Week 4: Anti-Microbials Flashcards
Describe selective toxicity
ability of a drug to injure a target cell or target organism without injuring other cells or organisms in contact with the target
Selective toxicity is achieved by targeting _____________________
differences in cellular chemistry of microbes and mammals
Antimicrobials include __________, __________ and __________ drugs.
Antibacterial
Antifungal
Antiviral
What are some of the mechanisms of action employed by antimicrobials?
Inhibitors of cell wall synthesis: Penicillins, Cephalosporins, Imipenem, Vancomycin, Caspofungin
Drugs that disrupt the cell membrane
Inhibitors of protein synthesis
Drugs that interfere with DNA and RNA
Antimetabolites
Drugs that suppress viral replication
Describe the difference between bactericidal and bacteriostatic
bactericidal : directly lethal to bacterial
Bacteriostatic: slow bacteria growth but do not cause death – elimination of bacteria must ultimately be accomplished by immune system
There are two primary ways in which microbes can acquire drug resistance – what are they?
Spontaneous mutation – creates resistance to 1 drug
Conjugation – bacteria of different species can share DNA including R factors (resistance factors). R factors can be passed from normal flora to pathogens. Causes multiple drug resistances
What are some microbial mechanisms of drug resistance?
Reduction of drug concentration at site of action: cease active uptake of drugs or increase active transport
Alter structure of drug target molecules
Produce a drug antagonist
Cause drug inactivation. Ex. Bacteria produce enzymes that inactivate penicillin
True or false - there is no benefit to drug resistance unless drugs are present
True
Explain how antibiotics promote drug resistance.
Mutation and conjugation are random events. There is no benefit to drug resistance unless drugs are present. Antibiotics kill all but those that are resistant, remove the competition for resources and create selection pressure favoring overgrowth of resistant microbes
True or false - Broad spectrum kill more competing organisms than narrow spectrum and facilitate less antibiotic resistance
False
Broad spectrum kill more competing organisms than narrow spectrum and facilitate MORE antibiotic resistance
A secondary infection that develops during the course of treatment for a primary infection is called a ________
Superinfection
Goal of therapy is to provide maximal antimicrobial effects with minimal harm to host. What are some factors to consider in the selection of therapy?
the infecting organism
drug-sensitivity of the organism
host factors (1. Site of infection – difficult to get antibiotics across BBB, to abscesses, to heart vegetations. Also prosthetics cause phagocytes to focus on attacking them and make them less effective against pathogens. 2. host defenses – if immune system impaired the antibiotics may not be enough to save people ex. HIV, chemo)
In antimicrobial selection, what are factors that may require the use of second-line agents?
Allergy
inability of drug to penetrate site
heightened patient susceptibility to toxicity
Other considerations: age, pregnancy, breastfeeding
Typically it is preferable to use a single antimicrobial to avoid developing multidrug resistant microbes, what are some scenarios which multiple antimicrobials may be indicated for?
initial therapy of severe infection
mixed microbe infections
prevention of resistance in TB
decreasing doses to limit toxicity
synergistic responses
What are examples of situations where prophylactic antibiotics may be indicated?
Surgery: cardiac, peripheral vascular, orthopedic, GI, hysterectomy, emergency c-section, contaminated surgery (perforated abdominal organs, compound fractures, animal bites)
Bacterial endocarditis: patients with congenital or valvular heart disease are susceptible to bacterial endocarditis following dental procedures or anything that can release bacterial into the bloodstream
Neutropenia (controversial)
Women with recurrent UTI, exposure to STI organisms
What are some examples of misuse of antimicrobials?
Viral infections – patients get all the risks of the drugs and no benefits
Treatment of fever of unknown origin (exception: antibiotics indicated in severely immunocompromised patients with fever)
Treatment without identifying organism and testing sensitivity
Drugs that weaken the cell wall include ..
