Antimicrobial Therapies 3 (Antimycobacterials / Antifungals ) Flashcards
ANTIMYCOBACTERIAL
DRUGS
A LITTLE BACKGROUND
• Mycobacteria are rod-shaped aerobic bacteria that grow slowly—their cell walls contain mycolic acids
• These pathogens produce lipophilic cell walls that stain poorly with a Gram stain—once stained, these bacilli do not lose color when made acidic—thus the name Acid Fast Bacilli
• These infections cause slow-growing granulomatous lesions—and can occur anywhere in the body
BEFORE WE BEGIN….
• Mycobacterium tuberculosis can cause latent TB infection and active TB
• M. tuberculosis is leading infectious cause of death worldwide— ¼ of the world’s
population is infected with TB
• There is increasing occurrence of
nontubercular Mycobacterium—M. avium-
intracellulare, M. chelonae, M. abscessus, M.
kansasii, M. fortuitum
• M. leprae causes leprosy
ANTIMYCOBACTERIAL
DRUGS
DRUGS IN THE FAMILY….
Ethambutol
Isoniazid [INH]—prototype drug
Pyrazinamide
Rifabutin
Rifampin
Rifapentine
SECOND LINE DRUGS FOR TB
Aminosalicylic acid
Bedaquiline
Capreomycin
Cycloserine
Ethionamide
Aminoglycosides/Fluroquinolones/Macrolides
CHEMOTHERAPY
FOR
TUBERCULOSIS
M. tuberculosis is slow growing and
requires treatment for months – years
LTBI can be treated for 9 months with
INH or 12 once a week higher doses of
INH + Rifapentine
Active TB has to be treated with several
drugs for several months
Multi-drug resistant TB is typically
treated for 2 years
EXTREMELY DRUG
RESISTANT [XDR]
TUBERCULOSIS
This is a bacilli that is resistant to INH and
Rifampin and is resistant to any
fluoroquinolone and at least 1 of 3 injectable
2nd line agents—Amikacin, Kanamycin or
Capreomycin
Resistance in M. tuberculosis, when it is treated with one drug—so multiple drug therapy is used to suppress resistant strains
1st line agents—INH, Rifampin, Ethambutol and Pyrazinamide are the DOC and highly efficacious with tolerable SE profiles
Rifabutin or Rifapentine can replace Rifampin in certain scenarios
Active disease ALWAYS requires multiple drugs—3 or more with proven in vitro activity against the isolate
Clinical improvement occurs quickly—
weeks, but therapy is continued much
longer to kill persistent organisms and
prevent relapse
Standard therapy is INH, Rifampin,
Ethambutol and Pyrazinamide for 8
weeks, then INH and Rifampin for 16
more weeks
HOW DO WE DEAL
WITH DRUG
RESISTANCE??
