Health and Pills

Guide To Good Health and Drugs: Tablets, Gels, Capsules

Intravenous Immune Globulin and Allergic Diseases

| Filed under Asthma

Glossary:

Immune globulin E (IgE): An antibody that generally makes up only 0.01% or less of the total immune globulin armoury in human blood, but which frequently appears at higher concentrations in allergic people. This antibody is implicated in reactions such as ragweed and hay fever allergies, most food and contact allergies, and allergy-related asthma.

Immune globulin G (IgG): Also known as gamma globulin, this is the most common of the immune globulins, accounting for approximately 80% of all those present in human blood. It is frequently given by injection to boost the immune system prior to possible exposure to infectious diseases (ie. before a visit to the tropics).

Degranulation: The release by cells of lysosomes (small, self-contained bundles of enzymes that normally remove and digest unwanted or deteriorated components of the cell). Once released, the lysosomes turn their attention to foreign material such as bacteria, and stimulate a cascade of immunological reaction.

Eosinophil: A mobile, antiparasitic white blood cell that hunts and kills foreign bacteria. Vital components of the body’s immune system, eosinophils are attracted to the scene of inflammation, where they can aggravate a hypersensitive reaction such as an asthmatic attack caused by allergy.

Immunologists are increasingly coming to view asthma in terms of inflammatory disease. That means that asthma results from a condition known as airway hyperresponsiveness, which involves inflammation prompted partly by the body’s own antibodies, specifically the antibody known as immunoglobulin E (IgE). That inflammation in turn stimulates the production of aggravating substances that cause muscles in the bronchial tract to contract and spasm. “Sensitized” lymphocytes (white blood cells formed in the lymphatic system) are also found in the bronchial fluid of asthmatics, further inflaming the cells of the airway. This is part of an extremely complex inflammatory process involving numerous types of cells and different chains of events, of which the end result is bronchial constriction and reduced air flow.

Corticosteroids are the most effective anti-inflammatory treatment for airway hyperresponsiveness, and are considered safe for use in the inhaled form. But when these fail, it sometimes becomes necessary for physicians to prescribe oral corticosteroids, which have a steroidal effect on the entire system. These drugs can suppress growth in children, cause weight gain, hypertension, cataracts, osteoporosis and even spontaneous bone fractures, and most specialists would use them only in the most extreme and intractable cases of asthma. Naturally, the discovery of a safe and effective anti-inflammatory agent that allowed patients to avoid or limit prolonged use of oral corticosteroids would be a welcome development. Treatments such as methotrexate, dapsone and even gold have shown some benefits, but none has been consistent enough to eliminate the need for systemic corticosteroid use.

As far back as the 1950s, it was noted that monthly injections of immunoglobulin reduced the rate of infections, particularly respiratory infections, in people with gamma globulin deficiency (an immune disease). Intravenous immune globulin (IVIG) has since shown signs of being a potent anti-inflammatory agent in patients with various conditions such as juvenile rheumatoid arthritis. It has the proven capacity to reduce fever and other more sophisticated measurements of inflammation such as levels of C reactive proteins (which are produced in the so-called acute phase response to inflammatory illness or injury). Moreover, IVIG may mimic some of the effects of immunotherapy with known allergens, blocking and neutralizing them before they can get to the IgE bound up in cells and start an allergic reaction. Finally, antibodies found in intravenous immune globulin would seem to limit the production of IgE in the first place. There is known to be a strong link between asthma and allergy, and allergic reactions in the airway are an important factor in many asthmatic attacks. For all of these reasons, IVIG seems a strong possible alternative to systemic corticosteroids.

To test the effectiveness of intravenous immune globulin therapy in asthma, researchers recruited eight steroid-dependent asthmatic children aged from six to 17. Every four weeks, the patients were given 2 g of intravenous immune globulin for each kilogram of body weight. The treatment continued for six months. To assess results, doctors compared symptoms of coughing, wheezing, shortness of breath and chest discomfort before and after IVIG, as well as any changes in medication, and the frequency with which the patients were forced to use beta-agonists to control episodes of exacerbated asthma. Since 40% to 85% of asthmatics tend to test positive for reactions to various common airborne allergens, researchers also carried out some skin-prick tests.

