Analgesic & Antipyretic (but not anti-inflammatory)
| Drug: Acetaminophen (generic, Tylenol ®, others) |
| Drug Class: Analgesic, Antipyretic |
| Mechanism of Action: A weak COX-1 and COX-2 inhibitor in peripheral tissues and posesses no significant antiinflammatory effects. Recent evidence suggest that it may inhibit a third enzyme COX-3 in the CNS. It has been proposed that COX-3 may be a splice variant of the COX-1 gene (but this is questionable). Acetaminophen produces analgesia by elevation of the pain threshold preipherally, and antipyresis through action on the hypothalamic heat regulating center. |
| Indications: mild to moderate pain such as headache, myalgia, postpartum pain, and other circumstances in which aspirin is also an effective analgesic. It is a prefered drug for the treatment of pain & fever in patients allergic to aspirin, when salicylates are poorly tolerated, in patients with bleeding disorders, history of peptic ulcers, and patients in whom bronchospasm is precipitated by aspirin. Acetaminophen is prefered to aspirin for the treatment of pain/fever in children with viral infections. |
| Pharmacokinetics: Well absorbed orally, with absorption being related to the rate of gastric emptying. Peak blood levels are usually reached in 30-60 mins. Acetaminophen is partially metabolized by hepatic microsomal enzymes and converted to acetaminophen sulfate and glucuronide, which are inactive. Less than 5% is excreted unchanged. A minor but highly active metabolite (N-acetyl-p-benzoquinone) is important in large doses because of its toxicity to both liver and kidney. The half life of acetaminophen is 2-3 hrs. With toxic doses or liver disease, the half-life may be increased two-fold or more. |
| Side Effects: In therapeutic doses, a mild reversible increase in hepatic enzymes may occasionally occure in the absence of jaundice. With larger doses, dizziness, excitement, and disorientation are seen. Ingestion of 15 g of acetaminophen may be fatal, death being caused by severe hepatotoxicity with centrilobular necrosis, sometimes associated with acute renal tubular necrosis. Early symptoms of hepatic damage include: nausea, vomiting, diarrhea & abdominal pain. Toxicity is treated with supportive therapy and N-acetylcysteine to neutralize the toxic metabolites. Clinical and laboratory evidence of hepatic toxicity may not be apparent until 48 to 72 hours post-ingestion. |
| Notes: Acetaminophen is equal to aspirin in analgesic and antipyretic effectiveness, but differs by lacking anti-inflammatory properties. It also does not affect uric acid levels and lacks platelet-inhibitiing properties. Note that acetaminophen is not a NSAID. Phenacetin is a prodrug that is metabolized to acetaminophen. Phenacetin is more toxic (associated with renal failure) than acetaminophen and therefore no longer has a rational indication. Phenacetin was withdrawn by the FDA from OTC medications in 1999. It is still in common use in other parts of the world. |
Reference: www.rxlist.com & Katzung's text |
Acetaminophen antidote
| Drug: N-acetylcysteine (Mucomyst ®) |
| Drug Class: Acetaminophen antidote |
| Mechanism of Action: A glutathione substitute that binds the toxic metabolite of acetaminophen. |
| Indications: If given within 8-16 hours following acetaminophen overdose, protects victims from fulminant hepato-toxicity and death. |
| Pharmacokinetics: available for either oral administration (acetaminophen antidote) or inhalation (mucolytic agent). |
Reference: www.rxlist.com |
Non Steroidal Anti-Inflammatory Drugs
| Drug: Aspirin (Acetylsalicylic acid, ASA) (generic) |
| Drug Class: NSAID |
| Mechanism of Action: Aspirin irreversibly inhibits both isoforms of COX. and inhibits platelet aggregation. Aspirin also interferes with the chemical mediators of the kallikrein system, thus inhibiting granulocyte adherence to damaged vasculature, stabilizing lysosomes, and inhibiting the chemotaxis of PMN leukocytes and macrophages. |
Indications: 1) Anti-inflammatory. Aspirin interferes with the chemical mediators of the kallikrein system, thus inhibiting granulocyte adherence to damaged vasculature, stabilizing lysosomes, and inhibiting the chemotaxis of PMN leukocytes and macrophages. 2) Analgesia. Aspirin is effective in reducing pain of mild to moderate intensity through its effects on inflammation and probably because it inhibits pain stimuli at a subcortical (central) site. It is not effective for severe visceral pain. 3) Antipyretic. Aspirin reduces elevated body temperature (but it has little effect on body temperature in normal healthy patients). This effect is probably mediated by both COX inhibition in the CNS and inhibition of IL-1 (which is released by macrophages during episodes of inflammation). 4) Antiplatelet Effects. Single low doses of aspirin (81 mg daily) produce a slightly prolonged bleeding time, which doubles if administration is continued for a week. The change is due to irreversible inhibition of platelet COX, so that aspirin's antiplatelet effect lasts 8-10 days (the life of the platelet). 5) MI Prophylaxis: Aspirin is indicated to reduce the risk of death and/or nonfatal myocardial infarction in patients with a previous infarction or unstable angina pectoris. 6) Transient Ischemic Attacks: Aspirin is indicated for reducing the risk of recurrent transient ischemic attacks (TIAs) or stroke in men who have transient ischemia of the brain due to fibrin emboli. There is currently no evidence that aspirin is effective in reducing TIAs in women, or is of benefit in the treatment of completed strokes in men or women. |
| Contraindications: hypersensitivity to NSAIDs or history of bleeding disorders, such as GI bleeding or hemophelia. Not recommended during pregnancy, but may be valuable in treating preeclampsia-eclampsia. Children and teenagers should not use this medicine for chicken pox or flu symptoms before a doctor is consulted about Reye's syndrome, a rare but serious illness reported to be associated with aspirin. |
| Pharmacokinetics: Aspirin is rapidly hydrolyzed primarily in the liver to salicylic acid, which is conjugated with glycine (forming salicyluric acid) and glucuronic acid and excreted largely in the urine. As a result of the rapid hydrolysis, plasma concentrations of aspirin are always low and rarely exceed 20 mcg/ml at ordinary therapeutic doses. The peak salicylate level for uncoated aspirin occurs in about 2 hours; however with enteric coated aspirin tablets this is delayed. The plasma half-life for aspirin is approximately 15 minutes; that for salicylate lengthens as the dose increases: Doses of 300 to 650 mg have a half-life of 3.1 to 3.2 hours; with doses of 1 gram, the half-life is increased to 5 hours and with 2 grams it is increased to about 9 hours. Salicylates are excreted mainly by the kidney. Studies in man indicate that salicylate is excreted in the urine as free salicylic acid (10%), salicyluric acid (75%), salicylic phenolic (10%) and acyl (5%) glucuronides and gentisic acid (<1%). |
Side Effects: Expected side effects are dose-dependent. With therapeutic doses, gastric upset, gastric and duodenal ulcers are the most common side effects. With high doses "salicylism" can occur - vomiting, tinnitus, decreased hearing, vertigo (reversible). Even larger doses cause hyperpnea through a direct effect on the medulla. At toxic doses, respiratory alkalosis followed by metabolic acidosis (salicylate accumulation), respiratory depression, and even cardiotoxicity an glucose intolerance can occur. Overdosage of 200 to 500 mg/kg is in the fatal range. |