• After susceptibility info is available, the regimen can be tailored to the individual
• 2nd line therapy for MDR-TB—disease resistant to INH and Rifampin—is treated with an aminoglycoside [Streptomycin, Kanamycin or Amikacin] or Capreomycin [all of these are injectables], a quinolone [Levofloxacin or Moxifloxacin], Ethambutol and Pyrazinamide [if sensitive to these] and one or more of these—Cycloserine, Ethionamide or PAS
For XDR-TB—Clofazimine and Linezolid
may be used
Patient adherence can be low with drug-
resistant disease as the therapy lasts more
than 6 months—DOT therapy is one
successful strategy to ensure completion
ISONIAZID
MOA
• Prodrug—activated by mycobacterial catalase peroxidase [KatG]
• Target enzymes that are essential for the synthesis of mycolic acid
• Inhibiting this acid leads to destruction of the tubercular cell wall
Antibacterial Spectrum
• Specific to M. tuberculosis
• M. kansasii may be susceptible at higher drug dosages
• Most nontubercular Mycobacteria are resistant to INH
• Drug works well on rapidly growing bacilli and intracellular organisms
Resistance
• Resistance follows chromosomal mutations
incapable of prodrug activation
• Acyl carrier mutated proteins
• Over expression of the target enzyme InhA
• Cross resistance can occur between INH and Ethionamide
Pharmacokinetics
• Readily absorbed after oral dose
• Food impairs absorption—especially high fat foods
• Drug diffuses into all body fluids, cell and caseous materials [necrotic tissue that looks lie cheese produced in the tubercular lesions]
• Drug levels in CSF is the same as in the serum
• INH undergoes N-acetylation and hydrolysis
• INH acetylation is genetically regulated, with fast acetylators having a 90” serum ½ life, while slow acetylators have a 3-4° serum ½ life
• Excretion is from glomerular filtration and secretion as metabolites
• Slow acetylators excrete more of the parent compound
ADEs
• Hepatitis
• If hepatitis is not recognized and INH is continued, death can be the result
• Chance of hepatitis increases with age, in those who are also on Rifampin and in those who drink ETOH daily
• Peripheral neuropathy—paresthesias of hands and feet—due to a relative Pyridoxine deficiency—daily supplementation with B6 is mandatory
• Convulsions—in those prone to seizures
• Rash and fever signal hypersensitivity
• INH inhibits breakdown of Carbamazepine and Phenytoin—so SE of these drugs of these can be amplified
RIFAMYCINS—
RIFAMPIN,
RIFABUTIN,
RIFAPENTINE
Group of similar macrocyclic antibiotics that are considered 1st line for TB
Rifampin has broader coverage
than does INH and can be used
for several bacterial infections
Resistant strains can occur
rapidly—so it is never given as
monotherapy for TB
MOA
• Blocks RNA transcription by interfering with the ß subunit of mycobacterial DNA-
dependent RNA polymerase
Antimicrobial Spectrum
• Bactericidal for intracellular and
extracellular mycobacteria, including M. tuberculosis, M. kansasii and M. avium complex [MAC]
• Effective for many Gram + and Gram –
pathogens and is used to prevent meningitis in those exposed to Meningococci or H. influenzae
• Highly active against M. leprae
Resistance
• Caused by mutations in affinity for the bacterial DNA-dependent RNA polymerase gene for the drug
Pharmacokinetics
• Absorption is adequate after oral dose
• Distribution occurs in all body fluids and organs
• Concentrations attained in the CSF are variable—10 to 20 percent of blood
concentrations
• Taken up by the liver and undergoes enterohepatic recycling
• Can induce liver CYP 450 enzymes and transporters—causing many drug interactions
• Rifampin undergoes autoinduction—causing shortened elimination ½ life over the 1st 2 weeks of dosing
• Elimination of the drug and its metabolites is via the bile and feces—a small amount
is excreted in the urine
• Urine/feces/other secretions will become orange-red in color; contact lens will be
stained
ADEs
• Nausea
• Vomiting
• Rash
• Hepatitis and death from liver failure [rare]
• Use cautiously in alcoholics, older patients and in those with chronic liver disease
• Modest increase in chance of liver
dysfunction when given with INH and Pyrazinamide
• When dosed intermittently at high dose, flu-like syndrome can occur—fever, chills, muscle aches that can progress to ARF, hemolytic anemia and shock
