ORAL ANTIDIABETIC AGENTS & NSAIDs

Inflammation

A normal, protective response to tissue injury that aims to inactivate or destroy invading organisms, remove irritants, and set the stage for tissue repair.

Rheumatoid Arthritis (RA)

An immune-mediated disease characterized by inappropriate activation of the immune system, leading to inflammation and damage to joints.

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

Medications that reduce inflammation, pain, and fever by inhibiting prostaglandin biosynthesis.

Disease-Modifying Antirheumatic Drugs (DMARDs)

Medications used to slow or arrest the tissue damaging process in immune-mediated diseases like RA.

Nonopioid Analgesics

Medications used to relieve pain without the use of opioids.

Drugs Used in Gout

Medications used to treat gout, a type of arthritis caused by the buildup of uric acid crystals in the joints.

Immune System

The body's defense system that can differentiate between self and nonself, but can become inappropriately activated in immune-mediated diseases.

T lymphocytes

White blood cells involved in the cell-mediated part of the immune system that are stimulated by WBC activation in RA.

Proinflammatory cytokines

Signaling molecules secreted by cells involved in the immune response, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1, which contribute to inflammation.

Rheumatoid factor

An inflammatory marker produced by B lymphocytes in RA to maintain inflammation.

Therapeutic Strategies

The goals of treating inflammation are to relieve symptoms, maintain function, and slow or arrest the tissue damaging process.

Pharmacotherapy

The use of medications to treat diseases or conditions.

Bioavailability

The extent to which a drug is absorbed and reaches the systemic circulation.

Protein-bound

Refers to the binding of a drug to proteins in the blood, such as albumin.

COX-1 and COX-2

Enzymes involved in prostaglandin biosynthesis, with COX-1 being constitutively active and COX-2 being induced at sites of inflammation.

GI Safety

Refers to the gastrointestinal safety profile of medications, including the risk of gastric ulcers and bleeding.

Cardiovascular Risks

The potential risks of medications on the cardiovascular system, such as fluid retention, hypertension, edema, and myocardial infarction.

Adverse Effects

Undesirable effects of medications, including central nervous system, cardiovascular, gastrointestinal, hematologic, hepatic, pulmonary, skin, and renal effects.

Aspirin

A nonsteroidal anti-inflammatory drug (NSAID) that is primarily used as an antiplatelet medication at low doses.

Nonacetylated Salicylates

Salicylate-based medications that are effective anti-inflammatory drugs but may be less effective as analgesics compared to aspirin.

COX-2 Selective Inhibitors

Medications that selectively inhibit the COX-2 isozyme involved in prostaglandin synthesis at sites of inflammation.

NSAIDs

Nonsteroidal anti-inflammatory drugs, including both COX-2 selective inhibitors and nonselective COX inhibitors.

Analgesics

Medications used to relieve pain.

Acetaminophen

An analgesic medication that lacks significant anti-inflammatory effects and is commonly used for mild to moderate pain and fever.

Ketorolac

An NSAID primarily used as a short-term analgesic for acute pain, not as an anti-inflammatory drug.

Tramadol

An analgesic medication used to treat moderate to severe pain.

Tramadol

A centrally acting synthetic analgesic that is structurally related to opioids.

Mechanism of action of Tramadol

Involves both non-opioid and opioid receptors, as naloxone, an opioid receptor blocker, only inhibits 30% of the analgesic effect of tramadol.

Tramadol's effects

Does not have significant anti-inflammatory effects, but may enhance 5-hydroxytryptamine (5-HT) release and inhibit the reuptake of norepinephrine and 5-HT.

Gout

A metabolic disease characterized by recurrent episodes of acute arthritis due to deposits of monosodium urate in joints and cartilage.

Uric acid in gout

Gout is usually associated with a high serum uric acid level (hyperuricemia), a poorly soluble substance that is the major end product of purine metabolism.

Colchicine

An alkaloid isolated from the autumn crocus, Colchicum autumnale, used in the treatment of gout.

Mechanism of action of Colchicine

Binds to the intracellular protein tubulin, preventing its polymerization into microtubules, leading to the inhibition of leukocyte migration and phagocytosis. It also inhibits the formation of leukotriene B4 and IL-1β.

NSAIDs used in gout

Indomethacin is commonly used in the initial treatment of gout. Other NSAIDs except aspirin, salicylates, and tolmetin have been successfully used to treat acute gouty episodes.

Uricosuric drugs

Probenecid and sulfinpyrazone are uricosuric drugs used to decrease the body pool of urate in patients with tophaceous gout or in those with increasingly frequent gouty attacks.

