pneumonia and

pulmonary cavitations
§ Can disseminate to other parts of the body in immunocompromised
patients
§ Usually affects immunocompromised patients 28
Endemic Fungal Infections
§ Histoplasmosis:
§ Amphotericin B
§  Itraconazole
§ Blastomycosis:
§ Amphotericin B
§ Itraconazole
§ Coccidiomycosis:
§ Amphotericin B
§ Fluconazole
§ Itraconazole 29
Cyptococcal Infection
§ Cryptococcus neoformans
§ Immunocompromised patients
§ Inhalation of spores
§ CNS disease: Amphotericin B + flucytosine à fluconazole

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POP QUESTION!

Which of the follow fungi is endemic to the Hoosier state?

A.  Blastomycosis
B.  Coccidiomycosis
C.  Histoplasmosis
D.  Both A and C

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 Immunobiologics:
Our Personal Body Guard
Catessa Howard, PharmD
Pharmacy Technician Lecture
February 26, 2018
Objectives
§ Describe the immune system and the types of immunity
§ Discuss the importance of disease prevention to public health
and how pharmacy personnel can contribute
§ Describe the different types of immunizations
§ List recommended immunizations for various populations and
purposes
§ Discuss the uses of monoclonal antibodies
§ Discuss the therapeutic uses of immunosuppression and list
agents used for this purpose
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Key Terms
§  Antitoxin
§  Centers for Disease Control and Prevention (CDC)
§  Immune globulin (immunoglobulin)
§  Immunity
● Active immunity
● Innate immunity
● Passive immunity
§  Immunocompromise
§  Immunosuppressive
§  Postexposure prophylaxis
§  Rejection
§  Serum (plural is sera)
§  Vaccine 34
Introduction
§ The immune system recognizes toxins or invading organisms that
enter the body
§ Foreign substances: Antigens
§ Body produces: Antibodies

§ Immunity:
§ Protecting from disease by the body’s defense system
h'ps://www.youtube.com/watch?v=PSRJfaAYkW4&t=121s
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36
 The Immune System
Lymphatic system:
Bone Marrow
Lymph nodes
Spleen
Thymus
Tonsils

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White Blood Cells (WBCs)

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Types of Immunity: Innate
§ Definition:
§ General protection against pathogens natural from birth
§ External barriers:
§ Skin
§ Mucous membranes
§ If barrier broken:
§ Body attempts to heal quickly
§ Inflammatory response and WBCs released
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Types of Immunity: Acquired
§ Definition:
§ Specific to an organism/antigen
§ Process:
§ Develops after exposure to antigen
§ Memory Cells
⎻ Activated lymphocytes (T cells/B Cells) remain in bloodstream

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Types of Immunity: Active
§ Definition:
§ Production of antibodies
§ Process:
§ Acquired from contracting an infectious disease
§ Vaccination

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Types of Immunity: Passive
§ Definition:
§ Transfer of antibodies from actively immune individual/animal
§ Process:
§ Mother to fetus
§ Immune globulin

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Passive Immunity
§ Sometimes diseases caused by bacterial infection are result of
toxins
§ Immunity is conferred by injecting toxoids altered so they can no
longer produce symptoms
§ Can be accomplished much more immediately than active
immunity
§ Administration of sera-containing antibodies and antitoxins
§ Example: immune serum can protect individuals who have
recently been exposed to a toxin
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⎻ Venom of poisonous snake
Post-exposure Prophylaxis
§ Definition:
§ Prevent illness or infection after acute exposure to a
nonimmune individual
§ Process:
§ Administration of specific immune sera/immunoglobulins

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History and Impact of Vaccines and Immunity
Long before the immune system was understood or the agents
that caused infection were known, it was recognized that people
who contracted and recovered from certain communicable
diseases had protection from them and did not get them again,
even exposed to patients who had the active disease.

h'ps://www.youtube.com/watch?v=rb7TVW77ZCs

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History and Impact of Vaccines and Immunity
§ Timeline:
§ 18th century: Edward Jenner exposed children to cowpox à
Immune to small pox
§ Vaccination – from vacca, Latin word for cow
§ Immunization:
§ Exposed to killed/weakened versions of pathogens that cause
disease
§ Vaccine:
§ Containing killed or weakened pathogens 46
Types of Vaccines

Live-attenuated Inactivated Boosters

• Most likely to • Killed • “Remind” the

confer lifelong pathogens immune
immunity • Multiple system by
after single doses stimulating its
dose memory of
the antigen
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Routes of Vaccine Administration
§ Intramuscular (IM)
§ Subcutaneous (SQ)
§ Some are oral
§ Intranasal