Drug Interactions
• Induces phase I CYP 450 enzymes and phase II enzymes—it can decrease the ½ life of co-administered drugs that are
metabolized by these enzymes
• HIV PIs
• Methadone
• OCP
• Prednisone
• Propranolol
• Quinidine
• Sulfonylureas
• Voriconazole
• Warfarin
This decreased ½ life may mean increasing the dose of the other drug, switch to a drug not affected by Rifampin or change Rifampin to Rifabutin
RIFABUTIN
Derivative of Rifampin—preferred to
treat TB in those that are HIV + on PIs
or several NNRTIs
It is less potent inducer of CYP 450
enzymes, thus less drug interactions
ADEs similar to Rifampin, but can also
cause uveitis, hyperpigmentation and
neutropenia
RIFAPENTINE
Has a longer ½ life than Rifampin
With INH, can be used weekly in those with LTBI and in selected HIV negative patients
with minimal pulmonary TB
PYRAZINAMIDE
Synthetic, oral agent used short-term
with INH, Rifampin and Ethambutol
MOA is unknown
Must be hydrolyzed by pyrazinamidase to pyrazinoic acid
Active against TB in acidic lesions and in macrophages
Distributes throughout body, penetrates
CSF
Can contribute to liver dysfunction
Causes uric acid retention [but gout
uncommon]
Most benefit occurs early in treatment—
so agent is only used 8 weeks in a 24
week regimen
ETHAMBUTOL
• Bacteriostatic and first line for mycobacteria
• Inhibits arabinosyl transferase—an enzyme important for the synthesis of mycobacterial cell wall
• Used with INH, Pyrazinamide and Rifampin pending cultures and susceptibility
• Distributes well throughout body, but CSF penetration is variable—question if it is adequate for TB meningitis
• Parent drug and metabolites are excreted in the urine
• ADEs—optic neuritis—which affects vision and ability to see red and green
• Risk increases with higher doses and in those with CKD
• Visual acuity and color discrimination should be checked before prescribing and periodically during therapy
• Uric acid excretion is decreased—caution in those with a history of gout
ALTERNATIVE SECOND LINE DRUGS
Streptomycin
• Aminoglycoside
• One of 1st TB drugs
• Action greatest for extracellular organisms
• If isolate is resistant to Streptomycin—can
be treated with Kanamycin or Amikacin [bacilli remain sensitive to these agents]
Para-Aminosalicylic Acid
• Works by folic acid inhibition
• Largely replaced by Ethambutol, but remains important part of many MDR-TB
regimens
Capreomycin
• Parenterally administered polypeptide that
inhibits protein synthesis very much like aminoglycosides
• Reserved to treat MDR-TB
• Careful monitoring of renal function and
hearing is needed
Cycloserine
• Oral TB drug that disrupts D-alanine incorporation into bacterial cell wall
• Distributes well throughout body fluids and CSF
• Excreted unchanged in the urine
• Accumulation in those with CKD
• ADEs—CNS disturbances [lethargy, difficulty concentrating, anxiety, SI] and
seizures have been seen
Ethionamide
• Structural analog of INH—disrupts mycolic acid synthesis
• MOA is not identical to INH, but some overlap in resistance patterns
• Widely distributed throughout the body and CSF
• Metabolism is in the liver to active and inactive metabolites
• ADEs limit its use—nausea, vomiting, hepatoxicity, hypothyroidism, gynecomastia,
alopecia, impotence and CNS have been reported
Fluoroquinolones
• Moxifloxacin and levofloxacin have a role
in MDR-TB
• Some NTM are also susceptible
Macrolides
• Azithromycin and Clarithromycin are used in regimens for several NTM—including MAC
• Azithromycin may be preferred for those at risk for drug interactions as Clarithromycin is both a substrate and an inhibitor of CP 450 enzymes
Bedaquiline
• ATP synthase inhibitor
• Approved to treat MDR-TB
• Given orally
• Active against many types of mycobacteria
• BB warning for QTc prolongation, monitoring of EKG is necessary
• Elevated LFTs has been seen, so these
must be monitored
• Metabolized by CYP 450 3A4
• Administration with strong CYP 450
3A4 inducers [such as Rifampin] should
be avoided
DRUGS FOR LEPROSY
• Skin infection with M. leprae
• Uncommon in US—but still a major problem world wide
DAPSONE
• Structurally related to sulfonamides; inhibits dihydropteroate synthase in the folate synthesis pathway
• Bacteriostatic for M. leprae; some resistant strains can be seen
