Speaker 1 00:00 Hi. Welcome to Rosalind Franklin University College of Pharmacy top 200 drugs podcast. Speaker 2 00:12 This podcast is produced by the pharmacy faculty members to supplement study material for students learning the top 200 drugs we're hoping that our real life clinical pearls and discussions from practicing pharmacists will help you study for your next drug quiz. Speaker 1 00:29 No participants have any conflicts of interest to disclose. This podcast is for educational purposes only and is not intended to treat a particular patient. This information should not be used in lieu of the judgment of a health care provider. Dr. Sean Kane 00:41 This podcast is copyright Rosalind Franklin University of Medicine and Science, and now on to the show. Welcome to week seven of the Rosalind Franklin University top 200 drugs podcast. I'm your co host, Dr. Kane. I'm Dr. Weatherton, and I'm Dr. Patel, and this week we'll be talking about antifungals and antiviral agents, as well as over the counter products that are also antiviral and antifungal. So without further ado, we'll go ahead and get started with our first drug, fluconazole. The brand name is Diflucan. Speaker 3 01:12 So Dr. Weatherton, would you want to tell us how these azole antifungals work? Speaker 4 01:16 Sure the azole antifungals inhibit an enzyme called 14 alpha demethylase. That enzyme produces a product called ergosterol, which is important for fungal cell membranes. Without that enzyme, cell membranes get holes in them and the cells die. Dr. Sean Kane 01:32 It just so happens that fluconazole is one of the best prototypic drugs that causes drug interactions and that inhibits metabolism of other drugs. Speaker 4 01:41 When we inhibit the metabolism of other drugs, what happens to their concentration? Speaker 3 01:46 The concentration of those drugs would increase in the body, so you can see toxicities related to those medications, Dr. Sean Kane 01:51 absolutely and from a pharmacist perspective, knowing drug interactions and that drug interactions could occur, is very, very Speaker 4 01:58 important, aside from cytochrome p4 50 inhibition. Are there any other adverse effects of fluconazole? Dr. Sean Kane 02:04 The main thing, I think of is increases in liver function tests, so a transaminitis. Speaker 4 02:09 I've heard that fluconazole can also prolong the QTC, but I have no idea what the QTC is. Dr. Patel, what is it? Speaker 3 02:16 QTC is basically it's an interval when you monitor your EKG, ECG rhythm, and fluconazole is known to prolong the QTC interval. Dr. Sean Kane 02:26 Patients, if they have a prolonged QTC, they're at risk for really bad cardiac dysrhythmias like torsade, whoa. Speaker 4 02:32 It sounds like fluconazole can have a lot of side effects. What good effects does it have? What's it used for? Dr. Sean Kane 02:38 So at least in the outpatient setting, vaginal candidiasis, it comes as a one pill and one package, and you just give it to the patient. You're good to go. They take it once, and for the most part, it's extremely effective. Speaker 4 02:50 So if you want to switch a patient going home on fluconazole from IV to PO, what's the ratio? Dr. Sean Kane 02:55 The ratio from IV to PO with fluconazole is a one to one conversion, because it's so water soluble, it does get renally eliminated, so we have to look out for renal adjustments for dosing. Speaker 3 03:06 So talking from pharmacokinetically friendly medication, let's talk about pharmacokinetically challenging medication, and that leads us to our second agent itraconazole. The brand name is Sporanox, yeah. Dr. Sean Kane 03:19 So unlike fluconazole or Diflucan, itraconazole or Sporanox is kind of the red headed, angry orphan child of the azole family. Speaker 4 03:28 One way to remember that is the brand name for itraconazole. Sporanox looks kind of like soprano, and you know that Tony Soprano is a very temperamental angry guy. Dr. Sean Kane 03:37 Why are we saying that it's so temperamental? What's the problem with itraconazole or Sporanox that we don't really see with fluconazole or Diflucan oral Speaker 4 03:46 absorption can be tricky, particularly since itraconazole is available as a oral capsule and as an oral solution, and the rules for giving both of those are different. Yeah. So one of Dr. Sean Kane 03:57 the things that is an issue, at least with the IV formulation, is that this drug, unlike fluconazole, that's pretty water soluble, this is very lipophilic or water insoluble, so they have to actually formulate it with