Steroid use among the children declined greatly from an average 154 mg per month before treatment to only 49 mg/month after IVIG. Likewise, use of beta-agonists was halved during IVIG treatment, reflecting the fact that asthmatic symptoms were greatly reduced. Evaluating the severity of six different symptoms such as coughing and nocturnal wheezing on a scale from 0 (no symptoms) to 4 (incapacitating symptoms), average monthly scores decreased from 32 before intravenous immune globulin to 17 after one month of treatment, and remained in the 16 to 18 range as long as therapy was continued.

Confirming the known link between allergy and asthma, seven of eight children had skin reaction to one or more needle-prick tests of common allergens, giving a total of 30 positive reactions before intravenous immune globulin injections began. Following IVIG therapy, only one of those reactions worsened, while two remained unchanged and 27 improved. The average decrease in sensitivity to allergens was a striking hundred-fold. All of these gains were lost when the intravenous immune globulin treatment was suspended for six months, yet when five of the patients restarted intravenous immune globulin therapy six months later their asthma symptoms and steroid requirements once again stabilized and their overall improvement, in fact, surpassed that of the first therapy period.

Perhaps the most notable result was that the average annual cost of hospitalization in the five children who continued with intravenous immune globulin went from over $40,000 to under $3,000. That is a significant change, especially when one bears in mind that asthma is the leading cause of emergency room visits and hospital internment in children. A similar dramatic improvement was seen in three adult patients suffering from a chronic disfiguring skin disease known as atopic dermatitis. Sensitivity to allergens was found to have declined on average thirty-fold, and symptoms of itching, scaling and discolouration retreated rapidly.

More research is needed to learn about the applications of this therapy in a whole range of diseases with both inflammatory and immune components. It remains to be seen what is an optimum dose and what are the limits of intravenous immune globulin. But it is clear that it offers hope to sufferers of many debilitating conditions and may help to free many patients from dangerous steroid dependency.

Drug-Induced Bone Disease Part 5

| Filed under Rheumatology

Other Mechanisms Inducing Hypocalcemia

Calcium Complexation: Many agents can induce hypocalcemia by causing complexes to form between the medication and serum calcium.This complexation of calcium is so rapid and massive that maximal PTH secretion is inadequate to compensate for the sudden drop in serum calcium. A classic example of this phenomenon is foscarnet, an antiviral agent often used in immunocompromised patients. Foscarnet chelates with calcium, resulting in a reduction in both total and ionized calcium serum levels. Ethylene glycol has also been identified with this complexation phenomenon.

Altered Gastric Acidity: Medications that alter gastric acidity may also impact the absorption of calcium from the diet. Drugs that increase gastric pH can also decrease the breakdown of fat necessary to complex with calcium, thus reducing gut absorption.H2-antagonists such as cimetidine have been implicated in this phenomenon. While not yet reported in the literature, other agents known to increase gastric pH can also inhibit gastric absorption of calcium salts through similar mechanisms. Such agents include the proton pump inhibitors omeprazole and lansoprazole.

In addition to its presence in antacid preparations, aluminum is found as a contaminant in several of the additives in total parenteral nutrition (TPN) solutions. Originally linked with protein hydralysates, total parenteral nutrition-induced metabolic bone disease still occurs in patients receiving chronic TPN. It is thought that calcium gluconate and potassium phosphate salts contain sufficient aluminum to impair bone formation or mineralization. Therefore, it has been suggested that the use of calcium acetate salts and sodium phosphate salts may reduce these risks.

Osteoporosis Drugs: Agents typically used to treat osteoporosis can themselves induce metabolic bone disease if used too aggressively. Calcitonin and bisphosphonates can cause chelation and end organ inhibition, resulting in an overall reduction in osteoclast bone resorption.Sodium fluoride, an agent often used to treat drug-induced osteoporosis, can also cause hypocalcemia by inducing excessive rates of skeletal mineralization. This can create calcium-chloride complexes.