• Also used to treat pneumonia from Pneumocystis jirovecii in the
immunosuppressed
• Well absorbed from the GI tract
• Distributed throughout the body, with high concentrations in the skin
• Hepatic acetylation
• Parent drug and metabolites are eliminated in the urine
• ADEs—hemolysis, methemoglobulinemia [highest risk in those with G6PD deficiency] and peripheral neuropathy
CLOFAZIMINE
• Phenazine dye
• MOA involves binding to DNA; its redox
properties causes formation of cytotoxic O2
radicals that are toxic to the bacilli
• Bactericidal
• Potentially useful to treat M. tuberculosis and NTM
• Recommended by WHO as part of a shorter
regimen [9-12 months] for MDR-TB
• Given orally; accumulates in the tissues, allowing intermittent therapy—does not enter the CNS
• Pink to brownish-black discoloration of the skin occurs—tell patient in advance
• Eosinophilic enteritis [requiring surgery] has occurred
• Has anti-inflammatory and anti-immune properties
• Erythema nodosum may not develop in patients on this drug
ANTIFUNGAL
DRUGS
OVERVIEW
• Infections from fungus are called mycoses
• May involve the skin only—cutaneous mycoses extending into the epidermis or may be subcutaneous or systemic
• Fungi have rigid cell walls composed of chitin rather than peptidoglycan [what is seen in bacteria]
• Fungal cell membrane contains ergosterol rather than cholesterol
• Fungi are generally resistant to antibiotics, and bacteria are resistant to antifungal agents
• Incidence of candidemia has been on the rise in the last decade—this is thought to be related to the increased number of patients with chronic immunosuppression—organ transplant patients, chemotherapy, biologics to treat autoimmune and/or HIV infection
ORGANISMS IN THE KINGDOM OF FUNGI…
• Newest bad actor—Candida auris
• Candida has 20 different species—it is a yeast that is considered part of our normal flora—overgrowth occurs in diabetics, those on long-term antibiotics and in those that are immunosuppressed
• Candidiasis is treated with polyenes, azoles, nucleoside analogs, echinocandins and allylamines—depending on infection site and
severity
• Echinocandins are preferred for invasive Candidiasis, candidemia and esophageal candidiasis
First isolated in 2009, this yeast is hard to
identify and difficult to treat
It affects all ages—especially those who have had long hospitalizations, been in an ICU, been in a NH, received indwelling medical devices or surgery, been on long term antibiotic therapy or TPN
MDR-C. auris is related to preventative use of antifungal drugs
90% of C. auris is resistant to Fluconazole, 30% is resistant to Amphotericin B and 5% are resistant to echinocandins
In 2019, in neonates 2 months and younger, the DOC is Amphotericin B deoxycholate
2nd line is liposomal Amphotericin B
If treatment fails, and no CNS
involvement has been identified, the
echinocandins can be considered
For adults and children older than 2 months, echinocandins are the DOC
AMPHOTERICIN B
MOA
• Naturally occurring polyene antifungal
produced from Streptomyces nodosus
• DOC for several life-threatening mycoses
• Binds to ergosterol in the plasma of the
fungus—it forms pores that require
hydrophobic interactions between the
lipophilic segment of the polyene antifungal and the sterol—the pores disrupt the membrane function and call cell death
Antifungal Spectrum
• Ether fungicidal or fungistatic—depending on the organism and concentration given
• Covers C. albicans, Histoplasma capsulatum, Cryptococcus neoformans,
Coccidioides immitis, Blastomyces
dermatitidis and many strains of Aspergillus
• Can be used to treat Leishmaniasis
Resistance
• Infrequent, but is from decreased ergosterol content of the fungal membrane
Pharmacokinetics
• Given slow IV infusion
• Insoluble in water and must be co-formulated with Na+ deoxycholate or artificial lipids to form liposomes [the liposomal preps are associated with less renal and infusion toxicities, but are more expensive]
• Extensively bound to plasma proteins and is distributed throughout the body
• Inflammation favors penetration into body fluids, but little is found in CSF, vitreous humor, peritoneal or synovial fluid
• Low levels of drug and its metabolites are excreted mainly in the urine over a long period
• The drug has a LOW therapeutic index
ADEs
Fever and Chills
