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MANOR REVIEW CENTER MODULE 6 SUPPLEMENT HANDOUT Updated APRIL 2018 Nico C. Fabian, RPh, MD

PHARMACEUTICAL MYCOLOGY • • • •

Fungi – eukaryotic, rigid cell walls All eukaryotic cells contain sterols (Ergosterol for fungi) Saphrophytes; No obligate anaerobe Taxonomic classification: Zygomycetes (aseptate fungi), Ascomycetes (sac fungi), Basidiomycetes (mushroom), Deuteromycetes (imperfect fungi) Yeast Molds Unicellular Filamentous Divide by budding Structural units = hyphae Buds – blastospores Aggregates of hyphaen = Elongates to form mycelia pseudohyphae i.e. Candida, Cryptococcus Dimorphic Fungi – grow as mold (natural reservoir, 25C at Saboraud Dextrose agar) or as yeast (tissues, 37C on Brain heart infusion agar. Example: Histoplasma capsulatum

•

I.

Dermatophytes • Molds which parasitize non-living integuments o Secretes keratinase • Infections classified as geophilic (acute), zoophilic (acute), or anthropophilic (milder, chronic) o known as ringworm infections due to the formation of raised, circular lesions. o commonly known as tinea (Latin for worm), and are named after the body part involved. o Tinea corporis (skin), capitis (head) [kerion kalbo vs. favus honey crust], manum (hands), pedis (feet), unguium (nails), cruris (groin) [hadhad] • Causative agents: Microsporum spp. Trichophyton T. mentagrophytes – tinea pedis (most spp. common) T. concentricum – tinea imbricata, “toquelau” Epidermophyton spp. • Diagnosis: KOH skin scrapings, Wood’s light (result:flourescence) • Management: Topical imidazole, keep the area dry

II.

A. Blastomycosis • Gilchrist’s disease, North American Blastomycosis • Blastomyces dermatitidis • Prefers men with soil contact • Rarest systemic fungal infection B. Paracoccidiodomycosis • South American Blastomycosis • Paracoccidioides brasiliensis • Tissue form likened to mariner’s wheel • Prefers men C. Coccidioidomycosis • San Joaquin Valley Fever • Coccidioides immitis • Prefers dark-skinned persons with soil contact D. Histoplasmosis • Histoplasma capsulatum • Resides in feces birds and bats • Common among cave explorers and people involved in “spelunking” • Presents as pneumonia V. A.

B.

Superficial Mycoses

A. Pityriasis versicolor • An-an • Etiology: Malassezia furfur (Before: Pityrosporum orbiculare/ovale) • Hypopigmented macules • “Spaghetti and meatballs” appearance on microscopy • Management: Selenium sulfide, Ketoconazole B. Tinea nigra • Etiology: Hortaea (Exophiala) werneckii (pigmented) • “black colonies” on culture • Brown macules on face, hand C. Black Piedra • Fungal infection of scalp hair • Etio: Piedraia hortae • Discrete, hard, dark brown to black nodules on the hair – firmly attached D. White Piedra • Fungal infection of facial, axillary, genital hair • Etio: Trichosporon spp. • Soft, white to yellowish nodules loosely attached to the hair Subcutaneous mycosis Initiated by traumatic implantation into subcutaneous tissues. A. Sporotrichosis • Etio: Sporothrix schenckii (thermally dimorphic fungus) • Horticulturists, forest rangers • Lymphocutaneous sporotrichosis – small, movable, nontender, subcutaneous nodule appears at puncture site then progressively involves proximal lymphatics. • As mold: daisy-like microconida • As yeast: cigarette butt apearance • Management: SSKI, Itraconazole, Fluconazole B. Chromomycosis • Etiology: Fonsecaea pedrosoi • Slow development of verrucous, cutaneous vegetations • Microscopy: copper-colored sclerotic bodies • Management: SSKI, Itraconazole, Fluconazole

C.

D.