Osteomalacia may also result from a deficiency or impaired utilization and/or excretion of inorganic phosphate. The result is hypophosphatemia. Patients with peptic ulcer disease who chronically use aluminum-containing antacids may be at risk of developing hypophosphatemia. This is due to complexation of the aluminum with the ionorganic phosphates residing in the intestine. As a result, an insoluable salt is formed.

Blood Transfusions/plasmapheresis: Other therapies — such as blood transfusions or plasmapheresis — may predispose patients to hypocalcemia due to the presence of the anti-clotting agents in the blood products. For example, calcium citrate salts present in blood products can induce hypocalcemia by chelating with serum calcium. Similarly, patients undergoing radiologic procedures with contrast dyes containing EDTA (ethylene diamine tetracetic acid) may also have an increased propensity to develop hypocalcemia as a result of chelation of calcium with EDTA. Fortunately, however, the resulting hypocalcemia in these cases appears to be mild.

Lifestyle Choices That Induce Bone Loss

Excessive alcohol use and smoking have been associated with osteoporosis.

Smoking: Tobacco smoking appears to have an antiestrogen effect. Estrogen prevents bone breakdown through several possible mechanisms, including blocking bone resorption by shortening the lifespan of osteoclasts. Osteoclasts are responsible for bone breakdown. In addition to undergoing the pharmacologic effects of tobacco, smokers tend to be less physically active and more prone to poor nutrition, thus increasing their risk for osteoporosis.Smokers should be encouraged to quit so as to reduce further tobacco-related bone loss.

Excessive Alcohol: Alcohol abuse is a risk factor for osteoporosis. Originally, malnutrition and liver disease, often associated with chronic alcohol abuse, were thought to predispose patients to osteoporosis. However, more recent research has shown that alcohol-associated bone disease is multifactorial. Hypocalcemia results from the transitory hypoparathyroidism seen with acute alcohol toxicity. Ethanol itself has been shown to inhibit osteoblast formation, thus decreasing the rate of bone formation. Ethanol also appears to induce the cytochrome P-450 system, which increases the rate of vitamin D metabolism. Ethanol also inhibits the renal and hepatic hydroxylation of vitamin D, further decreasing activation of already low levels of vitamin D.

Conclusion

Osteoporosis and related bone disorders easily come to mind when one pictures an elderly, postmenopausal female. However, it is important for pharmacists and other healthcare providers to recognize the potential for bone damage in a wider patient population, due to drug therapy. A number of drugs have been documented to directly interfere with the absorption and/or activities of calcium or vitamin D — agents critical to the proper maintenance of healthy bone. Other drugs may have a more indirect action on bone structure, such as agents that reduce magnesium stores. The net effect of lowered magnesium levels is reduced serum calcium levels, to the detriment of healthy bone. Pharmacists should be familiar with drugs that can alter calcium or vitamin D levels in patients. Patients at risk for bone disorders due to medications should be counseled about this risk and advised of steps they can take to prevent or minimize bone damage.

Drug-Induced Bone Disease Part 4

| Filed under Rheumatology

Glucocorticoid Therapy and Bone Loss

Patients receiving long-term glucocorticoid therapy for conditions such as inflammatory bowel disease and rheumatoid arthritis are also at risk of developing drug-induced bone loss. This effect appears to depend on dose and duration of therapy. Most bone loss has been documented to occur during initiation of treatment, with eventual plateaus achieved within 6 months to 1 year of therapy. Atraumatic fractures involving the vertebrae and ribs are seen in 30% to 50% of patients receiving chronic steroid therapy.

There are several mechanisms associated with glucocorticoid-induced bone loss. Steroids decrease bone remodeling by inhibiting osteoblast maturation and subsequent bone formation. Glucocorticoid use causes a net negative calcium balance and increased bone resorption due to suppressed intestinal absorption of calcium in conjunction with increased renal calcium and phosphate excretion and subsequent decrease in renal tubular calcium resorption.

Even the frequent use of inhaled steroids has been associated with induced bone loss and a decrease in bone density. These findings have been confirmed in a recent study conducted in 209 premenopausal asthmatic women who frequently inhaled steroids. The subjects were divided into three subgroups — two that used inhaled steroids at different dosages and a control group that did not use steroids. Bone density was assessed over a three-year period. The two subgroups using inhaled steroids showed decreases in bone density, with greater bone loss associated with higher steroid doses.