| Major drug interactions: Aspirin may contribute to increasing bleeding time by decreasing prothrombin in the plasma. Large doses have a hypoglycemic action that can enhance the effect of oral hypoglycemic drugs and affect the diabetic's insulin requirements. Large doses of aspirin are uricosuric, but smaller amounts may decrease the uricosuric effects of probenecid, sulfinpyrazone and phenylbutazone. Therefore aspirin is contraindicated in the treatment of pain & inflammation associated with gout. |
Reference: www.rxlist.com & Katzung's text |
| Drug: Ibuprofen (generic, Motrin, Rufen, Advil, Nuprin, ® others) |
| Drug Class: NSAID |
| Mechanism of Action: Nonselective Cox Inhibitor. |
| Indications: 1) relief of the signs
and symptoms of rheumatoid arthritis and osteoarthritis; 2) relief of mild to moderate pain; 3) treatment of primary dysmenorrhea. Analgesic, antipyretic, & at higher doses it is antiinflammatory. |
| Contraindications: history of drug hypersensitivity to NSAIDs |
| Pharmacokinetics: Ibuprofen is often prescribed at lower doses (<2400 mg/d) at which it has analgesic, but not anti-inflammatory efficacy. 2400 mg ibuprofen is equivalent to 4 g of aspirin in anti-inflammatory efficacy. The serum half-life is ~ 2.0 hours. |
| Side Effects: gastrointestinal complaints occur in patients, but in about half that for aspirin. |
| Major drug interactions: Concomitant administration with aspirin will antagonize the irreversible platelet inhibition induced by aspirin, and may thus limit the cardioprotective effects of aspirin. Ibuprofen can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis. During concomitant therapy with ibuprofen, the patient should be observed closely for signs of renal failure, as well as to assure diruretic efficacy. Ibuprofen may also increase lithium plasma levels in patients taking this drug, due to decreased renal clearance. Ibuprofen may be used in combination with gold salts and/or corticosteroids. Use of NSAIDs in patients who are receiving ACE inhibitors may potentiate renal disease states. |
Reference: www.rxlist.com |
| Drug: Naproxen (generic, Naprosyn, Anaprox, Aleve - OTC ®) |
| Drug Class: NSAID |
| Mechanism of Action: Nonselective Cox inhibitor |
| Indications: the treatment of rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, bursitis, and acute gout. It is also indicated in the relief of mild to moderate pain and the treatmentof primary dysmenorrhea. |
| Contraindications: history of drug hypersensitivity to NSAIDs |
| Pharmacokinetics: elimination half-life of Naprelan and conventional naproxen is approximately 15 hours. |
| Side Effects: the incidence of upper GI bleeding is low but still is double that of OTC ibuprofen (perhaps due to a dose effect). Rare cases of allergic pneumonitis. |
| Major drug interactions: similar to ibuprofen |
Reference: www.rxlist.com & Katzung's text |
| Drug: Nabumetone (Relafen ®) |
| Drug Class: NSAID (prodrug) |
| Mechanism of Action: Non selective COX inhibitor. A prodrug that is converted to a naproxen-like drug in the body. |
| Indications: acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis |
| Contraindications: similar to ibuprofen |
| Pharmacokinetics: It's half life of over 24 hrs permits once-daily dosing. Renal impairment results in a doubling of its half-life & increased plasma levels. |
| Side Effects: similar to other NSAIDs |
| Major drug interactions: similar to ibuprofen |
| Notes: An expensive NSAID. |
Reference: www.rxlist.com & Katzung's text |
| Drug: Diclofenac (generic, Cataflam, Voltaren ®) |
| Drug Class: NSAID |
| Mechanism of Action: Non selective COX inhibitor. |
| Indications: acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis; for the treatment of ankylosing spondylitis. Only Cataflam is indicated for the management of pain and primary dysmenorrhea, when prompt pain relief is desired, because it is formulated to provide earlier plasma concentrations of diclofenac |
| Contraindications: history of drug hypersensitivity |
| Pharmacokinetics: half life of 1-2 hrs. Accumulates in synovial fluid (one of it's sites of action) |
| Side Effects: adverse effects occur in about 20% of patients & include GI distress, GI bleeding & gastric ulceration. At doses of 150 mg/d diclofenac will impair renal blood flow & GFR. |
| Major drug interactions: similar to ibuprofen. Also, concomitant administration of diclofenac and aspirin is not recommended because diclofenac is displaced from its binding sites during the concomitant administration of aspirin |
Reference: www.rxlist & Katzung's text |
Disease-modifying antirheumatics
| Drug: Gold sodium thiomalate (Aurothiomalate, Aurothioglucose,Aurolate, Auranofin ®, Myochrysine ®) |
| Drug Class: Antirheumatic |
| Mechanism of Action: The predominant action appears to be a suppressive effect on the synovitis of active rheumatoid disease. Gold alters the morphology and functional capabilities of human macrophages, thereby inhibiting the production of monocyte chemotactic factor, IL-8 & IL-1beta. Intramuscular gold compounds may also alter lysosomal enzyme activity, reduce histamine release from mast cells, inactivate the first component of complement, and suppress the phagocytic activities of PMN leukocytes. |
| Indications: Patients who are nonresponsive to NSAIDs when treating active rheumatoid arthritis. The greatest benefit occurs in the early active stage. In late stages of the illness when cartilage and bone damage have occurred, gold can only check the progression of rheumatoid arthritis and prevent further structural damage to joints. It cannot repair damage caused by previously active disease. |
| Contraindications: Systemic lupus erythematosus. |
| Pharmacokinetics: Auranofin ® is an oral formulation, whereas Myochrysine ® is administered only by intramuscular injection, preferably intragluteally. Therapeutic effects from Myochrysine occur slowly. Early improvement, often limited to a reduction in morning stiffness, may begin after six to eight weeks of treatment, but beneficial effects may not be observed until after months of therapy. These compounds concentrate in synovial membranes, liver, kidney, spleen, lymph nodes & bone marrow. One month after an i.m. injection, ~80% of the drug is eliminated from the serum, but the total body half-life is approximately 1 year. |
| Side Effects: Dermatitis is the most common reaction (which may be aggrevated by exposure to sunlight). Stomatitis (mouth sores) is the second most common adverse reaction. Gold may be toxic to the kidney and produce a nephrotic syndrome or glomerulitis with hematuria. Danger signals of possible gold toxicity include: rapid reduction of hemoglobin, leukopenia below 4000 WBC/mm 3 , eosinophilia above 5 percent, platelet decrease below 100,000/mm 3 , albuminuria, hematuria, pruritus, skin eruption, stomatitis, or persistent diarrhea. |
| Major drug interactions: Gold salts should not be used concomitantly with penicillamine. |
Reference: www.rxlist & Katzung's text |
| Drug: Azathioprine |
| Drug Class: Immunosuppressive agent |
| Mechanism of Action: It is converted to mercaptopurine in the body, which then functions as a purine nucleic acid antimetabolite. It interferes with DNA synthesis, thereby destroying antigen stimulated lymphoid cells. |
| Indications: Azathioprine is indicated only in adult patients meeting criteria for classic or definite rheumatoid arthritis. Azathioprine should be restricted to patients with severe, active and erosive disease not responsive to conventional management including rest, aspirin or other non-steroidal drugs or to agents in the classof which gold is an example. It has also been used to treat Crohn's disease, multiple sclerosis and as an adjunct for the prevention of rejection in renal homotransplantation. |