Opportunistic Fungal Infections • Affect immunocompromised individuals Candidiasis • Candida albicans – part of the minor normal flora • Clinical manifestations: Oral thrush/Moniliasis – sore white patches in the mouth o Management: Nystatin (binds ergosterol) Diaper dermatitis o ManagementL Air dry or replace, Nystatin, Clotrimazole Candidemia – persistent fever in spite of antibiotics • Test: Beta-D-Glucan • DOC: Fluconazole Aspergillus spp. • Aspergillus fumigatus • Soil – where organism function as saphrophyte • Aerosolizes conidia which immunocompetent breathe daily but cleared by macrophages • Inhaled leading to Allergic Pulmonary aspergillosis o May lead to formation of fungus ball = Aspergilloma • Diagnosis: Galactomannan Ag testing; CT Scan (+) halo sign [early] and air crescent sign [late] • DOC: Voriconazole Mucormycosis • Zygomycosis • Leading pathogen: Rhizopus and Mucor • Common among the immunocompromised • Rhinocerebral mucormycosis Cryptococcus spp. • Cryptococcosis – AIDS defining condition (CD4+ T cells = controls the organism in the body) • C. neoformans – most common causative agent • Source: pigeon droppings • Transmission = inhalation of infectious borne particles • Meningitis – most common manifestation • Diagnosis: CALAS, India ink • Management: Amphotericin B + Flucytosine; Note Maintenance Fluconazole

VI. ANTI-FUNGAL AGENTS Drug Amphotericin B

MOA Bind to ergosterol leading to increased membrane permeability

Flucytosine

Interferes with DNA synthesis

Echinocandin (i.e. Caspofungin)

Inhibits B-(1,3) glucan synthase

Griseofulvin

Inhibits mitosis by binding to microtubule

III.

•

Remarks - “Queen of all antifungals” - Broad-spectrum - DOC vs. life-threatening fungal infections - IV and liposomal preparation - Amphotericin A = relatively less clinically important - Nephrotoxic - Anti-metabolite - Narrow spectrum (not used as monotherapy) - IV preparation - “Cidal” vs. Candida - “Static” vs. Asgergillus - Salvage therapy vs. invasive aspergillosis - Vs. ringworm infections - Increased absorption if taken with fatty foods

C. Mycetoma • Madura foot, maduromycosis • Etio: Pseudallescheria boydii • Draining sinuses + granules • Note True mycetoma/Eumycotic = true filamentous fungi IV. • •

Systemic Mycoses Enter via the respiratory tract Similar to TB but no person-to-person spread

associated protein Inhibits squalene - Vs. onchomycosis epoxidase - Allylamine AZOLES: Imidazole (less specific, more toxic) i.e. Ketoconazole, Miconazole, Clotrimazole st - 1 oral azole Ketoconazole Inhibit 14-alphasterol - Less specific vs. fungal demethylase CYP450 Terbinafine

For questions, suggestions, and clarification, please send an email to [email protected]. Do not be anxious about anything, but in every situation, by prayer and petition, with thanksgiving, present your requests to God. PHILIPPIANS 4:6

MANOR REVIEW CENTER MODULE 6 SUPPLEMENT HANDOUT Updated APRIL 2018 Nico C. Fabian, RPh, MD - Adverse effect: Gynecomastia, decreased libido AZOLES: Triazole (more specific, less toxic) Itraconazole Inhibit 14-alpha- VS. indolent, nonsterol meningeal fungal demethylase infections - Adverse effects: hypertension, rhabdomyolysis, hepatotoxicity Fluconazole - Absorbed irrespective of gastric activity - DOC vs. Candida - Adverse effect: SJS Voriconazole - DOC vs. aspergillosis - Adverse effect: transient visual changes Posaconazole - Vs. Rhizopus - Broadest spectrum among the azoles

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Reporting: Regular reporting information on antibiotic use and resistance to doctors, nurses and relevant staff • Education: Educating clinicians about resistance and optimal prescribing C. RESPONSIBILITIES OF PHARMACISTS IN ANTIMICROBIAL STEWARDSHIP • Promoting optimal use of antimicrobial agents • Reducing the transmission of infection • Educational activities III. CDC BIOTERRORISM AGENTS Category A The U.S. public health system and primary healthcare providers must be prepared to address various biological agents, including pathogens that are rarely seen in the United States. High-priority agents include organisms that pose a risk to national security because they • can be easily transmitted from person to person

