Jerry Barbee, Jr, PharmD, BCPS

Medications enable the management of HIV.

Throughout history, illnesses, diseases, and plagues have devastated humanity, eradicating thousands, even millions of people. The infamous Black Death nearly destroyed Europe in the 14th century, taking 50 million lives.

 The recent Ebola outbreak in West Africa claimed almost 11,300 lives.

 AIDS is a deadly disease caused by HIV that has claimed the lives of more than 34 million individuals since the first cases appeared in the early 1980s.

AIDS is a chronic, incurable disease that attacks the body’s ability to defend itself against infection and cancer. Untreated, HIV may progress to AIDS. Management of HIV is, however, now possible. New advancements in pharmacologic therapies and the promotion of safer behaviors aid in the prevention of the disease. HIV no longer means certain death for the affected patient. Pharmacists can assist patients in taking appropriate measures to prolong their lives.

Currently, more than 1.2 million Americans are living with HIV. According to AIDS.gov, “almost 1 in 8 (12.8%) are unaware of their infection.”

 HIV infection rates have stabilized to an estimated 50,000 new cases every year. Homosexual, bisexual, and other men who have sex with men (MSM) collectively make up the group most affected by HIV.

 MSM represented approximately 63% of all new infections in 2010.

As of 2010, 84% of newly diagnosed cases of HIV in women were primarily attributed to heterosexual sexual contact and 16% to injection drug use.

 African Americans and Hispanic Americans are disproportionately affected by HIV/ AIDS, with 44% and 21% of newly diagnosed cases of HIV in 2010, respectively.

Although there are disparities among the groups affected by this disease, the overall message is optimistic. New HIV infections are no longer on the rise, proving that prevention methods and community awareness are effective. However, the steady incidence of new HIV infections every year shows that our work is far from finished.

There are 2 types of HIV, subtypes 1 and 2. HIV-1 is the predominant form of the virus worldwide, while subtype HIV-2 primarily affects people in West Africa.

 HIV in both subgroups affects the CD4+ lymphocytes, decreasing immunity and increasing the risk of opportunistic infections and cancers.

 Two glycoproteins, glycoprotein 120 and glycoprotein 41, allow HIV attachment to the surface of the CD4+ cell.

 Interactions between the virus and chemokine co-receptors (CCR5 and CXCR4) trigger irreversible conformational changes to the receptors.

 Fusion of the membranes takes place, prompting the viral core to release itself into the CD4+ cell and allow HIV RNA the opportunity to replicate.

Reverse transcriptase is a unique enzyme HIV uses to create viral DNA from HIV RNA.

 A major reason HIV/AIDS is difficult to treat is that reverse transcription allows for numerous errors, yielding multiple mutations of each DNA strand, thereby promoting resistance.

 Following the creation of HIV DNA, the viral enzyme integrase integrates HIV DNA into the host CD4+ cell’s DNA.

 The viral DNA then continues to replicate. This replication creates more HIV DNA, which can then be transcribed into HIV RNA and translated into HIV proteins.

 HIV virions are cleaved by protease and bud from the cell surface and infect other CD4+ cells.

 Infected CD4+ cells have a significantly shorter half-life than uninfected cells, impeding the body’s ability to fight against infection.

				Associated with lactic acidosis and lipodystrophy. HLA-B*5701 testing should be done before use of abacavir.

				Associated with rash and lipid disorders that may require discontinuation, drug switch, or use with lipid-lowering agents.

				Lopinavir/ritonavir (LPV/RTV; Kaletra)

				Saquinavir (SQV; Invirase [hard-gel capsule]; Fortovase [soft-gel capsule])

				RTV is a booster agent for other protease inhibitors. Class is associated with gastrointestinal effects, lipohypertrophy, glucose intolerance, and lipid disorders. Protease inhibitors are often used in regimens for patients who fail a prior regimen.

				Raltegravir is associated with rhabdomyolysis and myopathy, and resistance to the drug develops easily.

CCR5 Receptor Antagonists (Entry Inhibitors)

				A tropism test is required prior to administration. Associated with a slightly increased risk of heart attack, abdominal pain, hepatotoxicity and other adverse events.

				Used in treatment-experienced patients, although not commonly. It is the only subcutaneous HIV medication. Associated with neutropenia and increased risk of pneumonia.

CCR5 = C-C chemokine receptor 5; NNRTI = non-nucleoside reverse transcriptase inhibitor; NRTI = nucleoside/nucleotide reverse transcriptase inhibitors. 

Articles

HIV/AIDS: Curbing the Epidemic

Pharmacists can help minimize risk for patients using pain medications.

There are currently more than 100 million Americans suffering from chronic pain, including 65% to 80% of terminal cancer patients, 62% of nursing home residents, and many others who must combat pain on a daily basis.

