Anti-HIV Agents: Protease Inhibitors – Antiviral Drugs

by Pravin Shukle, MD

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    00:01 Let’s move on to the protease inhibitors.

    00:03 Now the protease inhibitors are commonly used in HAART therapy and they’re associated with significant changes in carbohydrate metabolism.

    00:12 This might be due to inhibiting lipid regulating proteins in the human mammalian cell.

    00:20 They have sites similar to HIV protease.

    00:24 PI syndrome is another potential side effect with these medications.

    00:29 Now PI does not refer to protease inhibitors, it refers to primary immunodeficiency so PI syndrome is a primary immunodeficiency syndrome.

    00:40 It’s seen in about 50% of patients who are placed on protease inhibitors.

    00:45 The other potential side effects can include truncal obesity or you can get a buffalo hump which is a mound of fat just between the shoulder blades or you could get gynecomastia in our male patients.

    00:59 There’s also facial and peripheral lipodystrophy or disordered growth or proliferation of fat.

    01:06 There’s also hyperglycemia and insulin resistance in patients who take these medications and you can have elevated lipids including both triglyceride and cholesterol, so of course that’s going to be part of your therapy regimen.

    01:21 Atazanavir is one of the protease inhibitors that we use.

    01:25 The dosing occurs once a day which is quite convenient.

    01:28 It requires an acidic environment in the stomach for it to be properly metabolize so taking it with a antacid can reduce its effectiveness.

    01:38 It does penetrate barriers like the blood-brain barrier to enter into the central nervous system and interestingly enough it also penetrates the blood testes barriers so seminal fluid can be carrying this particular agent as well.

    01:54 It is excreted in the bile.

    01:56 Toxicity and adverse events with this medication include GI distress such as you know bloating, gassiness and stomach upset. You can have elevated bilirubin but interestingly enough this agent doesn’t cause an elevation in your cholesterol or your triglycerides, so you can see that some exam question maker is gonna take a look at that and say, aha, here’s a drug that doesn’t cause elevation of cholesterol and triglycerides, let’s put that in an exam question.

    02:27 So this is a useful little trick for you during exams.

    02:32 Remember this particular drug doesn’t cause elevation of cholesterol or triglycerides.

    02:36 In terms of other side effects it can cause peripheral neuropathy and of course like the other drugs it can cause a skin rash.

    02:43 Other agents are commonly used in combination therapies as well.

    02:47 They're often used to boost the effective of other therapies.

    02:50 We use them in caution though in patients who have a sulfur allergy because if you take a look at the structure, you have an exposed sulfa group.

    02:59 Toxicity and adverse events includes the G1 and GU side effects including liver toxicity and of course skin rash.

    03:07 Fosamprenavir or amprenavir are drug and prodrug - sorry, prodrug and drug, fosamprenavir is a prodrug to the other. It’s used in combination with other drugs like ritonavir to boost the effectiveness of therapies.

    03:24 It’s used in caution, again, because there’s an expose sulfa group to patients who have sulfa allergy.

    03:30 Toxicity and adverse side effects include GI and GU symptoms including G1 distress like stomach bloating.

    03:38 Skin rash is common in this drug category.

    03:42 You can also get parethesias as neurological symptoms.

    03:46 In terms of pregnancy, remember that this product not so much the drug itself but the product contains propylene glycol and therefore we don’t want to use it in pregnancy or in children.

    03:58 This isn’t on your exams but from practice point of view, the product has to put in propylene glycol to keep it stable and you can’t or you really don’t wanna use propylene glycol in pregnant or pediatric patients so that’s why we don’t use this product, this drug in those patient categories.

    04:22 Ritonavir is a very well-known protease inhibitors.

    04:25 It’s taken with meals, it’s cleared by the liver, it’s often used to boost other medications.

    04:31 Remember that it does have metabolism interaction so it can increase the either effectiveness or toxicity of other medications.

    04:41 Subtherapeutic doses inhibit the metabolism of other protease inhibitors like these listed here, so be aware that these drug does have metabolic effects as well as its anti HIV effects.

    04:57 Toxicity again includes GI irritation which can include abdominal symptoms.

    05:02 It has a bitter taste it’s a particularly bitter taste so patients will complain about that.

    05:07 There's an elevation of transaminases so you can get a transaminitis.

    05:11 Cholesterol can go up as can the triglyceride.

    05:14 Again, as with most of these medications, you can get a skin rash you can also get paresthesia’s as a neurological side effect.

    05:22 Saquinavir is another protease inhibitor that sometimes combined with ritonavir.

    05:26 It is both a substrate and an inhibitor of the cytochrome system so it can metabolic effects.

    05:34 Toxicity and side effects includes the GI and GU syndromes that we were talking about before.

    05:39 It can get a little bit more severe with this particular drug because you can actually get some vomiting with this medication as well.

    05:46 Again, side effects includes skin rash and paresthesia’s.

    05:49 Newer drugs are coming out in this category as well.

    05:53 They are often - the newer drugs are going to be both substrate and inducer of cytochrome P450 systems and of the P glycoprotein pathway so again drug interactions are important.

    06:06 There is an increased risk of rhabdomyolysis with the HMG-CoA reductase inhibitors.

    06:13 The toxicity and adverse events include GI and GU symptoms including nausea, vomiting, liver toxicity we spoke about that and guess what? This one also has germatologic and paresthesis side effects just like all of the other medications.

    About the Lecture

    The lecture Anti-HIV Agents: Protease Inhibitors – Antiviral Drugs by Pravin Shukle, MD is from the course Antimicrobial Pharmacology.

    Included Quiz Questions

    1. Protease inhibitors
    2. Nucleoside reverse transcriptase inhibitors
    3. Non-nucleoside reverse transcriptase inhibitors
    4. Integrase inhibitors
    5. Nucleotide reverse transcriptase inhibitors
    1. Atazanavir
    2. Ritonavir
    3. Fosamprenavir
    4. Amprenavir
    5. Darunavir
    1. Atazanavir
    2. Ritonavir
    3. Fosamprenavir
    4. Amprenavir
    5. Zolpidem
    1. Ritonavir
    2. Amprenavir
    3. Atazanavir
    4. Fosamprenavir
    5. Zidovudine

    Author of lecture Anti-HIV Agents: Protease Inhibitors – Antiviral Drugs

     Pravin Shukle, MD

    Pravin Shukle, MD

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