B-lactams (Penicillins and Cephalosporins)
Vancomycin
Telavancin
Fosfomycin
Penicillin drugs weaken the bacterial cell wall. What is the mechanism of action? Are they bactericidal or bacteriostatic?
Inhibition of transpeptidases – enzymes critical for cell wall synthesis – which disrupts synthesis of cell wall
Disinhibition (activation) of autolysins – bacterial enzymes that break down cell wall to permit growth – which actively destroys cell wall
Usually bactericidal
Penicillins bind to _____ on microbes.
Penicillin Binding Proteins (PBP) - which are only expressed during growth and division, therefore only active against bacterial under growth and division
How does bacterial resistance to penicillins occur?
Inability of penicillins to reach targets. Gram-negative bacteria have an additional outer membrane that some penicillins cannot penetrate
Inactivation of penicillins by bacterial enzymes – b-lactamases/penicillinases can be produced by bacteria to inactivate penicillins and other b-lactam drugs
Production of PBPs that have a low affinity for penicillins
Can you think of a famous example of a microbe that is resistant to penicillins?
MRSA – methicillin resistant staph. Aureus – resistant to all penicillins and most cephalosporins
Where is MRSA commonly found and what types of infections does it cause?
Often colonizes skin and nostrils of healthy people
Usually infects skin/soft tissues causing abscesses, boils, cellulitis and impetigo. Can cause fatal lung and bloodstream infections
How can we treat MRSA infections?
Healthcare associated HCA-MRSA usually treated with IV vancomycin, linezolid, daptomycin, telavancin, clindamycin, ceftaroline
Community associated CA-MRSA generally less dangerous than HCA. 20-30% of population is colonized. Causes many skin/soft tissue infections. Rarely causes necrotizing fasciitis, necrotizing pneumonia and severe sepsis. Usually treated with trimethoprim/sulfamethoxazole, minocyline, doxycycline, clindamycin.
True or false – Penicillins are broad-spectrum
False. Can be narrow or broad spectrum
Narrow spectrum penicillins, penicillinase sensitive: Penicillin G, Penicillin V
Narrow spectrum penicillins, penicillinase resistant (antistaphylococcal penicillins): Nafcillin, Oxacillin, Dicloxacillin
Broad-spectrum penicillins (aminopenicillins): Ampicillin, Amoxicillin
Extended-spectrum penicillin (antipseudomonal penicillin): Piperacillin
Penicillin G was the first penicillin. It is well distributed, undergoes minimal metabolism and is excreted by the kidneys mostly unchanged. Which pathogens are sensitive to Pen G?
Bactericidal to most gram-positive bacteria, gram-negative cocci, anaerobic bacteria and spirochetes
What is the primary adverse effect of Pen G?
The least toxic of all antibiotics and among the safest of all medications, allergic reactions are the principle concerns
True or false, penicillins are the most common drug allergy
True! Penicillins are the most common drug allergy. 0.4-7% of patients who receive penicillins experience an allergic reaction ranging from minor rash to anaphylaxis
Reactions can be immediate (2-30 minutes), accelerated (1-72 hours) or delayed (days to weeks)
Anaphylactic reactions are rare – incidence 0.004-0.04%, but they have a 10% mortality rate
True or false: patients can experience an allergic reaction to a penicillin even if they have never received a penicillin antibiotic
True! Prior exposure could occur from penicillins produced by fungi or present in foods of animal origin
True or false, patients allergic to one penicillin should not be considered allergic to all penicillins
False!
Patients allergic to one penicillin should be considered allergic to all penicillins. 1% display a cross-sensitivity to cephalosporins, more likely with a severe penicillin allergy
What is a difference between Pen G and Pen V?