 Chronic pain afflicts more patients in the United States than diabetes, coronary heart disease, stroke, and cancer combined.

 It reduces a patient’s independence and ability to perform many daily activities and puts a strain on social relationships, mood, and sleep patterns.

This decrease in overall functioning places a burden on the national economy, with total annual costs of health care and lost productivity attributable to pain ranging from $560 billion to $635 billion (2010 dollars) in the United States.

 With the number of patients suffering from pain increasing as the US population ages, the demand for pain management pharmacists will continue to rise.

The most widely accepted definition of pain is “an unpleasant sensory and emotional experience that is associated with actual or potential tissue damage or described in such terms.”

 There are, however, as many different definitions of pain as there are ways that pain can manifest itself in complex patients. Each directly influences the course of therapy for each individual.

Pain is classified by its duration and etiology. Duration of pain is classified in 2 categories: acute pain and chronic pain. Acute pain is a response to injury or tissue damage that generally does not last longer than it takes for normal healing to occur. Typically, this pain lasts less than 6 months, but may become chronic if not adequately treated. Chronic pain, on the other hand, persists longer than the normal course of time associated with injury, typically more than 3 to 6 months. In many cases, the initial injury may not be readily identifiable.

There are several etiologies of pain, including nociceptive pain and neuropathic pain. Nociceptive pain includes somatic pain, which arises from injury to body tissues and tends to be localized but varies in description and experience. Visceral pain is a nociceptive pain arising from the viscera mediated by stretch receptors; it is poorly localized, deep, dull, and cramping.

 Neuropathic pain manifests itself in abnormal neural activity secondary to disease, injury, or dysfunction of the nervous system. This type of pain can arise from the peripheral nervous system or the central nervous system.

Pain varies greatly in duration and etiology and often progresses or regresses as the pathology of the patient’s injury or disease state changes. In many cases, especially in chronic pain patients, complex pain states do not exist as a single well-defined pain, but rather as a mix of several types of pain.

There are many medications used to treat the various etiologies of pain. To maximize efficacy and minimize risk, therapies should be individualized for each patient’s pathology. The goal of proper pain management should always be to improve the patient’s quality of life, decrease the average pain rating, and improve overall functioning. Pharmacists must do their best to minimize patient risk associated with pain management. Proper medication therapy can reduce addiction, short- and long-term adverse effects, and risk of overdose.

For patients suffering from neuropathic pain including, but not limited to, peripheral neuropathic pain (eg, diabetic neuropathy, radiculopathy, postherpetic neuralgia) and central neuropathic pain (eg, post stroke pain, Parkinson’s disease pain, spinal cord injury pain, HIV myelopathy), there are many potential appropriate treatment options. These medications include tricyclic antidepressants, anticonvulsants, gabapentin, pregabalin, selective serotonin reuptake inhibitors, N-methyl-D-aspartate antagonists, topical lidocaine and capsaicin, opioid analgesics, and tramadol. It is the pharmacist’s responsibility to evaluate these medications. Pharmacists play a pivotal role in determining drug efficacy and in monitoring the side effects and interactions of multiple medications to help patients achieve good therapeutic outcomes.

When patients suffer from nociceptive pain, including somatic and visceral pain, certain classes of medications tend to have higher efficacy. These nociceptive pain medications include acetaminophen, nonsteroidal anti-inflammatory drugs, topical lidocaine, capsaicin, corticosteroids, skeletal muscle relaxants, opioid analgesics, and tramadol. Patients taking these medications need to be closely monitored by the pharmacist to ensure both dose and agent are appropriate for the patient’s comorbidities, age, and other possible medication interactions.

It is crucial that the pharmacist always perform a quick equianalgesic calculation to ensure that a patient’s new opioid medication is at a safe and effective dose (Online Table 1). When using the equianalgesic chart, an incomplete cross-tolerance dose reduction of 25% to 50% may be appropriate.

Pharmacist involvement can especially affect outcomes in pain management for patients with multiple disease states taking multiple medications for multiple types of pain. The incidence of adverse medication events is reduced with pharmacist intervention.

Nobody deserves to live with severe pain. Pharmacists can help patients live meaningful and productive lives with adequately managed pain. It is the responsibility of pharmacists to monitor patients’ 4 As: analgesia, activities of daily living, adverse events, and aberrant drug behaviors.

 Proper pain assessment is essential for understanding patients’ pain and providing highly effective treatment while simultaneously minimizing risk.

Assessment and proper planning can also help minimize patient risk. This can start with “The 10 Steps of Universal Precautions in Pain Medicine” (Online Table 2). By applying these recommendations, stigma is reduced and overall outcomes are improved.