| Contraindications: pregnancy, history of drug hypersensitivity |
| Pharmacokinetics: well absorbed from the GI tract, metabolized to mercaptopurine. The drug is inactivated by xanthine oxidase. |
| Side Effects: bone marrow suppression (leukopenia), anemia, skin rashes, fever, nausea, diarrhea. Hepatic dysfunction (jaundice, elevated aklaline phosphatase). |
| Major drug interactions: Allopurinol will decrease the metabolism of azathioprine. Patients taking allopurinol should take one forth to one third the usual dose of azathioprine. |
Reference: www.rxlist.com & Katzung's text |
| Drug: Chloroquine & Hydroxychloroquine (Plaquenil ®) |
| Drug Class: Antimalarial, Antirheumatoid |
| Mechanism of Action: the mechanism of action in rheumatic disease is unclear. The following mechanims have been proposed: suppression of T lymphocyte responses to mitogens, decreased leukocyte chemotaxis, stabilization of lysosomal enzymes, inhibition of DNA and RNA synthesis & trapping of free radicals. |
| Indications: improvement of symptoms in rheumatoid arthritis. There is no evidence that these drugs alter bony damage that can occur in arthritis. Restricted to use in adults since safe use of the drug in the treatment of juvenile rheumatoid arthritis has not been established. |
| Contraindications: the presence of retinal or visual field changes attributable to any 4-aminoquinoline compound (like chloroquine), and in patients with known hypersensitivity to 4-aminoquinoline compounds. |
| Pharmacokinetics: It usually takes several weeks to get any noticeable drug effect, and up to 3-6 months to obtain a maximal response. |
| Side Effects: Ocular toxicity at high doses. With acute overdosage - headache, drowsiness, visual disturbances, cardiovascular collapse and convulsions. |
Reference: www.rxlist & Katzung's text |
| Drug: Penicillamine (Cuprimine, Depen ®) |
| Drug Class: Heavy metal chelator |
| Mechanism of Action: |
| Indications: in adult patients with severe, active rheumatoid arthritis who have failed to respond to an adequate trial of conventional therapy. Also used in the treatment of Wilson's disease (a genetic disorder resulting in an accumulation of copper) & cystinuria. |
| Contraindications: use in pregnancy, history of penicillamine-related aplastic anemia or agranulocytosis. Because of its potential for causing renal damage, penicillamine should not be administered to rheumatoid arthritis patients with a history orother evidence of renal insufficiency. |
| Pharmacokinetics: two or three months may be required before the first evidence of a clinical response is noted |
| Side Effects: a high incidence of untoward reactions, some of which are potentially fatal. The use of penicillamine has been associated with fatalities due to certain diseases such as aplastic anemia, agranulocytosis, thrombocytopenia, Goodpasture's syndrome, and myasthenia gravis. Other side effects include drug fever, rash, lupus-like syndromes with positive antinuclear antibody tests, iron deficiency, decreased normal healing, decreased tensile strength of the skin due to alterations in collagen |
| Major drug interactions: gold salts (penicillamine will chelate them) |
| Notes: penacillamine is a metabolite of penicillin. It is rarely used because of its toxicity. |
Reference: www.rxlist.com & Katzung's text |
| Drug: Methotrexate (Amethopterin, Rheumatrex ®) |
| Drug Class: Antineoplastic agent |
| Mechanism of Action: the mechanism of action in rheumatoid arthritis is unknown;it may affect immune function. (Methotrexate inhibits dihydrofolic acid reductase, which interferes with DNA synthesis.). |
| Indications: the management of selected adults with severe, active, classical or definite rheumatoid arthritis who have had an insufficient therapeutic response to, or are intolerant of, an adequate trial of first-line therapy including full dose NSAIDs and usually a trial of at least one or more disease-modifying antirheumatic drugs. There is no evidence that it induces remission of rheumatoid arthritis nor has a beneficial effect been demonstrated on bone erosions. |
| Contraindications: pregnancy (methotrexate can cause fetal death or teratogenic effects when administered to a pregnant woman). Contraindicated in nursing mothers. Patients with immune deficiencies or blood dyscrasias (anemia, leukopenia, thrombocytopenia) |
| Pharmacokinetics: orally absorbed. Does not cross the blood brain barrier. Half life of 3-10 hrs. Effects can be seen as early as 3 to 6 weeks. |
| Side Effects: most commonly - ulcerative stomatitis, leukopenia, nausea, and abdominal distress. High doses can cause severe hematologic and gastrointestinal toxicity. |
| Major drug interactions: Caution should be used when NSAIDs and salicylates are administered concomitantly with lower doses of methotrexate. These drugs have been reported to reduce the tubular secretion of methotrexate and may enhance its toxicity. |
Reference: www.rxlist.com |
TNF-alpha blocking agents
| Drug: Adalimumab (Humira ®), Infliximab (Remicade ®), Etanercept (Enbrel ®) |
| Drug Class: Treatment of rheumatoid arthritis |
| Mechanism of Action: Adalimumab is a recombinant human anti-TNF monoclonal antibody. It complexes with soluble TNF-alpha and prevents its interaction with p55 and p75 surface receptors. This results in a down-regulation of macrophage & T cell function. Infliximab is a chimeric (25% mouse, 75% human) monoclonal antibody that binds with high affinity to soluble, and possibly membrane bound TNF-alpha. Etanercept is a recombinant fusion protein consisting of two soluble TNF p75 receptors bound to the Fc portion of human IgG1. It binds TNF-alpha and also inhibits lymphotoxin-alpha. |
| Indications: Treatment of rheumatoid arthritis and similar inflammatory disorders |
| Pharmacokinetics: Adalimumab and Etanercept are given s.c.. Infliximab is given i.v. |
| Side Effects: increased risk for macrophage-dependent infection (e.g. tuburculosis). |
Notes: See Immumopharmacology section for further deatils on Adalimumab & Infliximab |
| Reference: Katzung's text |
Drugs used in Gout
| Drug: Colchicine (generic) |
| Drug Class: A plant alkaloid used in the treatment of gout |
| Mechanism of Action: The exact mechanism of action of colchicine in gout is not completely known, but it involves (1) a reduction in lactic acid production by leukocytes, which results in a decrease in uric acid deposition, and (2) a reduction in phagocytosis, with abatement of the inflammatory response. |
| Indications: for treatment and relief of pain in attacks of acute gouty arthritis. It is also recommended for regular use between attacks as a prophylactic measure, and is often effective in aborting an attack when taken at the first sign of articular discomfort. |
| Contraindications: patients with a known hypersensitivity to the drug, and in those with serious gastrointestinal, renal, hepatic, or cardiac disorders, and in those with blood dyscrasias. |
| Pharmacokinetics: rapidly absorbed after oral administration. Large amounts of the drug and metabolites enter the intestinal tract in bile and intestinal secretions. |
| Side Effects: diarrhea, nausea, vomiting, abdominal pain. Bone marrow depression, hair loss, peripheral neuritis & myopathy. |
| Major drug interactions: Colchicine is inhibited by acidifying agents. The action of colchicine is potentiated by alkalinizing agents. Colchicine may increase sensitivity to the CNS depressants. Response to sympathomimetic agents’may be enhanced by colchicine. |
