Pharmacology of Protease Inhibitors

An estimated 1.2 million people over the age of 13 are living with HIV in the United States, according to the CDC. Almost 1 in 7 of these cases are estimated to be undiagnosed, a statistic that’s unlikely to decline anytime soon.

Medical intervention has proved invaluable, though. HIV medicines have transformed the lives of millions of people, now allowing them to live relatively normal lives. While immune-based risks remain an ongoing concern, they’re no longer always considered fatal risks.

Protease inhibitors are one such class. In this section, we examine the pharmacology of protease inhibitors – reviewing the principal members of this class, their mechanism of action, as well as their principal side effects.

Protease inhibitor pharmacology

There are seven main protease inhibitors we examine here. While protease inhibitors are also used in the treatment of HIV, this article focusses solely on those used to treat HIV. Among these drugs include:

  • Atazanavir
  • Darunavir
  • Lopinavir
  • Ritonavir
  • Saquinavir
  • Nelfinavir
  • Fosamprenavir

Saquinavir and ritonavir were first introduced in 1995 and, within two years, annual deaths from AIDS (in the US) fell from over 50,000 to around 18,000. Before the introduction of these two medicines, AIDS deaths were rising by around one-fifth each year.

Protease inhibitors are almost always used alongside other medicines. For example, lopinavir is taken alongside ritonavir. Ritonavir works to slow the breakdown of lopinavir, meaning the dose of lopinavir can be lowered. The risk of side effects declines, too. In general, ritonavir is not used for its anti-HIV potential, but for its ability to “boost” the clinical profile of other protease inhibitors (as with lopinavir).

Protease inhibitors work by inhibiting the enzyme, HIV protease; an enzyme responsible for enhancing HIV viral replication. In other words, protease inhibitors work to prevent protein cleavage of viral polyproteins, leading to a dulling of HIV replication.

Side effects

Protease inhibitors are known to cause a syndrome of potential side effects. These include lipodystrophy, hyperlipidemia, diabetes type 2 and kidney stones. Atazanavir is less likely to cause lipodystrophy compared to the other four drugs listed above.

There are also more common, though less serious side effects with each drug. For example, atazanavir is linked to yellowish skin, headache, nausea, difficulty sleeping, abdominal pain and fever. Rash is the most common side effect with darunavir.

Nelfinavir should be taken with food. Like fosamprenavir, diarrhea is one of their most common side effects. Taking nelfinavir with food decreases the risk of developing diarrhea as a side effect, though.

Know any other interesting facts about the pharmacology of protease inhibitors? If so, drop them into the comments section below. Click here to learn even more about the pharmacology of HIV medicines.

By | 2017-01-14T17:36:59+00:00 January 14th, 2017|Pharmacology Guides|0 Comments

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