• Occur 1-3 hours after IV infusion started; less with repeated infusions
• Premedication with APAP or a low dose of a
steroid helps to prevent
Renal Impairment
• Even though only a small amount is excreted in the urine, patients can have a decrease in their GFR and decrease in their renal tubular functioning
• Renal function usually returns to baseline
when drug is stopped, but residual damage can persist if high doses were needed
• Azotemia is made worse if patient is on other nephrotoxic drugs—aminoglycosides,
Cyclosporine, Vancomycin—good hydration can reduce azotemia
• Loading patient with NS infusion before
Amphotericin dose or use of the liposomal
Amphotericin B minimizes risk of renal damage
Hypotension
• Shock-like fall in BP accompanied by low K+ can occur—potassium supplement is
required
• Be careful in those on Digoxin and other agents that can cause K+ fluctuations
Thrombophlebitis
• Adding heparin to the infusion prevents this ADE
ANTIMETABOLITE
ANTIFUNGALS
• Flucytosine [5FC] Ancobon
• Synthetic pyrimidine
antimetabolite
• Used with other antifungals
MOA
• Enters fungal cell through cytosine specific
permease; it is converted to a series of
compounds that disrupt nucleic acid and protein synthesis
• Amphotericin B increases cell permeability, allowing more 5FC to penetrate the leading to synergistic benefits
Antifungal Spectrum
• Fungistatic
• Effective with Itraconazole to treat
Chromoblastomycosis
• Used with Amphotericin B to treat systemic
mycosis and meningitis from C. neoformans and C. albicans
• Can be used for CandidaUTIs when fluconazole is not appropriate [resistance can occur with repeated courses]
Resistance
• May occur from decreased levels of
enzymes in the conversion of 5-FC to
5-FU and other metabolites
• Resistance is less with a combination
of %-FC + a 2ndantifungal agent
• Not used as a single agent
Pharmacokinetics
• Well absorbed after oral dose
• Distributes throughout body water and penetrates well into CSF
• 5 –FU is detectable in patient and is likely the result of the metabolism of 5-FC by intestinal bacteria
• Excretion of parent drug and metabolites is via glomerular filtration—dose must be reduced in those with renal disease
ADEs
• Reversible neutropenia
• Thrombocytopenia
• Dose related bone marrow depression
• Reversible hepatic dysfunction and
elevated LFTs has been seen
• Nausea
• Vomiting
• Diarrhea
• Severe endocarditis has been reported
AZOLE
ANTIFUNGALS
Fluconazole [Diflucan]—prototype drug
Itraconazole [Sporanox]
Posaconazole [Noxafil]
Voriconazole [Vfend]
Isavuconazole [Cresemba]
Azoles are made up of 2 different classes of drugs—the Imidazoles and the Triazoles
They have similar MOA and spectra, but the
pharmacokinetics and therapeutic uses vary
In general—the Imidazoles are used topical for cutaneous infections while the Triazoles are given systemically for treatment or prevention of cutaneous and systemic mycoses
Most of the Imidazoles are discussed under
dermatologic drugs
MOA
• Fungistatic
• Inhibit 14-a demethylase and block
demethylation of lanosterol to ergosterol
• Inhibiting ergosterol biosynthesis disrupts fungal membrane structure and function
Resistance
• Is becoming common, especially when prolonged therapy is needed in
immunosuppressed patients
• Mechanism of resistance—mutations in 14-a demethylase gene that leads to decreased azole binding and efficacy
• Some fungi develop efflux pumps that pump the drug out of the cell or have
reduced ergosterol in the cell wall
Drug Interactions
• All azoles inhibit CYP 450 3A4 to some degree
• Patients on other meds that are substrates for this isoenzyme can have increased concentrations and toxicity
• Itraconazole, Voriconazole are metabolized by CYP 450 3A4 and other CYP 450 isoenzymes—so, concomitant use of potent CYP 450 inhibitors [Ritonavir] and inducers [Rifampin, Phenytoin] can lead to increased ADEs or clinical failure of the these [2] azoles
Contraindications
• All oral azoles are teratogenic
• Avoid in pregnancy unless the potential
benefit outweighs the risk
FLUCONAZOLE
1st triazole antifungal—Diflucan
It is the least active of all triazoles—spectrum
limited to yeast and some dimorphic fungi
No role in treating Aspergillus or Zygomycosis
Very active against Cryptococcus neoformans, C. albicans and C. parapsilosis
Resistance is a concern with C. krusei and C.