| Notes: Colchicine is not an analgesic, though it relieves pain in acute attacks of gout. It is not a uricosuric agent and will not prevent progression of gout to chronic gouty arthritis. It does have a prophylactic, suppressive effect that helps to reduce the incidence of acute attacks and to relieve the residual pain and mild discomfort that patients with gout occasionally feel. |
Reference: www.rxlist.com & Katzung's text |
| Drug: Allopurinol (generic, Zyloprim ®) |
| Drug Class: Xanthine oxidase inhibitor |
| Mechanism of Action: Inhibits xanthine oxidase, resulting in a decrease in synthesis of uric acid. |
| Indications: 1) The management of patients with signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis and/or nephropathy). Also: 2) the management of patients with leukemia, lymphoma and malignancies who are receiving cancer therapy which causes elevations of serum and urinary uric acid levels. Allopurinol treatment should be discontinued when the potential for overproduction of uric acid is no longer present. 3) the management of patients with recurrent calcium oxalate calculi whith abnormally high daily uric acid excretion. |
| Contraindications: in patients who have developed a severe reaction to allopurinol. |
| Pharmacokinetics: Allopurinol is metabolized to alloxanthine, which inhibits xanthine oxidase with a long duration of action, so that allopurinol can be given once daily. |
| Side Effects: skin rash. Skin reactions can be severe and sometimes fatal. Therefore, treatment with allopurinol should be discontinued immediately if a rash develops ( |
| Major drug interactions: concentrations of chemotherapeutic mercaptopurines given concomittantly with allopurinol must be given with a reduction in dosage of ~75%. Allopurinol may increase the effect of cyclophosphamide & inhibit the metabolism of probenecid & oral anticoagulants. Allopurinol may increase hepatic iron concentration. |
| Notes: Treatment of gout with allopurinol and uricosuric agents is begun with the expectation that it will be continued for years, if not for life. |
Reference: www.rxlist & Katzung's text |
| Drug: Probenecid (generic) |
| Drug Class: Uricosuric drug |
| Mechanism of Action: Uricosuric drugs are organic acids that act at the anionic transport sites of the renal tubule. Uric acid is freely filtered by the golmerulus. Probenecid (& sulfinpyrazone) inhibit the active transport sites that cause net reabsorption of uric acid in the proximal tubule of the kidney. As the excretion of uric acid increases, the body's pool of urate decreases, although the plasma concentration may not be greatly reduced. Topaceous deposits of urate can be reabsorbed, with relief of arthritis and remineralization of bone. |
| Indications: if several acute attacks of gouty arthritis have occured, when there is evidence of tophi, or when plasma levels of uric acid in patients with gout are so that tissue damage is inevitable. Therapy should not be started until 2-3 weeks after an acute attack. |
| Pharmacokinetics: completely reabsorbed by renal tubules & metabolized very slowly. |
| Side Effects: GI irritation, allergic dermatitis (rash). Nephrotic syndrome has occured. Rarely causes aplastic anemia. |
| Major drug interactions: Probenicid affects the reabsorptioin of weak acids in the kidney & can elevate plasma levels of various drugs that are weak acids by that mechanism. In particular, probenicid intereferes with the renal excretion of conjugated sulfonamides (it produces an insignificant increase in free sulfonamide plasma concentrations but a significant increase in total sulfonamide plasma levels). Probenicid interefers with the renal secretion of penicillin and thereby elevates the plasma concentrations of penicillin and other beta-lactams. Aspirin - antagonizes the uricosuric action of probenecid. |
| Notes: Associated with the increase in uric acid excretion is a risk of forming renal stones. Therefore the urine volume should be maintained at a high level, and at least in early treatment, uring pH should be kept above 6.0 by administering alkalai. Probenicid is also available in a formulation combined with colchicine. |
Reference: www.rxlist.com & Katzung's text |
| Drug: Sulfinpyrazone (generic, Anturane ®) |
| Drug Class: Uricosuric drug |
| Mechanism of Action: (see above - same as probenicid). Also weakly anti-inflammatory |
| Indications: Chronic gouty arthritis or intermittent gouty arthritis |
| Contraindications: Patients with an active peptic ulcer or symptoms of gastrointestinal inflammation or ulceration should not receive the drug. |
Reference: www.rxlist.com |
Immunosuppressants
| Drug: Prednisone (generic, Meticorten ®) |
| Drug Class: Glucocorticoid (synthetic) |
| Mechanism of Action: Effects are mediated by binding to glucocorticoid receptors. When stimulated, these receptors alter the transcription of various target genes. In the absence of the hormonal ligand, glucocorticoid receptors are primarily cytoplasmic & exist as oligomeric complexes with heat shock proteins. When free hormone in the cytoplasm binds to the receptor, a conformational change occurs and it dissociates from heat shock protein. The hormone-receptor complex is transported to the nucleus, where it interacts with DNA and nuclear proteins. By this type of mechanism, glucocorticoids are thought to interfere with the cell cycle of activated lymphoid cells. They inhibit the production of inflammatory mediators, including PAF, leukotrienes, prostaglandins, histamine and bradykinin. In monocytes and neutrophils, glucocorticoids cause diminished chemotaxis & impaired bactericidal & fungicidal activities. A mechanism that contributes to the decrease in the synthesis of inflammatory mediators produced by glucocorticoids is an inhibition of phospholipase A2 as well a downregulation of the expression of Cox-2 (but not Cox-1), thus reducing the amount of enzyme available to produce prostaglandins. By inhibiting IL-1 production by monocytes, they cause a decrease in IL-2 and IFN-gamma production. Although cellular immunity is affected more than humoral immunity, the primary antibody response can also be diminished. Continuous administration increases the catabolic rate of IgG, the major class of antibody immunoglobulins. |
| Indications: used for its potent anti-inflammatory effects in disorders of many organ systems. Used alone or in conjuction with other immunosuppressive agents to prevent transplant rejection. Used to minimize allergic reactions that may occur with the use of monoclonal antibodies & to treat autoimmune diseases. Prednisone is one of the most commonly used immunosuppressants. |
| Contraindications: Systemic fungal infections and known hypersensitivity to components of the drug formulation. Persons who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chicken pox or measles. |
| Pharmacokinetics: Prednisone is rapidly converted to the active product prednisolone in the body. Prednisone has an intermediate duration of action compared to other glucocorticoids. |
| Side Effects: High-dose, long-term glucocorticoid therapy can produce severe toxicities that can include effects such as sodium retention, fluid retention, muscle weakness, steriod myopathy, loss of muscle mass, osteoporosis, tendon rupture, particularly of the Achilles tendon, peptic ulcer with possible perforation and hemorrhage; pancreatitis, impaired wound healing, thin fragile skin, menstrual irregularities; development of Cushingoid state; secondary adrenocortical and pituitary unresponsiveness, posterior subcapsular cataracts, increased intraocular pressure, glaucoma, growth inhibition, diabetogenesis & psychoses just to name a few. |
| Notes: Corticosteroids may mask some signs of infection, and new infections may appear during their use |