The authors concluded that, while inhaled steroid use should not be discouraged in this patient population, careful attention should be given to ensure that patients receive adequate amounts of calcium and vitamin D. In addition, bone mineral density should be measured every six months so that alternative therapies and interventions can be considered before excessive bone loss occurs. Although this study involved females, the authors suggest that similar results could be expected in males receiving similar doses of inhaled steroids.

Anticoagulants and Bone Loss

Heparin Use: The development of osteoporosis has long been associated with chronic heparin therapy. The mechanism for heparin-induced osteoporosis has not yet been established, although several theories have been postulated. Some theories include abnormalities in vitamin D metabolism, enhanced osteoclast activity and diminished osteoblast activity. Patient complaints of back pain, in addition to vertebral compression fractures and a decrease in bone mineral density, have been documented. The severity of osteoporosis has been associated with the duration as well as the daily dose of heparin. Research by Rupp, et al. and Griffith, et al. places patients receiving doses greater than 30,000 units per day for more than three months at greater risk. Treatment typically involves discontinuation of heparin. Both unfractionated and the new low molecular weight (LMW) heparin products have been implicated, although animal studies suggests a lower incidence of osteoporosis with LMW heparin.

Warfarin Use: Heparin is the not the only anticoagulant associated with bone disease. Chronic therapy with warfarin has been associated with bone loss via a reduction in carboxylated fragments of osteocalcin — the major noncollagenous protein contained in bone. The normal metabolism of vitamin K involves gamma carboxylation of osteocalcin, which maintains bone growth. Knaper and colleagues noted a reduction in bone turnover among postmenopausal women receiving supplemental vitamin K. This contradicted research by Rosen, et al., who reported no difference in skeletal integrity in adults receiving long-term warfarin versus controls.Additional research is warranted to determine the significance of warfarin-associated bone loss.

Thyroxine and Bone Loss
Excessive therapy with thyroxine has also been associated with bone loss. Thyroid supplements are one of the most frequently prescribed medications; more than 10% of postmenopausal women receive thyroid hormone replacement. Euthyroid patients receiving suppressive thyroxine therapy are also at risk.As with other cases of drug-induced bone disease, dose and duration of therapy are implicated.Exogenous hyperthyroidism-induced bone loss is due to increased bone resorption, subsequent decreases in PTH, and increases in ionized calcium. Maintaining thyroid hormone replacement at physiologic doses appears effective in minimizing bone loss due to therapy.

Drug-Induced Bone Disease Part 3

| Filed under Rheumatology

Agents That Impair Absorption of Calcium

Medications that impair the absorption of calcium can have a negative impact on serum calcium levels. The malabsorption of calcium has been documented in patients receiving colchicine, mineral oil, or sodium sulfonated polystyrene resin. Similarly, agents known to enhance the renal excretion of calcium — such as loop diuretics — also predispose patients to hypocalcemia.

Magnesium Depletion: In addition to medications that directly alter serum calcium levels, agents that deplete the body of magnesium ultimately cause hypocalcemia. In fact, drug-induced hypocalcemia is often due to a depletion of magnesium stores. Magnesium deficiency can induce a transient hypoparathyroidism by reducing the secretion of parathyroid hormone (PTH) and a blunted PTH response. This result is an inhibition of the hypocalcemic feedback loop. Other agents that suppress PTH secretion — with resulting inhibition of the hypocalcemic feedback loop — include aluminum salts and excessive alcohol.

Cisplatin, Aminoglycosides, Cyclosporine: Cisplatin, aminoglycosides, and cyclosporine are known to increase magnesium wasting through a variety of mechanisms. Cisplatin-induced hypomagnesemia is dependent on dose and duration of therapy. Cisplatin induces hypomagnesemia by causing direct injury to the mechanisms of magnesium reabsorption in the ascending limb of the loop of Henle and the distal tubule. Forastiere and colleagues reported that the total exposure of free platinum contributes to direct injury and renal toxicity. Mavichak, et al. have also suggested that cisplatin causes lesions in the distal renal tubules responsible for renal magnesium losses. Carboplatin, an antineoplastic agent with a chemical structure similar to cisplatin, has been reported to have a lower incidence of hypomagnesemia.