Similar to pen G except is stable in stomach acid and can be used for oral therapy
Must be taken with food
What are the two broad spectrum Penicillins (Hint: they are Aminopenicillins)
Ampicillin: useful for enterococcus fecalis, proteus mirabilis, E. coli, salmonella, shigella and h.influenzae. More likely to cause rash and diarrhea than any other penicillin
Amoxicillin: similar to ampilicillin but more acid-stable, therefore preferred for oral therapy
Combination medications are available of Ampicillin/Sulbactam and Amoxicillin/Clavulanic acid. What is the benefit of these additives?
inhibitors of b-lactamases – decreasing inactivation and therefore resistance
There is one Extended-Spectrum Penicillin. It targets everything the aminopenicillins target and pseudomonas aerginosa, Enterobacter species, proteus species, bacterocides fragilis and many klebsiella species.
What is this drug? (Hint: we use it a lot in acute care in combination with a b-lactamase inhibitor)
Piperacillin/ Tazobactam
What do the drugs cephalosporins, vancomycin, telavancin and fosfomycin have in common with the penicillins ?
disrupt the bacterial cell wall and cause lysis and death
All are b-lactam drugs with the exceptions of vancomycin, telavancin and Fosfomycin
What is the most widely used group of antibiotics?
Cephalosporins
Outline the MOA of cephalosporins. (hint: similar to penicillins)
bind to PBPs - disrupt cell wall synthesis and activate autolysins causing death by lysis - Bactericidal
Most effective against cells undergoing active growth and division
What is the most common cause of resistance to cephalosporins?
Resistance most often caused by b-lactamases, sometimes referred to as cephalosporinases. 1st generation sensitive to b-lactamases, 2nd generation less sensitive, 3rd, 4th, and 5th generation highly resistant
Can also be caused by altered PBPs with low affinity for cephalosporins. Ex. MRSA resistant to most cephalosporins, except 5th generation Ceftaroline
True or False, cephalosporins are broad spectrum
True. 1st- 5th generation drugs, named in order of development
As progress from 1st to 5th there is increasing activity against gram-negative bacteria and anaerobes, increasing resistance to destruction by b-lactamases and increasing ability to reach CSF
Can you think of a few drug names in the cephalosporin family? (Hint, they all start with Cef-)
Listed by generation…
1st: Cefadroxil, Cefazolin, Cephalexin
2nd: Cefaclor, Cefotetan, Cefoxitin, Cefprozil, Cefuroxime
3rd: Cefdinir, Cefditoren, Cefixime, Cefotaxime, Cefpodoxime, Ceftazidime, Ceftibuten, Ceftriaxone,
4th: Cefepime, Ceftolozane
5th: Ceftaroline
True or false, Cephalosporins must be administered parenterally (IV or IM)
False. Many must be parenterally administered (IM or IV). 10 cephalosporins can be administered po, only one can be administered po or parenterally – cefuroxime
Outline the general pharmacokinetics of cephalosporins
Poor GI absorption
Distributes well to most tissues/body fluids except for ocular fluids. 1st and 2nd generation have low CSF penetration
Eliminated mostly by the kidneys. Reduce doses in renal insufficiency. Ceftriaxone is eliminated by the liver and does not require dose adjustment in renal insufficiency.
The primary adverse effect of cephalosporins is the same as penicillins, as they are all b-lactams. What is it?
Hypersensitivity reactions most common adverse reactions
Similar structure to penicillins, cross-sensitivity happens in 1% of patients allergic to penicillins. Safe for patients with mild penicillin allergies, unsafe for severe penicillin allergies
Well tolerated, one of safest groups of antimicrobials
All cephalosporins can promote c.diff infection
What are some drug interactions of note for cephalosporins?
Alcohol can dangerously interact with cefazolin and cefotetan
Cefotetan, cefazolin and ceftriaxone can promote bleeding as they contain a side chain that interferes with vit k metabolism and can inhibit the formation of clotting factors. Caution needed if given with other drugs that promote bleeding (anticoagulants, thrombolytics, NSAIDS, other anti-platelets) — INTERESTING – I often give ceftriaxone and anticoags and had no idea of this risk.