References: www.rxlist.com, Katzung's text (see Chapters 39 &56) & Goodman & Gillman's 10th Edition (Chapter 26). |
| Drug: Cyclosporine (Sandimmune, Neoral, SangCya ®) |
| Drug Class: Immunosuppressant |
| Mechanism of Action: Cyclosporine is a fat-soluble cyclic polypeptide antibiotic that acts at an early stage in the antigen receptor-induced differentiation of T cells and blocks their activation. Cyclosporine binds to and forms a complex with the intracellular protein cyclophilin, resulting in the inhibition of calcineurin, a phosphatase that is necessary for activation of a T cell-specific transcription factor (NF-AT). NF-AT is involved in the synthesis of interleukins (e.g. IL-2) by activated T cells. In vitro studies indicate that cyclosporine inhibits the gene transcription of IL-2, IL-3, IFN-gamma, and other factors produced by antigen-stimulated T cells. Cyclosporine produces a specific and reversible inhibition of immunocompetent lymphocytes in the G0-or G1-phase of the cell cycle. T-lymphocytes are preferentially inhibited. The 1-helper cell is the main target, although the 1-suppressor cell may also be suppressed. |
| Indications: a potent immunosuppressive agent which in animals prolongs survival of allogeneic transplants involving skin, heart, kidney, pancreas, bone marrow, small intestine, and lung. |
| Contraindications:known drug hypersensitivity to the product |
| Pharmacokinetics: can be given orally or i.v. The absorption of cyclosporine from the gastrointestinal tract is incomplete and variable.Metabolized by P-450 isoforms & excreted in the bile. Elimination half life is 24 hrs. |
| Side Effects: Numerous toxicities, including - nephrotoxicity, hypertension, hyperglycemia, liver dysfunction, hirsutism, gum hyperplasia. |
| Major drug interactions: Numerous! Drugs That Exhibit Nephrotoxic Synergy: gentamicin, amphotericin B, cimetidine, trimethoprim with sulfamethoxazole, tobramycin, ketoconazole, ranitidine, vancomycin, melphalan, diclofenac, azapropazon. Drugs That Increase Cyclosporine Levels (P-450 inhibitors): diltiazem, ketoconazole, danazol, erythromycin, nicardipine, fluconazole, bromocriptine, methylprednisolone, verapamil, itraconazole, metoclopramide, amphotericin B. Drugs That Decrease Cyclosporine Levels (P-450 inducers): rifampin, phenytoin, phenobarbital, carbamazepine. |
References: www.rxlist.com |
| Drug: Tacrolimus [FK506] (Prograf ®) |
| Drug Class: Immunosuppressant macrolide antibiotic |
| Mechanism of Action: tacrolimus binds to the immunophilin FK-binding protein (FKBP), forming a complex, and results in the inhibition of calcineurin, which is necessary for the activation of the T-cell specific transcription factor NF-AT. Its mechanism is "similar" to cyclosporin in that its mechanism involves the inhibition of calcineurin. |
| Indications: The same as for cyclosporine - inhibiting immune responses in organ transplantation. Also used as a topical treatment for atopic dermatitis & psoriasis. |
| Contraindications: known hypersensitivity to this preparation, including HCO-60 (polyoxyl 60 hydrogenated castor oil). |
| Pharmacokinetics: oral or i.v. administration. Metabolized by P-450 (CYP3A) w/ the potential for drug interactions. |
| Side Effects: tremor, headache, diarrhea, hypertension, nausea, and renal dysfunction. |
| Major drug interactions: Due to the potential for additive or synergistic impairment of renal function, care should be taken when administering tacrolimus with drugs that may be associated with renal dysfunction.Tacrolimus is metabolized mainly by CYP3A. Substances known to inhibit or induce this enzyme may decrease or increase the metabolism of tacrolimus with resultant changes in plasma concentrations (see rxlist.com for further details). Immunosuppressants may affect vaccination. Therefore, during treatment with Prograf, vaccination may be less effective. |
| Notes: increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression |
References: www.rxlist.com |
| Drug: Sirolimus [rapamycin] (Rapamune ®) |
| Drug Class: Immunosuppressant |
| Mechanism of Action: Sirolimus inhibits T lymphocyte activation and proliferation that occurs in response to antigenic and cytokine (Interleukins IL-2, IL-4, and IL-15) stimulation by a mechanism that is distinct from that of other immunosuppressants. Sirolimus also inhibits antibody production. In cells, sirolimus binds to the immunophilin, FK Binding Protein-12 (FKBP-12), to generate an immunosuppressive complex. The sirolimus:FKBP-12 complex has no effect on calcineurin activity. This complex binds to and inhibits the activation of the mammalian Target Of Rapamycin (mTOR), a key regulatory kinase. This inhibition suppresses cytokine-driven T-cell proliferation, inhibiting the progression from the G 1 to the S phase of the cell cycle (see figure 5 in Dr. Beckman's handout). |
| Indications: the prophylaxis of organ rejection in patients receiving renal transplants. It can be used in combination with other immuosuppressants (cyclosporine, tacrolimus, glucocorticoids). Topical sirolimus is used in some dermatologic disorders & in combination with cyclosporine in the management of uveoretinitis. |
| Contraindications: patients with a hypersensitivity to sirolimus or its derivatives or any component of the drug product. |
| Pharmacokinetics: Sirolimus is a substrate for both cytochrome P450 (CYP3A4) and P-glycoprotein. |
| Side Effects: Toxicities can include profound myelosuppression (esp. thrombocytopenia), hepatotoxicity, diarrhea, hypertriglyceridemia & headache. |
| Major drug interactions: The pharmacokinetic interaction between sirolimus and concomitantly administered drugs is based upon drugs that effect CYP3A4 and P-glycoprotein activity (see rxlist.com). |
References: www.rxlist.com & Katzung's text |
Cytotoxic Drugs
| Drug: Azathioprine (generic, Imuran ®) |
| Drug Class: Immunosuppressant |
| Mechanism of Action: an immunosuppressive antimetabolite. It interferes with purine nucleic acid metabolism at steps required for lymphoid cell proliferation that follows antigenic stimulation. The purine analogs are thus cytotoxic and destroy stimulated lymphoid cells. Cellular immunity as well as primary and secondary serum antibody responses can be blocked by these agents. |
| Indications: an adjunct for the prevention of rejection in renal homotransplantation. It is also indicated for the management of severe, active rheumatoid arthritis unresponsive to rest, aspirin or other nonsteroidal anti-intlammatory drugs, or to agents in the class of which gold is an example |
| Contraindications: should not be used to treat rheumatoid arthritis in pregnant women. Patients with rheumatoid arthritis previously treated with alkylating agents cyclophosphamide, chlorambucil, melphalan or others) may have a prohibitive risk of neoplasia if treated with azathioprine. |
| Pharmacokinetics: Azathioprine is a prodrug that is metabolized to mercaptopurine (the active form). Xanthine oxidase splits much of the active material to 6-thioruric acid prior to excretion in the urine. |
| Side Effects: hematologic (leukopenia and/or thrombocytopenia) and gastrointestinal (nausea & vomiting). The risks of secondary infection and neoplasia are also significant. |
| Major drug interactions: Patients taking allopurinol should have the dose of azathioprine reduced to one third to one forth the usual amount to prevent toxicity. |
References: www.rxlist & Katzung's text |
| Drug: Cyclophosphamide (Cytoxan, Neosar ®) |
| Drug Class: Immunosuppressant |
| Mechanism of Action: an alkylating agent that is one of the most efficacious immunosuppressive drugs available. Destroys proliferating lymphoid cells. Greater effect on B cells than on T cells. |