Renal wasting of magnesium is also fairly common in patients receiving prolonged, high doses of aminoglycosides. Aminoglycosides can inhibit the proximal tubular transport of magnesium in the kidney, predisposing patients with poor magnesium intake to lower magnesium levels. Transplant patients receiving cyclosporine also may experience severe hypomagnesemia due to increased urinary excretion of magnesium.Table 2 lists agents known induce hypocalcemia by depleting magnesium stores. Treatment for hypocalcemia induced by hypomagnesemia involves correcting hypomagnesemia first, then managing serum calcium levels.

Table 2: Mechanisms of Action Associated with Drug-Induced Bone Disease

Proposed Mechanism Associated Agents Specific Medications
Promotion of
calcium excretion		 Loop diuretics
Saline infusions
Glucose loading osmotic diuretics
Aminoglycosides
Growth hormone
Prostaglandins
Thyroid hormones
Aluminum-containing antacids
Total parenteral nutrition
Potassium-sparing diuretics 		Furosemide (Lasix), Bumetanide (Bumex), ethacrynic acid (Edecrin)
Mannitol, sucrose, urea
Gentamicin (Garamycin), amikacin (Amikin), tobramycin (Nebcin), netilmicin (Netromycin)
Somatropin (Nutropin, Protropin, Saizin)
Alprostadil (Prosin VR, Caverject, Edex)
Levothyroxine (Levoxyl, Synthroid)
Aluminum hydroxide (Amphojel)
Triamterene (Dyrenium)
     
Inhibition of bone turnover Retinoic acid derivatives
Aminoglycosides
Alkylating agents 		Retinoin (Retin-A)
Gentamicin (Garamycin), amikacin (Amikin) tobramycin (Nebcin), netilmicin
Cisplatinum (Platinol), carboplatin (Paraplatin)
     
Direct inhibition of
osteoclastic activity		 Antineoplastic agents Mithramycin (plicamycin, Mithracin)
     
Reduction in rate of
osteoblastic/osteoclastic activity		 Aluminum Aluminum hydroxide (Amphojel)
     
Reduction in
calcium absorption		 Corticosteroids
Lubricant laxatives
Diphenylmethane laxatives
Barbiturate anticonvulsants
Sodium polysulfonated
   polystyrene resin		 Prednisone, dexamethasone, triamcinolone (Azmacort)
Mineral oil (Agoral Plain)
Phenolphthalein (Feen-a-Mint, Ex-Lax)
Phenobarbital (Luminal)
Kayexalate, SPS
     
Interference with renal
activation of Vitamin D		 Anticoagulants
Corticosteroids		 Heparin
Prednisone, dexamethasone, triamcinolone (Azmacort)
     
Interference with
Vitamin D metabolism		 Anticonvulsants
Ethanol
Hypnotics		 Phenytoin (Dilantin) phenobarbital (Luminal)
Glutethimide (Doriden)
     
Reduction in serum
magnesium levels secondary
to renal tubular damage		 Aminoglycosides
Antiprotozoal, antibiotic
Immunosuppressants
Antifungal agents
Ethanol		 Gentamicin (Garamycin), amikacin (Amikin), tobramycin (Nebcin), netilmicin (Netromycin)
Pentamidine (Pentam)
Cyclosporine (Sandimmune, Neoral, Sangcya)
Amphotericin B (Fungizone)
     
Impaired Vitamin D absorption Antilipemic Cholestyramine (Questran), Colestipol (Colestid)
     
Complexation of calcium Chelating agents
Ammonium detoxicants
Phosphate supplements
Antivirals
Blood products (calcium citrate) 		Edetate disodium (EDTA, Endrate, Chealamide)
Neomycin (Mycifradin)
Sodium/potassium phosphate salts (K-Phos, Neutra-Phos, Fleet Enema)
Foscarnet (Foscavir)
     
Reduction in parathyroid
hormone secretion		 Aluminum
Ethanol		 Total parenteral nutrition, aluminum hydroxide (Amphojel)
     
