Fungal infections + antifungal chemotherapy

Question 1

What are dermatophytes and examples?

Answer 1

fungi that can cause superficial infection of skin, hair and nails such as Trichophyton, Microsporum and Epidermophyton`

Question 2

How do Tinea and ringworm survive?

Answer 2

by spreading from host to host, can be zoophilic or anthrophilic

Question 3

What is Tinea Pedis and its risk factors and symptoms?

Answer 3

Athletes foot, fungal infection between the toes, risk factors include damp feet, tight shoes with poor ventilation and being barefoot in communal areas. Symptoms include itching, flaking, maceration, splitting and fissure, burning, inflammation and pain

Question 4

What is candida and what is the most prevalent form?

Answer 4

A type of yeast, most common cause of superficial skin infection and candida Albicans which causes thrush is the most prevalent. Thrush is characterised by creamy white plaques/ discharge, itchiness and swelling may also present

Question 5

What is systemic candidiasis?

Answer 5

when candida affects multiple organs, can cause eye infections, CNS infection (meningitis), pneumonia, UTIs and endocarditis

Question 6

Describe candida transmission

Answer 6

can be exogenous or endogenous

Question 7

What treatment was first available for fungal infections?

Answer 7

active azoles and amphotericin B

Question 8

What are the treatment options for tinea?

Answer 8

OTC creams, sprays or powders, azoles which suppress growth and allylamines such as terbinafine which are fungicidal. Other options are: Zinc undecylenate/undecylenic acid or Tolnaftate 1%

Question 9

What are the treatment options for nail infections?

Answer 9

2 OTC topical agents specifically for infected nails are: Urea 40% (canespro) amd Amorolfine 5% (Curanail)

Question 10

When should you refer a patient with a nail infection to GP?

Answer 10

when they come with more than 2 infected nails

Question 11

What are the treatment options for oral candida?

Answer 11

Oral Miconazole gel (Daktarin) for a week

Question 12

What are the treatment options for vaginal thrush?

Answer 12

intravaginal Clotrimazole cream or pessary & women aged 16-60 can be given single dose 150mg Fluconazole capsule

Question 13

What patient counselling should a pharmacist give on self-care to prevent fungal infections?

Answer 13

washing and drying clothes thoroughly, avoid sharing towels, wash clothes and towels frequently, wear loose fitting clothes, cotton socks, keep feet cool, avoid scratching

Question 14

What is a pharmacists’ role in anti-fungal stewardship?

Answer 14

prescription review, de-escalating when appropriate, optimising drug therapy, monitoring and restoring immune response

Question 15

What types of antifungal treatments are there?

Answer 15

7, Polyene antifungals, Imidazole antifungals, Triazole antifungal, Allylamines –terbinafine, Echinocandin antifungals, Antimetabolite antifungals & Griseofulvin

Question 16

Give 3 serious fungal diseases

Answer 16

Blastomycosis: affects lungs of healthy patient, Pneumocystis pneumonia: important in AIDS patients, treat with co-trimoxazole and anti-leishmaniasis & Cryptococcosis or Crytococcal meningitis: big cause of death in AIDS patients

Question 17

How do fungal diseases occur?

Answer 17

colonisation occurs when spores of fungus are inhaled, aspergillius spores ubiquitous in air and affects the lungs

Question 18

Describe the structure of fungi

Answer 18

unicellular eurkaryotes, no cell walls, cell membranes contain ergosterol instead of cholesterol, GPI, glucan, chitin

Question 19

What are polyene antifungals, some examples and their MoA?

Answer 19

antifungals with hydrophobic part inside membrane and hydrophilic outside membrane, eg Amphotericin B which is a natural product from Streptomyces nodosus (soil bacterium) which binds to ergosterol in fungal cell membrane and amphotericin- ergosterol complex form pores in membrane causing leakage, Structure of polyene antifungals: multiple chiral centres made of units of acetate with alternating oxygen pattern

Question 20

What is Amphotericin B used to treat?

Answer 20

Oral infections by local application, used IV to treat systemic fungal infections. Toxic to kidneys

Question 21

What is Nystatin and how does it work?

Answer 21

Closely related polyene, from strains of Streptomyces Noursei, binds to ergosterol used to treat candida Albicans infections of skin, available as creams and ointments

Question 22

Cholesterol and ergosterol are both derived from what?

Answer 22

squalene, differ by a couple of extra bonds and a methyl group

Question 23

What is Terbinafine and how does it work?

Answer 23

hydrophobic drug which inhibits squalene epoxidase, a rate-limiting in ergosterol synthesis, used topically or orally for skin infections

Question 24

What is the purpose of cytochrome p450 14 α demethylase?

Answer 24

enzyme that catalyses a reaction most susceptible to attack in the conversion of squalene to ergosterol

Question 25

What are some examples of azole antifungals and how do they work?

Answer 25

3 IMIDAZOLES: ketoconazole, Miconazole, ticonazole, 4 TRIAZOLES: fluconazole, itraconazole, voriconazolem posaconazole, they all inhibit CYP450 14 α- demethylase

Question 26

Why can’t azoles and polyenes be given together?

Answer 26

polyenes rely on sterol binding in order to function

Question 27

How do echinocandin antifungals work?

Answer 27

Target 1,3 – β glucan synthesis. Β glucans are carbohydrate polymers that provide cross-links to other cell wall components, similar to peptidoglycan. Example: Caspofungin, Anidulafungin and micafungin

Question 28

How do antimetabolite antifungals work giving some examples?

Answer 28

5-Fluorocytosine acts as an inhibitor of both DNA and RNA synthesis via the intracytoplasmic conversion of 5-fluorocytosine to 5-fluorouracil. Mainly used in combo with Amphotericin B

Question 29

What is the MoA of Griseofulvin?

Answer 29

interferes with microtubule assembly, produced from strains of penicillium fungi, orally used to treat skin infections, doesn’t inhibit candida