| Indications: effective against autoimmune disorders (systemic lupus erythematosus & multiple sclerosis) & in patients with autoimmune hemolytic anemia. Can inhibit an established immune response. Typically used as a drug of 2nd choice after another drug has been found to be ineffective (because of its greater toxicity). |
| Contraindications: patients with severely depressed bone marrow function |
| Side Effects: nausea, vomiting, electrolyte disturbances, cardiotoxicity |
References: www.rxlist & Katzung's text |
| Drug: Mycophenolate mofetil (CellCept ®) |
| Drug Class: Immunosuppressant |
| Mechanism of Action: a semisynthetic "prodrug" derivative of mycophenolic acid (the active form). It inhibits the de novo synthesis of purines by inhibiting inosine monophosphate dehydrogenase (IMPDH). It inhibits a series of T and B lymphocyte responses, including mitogen and mixed lymphocyte responses. |
| Indications: Renal & Cardiac Transplants. Indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal transplants and in patients receiving allogeneic cardiac transplants. CellCept can be used concomitantly with cyclosporine and corticosteroids. |
| Pharmacokinetics: Mycophenolate mofetil is a prodrug that is hydrolyzed to mycophenolic acid. Administered as a prodrug to enhance bioavailability. |
| Side Effects: GI side effects |
References: www.rxlist & Katzung's text |
Antibody Reagents
| Drug: Anti-Thymocyte globulin [ATGAM] (Thymoglobulin ®) |
| Drug Class: Immunosuppressive antibody |
| Mechanism of Action: contains cyctotoxic antibodies that bind to molecules on the surface of human T lymphocytes. They can deplete circulating lymphocytes by direct cytotoxicity (complement & cell-mediated), and also block lymphocyte function by binding to cell surface molecules involved in the regulation of cell function. |
| Indications: 1) used in combination with other agents to treat acute rejection in kidney transplants; 2) prior to bone marrow transplantation to prevent graft-host reactions; 3) has induced remissions in aplastic anemia. |
| Pharmacokinetics: administered parenterally. |
| Side Effects: fever & chills |
References: Dr. Beckman's handout |
| Drug: Rho (D) Immune Globulin Micro-Dose (BayRho-D, RhoGam, Win-Rho ®) |
| Drug Class: Specific IgG Antibody to Rho (D) antigen of the red cell |
| Background: Rh-negative mothers can become sensitized to the D antigen on red cells in an Rho (D)-positive or Du-positive infant, when fetal red cells leak into the mother's blood stream during child birth. In subsequent pregnancies, maternal antibody against Rh-positive cells is transfered to the fetus during the 3rd trimester, leading to the development of hemolytic disease of the newborn. |
| Mechanism of Action: When injection of Rho(D) antibody is given to the mother 24-72 hrs after the birth of an Rh-positive baby, the mother's own antibody response to the foreign Rho (D)-positive cells is suppressed because the baby's red cells are cleared from the circulation before the mother can generate a B cells response against Rho(D). Therefore she has no memory B cells that can activate upon subsequent pregnancies with an Rho(D)-positive fetus. |
| Indications: prevention of Rh hemolytic disease of the newborn. |
| Pharmacokinetics: Given i.m. Note: Rho(D) is given to the mother, and NOT the infant. |
| Side Effects: infrequent local discomfort at the injection site, slight temperature elevation. |
References: Katzung's text. |
| Drug: Muromonab-CD3 [OKT3] (Orthoclone OKT3 ®) |
| Drug Class: Monoclonal Antibody |
| Mechanism of Action: A murine monoclonal antibody directed against the CD3 molecule on the surface of human thymocytes and mature T cells. Blocks both killing by cytotoxic T cells and several other T cell functions. |
| Indications: treatment of renal allograft rejection. |
References: Katzung's text |
| Drug: Infliximab (Remicade ®) |
| Drug Class: Monoclonal Antibody / TNF- alpha antagonist |
Mechanism of Action: neutralizes the biological activity of TNFalpha by binding with high affinity to the soluble and transmembrane forms of TNFalpha and inhibits binding of TNFalpha with its receptors. Biological activities attributed to TNFalpha include: induction of pro-inflammatory cytokines such as interleukins (IL) 1 and 6, enhancement of leukocyte migration by increasing endothelial layer permeabilityand expression of adhesion molecules by endothelial cells and leukocytes, activation of neutrophil and eosinophil functional activity, induction of acute phase reactants and other liver proteins, as well as tissue degrading enzymes produced by synoviocytes and/or chondrocytes. |
| Indications: Rheumatoid arthritis: in combination with methotrexate, is indicated for reducing signs and symptoms, inhibiting the progression of structural damage and improving physical function in patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to methotrexate. Crohn’s disease: for reducing the number of draining enterocutaneous and rectovaginal fistulas and maintaining fistula closure in patients with fistulizing Crohn’s disease. |
| Pharmacokinetics: parenteral administration |
| Side Effects: increased incidence of lymphoma |
References: www.rxlist & Katzung's text |
| Drug: Daclizumab (Zenapax ®) |
| Drug Class: Monoclonal Antibody / IL-2 Antagonist |
| Mechanism of Action: IgG1 that binds to CD25 (alpha subunit of the IL-2 receptor), blocking IL-2 from binding to activated lymphocytes, which is an immunosuppressive action. It functions as an IL-2 antagonist |
| Indications: prophylaxis of actue organ rejection in renal transplant patients. Usually combined with glucocorticoids & cyclosporine. |
| Pharmacokinetics: Given i.v. in a series of doses. Daclizumab saturates the Tac subunit of the IL-2 receptor for approximately 120 days post-transplant. |
References: www.rxlist & Katzung's text |
| Drug: Etanercept (Enbrel ®) |
| Drug Class: Monoclonal Antibody / TNF receptor fusion protein |
| Mechanism of Action: A dimer of human IgG1 and the TNF receptor. Etanercept binds to both TNF-alpha and TNF-beta, inhibiting TNF-mediated inflammation. |
| Indications: Adult rheumatoid arthritis, polyarticular course junvenile rhematoid arthritis, psoriatic arthritis. May be used in combination with methotrexate. |
| Pharmacokinetics: Shorter duration of action compared to imfliximab & must begiven s.c. twice a week. |
References: www.rxlist & Katzung's text |
Immunomodulatory
| Drug: Thalidomide (Thalomid ®) |
| Drug Class: Immunomodulatory agent & sedative |
| Mechanism of Action: the immunologic effects of this compound can vary substantially under different conditions, but, may be related to suppression ofexcessive tumor necrosis factor-alpha (TNF-alpha) production and down-modulation of selected cell surface adhesion molecules involved in leukocyte migration. Has antiangiogenic effects as well. |
| Indications: Over 40 different indications including multiple myeloma, management of the skin manifestations of lupus erythematosus & the cutaneous manifestations of moderate to severe erythema nodosum leprosum (ENL). |
| Contraindications: IF THALIDOMIDE IS TAKEN DURING PREGNANCY, IT CAN CAUSE SEVERE BIRTH DEFECTS OR DEATH TO AN UNBORN BABY. |
| Side Effects: Extensive side effects including teratogenesis, peripheral neuropathy, hypothyroidism, thrombosis. |
References: www.rxlist & Katzung's text |
Natural Adjuvants
| Drug: Aldesleukin (Proleukin ®) |
Drug Class: Recombinant Interleukin-2 |
| Mechanism of Action: possesses the biological activities of human native interleukin-2. As such it can cause: a) enhancement of lymphocyte mitogenesis and stimulation of long-term growth of human interleukin-2 dependent cell lines; b) enhancement of lymphocyte cytotoxicity; c) induction of killer cell (lymphokine-activated (LAK) and natural (NK)) activity; and d) induction of interferon-gamma production. |