Penicillins, Cephalosporins and ________ are all b-lactam antibiotics
Carbapenems
Can you think of any carbapenems? (hint: they end in “-penems”)
Imipenem, meropenem, ertapenem, doripenem
Parenteral administration only
True or false, carbapenems are very broad spectrum, including coverage for MRSA
False – Carbapenems are very broad spectrum but none are active against MRSA
What is the MOA for carbapenems? (hint – same as penicillins and cephalosporins)
binds to PBP, cell wall weakening, lysis and death
Of note: resistant to b-lactamases, can penetrate gram-negative cell envelope.
Outline basic carbapenem pharmacokinetics
not absorbed by GI, IVonly, well distributed, including to CSF, primarily renal elimination – reduce dose in renal impairment
True or false, there are many serious adverse effects/drug reactions to be aware of for carbapenems
False
well tolerated, GI effects (nausea, vomiting, diarrhea)
Bacterial or fungal superinfections in 4% of patients
Cross sensitivity with penicillin allergies – 1%.
Drug reaction: reduces blood levels of valproate. Avoid combination or provide supplemental anti-seizure therapy
True or false: meropenem is the most widely used antibiotic in US hospitals
False – Vancomycin is the most widely used antibiotic in US hospitals
What are indications for Vancomycin?
Indications: Active against only gram-positive bacteria
Especially active against S.aureus and staphylococcus epidermis, including MR. Also useful for streptococci, penicillin-resistant pneumococci and CDI
Reserved for severe infections
c.diff infection (CDI), MRSA, serious infections with susceptible organisms in patients allergic to penicillins
Although it is not a b-lactam drug, Vanco’s MOA is similar to the penicillins, cephalosporins and carbapenems – what is the MOA? What is the difference from the b-lactams?
Similar to b-lactam antibiotics, inhibits cell wall synthesis and causes lysis and death. Does this by binding to precursor molecules for cell wall biosynthesis (not PBPs)
Vancomycin is usually given IV except in the treatment of _____
c.diff infection – given orally (or other intestinal infections)
Vanco has poor GI absorption, is relatively well distributed except for CSF and is eliminated unchanged by the kidneys. What is the primary adverse effect of vanco?
Renal toxicity – requires monitoring of serum drug levels and creatinine levels
There are 3 other antibiotics which inhibit bacterial cell wall synthesis. What are they?
Telavancin, Aztreonam, Fosfomycin
Matching
- Telavancin
- Aztreonam
- Fosfomycin
A. monobactam (b-lactam antibiotic) which is narrow spectrum for gram-negative aerobic bacteria and highly resistant to b-lactamases
B. lipogylcoprotein. A synthetic derivative of vanco. Active against only gram-positive bacteria. Reserved for infections resistant to vanco. Also has A/E of renal toxicity plus QT prolongation
C. Unique antibiotic for single-dose therapy in women with uncomplicated UTIs caused by e.coli or e.faecalis
- Telavancin - B. lipogylcoprotein. A synthetic derivative of vanco. Active against only gram-positive bacteria. Reserved for infections resistant to vanco. Also has A/E of renal toxicity plus QT prolongation
- Aztreonam A. monobactam (b-lactam antibiotic) which is narrow spectrum for gram-negative aerobic bacteria and highly resistant to b-lactamases
- Fosfomycin C. Unique antibiotic for single-dose therapy in women with uncomplicated UTIs caused by e.coli or e.faecalis
Clostridiodies difficile is a gram-positive, spore-forming, anaerobic bacillus that infects the bowel – how does c-diff cause injury?
Injury results from release of toxins A and B
What are treatment options for c-diff infection (CDI)
Usually treated with metronidazole, vancomycin or fidaxomicin.
Stop the antibiotic that caused the CDI – in 25% of patients with mild CDI this will cause resolution
Start a different antibiotic to eradicate CDI.
What almost always precedes CDI?
use of antibiotics – kill off normal gut flora and allow c.diff to flourish.