Allopurinol

The preferred and standard-of-care therapy for gout during the period between acute episodes. It reduces total uric acid body burden by inhibiting xanthine oxidase.

Febuxostat

A non-purine xanthine oxidase inhibitor used in the treatment of gout.

Pegloticase

A recombinant mammalian uricase used for the treatment of refractory chronic gout. It converts uric acid to allantoin, a highly soluble compound that can be easily eliminated by the kidney.

Glucocorticoids

Used in the treatment of severe symptomatic gout. Prednisone is the most commonly used oral corticosteroid.

Interleukin-1 inhibitors

Drugs targeting the IL-1 pathway, such as anakinra, canakinumab, and rilonacept, used for the treatment of gout.

Sulfonylureas

Oral antidiabetic agents that primarily stimulate insulin release by binding to the sulfonylurea receptor.

Mechanism of action of Sulfonylureas

Bind to a high-affinity sulfonylurea receptor associated with a beta-cell inward rectifier ATP-sensitive potassium channel, leading to depolarization, calcium influx, and insulin release.

First-generation sulfonylureas

Tolbutamide, chlorpropamide, and tolazamide. Metabolized by the liver and have shorter durations of action compared to second-generation sulfonylureas.

Second-generation sulfonylureas

Glyburide, glipizide, gliclazide, and glimepiride. More potent than first-generation agents and have lower risk of drug-drug interactions.

Meglitinide analogs

Repaglinide and mitiglinide. Modulate beta-cell insulin release by regulating potassium efflux through potassium channels.

Nateglinide

A d-phenylalanine derivative that stimulates rapid and transient release of insulin from beta cells. Reduces postprandial rise in blood glucose levels.

Metformin

The only biguanide currently available in the United States, used to treat type 2 diabetes by reducing hepatic glucose production.

Lactic acidosis

A potential complication associated with the use of biguanides, such as phenformin, which led to its discontinuation in the United States.

AMP-activated protein kinase

The enzyme activated by metformin, which plays a role in reducing hepatic glucose production.

Euglycemic agents

Another term for biguanides, such as metformin, which help maintain normal blood glucose levels.

Renal insufficiency

A condition in which the kidneys are unable to function properly, leading to the accumulation of biguanides and an increased risk of lactic acidosis.

First-line therapy

Biguanides, like metformin, are recommended as the initial treatment for type 2 diabetes.

Insulin-sparing agent

Metformin helps reduce the need for insulin in the treatment of hyperglycemia without causing weight gain or hypoglycemia.

Combination therapy

Metformin can be used in combination with insulin secretagogues or thiazolidinediones when oral monotherapy is inadequate.

Prevention of type 2 diabetes

Metformin has been shown to be effective in preventing the onset of type 2 diabetes in middle-aged, obese individuals with impaired glucose tolerance and fasting hyperglycemia.

Gastrointestinal toxicities

Common side effects of metformin include anorexia, nausea, vomiting, abdominal discomfort, and diarrhea.

Vitamin B12 deficiency

Metformin can interfere with the absorption of vitamin B12, leading to a deficiency, especially after long-term use.

Lactic acidosis

A serious complication of metformin therapy, more likely to occur in conditions of tissue hypoxia and renal failure.

Thiazolidinediones

A class of drugs that decrease insulin resistance by activating peroxisome proliferator-activated receptor gamma (PPAR-?) receptors.

Hepatic toxicity

Troglitazone, an older thiazolidinedione, was withdrawn from the market due to its association with liver failure.

Insulin sensitivity

Thiazolidinediones increase insulin sensitivity in adipose tissue, liver, and skeletal muscle.

Fluid retention

Thiazolidinediones can cause fluid retention, which may lead to heart failure in patients with New York Heart Association class III and IV cardiac status.

Bone fractures

Thiazolidinediones, especially when used in combination with a sulfonylurea or insulin, may increase the risk of atypical extremity bone fractures in women.

Dipeptidyl peptidase 4 (DPP-4) inhibitors

Drugs that inhibit the degradation of GLP-1 and GIP, prolonging their action and enhancing glucose-induced insulin secretion.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors

Medications that inhibit the reabsorption of glucose in the kidneys, leading to glycosuria and lower glucose levels in type 2 diabetes.

Islet amyloid polypeptide (IAPP) analog

Pramlintide, an analog of IAPP, used to reduce glucagon secretion, slow gastric emptying, and decrease appetite in insulin-treated type 1 and type 2 diabetes patients.