• • •

result in high mortality rates and have the potential for major public health impact might cause public panic and social disruption

require special action for public health preparedness. Agents/Diseases

ADDITIONAL NOTES FROM FEEDBACK I. PHARMACISTS IN EMERGENCY MEDICINE • Emergency medicine is an interdisciplinary area that covers medical care in an emergency room, trauma center and intensive care unit. It also provides prehospital emergency medical service and disaster medicine. • Basic life support and first-aid ability are mandatory to all the medical professionals who take care of patients. A. ROLES OF PHARMACIST • Pharmacists are expected to play major roles as a member of the emergency medical team. o Administration guidance o Analysis of intoxicating substance o Formulary management o Identification of a tablet o Inventory management o Medication delivery o Therapeutic drug monitoring B. EMERGENCY PREPAREDNESS GENERAL PRINCIPLES •

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• •

Pharmacists should have a key role in the planning and execution of o Pharmaceutical distribution and control o Drug therapy management of patients The expertise of the pharmacist should be sought in o Developing guidelines for the diagnosis and treatment of casualties and exposed individuals, o Selecting pharmaceuticals and related supplies for national and regional stockpiles and local emergency inventories in emergencypreparedness programs o Ensuring proper packaging, storage, handling, labeling, and dispensing of emergency supplies of pharmaceuticals o Ensuring appropriate deployment of emergency supplies of pharmaceuticals o Ensuring appropriate education and counseling of individuals who receive pharmaceuticals from an emergency supply in response to a disaster Pharmacists should be in a position to advise public health officials on appropriate messages to convey to the public In the event of a disaster, pharmacists should be called on to collaborate with physicians and other prescribers in managing the drug therapy of individual victims.

II. PHARMACISTS AND ANTIBIOTICS A. LEADING CAUSES OF NOSOCOMIAL INFECTIONS • The ESKAPE pathogens are the leading cause of nosocomial infections throughout the world. o Enterococcus faecium o Staphylococcus aureus o Klebsiella pneumoniae o Acinetobacter baumannii o Pseudomonas aeruginosa o Enterobacter species B. CDC CORE ELEMENTS OF HOSPITAL ANTIBIOTIC STEWARDSHIP PROGRAM

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Leadership Commitment: Dedicating necessary human, financial and information technology resources

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Accountability: Appointing a single leader responsible for program outcomes.

• • • • • •

Anthrax (Bacillus anthracis)

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result in moderate morbidity rates and low mortality rates

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Brucellosis (Brucella species)

Botulism (Clostridium botulinum toxin) Plague (Yersinia pestis) Smallpox (variola major) Tularemia (Francisella tularensis)

Viral hemorrhagic fevers, including o Filoviruses (Ebola, Marburg) o Arenaviruses (Lassa, Machupo) Category B Second highest priority agents include those that • are moderately easy to disseminate; require specific enhancements of CDC’s diagnostic capacity and enhanced disease surveillance. Agents/Diseases

• • • • • • • •

Epsilon toxin of Clostridium perfringens Food safety threats (Salmonella species, Escherichia coli O157:H7, Shigella) Glanders (Burkholderia mallei) Melioidosis (Burkholderia pseudomallei) Psittacosis (Chlamydia psittaci) Q fever (Coxiella burnetii) Ricin toxin from Ricinus communis (castor beans) Staphylococcal enterotoxin B Typhus fever (Rickettsia prowazekii)

Viral encephalitis (alphaviruses, such as eastern equine encephalitis, Venezuelan equine encephalitis, and western equine encephalitis]) • Water safety threats (Vibrio cholerae, Cryptosporidium parvum) Category C Third highest priority agents include emerging pathogens that could be engineered for mass dissemination in the future because of • availability

• •

ease of production and dissemination potential for high morbidity and mortality rates and major health impact.

Agents

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Emerging infectious diseases such as Nipah virus and hantavirus

QUALI/QUANTI PRACTICE PROBLEMS Determine the amount of NaOH (MW: 40) pellets that should be weighed to prepare 0.25 L of a 0.05 M solution. A 25 gram sample of NaHCO3 consumed 15.00 mL of 1 N Sulfuric Acid VS. Determine the

Molarity =

weight MW Liter

weight 40 0.255L Answer: 0.5 grams or 500 mg 2NaHCO3 + H2S04 à Na2SO4 + 2H2O + 2CO2 0.05 =

N*V*

MW (f ∗ 1000)...