something called Hydroxypropyl beta cyclodextrin. Whoa, that's a mouthful, and it doesn't matter that you know that it's formulated in that but it does matter that you know that the IV formulation contains this solubilizing agent and that can accumulate in patients who have renal dysfunction and cause problems. From the point of view of counseling patients, we discuss how to take the drug very differently between the capsule form and the oral solution form. So the Speaker 4 04:33 bioavailability is different based on which oral delivery option you choose. I personally like the capsules best because you get to take them with a meal. However, how is the best way to take the solution on an empty stomach? So remembering that can be a bit of a pain in the cell membrane, I guess so. Dr. Sean Kane 04:50 Why are we using itraconazole? Why not just use fluconazole for everyone? Speaker 3 04:54 Well, itraconazole has a little broader spectrum, which means it covers certain endemic dimorphic fungi. Did you say fungi? Yes, I did. Dr. Sean Kane 05:04 Is it fungi or fungi? Speaker 4 05:06 Or fun guy? You know so much about these. Dr. Kane, you're really a fun guy Speaker 3 05:11 who knows. I think they're all right. So this endemic dimorphic fungi is found in soil. However, they can be pathogenic, which primarily attacks Speaker 4 05:19 your lungs. What are the adverse drug reactions to itraconazole like so similar to Speaker 3 05:24 fluconazole, we do see QTC prolongation. We, however, have some rare side effects, such as hearing loss as well as photosensitivity. Speaker 4 05:34 Well, since we're on a on an azole role, let's move right along to ketoconazole or Nizoral. We learned that fluconazole or Diflucan can inhibit some things within the human body that it's not meant to does ketoconazole or Nizoral have similar abilities, absolutely Dr. Sean Kane 05:51 so it has extensive inhibition of a number of different enzymes. So we see a lot of drug interactions with the oral form of ketoconazole or Nizoral. Speaker 4 06:01 What sort of things can we use the topical agents for? So really, Dr. Sean Kane 06:04 what we commonly will see ketoconazole or Nizoral used for is ringworm. So tinea corporis for ringworm anywhere in the body, tinea cruris, which is jock itch, and tinea pedis, which is athlete's foot. There's a number of other skin disorders that it's also used for, but these are the main ones, and there Speaker 3 06:24 is a topical shampoo form is available for a treatment of dandruff as well. Dr. Sean Kane 06:28 Now, moving on from the antifungals to the antivirals, one of the antivirals that we'll be discussing this week is actually a fairly popular drug called oseltamivir, or Tamiflu, is the brand name Unknown Speaker 06:39 I've heard of that? Dr. Patel, what does Speaker 3 06:41 Tamiflu do? Tamiflu basically inhibits influenza type A and influenza type B virus. And mechanism is it inhibits the influenza neuraminidase. So we can use this medication both for prevention and the treatment of influenza. Dr. Sean Kane 06:57 So do we have to dose the drug differently if we're trying to prevent influenza versus treating influenza, definitely. Speaker 3 07:03 So for prevention, the doses daily versus for treatment. It's a twice Speaker 4 07:07 a day administration. So a Tamiflu a day keeps the doctor away. You got it? Dr. Brotherton, Dr. Sean Kane 07:13 do we see any adverse reactions from Tamiflu or oseltamivir? Speaker 3 07:16 The major side effect reported with this medication is mainly GI symptoms such as nausea, vomiting, abdominal pain or diarrhea. However, you can rarely see patient complaining of rash or some neuropsychiatric events such as delirium, hallucination, etc. However, delirium and hallucination can very well be part of just having plain old flu. Unknown Speaker 07:39 How is this agent supplied. Dr. Sean Kane 07:40 So the main formulation I'm familiar with is the capsules that we see a lot outpatient. Speaker 4 07:45 There is an oral suspension that sometimes comes in when it's not on back order, which is most of the time. The good news is that you can make the capsules into an oral suspension by mixing them with any sweetened liquid, like plain cherry syrup within the pharmacy, or if somehow that's unavailable, you can use chocolate syrup or caramel topping sweet Hershey's. Oh, I have a question. If I have a patient taking oseltamivir, is it okay to give them the flu vaccine? Dr. Sean Kane 08:15 That's a great question. Dr. Weatherton, it really depends on what vaccine