glabrata
Used to prevent invasive fungal infections in BMT patients DOC for Cryptococcus neoformans after induction therapy with Amphotericin B and Flucytosine, and is
used for treatment of Candidemia and
Coccidioidomycosis
Effective against most forms of mucocutaneous Candidiasis
Can be used as single dose treatment for
vulvovaginitis
Available oral and IV
Absorbed well after oral dose
Distributes widely to body fluids and tissues
Majority of the drug is excreted unchanged via the urine
Doses must be reduced in those with renal disease
ADEs—nausea, vomiting, headache and skin
rashes
ITRACONAZOLE
Synthetic triazole with broad antifungal
spectrum compared to Fluconazole
DOC in Blastomycosis, Sporotrichosis,
Paracoccidioidomycosis, Histoplasmosis
Rarely used for Candida or Aspergillus—
because of more effective agents
Available as capsules, tablets and solution
Sporanox distributes well in tissues—including bone and adipose
Extensively metabolized by the liver; drug and its metabolized are excreted in the urine and feces
ADEs—nausea, vomiting, rash, low K+, HTN,
edema, headache; liver toxicity can occur when given with other liver toxic drugs
It is a negative inotropic effect—avoid in those with ventricular dysfunction or HF
POSACONAZOLE
• Synthetic triazole—broad spectrum antifungal similar to Itraconazole
• Noxafil comes in oral suspension, tablets or IV
• Used for treating and prevention of invasive Candida and Aspergillus in the
immunocompromised
• Used in invasive fungal infections from
Scedosporium and Zygomycetes
• Low bioavailability and should be given with food
Not metabolized by CYP 450—eliminated by
glucuronidation
Drugs that increase gastric pH [PPIs] can
decrease the absorption of oral Posaconazole, and should be avoided
Due to potent inhibition of CYP 450 3A4,
concomitant used of Ergots, Atorvastatin,
Citalopram and Risperidone are contraindicated
VORICONAZOLE
Synthetic triazole related to Fluconazole—broad spectrum antifungal available orally and IV
Has replaced Amphotericin B as the DOC for
invasive Aspergillus
Approved to treat invasive candidiasis, as well as Scedosporium and Fusarium
High oral bioavailability and penetrates into
tissues well
Extensively metabolized by CYP 450 2C19, 2C9, 3A4 and metabolites are excreted in the urine
Inhibitors and inducers of these isoenzymes can affect levels of Vfend—causing toxicity or clinical failure
This drug displays non-linear kinetics—which can be affected by drug interactions and pharmacogenetic variability—CYP 450 2C19
polymorphisms
High trough levels are associated with visual and auditory hallucinations and an increased risk of liver damage
It is also an inhibitor of CYP 450 2C19, 2C( and 3A4—drugs that are substrates of these isoenzymes are impacted by this drug
Contraindicated with Rifampin, Rifabutin, Carbamazepine and St. John’s wort
ISAVUCONAZOLE
• Cresemba is broad spectrum antifungal which is supplied as the prodrug
Isavuconazonium in oral and IV forms
• The prodrug is rapidly hydrolyzed by esterases in the blood to Isavuconazole
• Coverage similar to Voriconazole—approved for invasive Aspergillus and invasive mucormycosis
• High bioavailability after oral dose; distributes well into the tissues
• Metabolized by CYP 450 3A4/5 and uridine diphosphate-glucoronosyltransfereases
