Pharmacology- Musculoskeletal Issues & Non-opioid Analgesia (Nsaid's)

Gout is caused by the buildup of uric acid in the body. Uric acid is a waste product that is normally excreted through the kidneys. However, in people with gout, there is an overproduction or underexcretion of uric acid, leading to its accumulation in the joints. This can result in the formation of urate crystals, causing inflammation, pain, and swelling characteristic of gout.

Reye syndrome is a rare but serious disease that most often affects children ages 6 to 12 years old. It can cause brain swelling and liver damage. It may be related to using aspirin to treat viral infections. Reye syndrome can lead to brain damage, liver damage, and death.

COX-2 inhibitors were developed to inhibit prostaglandin synthesis at sites of inflammation, and they have a higher incidence of cardiovascular (CV) thrombotic events. This suggests that COX-2 inhibitors specifically target the COX-2 enzyme, which is responsible for inflammation, while sparing the COX-1 enzyme, which is involved in protecting the stomach lining and promoting platelet aggregation. As a result, the inhibition of COX-2 without affecting COX-1 can lead to an increased risk of CV thrombotic events.

NSAIDs, or nonsteroidal anti-inflammatory drugs, can decrease the sensitivity of blood vessels to bradykinin and histamine, which are substances involved in inflammation. They can also affect T lymphocytes, which are a type of white blood cell involved in the immune response. Additionally, NSAIDs can reverse vasodilation, which is the widening of blood vessels that occurs during inflammation. Therefore, the statement that NSAIDs decrease sensitivity to bradykinin and histamine, affect T lymphocytes, and reverse vasodilation of inflammation is true.

Aspirin is considered the original NSAID (nonsteroidal anti-inflammatory drug) because it was the first NSAID to be discovered and widely used. It was first synthesized in 1897 and has been used for its analgesic, anti-inflammatory, and antipyretic properties ever since. Aspirin works by inhibiting the production of prostaglandins, which are responsible for pain, inflammation, and fever. Its effectiveness and widespread use have made it a cornerstone in the treatment of various conditions, including headaches, fever, and mild to moderate pain.

NSAIDs (non-steroidal anti-inflammatory drugs) exert their antiplatelet effect by blocking the COX-1 enzyme. COX-1 is responsible for the synthesis of thromboxane, a molecule that promotes platelet aggregation and blood clot formation. By inhibiting COX-1, NSAIDs reduce the production of thromboxane, leading to decreased platelet aggregation and a decreased risk of blood clots. COX-2, on the other hand, is involved in the production of prostaglandins that mediate inflammation and pain.

R.I.C.E stands for Rest, Ice, Compression, Elevation. This acronym is used in the nonpharmacologic treatment of MK pain. Rest refers to avoiding activities that worsen the pain and allowing the injured area to heal. Ice involves applying cold packs or ice to reduce inflammation and numb the area. Compression is the application of pressure to reduce swelling and support the injured area. Elevation refers to raising the injured area above the level of the heart to reduce swelling and promote blood flow.

Colchicine is the correct answer because it is a medication used specifically for acute gout attacks. It is known to cause significant gastrointestinal distress, including symptoms such as diarrhea, nausea, vomiting, and abdominal pain. Febuxostat, allopurinol, and probenecid are also used in the management of gout, but they do not typically cause significant gastrointestinal side effects.

Acetaminophen is the first-line treatment for musculoskeletal (MSK) pain. It is a commonly used over-the-counter pain reliever that helps reduce pain and fever. Acetaminophen works by inhibiting the production of certain chemicals in the body that cause pain and inflammation. It is considered a safe and effective option for managing MSK pain, especially for individuals who cannot take nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin, ibuprofen, or Aleve due to allergies or other medical conditions.

Allopurinol is the correct answer because it is a medication used for the management of gout. It works by reducing the synthesis of uric acid, which is the main cause of gout. By inhibiting the production of uric acid, allopurinol helps to prevent the formation of urate crystals in the joints, which can cause inflammation and pain. This medication is commonly prescribed for individuals with gout to help control symptoms and prevent future gout attacks.

Treatment Mechanisms of Gout
Aims of treatment:
• decrease symptoms of an acute attack
• decrease risk of recurrent attacks
• lower serum urate levels

If a patient has moderate pain, it is recommended to consider starting NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) at the same time as nonpharmacologic treatment. NSAIDs are commonly used to relieve pain and reduce inflammation. They work by inhibiting the production of certain chemicals in the body that cause pain and inflammation. Therefore, using NSAIDs alongside nonpharmacologic treatments can provide effective relief for moderate MSK (Musculoskeletal) pain.

Colchicine is the correct answer because it is a drug commonly used for treating inflammation of acute gouty arthritis. It is preferred over the previously popular drug, allopurinol, because allopurinol can cause diarrhea as a side effect. Therefore, colchicine is now more commonly used due to its effectiveness and lower risk of causing diarrhea.