the patient will receive. Speaker 4 08:19 Well, most of my patients get the injectable, inactivated vaccine. Is that an issue? Speaker 3 08:24 So that shouldn't be a problem. But if your patient's getting intra nasal, which is an attenuated form of influenza vaccine, then there is a theoretical interaction. Speaker 4 08:34 And I think the idea there is that that vaccine counts on the flu virus to replicate, and if we're giving Tamiflu, the virus can't replicate because it's doing its job. Dr. Sean Kane 08:43 So kind of continuing with our theme of antivirals, the next two agents are actually fairly similar. The first is Acyclovir, the brand name is Zovirax, and this is an antiviral treatment used for herpes simplex or HSV and herpes zoster, which is Varicella Zoster virus or VZV which is also better known as shingles. Speaker 4 09:05 So you're saying that Acyclovir, Zovirax is a really good medicine for both patients with chicken pox and shingles. Dr. Sean Kane 09:13 Actually not. Acyclovir is about 10 times more potent for the HSV virus or Herpes Simplex than the VCV virus or shingles. Speaker 3 09:22 So then, what other purpose does Acyclovir serve? Dr. Sean Kane 09:26 HSV encephalitis, which is a form of meningitis Speaker 3 09:29 and commonly as an outpatient It's also used for genital or oral herpes. Dr. Sean Kane 09:34 So how does Acyclovir work? So the Speaker 3 09:36 Acyclovir is technically a pro drug and that is converted into a toxic metabolite within the cell that are replicating the viral thymidine kinase. And basically this is an enzyme that is specific to both HSV as well as VCV, and the activated Acyclovir causes the premature DNA chain termination. And in the viral viral cells. Speaker 4 10:02 That sounds bad when you're treating a patient with Acyclovir, Zovirax. How often is it dosed? Speaker 3 10:09 So dosing can become a cumbersome for patients. It's approved by FDA to be taken five times daily, and that's a that's an oral dosing. However, most commonly, it's prescribed as every every eight hour of dosing, Speaker 4 10:23 five times a day. Holy cow. Why do we have to give it so often? Well, Acyclovir is overex is not absorbed very well when it's given by mouth, only about 10 to 20% of every dose is getting where it needs Dr. Sean Kane 10:35 to go. So as far as adverse effects of Acyclovir, it's really the common nausea, vomiting, diarrhea type problems, but the drug itself isn't very water soluble, so especially in patients who take it, who get dehydrated, it can actually crystallize in the urine and cause what's called nephrolithiasis, which the more common term is kidney stones. Is there any way to avoid that? So when you counsel a patient taking Acyclovir, recommend that they should drink it with a full glass of water to ensure that they remain hydrated. Speaker 4 11:03 Since Acyclovir needs to be dosed five, five times a day, it sure would be nice if there was a once or twice a day drug that we could take that would do the same thing. Does such a thing exist? Speaker 3 11:13 Dr. Patel, oh, you got it. There is a cousin of Acyclovir, and the name is valacyclovir, and the brand name goes by is Valtrex, and basically there is an addition of amino acid named valine added to the chemical structure of Acyclovir, and that is why the name is valacyclovir. Dr. Sean Kane 11:32 So what do we accomplish by adding the valine onto the Speaker 4 11:34 drug structure? It's easier to absorb from the gut, and so our bioavailability goes up. Dr. Sean Kane 11:40 So we've essentially increased our bioavailability just by putting this single amino acid on Acyclovir to make valacyclovir or Valtrex. Unknown Speaker 11:49 Does Valtrex work any differently than Acyclovir? Speaker 3 11:52 It has the same mechanism of action as Acyclovir. What about the side effects? It has the same side effects as Acyclovir, all right. Dr. Sean Kane 12:01 So moving on to our over the counter medications for this week. The first one is docosanol or Speaker 4 12:06 Abreva. I've heard about this. It cures cold sores, right? Dr. Sean Kane 12:09 I wouldn't say it cures cold sores, Speaker 3 12:12 but it basically reduces the time period that you're going to have cold sore. Speaker 4 12:17 Well, it must reduce it a lot. It's pretty expensive. How well does it work? Dr. Sean Kane 12:21 As far as how effective it is, it'll reduce the duration of a cold sore by about 18 hours. Unknown Speaker 12:27 How often do you have to apply Abreva? Speaker 3 12:29 Application is recommended about five times a