Other risk factors are older age, GI surgery, serious illness, prolonged hospitalization and immunosuppression
Which antibiotics are highest risk for CDI?
clindamycin, 2nd and 3rd generations cephalosporins and fluoroquinolones ciprofloxacin and levofloxacin
True or false, CDI can cause death
True. Symptoms range mild-severe
mild (abdo discomfort, nausea, fever and diarrhea)
severe (toxic megacolon, pseudomembranous colitis, colon perforation, sepsis, death)
Complications: dehydration, electrolyte disturbances. Bowel perf, renal failure, sepsis, death
Recurrence of CDI is seen ____ percent of the time after successful treatment
15-30%
T/F Fluroquinolones are broad spectrum
true
Generally, how do fluoroquinolones work?
Disrupt DNA replication and cell division
Side effects of fluoroquinolones are generally mild, however, adverse effects do include….
Risk of tendinitis, tendon rupture; risk of phototoxicity; increased risk of c. difficile. Can exacerbate muscle weakness in patients with myasthenia gravis.
What is the protype drug for fluoroquinolones (/ an example of this class)
Ciprofloxacin
Mechanism of action for ciprofloxacin
Rapidly bactericidal; inhibits two enzymes needed for DNA replication and cell division. Selective toxicity arises as mammalian equivalents of this enzyme have a low affinity for fluroquinolones.
Describe the antimicrobial spectrum of Ciprofloxacin.
Broad spectrum, including most aerobic gram negative bacteria and some gram positive bacteria. Most urinary tract pathogens (including E coli and Klebsiella species) are sensitive. Also highly active against bacteria that cause enteritis (i.e., Salmonella, shigella, campylobacter, E. Coli. Other sensitive organisms are anthracis, pseudomonas aeruginosa, h. influenzae, meningococci, and many streptococci. Fair to poor activity against anerobes; c. diff is resistance
Describe the pharmacokinetics of ciprofloxacin
May be given orally or IV. High concentrations in the urine, stool, bile, saliva, bone, and prostate tissue; low concentrations in the CSF. Plasma half life 4 hours. Hepatic elimination and renal excretion.
Describe the therapeutic uses of Ciprofloxacin
Wide variety of infections, including infections of resp tract, gu tract, gi tract, bones, joints, skin, soft tissues. Preferred tx for anthrax for those who have inhaled spores. Poor choice for staph (high rates of resistance). Generally avoided in <18yo (due to tendon rupture risk), but indicated for complicated urinary tract and kidney infections caused by e.coli and post exposures prophylaxis/ treatment of anthrax.
Describe the adverse effects of ciprofloxacin
Mild adverse effects include GI reactions, CNS effects (dizziness, headache, restlessness, confusion), candida infections of pharynx/ vagina. Rarely, seizures have occurred. Can damage tendons (highest risk if 60+, taking glucocorticoids), pose a risk for photosensitivity, and increase risk for c. diff. Can exacerbate muscle weakness in myasthenia gravis.
Describe what drug/ food interactions to be aware of when prescribing ciprofloxacin
Absorption can be reduced by cations (i.e., aluminum, magnesium, iron, zinc, calcium, milk/ dairy). Can elevate blood levels of theophylline, warfarin, and tinidazole. a
What is Metronidazole used to treat?
Protozoal infections and infections caused by obligate anaerobic bacteria. Lethal to anaerobes only.
MOA of Metronidazole?
Taken up by cell, converted into active form (only anaerobes can do the conversion). Active form interacts with DNA and causes strand breakage, resulting in inhibition of nucleic acid synthesis and cell death.
Describe the antibacterial spectrum of Metronidazole
Antiprotozoal; Obligate anerobes only (bacteriode fragilis, c. diff, and others).
Therapeutic uses of Metronidazole
Anerobic bacterial infections, including infections of CNS, abdo organs, bones, joints, skin/ soft tissues, GU tract. Frequently these infections also involve aerobic bacteria, so therapy must also include a drug active against them. Used for treating C.diff. Prophylaxis for surgical procedures. Used to eradicate H. pyloria with tetracycline and bismuth subsalicylate.