The rational indications for allopurinol administration include chronic tophaceous gout, when tophi reabsorption is more rapid with uricosuric agents, when probenecid or sulfinpyrazone cannot be used, presence of renal functional impairment, and in a patient with recurrent renal stones. Allopurinol is used to reduce the production of uric acid in the body, which helps prevent the formation of uric acid crystals and the development of gout and kidney stones. Therefore, all of the above indications are valid reasons for allopurinol administration.

Probenecid is the correct answer because it inhibits the secretion of weak acids, including penicillin and methotrexate, and also inhibits the reabsorption of uric acid. This makes it an effective treatment for chronic gout when taken orally. Allopurinol is also used to treat gout, but it works by reducing the production of uric acid rather than inhibiting its secretion or reabsorption. Febuxostat and colchicine are other medications used to treat gout, but they do not have the same mechanism of action as probenecid.

Probenecid is a medication used to treat gout by reducing the levels of uric acid in the body. However, it is a sulfa drug, meaning it contains a sulfonamide group. Therefore, if a patient is allergic to sulfonamides, they should not use Probenecid as it may trigger an allergic reaction.

NSAIDs (Nonsteroidal anti-inflammatory drugs) are the first-line treatment for gout in patients with acute symptoms. Gout is a form of arthritis caused by the buildup of uric acid crystals in the joints, leading to severe pain and inflammation. NSAIDs help reduce pain, inflammation, and swelling by inhibiting the production of prostaglandins, which are responsible for these symptoms. They are effective in providing relief and are commonly prescribed to manage acute gout attacks. Other options like colchicine, corticosteroids, and uricosuric drugs may be used in certain cases, but NSAIDs are the preferred initial treatment.

Colchicine works by inhibiting microtubules involved in the chemotaxis of neutrophils. It is a good drug of 2nd choice for treating gout, especially when NSAIDs are contraindicated.

Colchicine works best when taken very early in an attack of gout (e.g. at the first sign of joint discomfort), as it will reduce the activation & chemotaxis of neutrophils to the site of inflammation. It can also be combined with NSAIDs (when NSAIDs are not contraindicated).

Salicylates should not be used concurrently with Uricosuric Agents because they can antagonize its effect. Salicylates, such as aspirin, have been shown to decrease the excretion of uric acid, which is the opposite effect of Uricosuric Agents. This can lead to increased levels of uric acid in the body and potentially worsen the symptoms of gout. Therefore, it is important for patients to avoid using salicylates while taking Uricosuric Agents to ensure the effectiveness of the medication.

Allopurinol and Febuxostat are both medications that reduce the production of uric acid by inhibiting xanthine oxidase, the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid. These medications work by blocking the activity of xanthine oxidase, thereby reducing the amount of uric acid produced in the body. Probenecid, on the other hand, works by increasing the excretion of uric acid from the body, while colchicine is used to treat gout symptoms but does not directly affect uric acid production. Therefore, the correct answer is Allopurinol and Febuxostat.

Colchicine is the correct answer because it is a gout medication that can enhance the effects of CNS depressants and sympathomimetic agents. It can also interfere with vitamin B12 absorption and have increased toxicity when used concurrently with clarithromycin, erythromycin, and grapefruit juice. This suggests that colchicine has potential interactions and side effects that should be considered when prescribing or taking it.

Allopurinol and Febuxostat are both gout medications that decrease the concentrations of less soluble uric acid. By doing so, they help to prevent the precipitation of uric acid crystals in joints and tissues. This is important because the accumulation of uric acid crystals is what causes the painful symptoms associated with gout. Therefore, Allopurinol and Febuxostat are effective in reducing the frequency and severity of gout attacks by lowering uric acid levels in the body.

The correct answer includes acetaminophen, NSAIDs, COX-2 inhibitors, and intraarticular injection of steroids. These agents are commonly used in the pharmacologic treatment of osteoarthritis (OA). Acetaminophen is a non-opioid analgesic that helps relieve pain. NSAIDs (nonsteroidal anti-inflammatory drugs) reduce inflammation and alleviate pain. COX-2 inhibitors specifically target the COX-2 enzyme, which is responsible for inflammation and pain. Intraarticular injection of steroids involves injecting corticosteroids directly into the affected joint to reduce inflammation and provide pain relief. These agents are commonly prescribed to manage the symptoms of OA and improve the patient's quality of life.

Acute attacks of gouty arthritis occur early in treatment with allopurinol because allopurinol inhibits the enzyme xanthine oxidase, which leads to a decrease in uric acid production. As a result, urate crystals that have accumulated in the tissues start to dissolve and move from the tissue into the plasma, causing an acute gouty attack. Therefore, the correct answer is "urate crystals move from tissue to plasma."

This question is asking for the general adverse drug effects (ADE) associated with NSAIDs. The correct answer includes headaches, tinnitus, fluid retention, hypertension, nausea, and vomiting. These are common side effects that can occur when taking NSAIDs.