| Indications:1) the treatment of adults with metastatic renal cell carcinoma (metastatic RCC). 2) for the treatment of adults with metastatic melanoma. |
References: www.rxlist & Katzung's text |
| Drug: Interferon - alpha-2a (Roferon-A ®) |
| Drug Class: Cytokine |
| Mechanism of Action: it is believed that direct antiproliferative action against tumor cells, inhibition of virus replication and modulation of the host immune response play important roles in antitumor and antiviral activity. |
| Indications: the treatment of chronic hepatitis C, hairy cell leukemia, AIDS-related Kaposi's sarcoma, and hepatitis B and C infections. |
References: www.rxlist & Katzung's text |
| Drug: Interferon - beta-1a (Intron-A, Betaseron ®) |
| Drug Class: Cytokine |
| Mechanism of Action: Interferon beta-1b has been shown to possess both antiviral and immunoregulatory activities. The mechanisms by which Betaseron exerts its actions in multiple sclerosis (MS) are not clearly understood. |
| Indications: for use in ambulatory patients with relapsing-remitting multiple sclerosis to reduce the frequency of clinical exacerbations. |
References: www.rxlist & Katzung's text |
| Drug: Interferon - gamma-1b (Actimmune ®) |
| Drug Class: Cytokine |
| Indications: treatment of chronic granulomatous disease |
References: Katzung's text |
Antimetabolite
| Drug: Methotrexate (Rheumatrex ®) |
| Drug Class: Antimetabolite |
| Mechanism of Action: inhibits dihydrofolic acid reductase. Dihydrofolates must be reduced to tetrahydrofolates by this enzyme before they can be utilized as carriers of one-carbon groups in the synthesis of p.r.n. nucleotides and thymidylate. Therefore, methotrexate interferes with DNA synthesis, repair, and cellular replication. Actively proliferating tissues such as malignant cells, bone marrow, fetal cells, buccal and intestinal mucosa, and cells of the urinary bladder are in general more sensitive to this effect of methotrexate. When cellular proliferation in malignant tissues is greater than in most normal tissues, methotrexate may impair malignant growth without irreversible damage to normal tissues. The mechanism of action in rheumatoid arthritis is unknown;it may affect immune function. Clarification of methotrexate's effect on immune activity and its relation to rheumatoid immunopathogenesis await further studies. |
| Indications: neoplastic diseases, psoriasis, rheumatoid arthritis |
| Contraindications: Methotrexate can cause fetal death or teratogenic effects when administered to pregnant women. |
| Side Effects: the most frequently reported adverse reactions include ulcerative stomatitis, leukopenia, nausea, and abdominal distress. |
| Major drug interactions: Leucovorin is indicated to diminish the toxicity and counteract the effect of inadvertently administered overdosages of methotrexate |
References: www.rxlist & Katzung's text |
| Drug: Prednisone (generic, Meticorten ®) |
| See Immunopharmacology section above |
| Drug: Hydrocortisone [Cortisol] (generic, Cortef, Hydrocortone, Solu-Cortef ®) |
| Drug Class: Glucocorticoid (Naturally occurring, Short-acting) |
| Mechanism of Action: see prednisone for details on the mechanism of action of glucocorticoids. (Inhibits PLA2 and downregulate COX-2, alters gene experession). |
| Indications: as replacement therapy in adrenocortical deficiency states such as primary adrenocortical insufficiency (Addison's disease) or secondary adrenocortical insufficiency. They are also used for their potent anti-inflammatory effects in disorders of many organ systems (e.g. lupus, rheumatoid arthritis, asthma). |
| Contraindications: Systemic fungal infections. Hypersensitivity to this product |
| Side Effects: Permanent: aseptic necrosis of femoral & humoral heads, cataracts. Reversible: fluid retention, hyperglycemia, hypertension, peptic ulcers, osteoporosis, myopathy, mood disorders, impaired wound healing, development of a Cushionoid state (this is the short list - see predisone for more). |
| Pharmacokinetics: Cortisol is sometimes refered to as the "stress hormone" since it is elevated under stress and produces an elevation in glood glucose (amongst other effects). It's synthesis & secretion is tightly regulated by the CNS. Cortisol is synthesized from cholesterol, and its rate of secretion follows a circadian rhythm governed by pulses of ACTH that peak in the early morning & after meals. Mostly (90%) bound to corticosteroid-binding globulin (CBG) in the plasma at physiologic levels. The half life in the circulation is normally 60-90 mins, but it's half life may be increased when stress, hyperthyroidism or liver disease is present. Cortisol is inactivated by P450 enzymatic reduction in the liver. |
References: www.rxlist & Katzung's text |
| Drug: Dexamethasone (generic, Decadron, others ®) |
| Drug Class: Glucocorticoid (Long-acting) |
| Mechanism of Action: Similar to Prednisone & Cortisol. However, at equipotent anti-inflammatory doses, dexamethasone almost completely lacks the sodium-retaining property of hydrocortisone and closely related derivatives of hydrocortisone. |
| Indications: The dexamethasone suppression test is used for the diagnosis of Cushing's syndrome (adrenocortical hyperfunction) & in the differential diagnosis of depressive psychiatric states. In Cushing's disease there is typically a bilateral adrenal hyperplasia secondary to an ACTH-secreting pituatary adenoma, resulting in glucocorticoid hypersecretion, which can produce protein loss, poor wound healing, mental depression, etc. In patients with Cushing's disease, an appropriate dose of dexamethasone will produce a ~50% reduction in hormone levels. Note: dexamethasone would not suppress glucocorticoid release from adrenal tumors, hence it is a useful diagnostic test for distinguishing between the two disorders. |
References: www.rxlist & Katzung's text |
| Drug: Triamcinolone [Triamcinolone acetonide] (generic, Aristocort, Kenacort ®) |
| Drug Class: Corticosteroid (lipid soluble, inhalational formulation) |
| Indications: the maintenance treatment of asthma as prophylactic therapy. This inhalation aerosol is also indicated for asthma patients who require systemic corticosteroid administration, where adding triamcinolone may reduce or eliminate the need for the systemic corticosteroids. |
| Pharmacokinetics: Available in oral, injectible, & topical/inhalational formulations. The inhaled route makes it possible to provide effective local anti-inflammatory activity with reduced systemic corticosteroid effects. Though highly effective for asthma, glucocorticoids do not affect asthma symptoms immediately. While improvement in asthma may occur as soon as one week after initiation of Inhalation aerosol therapy, maximum improvement may not be achieved for 2 weeks or longer. Intermediate -acting. |
References: www.rxlist & Katzung's text |
| Drug: Fludrocortisone (generic, Florinef Acetate ®) |
| Drug Class: Mineralcorticoid (Synthetic) |
| Mechanism of Action: has salt & water retaining properties |
| Indications: In the treatment of adrenocortical insufficiency (e.g. Addison's dx.) associated with mineralcorticoid deficiency. The most widely used mineralcorticoid (also has glucorcorticoid activity). |
| Side Effects: Most adverse reactions are caused by the drug's mineralocorticoid activity (retention of sodium and water) and include hypertension, edema, cardiac enlargement, congestive heart failure, potassium loss, and hypokalemic alkalosis. |
| Pharmacokinetics: Oral administration. |