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POP QUESTION!
Receiving a vaccination confers which type of immunity?
A.  Active
B.  Passive
C.  Innate

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Centers for Disease Control and Prevention (CDC)
§ Release vaccine schedules and recommend vaccinations to
prevent diseases for children and adults

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Pharmacy Role
§ Inventory control, stock rotation, and careful ordering practices
§ Records of productsVaccines should be kept
and lot numbers received, dispensed, and
administered within their parOcular
§ Knowledge and practice temperature range
of proper vaccine transport and storage
conditions on theIf vaccines need reconsOtuted,
labeling of each practice
§ Reconstitution of vaccines
oQen they only have short
Omes unOl they expire
§ Promoting recommend vaccinations
§ Technicians assist by ensuring stocks of immunization supplies
are available and in date
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Vaccines Given in Indiana Pharmacies
§ Influenza
§ Hepatitis A
§ Hepatitis B
§ HPV
§ Measles, mumps, rubella
§ Haemophilus influnezae type B
§ Pneumococcal
§ Tetanus, diphtheria, pertussis
§ Herpes zoster 52
Immunocompromised
§ Patients with a weakened immune system
§ Often unable to mount a full immune response to a vaccine
§ Types:
§ HIV/AIDS
§ Medications
⎻ Transplants
⎻ Autoimmune diseases
§ Cancer
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Immunosuppression
§ Often used after transplants and for autoimmune diseases
§ To stop the body from “attacking” itself (autoimmune disease)
or a newly transplanted graft (cells/organ)

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Immunosuppressive Agents: Corticosteroids
§ Corticosteroids:
§ Frequently used post transplant or during the surgery to
prevent rejection
§ IV = methylprednisolone
§ PO = prednisone

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 Immunosuppressive Agents: Antimetabolites
§ Antimetabolites:
§ Inhibit chemical reactions necessary for formation of T-Cells
and B-Cells
Generic Brand Formulation Side effects
Azathioprine Imuran PO Reduces WBCs
IV Black Box Warning = increased
risk of malignancy
GI upset
Mycophenolate CellCept® PO GI Upset
IV Blood disorders
Infection 56
 Immunosuppressive Agents: Calcineurin inhibitors
§ Mechanism of action:
§ Block T Cell production
Generic Brand Formulation Side Effects
Cyclosporine SandIMMUNE IV Drug interactions
Gengraf PO Infection
Nephrotoxicity
Neurotoxicity
Tacrolimus Prograf IV Drug interactions
PO Infection
Nephrotoxicity 57
Neurotoxicity
 Immunosuppressive Agents: mTOR inhibitors
§ Mechanism of action:
§ Changing the way T-Cells respond to antigenic stimulation
Generic Brand Formulation Side effects
Sirolimus Rapamune® PO Drug interactions

Everolimus Zortress® PO Drug interactions

Afinitor®

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Immunosuppressive Agents: Contd.
§ Belatacept (Nulojix®)
§ Selective T-cell costimulation blocker
§ Binds to antigen presenting cells and prevents their activation and
proliferation
§ Formulation: IV
§ Side effects:
§ Anemia
§ Constipation
§ Cough
§ Headache 59

§ Malignancies
Immunosuppressive Agents: Contd.
§ Antibody preparations: Suppress the immune system by depleting its
resources
§ Antithymocyte globulins
§ Rabbits/horses
§ SE: suppression of blood cell formations, anaphylaxis, rash, difficulty breathing,
blood pressure changes
§ Muromonab-CD2
§ Specific to CD3 cell
§ SE: fevers, chills, itching, blood pressure changes
§ IL-2 receptor antagonists: Basiliximab
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§ SE: Hypertension, headache, tremor, GI, infection.
POP QUESTION!
Which of the following is a calcineurin inhibitor?
A.  Antithymocyte globulin
B.  Tacrolimus
C.  Mycophenolate
D.  Sirolimus

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Summary
§ The immune system is the body’s main defense against disease
caused by invading pathogens and toxins
§ Acquired immunity enables body to fight infectious disease
§ Active immunity, due to exposure to pathogenic agents, can be
induced by vaccination, causing antibodies to form

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Brand Generic Mash Up:

Rapamune® Zortress®

CellCept® Sirolimus

Everolimus Mycophenolate 63
Questions?

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