McKenna's Pharmacology for Nursing, 2e

135

C H A P T E R 1 0  Antiviral agents

Loss of T cell function causes acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) , diseases that are characterised by the emergence of a variety of opportunistic infections and cancers that occur when the immune system is depressed and unable to function properly. The HIV mutates over time, presenting a slightly different configuration with each new genera- tion. Treatment of AIDS and ARC has been difficult for two reasons: (1) the length of time the virus can remain dormant within the T cells (i.e. months to years), and (2) the adverse effects of many potent drugs, which may include further depression of the immune system. A com- bination of several different antiviral drugs is used to attack the virus at various points in its life cycle to achieve maximum effectiveness with the least amount of toxicity. The types of antiviral agents that are used to treat HIV infections are the non-nucleoside and nucleoside reverse transcriptase inhibitors, the protease inhibitors and three newer classes of drugs—the fusion inhibitors , CCR5 coreceptor antagonists , and integrase inhibitors (Table 10.3). Collectively, these drugs are known as antiretrovi- ral agents. The HIV virus poses a serious health risk. The person and the family of the person diagnosed with HIV infection will need tremendous support and teaching to cope with the disease and its treatment. See Box 10.3 for public education information regarding AIDS. N on - nucleoside reverse transcriptase inhibitors The non-nucleoside reverse transcriptase inhibitors have direct effects on the HIV virus activities within the cell. The non-nucleoside reverse transcriptase inhibi- tors available include efavirenz ( Stocrin ) and nevirapine ( Viramune ). Therapeutic actions and indications The non-nucleoside reverse transcriptase inhibitors bind directly to HIV reverse transcriptase, blocking both RNA and DNA-dependent DNA polymerase activities. They prevent the transfer of information that would allow the virus to carry on the formation of viral DNA. As a result, the virus is unable to take over the cell and reproduce. These antiviral agents are indicated for the treatment of people with documented AIDS or ARC who have decreased numbers of T cells and evidence of increased opportunistic infections in combination with other antiviral drugs (see Table 10.3). Pharmacokinetics Efavirenz is absorbed rapidly from the GI tract, reaching peak levels in 3 to 5 hours. Efavirenz is metabolised in the liver by the cytochrome P450 system and is excreted in the urine and faeces with a half-life of 52 to 76 hours.

Nevirapine is recommended for use in adults and children older than 2 months. After rapid GI absorption with a peak effect occurring at 4 hours, nevirapine is metabolised by the cytochrome P450 system in the liver. Excretion is through the urine with a half-life of 45 hours. Contraindications and cautions There are no adequate studies of non-nucleoside reverse transcriptase inhibitors in pregnancy, so use should be limited to situations in which the benefits clearly outweigh any risks. Adverse effects The adverse effects most commonly experienced with these drugs are GI related—dry mouth, constipation or diarrhoea, nausea, abdominal pain and dyspepsia. Dizziness, blurred vision and headache have also been reported. A flu-like syndrome of fever, muscle aches and pains, fatigue and loss of appetite often occurs with the anti-HIV drugs, but these signs and symptoms may also be related to the underlying disease. Clinically important drug–drug interactions There is a risk of serious adverse effects if efavirenz is combined with midazolam, rifabutin, triazolam or ergot derivatives; these combinations should be avoided. There may be a lack of effectiveness if nevirapine is combined with hormonal contraceptives or protease inhibitors. St John’s wort should not be used with these drugs; a decrease in antiviral effects can occur. Prototype summary: Nevirapine Indications: Treatment of HIV-1–infected people who have experienced clinical or immunological deterioration, in combination with other antiretrovirals. Actions: Binds to HIV-1 reverse transcriptase and blocks replication of the HIV by changing the structure of the HIV enzyme. Pharmacokinetics: Route Onset Peak Oral Rapid 4 hours T 1/2 : 45 hours, then 25 to 30 hours; metabolised in the liver and excreted in the urine. Adverse effects: Headache, nausea, vomiting, diarrhoea, rash, liver dysfunction, chills, fever.

N ucleoside reverse transcriptase inhibitors

The nucleoside reverse transcriptase inhibitors (Table 10.3) were the first class of drugs developed to