Impaired calcium absorption
secondary to decreased gastric
pH and impaired fat breakdown		 H2-blockers Cimetidine (Tagamet), ranitidine (Zantac), famotidine (Pepcid), nizatidine (Axid)

Drug-Induced Bone Disease Part 2

| Filed under Rheumatology

Agents That Impair Absorption of Vitamin D

Older Anticonvulsants: Older anticonvulsants, such as carbamazepine, phenobarbital and phenytoin, have been associated with drug-induced osteomalcia.It has been postulated that these agents increase the degradation of 25(OH)D3, the predominant circulating metabolite. However, many early studies were confounded because they were conducted on institutionalized patients who were predisposed to other risk factors, such as poor dietary vitamin D intake and/or reduced exposure to sunlight. Tolman and colleagues reported a positive correlation between the incidence of osteomalacia and the duration of anticonvulsant therapy; they documented the development of bone disease in over 75% of patients receiving anticonvulsant therapy for periods greater than 10 years. Hahn, et al. also reported that phenytoin reduced calcium absorption by directly inhibiting intestinal transport.

Chronic Laxative Use: Laxative abuse has also been implicated in compromised bone status. The overuse of cathartics has been associated with malabsorption of vitamin D and calcium. Use of irritant laxatives such as phenolphthalein and bisacodyl may damage the structural integrity of the intestinal mucosa and cause impaired colonic reabsorption, steatorrhea, and malabsorption of vitamin D and calcium. Orally ingested mineral oil can coat ingested food particles along with the surface of the intestines. It forms a mechanical barrier to the digestion and absorption of nutrients. Mineral oil also increases gastric motility, which reduces the time required to adequately absorb ingested nutrients. Moreover, studies have shown that mineral oil — especially if taken at mealtime or during the postprandial absorptive period, when nutrients are absorbed — can prevent the absorption of vitamin D.

Other Agents: Other agents that impair the absorption of vitamin D and have shown documented increased risk of deficiency include the absorbable and nonabsorbable types of hypo-lipidemic drugs. Similarly, cholestyramine, an anion-exchange resin, has been found to bind bile salts and interfere with the bioavailability of numerous fat-soluble nutrients, including vitamin D. Knodel and colleagues associated large doses of cholestyramine (>32 g/day) with the malabsorption of fat-soluble vitamins. They also observed cholestyramine-induced osteomalacia resulting from impaired absorption of vitamin D.

Agents That Cause Secondary Impairment of Vitamin D

Isoniazid/cimetidine: Medications that inhibit the hepatic and/or renal hydroxylation of vitamin D subject patients to increased development of bone disease due to the secondary impairment of calcium absorption. For example, drugs such as isoniazid and cimetidine inhibit the hepatic and renal hydroxylation of vitamin D. This results in a functional vitamin D deficiency — with a secondary impairment of calcium absorption. Odes, et al. concluded that even short-term therapy with cimetidine altered vitamin D metabolism in humans. The researchers concluded this after monitoring levels of 25(OH)D3 for 30 days in patients receiving treatment. Calcium channel blockers such as verapamil can also have a negative impact on vitamin D levels by decreasing its hydroxylation in the body.In addition, medications that promote the catabolism of vitamin D metabolites, such as phenytoin and phenobarbital, have the same effects.

Drug-Induced Bone Disease Part 1

| Filed under Rheumatology

One of the most prevalent of the degenerative diseases in the United States today, osteoporosis affects over 10 million individuals. An additional 18 million are at risk of osteoporosis due to low bone density. The majority of patients affected are postmenopausal females. The number of cases of osteoporosis is expected to rise substantially in the next several decades, as life expectancy increases and the world population expands. This growing elderly population inevitably will be affected by multiple pathological processes that require drug therapy. Unfortunately, some medications may cause hypocalcemia and accelerate bone loss. Patients who experience these effects can present with osteoporosis, osteopenia, and/or osteomalacia.