day. Whoa, I have other hobbies. Dr. Sean Kane 12:35 So before we move on, I just wanted to point out that Abreva is only approved for use on the face, as opposed to other places where one might find HSV infection. Speaker 3 12:44 So going from an OTC antiviral medication, let's talk about some OTC anti fungal medications available. The first agent we are talking about is terbinafine. The brand name is Lamisil AT so Dr. Sean Kane 12:58 Lamisil AT or terbinafine, is available over the counter as a cream, a spray and a gel. The spray Speaker 4 13:05 in particular, as well as possibly the gel, they contain alcohol. So if your patient's got broken or irritated skin, please don't recommend them the spray or the gel. It'll really irritate that skin more. Dr. Sean Kane 13:17 What are we actually using it for? Speaker 3 13:19 We're using this over the counter formulations to treat jock itch or ringworm infection, it is definitely not appropriate for nail fungus or vaginal yeast infection and for those jock itch and ringworm infection, the treatment usually lasts about seven days. Unknown Speaker 13:36 Whoa. Well, how does this terbinafine or Lamisil Dr. Sean Kane 13:39 AT work? So kind of similarly to our azole antifungals, where they inhibit an enzyme to make the ergosterol, we inhibit a different enzyme using terbinafine called squalene epoxidase, so the inhibition will prevent the synthesis of ergosterol, which again is vital for the production of the cell membrane to keep it stable. Speaker 4 14:01 Now, I've heard that Lamisil or terbinafine is also available as oral tablets, but I can't find them in the over the counter section. Speaker 3 14:08 Oh no, Dr. Weatherton, you're not going to find it in the aisle. You're going to have to come to the pharmacy with a prescription, because it's only available as prescription for the oral tablets. That is correct. And these oral tablets are used for the fungal nail infection. Speaker 4 14:23 Now, I've been to the OTC aisle, and I've seen all different kinds of Lamisils. Lamisil AF, Lamisil AT are all of those agents containing terbinafine? Dr. Sean Kane 14:34 Absolutely not so looking at Lamisil AF contains a different medication called tolnaftate. It's less effective. You have to apply it to the affected area four times as long, so four weeks instead of one week. It's a totally different medication. But the average consumer would have no idea if they didn't look at the back of the box. Speaker 4 14:52 So the over the counter Lamisil, which contains terbinafine is going to be Lamisil. Unknown Speaker 14:58 What? Lamisil? AT. Dr. Sean Kane 15:00 so the other over the counter antifungal that we'll be concluding with is Clotrimazole or Miconazole, both of which are under the flagship brand name, Lotrimin AF. Speaker 4 15:11 Now miconazole, to me, sounds a lot like fluconazole. Does it work in the same way? Dr. Sean Kane 15:17 Actually, it does. Again, it inhibits the 14 alpha demethylase, enzyme that fungal cells make to create the cell membrane. Speaker 3 15:25 And this formulation is available in powder spray as well as suppository form. Dr. Sean Kane 15:29 So there's a different medication called Lotrimin Ultra that contains butenafine, which works similarly to terbinafine, but is under the brand name of Lotrimin Ultra Speaker 4 15:40 Dr. Patel, what are miconazole and Clotrimazole in the Lotrimin creams, powders and sprays used for Speaker 3 15:47 both of the medication, if you're using topical form, are used to treat athlete's foot, jock itch and ringworm. However, the vaginal suppository forms are used for vaginal Candidal infection. All right, Dr. Sean Kane 16:00 so as a review of the medications for this week, we have fluconazole, brand name is Diflucan, Unknown Speaker 16:06 Itraconazole, brand name is Speaker 3 16:08 Sporanox, ketoconazole, brand name is Nizoral Dr. Sean Kane 16:12 oseltamivir, brand name is Tamiflu, Acyclovir or Speaker 3 16:16 Zovirax, and the cousin of Acyclovir, Valtrex Dr. Sean Kane 16:20 our over the counter medications were docosanol or Abreva terbinafine or Lamisil AT Speaker 3 16:26 Clotrimazole or miconazole. Brand name, Lotrimin AF. Dr. Sean Kane 16:30 This concludes the week seven podcast. Again, my name is Dr. King. I'm Dr Unknown Speaker 16:35 weatherton, and I'm Dr. Patel. Study hard. Speaker 1 16:40 This has been an educational production by the Rosalind Franklin University, College of Pharmacy. The theme music for this podcast is an excerpt of Metro Mix by seesaw released under Creative comic books.