Echinocandins

Definitions & Key takeaways

Echinocandins are a class of antifungals, mainly used to treat infections caused by candida species and aspergillus species. They work by disrupting the formation of the fungal cell wall, leading to cell death. They inhibit eta-1,3-D-glucan synthase, an enzyme necessary for the synthesis of major fungal cell components known as Beta glucans. Echinocandins are generally well-tolerated and have a low risk of serious adverse effects.

The most common side effects are facial flushing, nausea, vomiting, and skin rash. Rare but serious side effects include anaphylaxis (a life-threatening allergic reaction) and Stevens-Johnson syndrome (a severe skin reaction).

Chapters:

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Introduction0:00–0:28

Echinocandins are a novel class of medications used to treat mycoses, or fungal infections. Mycoses can be localized skin infections, or develop into systemic infections in immunodeficient patients.
Antifungals work either through fungistatic action, meaning that they inhibit fungal growth, or through fungicidal action, meaning they kill the fungi.
Now, most fungi have a protective cell wall made of different carbohydrate molecules. Some fungal species have beta glucans which are polysaccharide polymers that are cross linked with other carbohydrate molecules to make a strong fungal cell wall.

Pathology0:28–1:00

Beta glucans are produced by an enzyme on the cell membrane called beta-1,3-D-glucan synthase. This enzyme is not found in human cells which makes it a good target for antifungal medications.
Now, echinocandins are a type of medication that noncompetitively bind to and inhibit beta-1,3-D-glucan synthase. This weakens the cell wall and prevents it from being repaired.

Mechanism of action1:00–2:52

The cell wall gradually deforms more and more until it ruptures, causing the cell to die. Echinocandins are only available via IV since they are not well absorbed through the GI tract.
Medications in this class include anidulafungin, micafungin, and caspofungin. They are only effective against fungal species that have beta-1,3-D-glucan synthase, but it’s extremely rare for these organisms to have resistance to these medications.
Because of this, echinocandins are often used to treat fungal infections that are resistant to the more common antifungal medications like amphotericin-B and the “azole” medications like fluconazole.
Echinocandins are used to treat mucocutaneous candidiasis, which affect the skin, nails, and oral mucosa, or disseminated candidiasis, where the infection spreads to multiple organ systems through the blood, causing endocarditis, endophthalmitis, and osteomyelitis.
This is only seen in people with a compromised immune system like those with an HIV infection, or patients undergoing chemotherapy.
Echinocandins are also used to treat invasive aspergillosis. Normally, aspergillus species cause bronchopulmonary aspergillosis in immunocompetent people with chronic lung diseases like cystic fibrosis, chronic obstructive pulmonary disease, or tuberculosis.
In immunocompromised people, the infection can spread into the blood, causing invasive aspergillosis which can very quickly become fatal.

Toxicity2:52–3:25

Caspofungin is metabolized by the liver, but it’s also hepatotoxic so liver enzymes should be monitored. It is generally approved for use in children and in the elderly, but not in pregnant or lactating women.
Echinocandins cause histamine release and result in side effects like facial flushing, GI distress, and rash. They are also potentially hepatotoxic and the medications should be stopped if there’s an elevation in liver enzymes.
So, let’s make a mnemonic to help you memorize and retain all these crazy pharm facts! It’s Karaoke night and we have Caspo, the ghost of a fun guy, for caspofungin.

Memory palace3:25–4:41

He’s singing into a mushroom shaped microphone, for micafungin. On the screen, the lyrics show “I NEED YOUR LOVIN” which represents anidulafungin.
In the background, the walls are breaking apart, and a guy is trying to fix it with glue. This represents glucan synthase which is the target enzyme for these drugs.
The audience represents the indication for echinocandins, so there are some candy mushrooms for candidiasis, and a few gun wielding asparagus, for invasive aspergillosis.
For side effects, let’s have 2 snakes having a date night since the symptoms are caused by hisssstamine. One snake has red polka dots representing the rash, and her face is flushed red since she’s shy.
The other snake got food poisoning and is vomiting profusely. This might be because their dinner is a big chunk of liver, representing hepatotoxicity.
All right, as a quick recap. Echinocandins are a class of antifungal medications that inhibit the synthesis of beta glucans, which are vital structural components of fungal cell walls.

Review4:41–5:17

Without these polypeptides the fungal cell wall will deform and the cell will rupture. Echinocandins are only effective against fungi with beta-1,3-D-glucan synthase, and these include candida species and aspergillus species.
These medications are well tolerated, with little mild side effects caused by histamine release. But wait, there's more: Here's a mind map with all of the mnemonics from the video.

Mind map5:17–5:28

Go ahead and pause the video so you can test yourself to see what you remember. Stay tuned for the answers at the end.