MOA of Daptomycin?
Inserts into bacterial cell membrane, forming channels that permit efflux of intracellular potassium. This depolarizes the cell and inhibits synthesis of DNA, RNA, proteins, causing cell death.
Antibacterial spectrum of Daptomycin?
Gram positive bacteria (cannot penetrate gram negative outer membrane). Rapidly bactericidal to streptococci (including MRSA, vancomycin resistant s. aureus), enterococci, and most other aerobic and anerobic gram positive bacteria. More rapidly bactericidal than vanco, linezolid.
Therapeutic use of Daptomycin?
(1) Blood stream infection (including endocarditis) with S. aureus (2) complicated skin and skin structure infections caused by susceptible strains of staph, strep, E. faecalis. Do not use for CAP (higher death rates than alternative options).
Describe the pharmacokinetics of Daptomycin
Admin by IV infusion; significant amount bound to plasma proteins. Minimal metabolism. Excreted unchanged in urine. Half life 9 hours. Reduce doses with severe renal impairment.
Describe the adverse effects of Daptomycin
Generally well tolerated, most common are constipation, nausea, diarrhea, injection site reactions, headache, insomnia, and rash. May pose risk for myopathy (measure CK levels weekly, and warn patients to report muscle pain/ weakness).
Any drug interactions to be aware of when using Daptomycin?
Devoid of significant reactions. When used with tobramycin, may increase daptomycin levels and decrease tobramycin levels.
What are the two major groups of antifungal agents?
Drugs for systemic mycoses and drugs for superficial mycoses
What are the four classes of drugs used for treating systemic antifungal infections?
Polyene antibiotics
Azoles
Echinocandins
Pyrimidine analogs
What kind of drug is Amphotericin B?
Polyene antibiotic
MOA Amphotericin B?
Binds to fungal cell membrane (ergosterol), increasing permeability. Leaking of intracellular ions reduces viability. May be fungistatic or fungicidal, depending on concentration of drug
Describe the microbial susceptibility to Amphotericin B
Broad spectrum of fungi
Some protozoa
Resistance is rare
Therapeutic use of Amphotericin B
Drug of choice for most systemic mycoses. Prolonged (weeks to months) treatment
Describe the pharmacokinetics of Amphotericin B
A- poorly absorbed, so cannot do oral therapy. IV only.
D- when leaving vascular system, binds to sterol containing membranes of tissue. Does not readily penetrate CSF
M/E- little is known. Reduce dose/ frequency in renal impairment. Complete elimination takes a long time.
Adverse effects of Amphotericin B
Many. Should be in hospital for use. Black box- only use in life threatening infection. Infusion reactions, nephrotoxicity (may normalize or be irreversible), bone marrow suppression.
Drug interactions of Amphotericin B
Avoid use with other nephrotoxic drugs.
What is the MOA of Azoles drugs?
Inhibit synthesis of ergosterol and disrupt the fungal cell membrane.
Examples of Azoles?/
Itraconazole, ketoconazole, fluconazole…
How are Azoles given?
Can be given orally
Spectrum of Azoles?
Broad spectrum
Metabolism of Azoles
p450. Can increase levels of many other drugs
Briefly describe the MOA, therapeutic use, pharmacokinetics, and adverse effects of Itraconazole
MOA- inhibits synthesis of ergosterol (leakage of cell components)
Therapeutic use- broad spectrum antifungal. Can be used systemically or for superficial infection.
Pharmacokinetics- can be given orally, distributed to lipophilic fluids (do not go to CSF), extensive hepatic metabolism, excreted in urine.
Adverse effects- well tolerated, can include GI, rash, headache, abdo pain, edema. Serious adverse effects are cardiac suppression (reversible) and liver failure.
Be aware of drug interactions as inhibits p450 (i.e., warfarin, cyclosporin, digoxin)
MOA of echinocandins?