• Co-administration with other potent CYP 450 3A4 inhibitors and inducers is
contraindication
Cresemba is also an inhibitor of CYP
450 3A4 isoenzyme, thus increasing
the concentration of drugs that are
substrates of CYP 450 3A4
ADEs—nausea, vomiting, diarrhea,
hypokalemia
THE ECHINOCANDINS
• Capsofungin—Cancidas
• Micafungin—Mycamine
• Anidulafungin—Eraxis
• These drugs interfere with the synthesis of the fungal cell wall and inhibit the synthesis of ß [1,3] D-glucan, leading to lysis and cell death
• All of these agents are given IV once daily
Micafungin is the only agent that does not require a loading dose
Potent against Aspergillus and most Candida ssp.—including those resistance to azoles
Minimal activity against other fungi
ADEs—fever, rash, nausea, phlebitis
Must be given by slow IV infusion to prevent a histamine induced flushing seen with rapid infusion
CAPSOFUNGIN
• Cancidas—prototype drug
• 1st line for those with invasive Candida—
including candidemia
• 2nd line for invasive Aspergillosis in those who have failed or cannot take Amphotericin B or an azole
• Co-administration with CYP 450 enzyme
inducers [Rifampin] mandates an increase in
Capsofungin dose
• Should not be given with Cyclosporine—due to
elevation of LFTs
MICAFUNGIN
AND
ANIDULAFUNGIN
1st line options for invasive Candidiasis,
including candidemia
Micafungin is also indicated for prevention of invasive Candidainfections in those undergoing stem cell transplants
These drugs are not substrates for CYP
450 enzymes and not have any associated drug interactions
DRUGS FOR CUTANEOUS MYCOTIC INFECTIONS
• Mold-like fungi that cause cutaneous
infections are called dermatophytes—or
tinea
• Tinea is classified by the part of the body
affected
• 3 fungi cause the majority of these
infections—Trichophyton, Microsporum
and Epidermophyton
Squalene Epoxidase
Inhibitors
• Act by inhibiting squalene epoxidase; blocking the biosynthesis of ergosterol, essential part of the fungus cell wall
• Terbinafine [Lamisil]
Griseofulvin
• Disrupts mitotic spindle and inhibits fungal mitosis
Nystatin
• Polyene antifungal and its MOA is similar to
Amphotericin B
Imidazoles
• Butoconazole
[Gynazole]
• Clotrimazole [Desenex;
Lotrim AF]
• Econazole [Spectazole]
• Ketoconazole [Nizoral]
• Miconazole [Zeasorb]
• Oxiconazole [Oxistat]
• Sertaconazole [Ertaczo]
• Sulconazole [Exelderm]
• Terconazole [Terazol]
• Tioconazole [Monistat]
Tolnaftate
• Topical thiocarbamate that distorts hyphae
and stunts mycelial growth in susceptible fungi
• Tinactin
Efinaconazole
• Topical triazole antifungal used to treat onychomycosis of toenails from
Trichophyton rubrum and Trichophyton
mentagrophytes
• Requires 48 weeks of therapy
• Effective against Candida albicans
• Jublia
Ciclopirox
• Pyridine antimycotic, inhibits the transport
of essential parts of the fungal cell, and
interferes with DNA/RNA and proteins
• Effective against Epidermophyton,
Microsporum, Candida ssp. and Malassezia
• The shampoo can be used for seborrheic
dermatitis
• Comes in cream, gel, suspension and nail
lacquer
• Loprox / PenLac
Tavaborole
• Inhibits aminoacyl-transfer ribonucleic acid synthetase, preventing fungal protein
synthesis
• Active against Trichophyton rubrum, Trichophyton mentagrophytes and Candida
albicans
• Topical solution to treat toenail fungus—48 weeks of treatment required
• Kerydin