Osteoporosis, Osteopenia, Osteomalacia

Defined as a reduction in bone mineral mass and an increase in the porosity of remaining bone cortices and trabeculae, osteoporosis is associated with bone thinning. In addition, there is a resultant decrease in bone strength and increased susceptibility to skeletal fracture — even with minimal trauma. Osteopenia is the loss of bone density, as seen on radiographic exam. The reduced density may occur in all bones or be limited to a specific bone, as in the case of disuse atrophy. Osteomalacia and rickets are disorders that involve the softening of bone due to a failure of osteoid matrix cells to mineralize properly. This failure to mineralize occurs as a result of vitamin D deficiency and inadequate intestinal absorption of calcium and phosphorus.

While none of the above disorders is involved in development of bone disease, all are associated with an alteration in normal bone development. Although in osteoporosis there is typically a net excess of bone resorption in relation to bone formation, the exact amount may vary from patient to patient. Numerous factors may increase the risk of developing bone disease, including the use of certain medications. Table 1 provides a list of medications associated with inducing bone disease.

Table 1: Agents Associated with
Inducing Bone Disease
Acetazolamide
Aldesleukin
Alendronate
Alprostadil
Aluminum
Amifostine
Amikacin
Amphotericin B
Amphotericin B
   liposome
Basiliximab
Bleomycin
Busulfan
Bumetanide
Capreomycin
Carboplatin
Cholestyramine
Cisplatin
Citrate liposome
Citrate salts
Clodronate
Codeine
Colestipol
Corticotropin
Coumadin
Daunorubicin Didanosine
Diethylstilbestrol
Doxorubicin
   hydrochloride
   liposome
Edetate disodium
Epinphrine
Ethacrynic acid
Etidronate
   disodium
Fluocortolone
Fluoride salts
Fluorouracil
Foscarnet
Furosemide 		Gallium nitrate
Gentamicin
Glucocorticoids
Glutethimide
Growth hormone
Heparin
Ibandronate
Interferon alfa-N1
Interferon beta-1B
Interferon gamma
Isoniazid
Leucovorin
Lithium
Magnesium
Mineral oil
Mithramycin
Morniflumate
Neomycin
Netilmicin
Niflumic acid
Pamidronate
Pentamidine
Phenobarbital
Phenytoin
Phosphates
Polymyxin B
Retinoic acid
Sargramostim
Sodium
   polystyrene
   sulfonate
Tamoxifen
Teceleukin
Terbutaline
Teriparatide
Tobramycin
Torsemide
Triamterene
Warfarin
Zolendronate

Agents Needed for Bone Maintenance

The primary agents responsible for bone remodeling and mineral metabolism are parathyroid hormone (PTH), vitamin D, and calcitonin.

Role of PTH: Parathyroid hormone stimulates bone resorption by stimulating increased reabsorption of calcium and decreased phosphorus reabsorption in the kidney. PTH also increases the renal production of 1,25-dihydroxy D3 (calcitriol), thus increasing the intestinal absorption of calcium and phosphorus. This ultimately leads to bone mineralization and resorption. The outcome is a net increase in ionized serum calcium levels.

Role of Vitamin D: Vitamin D is necessary for proper bone maintenance. It can be ingested from dietary sources such as fatty fish or from fortified foods such as milk, bread products, cereals and margarine. Alternatively, it can be synthesized endogenously in the skin during sun exposure. Regardless of its source of origin, vitamin D must be hydroxylated in the liver to its major circulating form — 25(OH)D3. Twenty-five (OH)D3 is biologically inert on calcium metabolism at physiological concentrations; it requires further hydroxylation in the kidney to its biologically active metabolite, 1,25(OH)2D3 (calcitriol).

The active form of vitamin D primarily maintains serum calcium levels within normal range. It accomplishes this by enhancing the efficiency of intestinal calcium absorption and/or mobilizing calcium stores from bone. Any medication that interferes with the metabolic conversion of vitamin D to its active form will impair calcium absorption and alter bone status. For example, even the topical application of sunscreen products containing para-amino benzoic acid (PABA), with a protection factor of 8, can almost completely eliminate the in vivo cutaneous synthesis of vitamin D and predispose chronic users to osteoporosis.Table 2 provides a list of medications and respective mechanisms involved in precipitating bone disease.