Disrupt fungal cell wall (NOT membrane like azoles or amphotericin)
Spectrum of echinocandins?
Narrow- limited to aspergillus and candida
Administration of echinocandins?
Cannot be dosed orally.
Adverse effects of echinocandins?
Generally well tolerated. Avoid in pregnancy and monitor closely in liver dysfunction.
Example of an echinocandin?
Caspofungin
Flucytosine is a pyrimidine analog used for serious infections caused by which fungi?
Candida, cryptococcus
*note, usually always used with Amphotericin B as resistance is common
MOA of Flucytosine?
Taken up by fungal cells and converted to F-flurouracil, a powerful antimetabolite. Disruption of DNA and RNA synthesis.
Pharmacokinetics of flucytosine?
Well absorbed by GI tract, well distributed through body. Good access to CSG. Eliminated by kidneys. Reduce dosage in renal failure.
Adverse effects of flucytosine?
Bone marrow suppression, hepatotoxicity, can be nephrotoxic.
Superficial mycoses are caused by what 2 groups of organisms?
1) Candida species
2) Dermatophytes
What drug classes are used in treatment of superficial mycoses?
Azoles, griseofulvin, polyene antibiotics, allylamines, and others (tolnaftate, undecylenic acid, ciclopirox)
What is used in the treatment of tinea corporis?
Topical azole or allylamine. Continue treatment for 1 week after symptoms are cleared. Severe infection may require systemic antifungal (i.e. griseofulvin)
What is used in the treatment of tinea cruris?
Respond well to topical therapy. Continue treatment for 1 week after symptoms are cleared. If severe inflammation, may need a systemic antifungal (i.e., clotrimazole) or topical/ systemic glucocorticoid.
What is used in the treatment of tinea capitis?
Difficult to treat. Topical drugs not likely to work. Oral griseofulvin for 6-8 weeks is considered standard therapy. Or oral terabinafine for 2-4 weeks
What is used in the treatment of vulvovaginal candidiasis?
1-3 days of topical therapy. Oral therapy (i.e., single dose fluconazole) may be used.
What is used in the treatment of oral candidiasis?
Topical agents like nystatin, clotrimazole, miconazole. In immunocompromised patient, fluconazole or ketoconazole is usually required.
How is onychomycosis treated?
Caused by candida or dermatophytes. Oral or topical therapy. Both have low success rates. Common oral agents are terbinafine, itraconazole. Common topical agents are ciclopirox, tavaborole, efinazonazole.
What are topical azoles active against?
Broad spectrum- dermatophytes and candida. Antifungal effects result from inhibiting synthesis of ergosterol (component of fungal cell membrane)
What is griseofulvin?
An orally administered antifungal to treat superficial mycoses.
MOA of griseofulvin?
Drug is deposited into keratin precursor cells of skin/ hair/ nails. New keratin is resistant to fungal agent as griseofulvin inhibits fungal mitosis (binds to microtubules). Fungicidal.
Pharmacokinetics of griseofulvin?
Administration is oral, enhanced by fatty meal. Deposited in keratin precursors. Hepatic metabolism and renal excretion.
Therapeutic uses of griseofulvin?
Dermatophyte infection of skin, hair, nails. NOT active against candida. May require months to a year of treatment.
What class of drug does nyastatin belong to?
Polyene antibiotics
What type of infection is nyastatin used for?
Candidiasis (skin, mouth, esophagus, vagina), Can be given orally or topically.
Allylamines are used in the treatment of systemic fungal infections. What are 3 common allylamines?
Naftifine, terbinafine, and butenafine.
Describe indication/ use of naftifine.
Active against a broad spectrum of pathogenic fungi; approved only for topical dermatophytes. May cause burning or stinging.
Describe indication/ use of terbinafine.
Highly active against dermatophytes and less active against candida. Available topically and orally. Used for ringworm (tinea’s) and onychomycosis.