References: www.rxlist & Katzung's text |
| Drug: Methylprednisolone (generic, Medrol, Depo-Medrol, Solu-Medrol ®) |
| Drug Class: Glucocorticoid (Medium - acting) |
References: www.rxlist & Katzung's text |
| Drug: Mifepristone [RU-486] (Mifeprex ®) |
| Drug Class: Termination of Pregnancy |
| Mechanism of Action: binds strongly to progesterone receptors & inhibits the actions of progesterone. |
| Indications: "Morning after" contraception. Effective as a postcoital contraceptive when combined with a prostaglandin. The combination of a single dose of mifepristone & a vaginal perssary containing prostaglandin E1has been found to terminate pregnancy in over 95% of patients treated during the first 7 weeks after conception. |
| Side Effects: vaginal bleeding |
References: www.rxlist & Katzung's text |
| Drug: Metyrapone |
| Drug Class: Inhibitor of Glucocorticoid Synthesis |
| Mechanism of Action: Inhibits 11-hydroxylation, interfering with cortisol & corticosterone synthesis. In the normal pituitary gland, there is a compensatory increase in 11-dexoycortisol secretion. This response is a measure of the capacity of the anterior pituitary to produce ACTH and this has been adopted for clinical use as a diagnostic test. |
| Indications: Diagnostic test of pituitary function. It may be useful for reducing cortisol production to normal levels in Cushing's syndrome. A normal response (reduction in cortisol or its metabolites in urine) indicates that the elevated cortisol levels are not due to a cortisol-secreting adrenal carcinoma or adenomal, since secretion by such tumors produces suppression of ACTH & atrophy of normal adrenal cortex. |
| Side Effects: transient dizziness & GI disturbances |
References: Katzung's text |
| Drug: Hydrocortisone (Westcort, Pandel ®) |
| Drug Class: Topical Corticosteroid |
| Mechanism of Action: The original topical glucocorticoid (natural). |
| Indications: a medium potency corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid - responsive dermatoses in patients 18 years of age or older. |
| Side Effects: burning & stinging sensation. Topically applied corticosteroids can be absorbed in sufficient amounts to produce systemic effects. |
| Pharmacokinetics: Only minimally (1%) absorbed following application to normal skin, although this is dependent on the region of the body. |
References: www.rxlist & Katzung's text |
| Drug: Triamcinolone acetonide (®) |
| Drug Class: Topical corticosteriod |
| Mechanism of Action: (see section above) more lipid soluble than hydrocortisone |
| Indications: Inflammatory dermatoses, severe psoriasis. |
References: www.rxlist & Katzung's text |
Acne
| Drug: Tretinoin [Retinoic acid] (Renova ®) |
| Drug Class: Topical Acne Preparation (acid form of vitamin A) |
Mechanism of Action: It's action in acne has been attributed to decreased cohesion between epidermal cells & increaesd epidermal cell turnover. This is thought to restult in the expulsion of open comedones* & the transformation of closed comedones into open ones. Prolonged use promotes dermal collagen synthesis, new blood vessel formation & thickening of the dermis, which helps diminish fine lines and wrinkles. Other effects: stabilizes lysosomes, increases RNA polymerase activity, increases PGE2, cAMP & cGMP levels, increases incorporation of thymidine into DNA. |
| Indications: an effective topical treatment for acne vulgaris. |
| Contraindications: Retinoic acid may increase the tumorigenic effect of sun (ultraviolet light), therefore limited exposure to sunlight & use of a sunscreen is recommended. |
| Side Effects: eyrthema & dryness |
| Pharmacokinetics: Should be applied dry skin only. |
Comedone Defintion:* A plug of sebaceous and dead skin material stuck in the opening of a hair follicle. The follicle may be open (blackhead) or almost closed (whitehead). |
References: Katzung's text |
| Drug: Isotretinoin (Accutane ®) |
| Drug Class: Synthetic retinoid / Acne medication |
| Mechanism of Action: Exact mechanism is unclear. It appears to inhibit sebaceous gland size & function. |
| Indications: Severe cystic acne that is recalcitrant to standard therapies |
| Contraindications: pregnancy. Teratogenicity is a significant risk. Women of child bearing potential must use an effective form of contraception for at least 1 month before, throughout, and for one or more menstrual cycle following therapy with isotretinoin. A serum pregnancy test must be obtained 2 months before starting therapy. |
| Side Effects: dryness & itching of the skin & mucous membranes. Other side effects are rare. |
| Pharmacokinetics: administered orally. Well absorbed, extensively bound to plasma albumin & has an elimination half life of 10-20 hrs. |
References: Katzung's text |
Psoriasis
| Psoriasis: |
| A chronic but treatable autoimmune skin disease experienced by an estimated 5-6 million Americans and about 80 million people around the world. Psoriasis of the skin has several common symptoms. It is often itchy and may cause painful drying, cracking, or blistering of the skin. Psoriasis affecting the joints (psoriatic arthritis) can cause pain and make movement more difficult. |
| References:psoriasissupport.com, emedicinehealth.com |
| Drug: Tazarotene (Tazorac ®) |
| Drug Class: Drug for Psoriasis |
| Mechanism of Action: An acetylenic retinoid that is hydrolyzed to its active form by an esterase. The active metabolite, tazarotenic acid, binds to retinoid acid receptors, resulting in modified gene expression. The precise mechanism of action in psoriasis is unknown, but may related to both anti-inflammatory & antiproliferative actions. |
| Indications: treatment of psoriasis |
| Contraindications: Women of child bearing age should be adivised of its teratogenic potential prior to use, and must use adequate birth control measures while on therapy. |
| Side Effects: teratogenic systemic concentrations may be achieved if applied to more than 20% of the total body surface area. Burning or stinging sensation & peeling. Sensitization to sunlight. |
| Major drug interactions: avoid concomitant use of other agents that dry the skin |
| Pharmacokinetics: absorbed percutaneously, limited to once daily application of less than 20% body surface area. |
References: www.rxlist & Katzung's text |
| Drug: Calcipotriene (Dovonex ®) |
| Drug Class: Drug for Psoriasis |
| Mechanism of Action: a synthetic vitamin D3 derivative shown to be effective in treating the plaque type of psoriasis vulgaris of moderate severity. |
| Indications: plaque type of psoriasis vulgaris of moderate severity |
| Contraindications: Women of child bearing age should be adivised of its teratogenic potential prior to use, and must use adequate birth control measures while on therapy. |
| Side Effects: burning, itching, mild irritation |
| Pharmacokinetics: administered topically. Approximately 6% of the topically applied 0.005% ointment is absorbed through the psoriatic plaques, resulting in transient elevation of serium calcium in less than 1% of subjects. |
References: www.rxlist & Katzung's text |
| Drug: Mometasone (Elocon ®) |
| Drug Class: Topical Corticosteroid |
| Mechanism of Action: (same as for other corticosteroids) |
| Indications: a medium potency corticosteroid indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses. |
| Contraindications: hypersensitivity to corticosteroids |
| Side Effects: Reported reactions (<5%) include burning, pruritus, and skin atrophy. |
| Pharmacokinetics: topical lotion/cream |
References: www.rxlist & Katzung's text |
T cell lymphoma
| Drug: Denileukin diffitox (Ontak ®) |
| Drug Class: Treatment of Cutaneous T cell lymphoma |
| Mechanism of Action: |