Drugs Add Years of Life

| Filed under Drugs

Big gainer: persons with cardiovascular diseases.

The good news for many Americans is that persons with diseases treatable by drugs, such as stomach ulcers and hypertension, are living longer. The death rate from these diseases has plunged thanks to the introduction of beta-blockers, proton pump inhibitors, and other drugs. A recent study in JAMA found that nonsmokers who comply with their drug therapy and who thereby maintain normal blood pressure and cholesterol levels can add 6 to 9 years to their lives. As the chart shows, the death rates from rheumatic fever and heart disease, atherosclerosis, stomach ulcers, ischemic heart disease and emphysema have significantly decreased between 1965.

Breakthrough Drugs

Breakthrough medications and vaccines have had a tremendous impact on longevity in the past 65 years. First came the anti-infective drugs, such as sulfa in 1935, that set the stage for the development of penicillin. The years between 1938 and 1953 are heralded as the “Age of Antibiotics?because of the large number of anti-infective agents introduced. Vaccines then followed as the major force in eradicating deaths from diphtheria, syphilis, whooping cough, polio, and measles. Since 1920, the combined death rate from the flu and pneumonia has been reduced by 85%.

Recent Advances

New discoveries in genetics are leading to advances in therapies for cystic fibrosis, Parkinson’s disease, and cancer. In 1997, the death rate from AIDS dropped by nearly half, the biggest single-year decline in history for a major cause of death. These advances are coming in time to prevent a major “epidemic?in disease as the Baby Boom population ages. Demographic trends indicate that more than 50 million Americans past age 65 will be at risk for various degenerative diseases by 2050. But the fact is that today Americans can expect to live more than 76 years. In 1920 life expectancy at birth was 54 years. For every 5 years since 1965, an additional year has been added to life expect

Coronary Heart Disease Risk Factors Part 2

| Filed under Cardiovascular Diseases

Patient Counseling
Pharmacists can take on a variety of roles in the management of lipid disorders. Several reports have described pharmacists’ involvement in the management of dyslipidemias. Particularly in the community setting, pharmacists are uniquely positioned to assist with screening, managing, and educating patients with lipid disorders. Typically, pharmacists’ activities include interviewing patients to assess medical histories, ascertaining risk factors and other pertinent information, assessing lipid profiles, tressing the treatment, and providing patient education and follow-up.

Hypertension and Diabetes Risk Factors in the African American Population
The high prevalence of hypertension and diabetes in African Americans increases their risk for CHD. The presence of cholesterol abnormalities (i.e., increased LDL, triglycerides, and decreased HDL) in conjunction with these two major risk factors puts this population at an even greater risk for cardiovascular morbidity and mortality. It is imperative that pharmacists recognize this population as one requiring special considerations with regard to monitoring and counseling. Hypertension appears to increase with the prevalence of certain lifestyles. In the rural South (as well as in other areas), certain cultural food preferences still exist. For example, chitterlings, salt back, pickled pig parts, fat back, sweet potato pie, and boiled peanuts are major components of many African American diets. Many of these foods are high in fat and sodium, and low in potassium. Diets high in fried foods and low in fruits, vegetables, and grains pose significant challenges for the patient with dyslipidemia, making lifestyle modifications more critical. The assistance of a dietitian may be particularly useful for recommending low-fat, low-sodium alternatives to the patient.

Case Study
M.G. is a 64-year-old African American female who presented to the clinic for a follow-up for her hypertension. She was last seen in clinic 3 months ago. She has a history of hypertension (dx one year ago), obesity, and headaches. She has a negative family history of premature heart disease and diabetes. M.G. reports discontinuing her Altace 10 mg two months ago due to lightheadedness. The patient lives with her husband, daughter and grandchildren. She denies alcohol and current tobacco use. M.G. is retired and engages in limited physical activity. Her typical breakfast consists of eggs, bacon, grits and biscuits and occasionally whole milk with cereal. For dinner she has fried fish and chicken 3x per week, rice, potatoes, and greens. She enjoys baking pies and often has pie and ice cream with her grandchildren. At least 3–4x per week M.G. eats 1–2 bananas. In addition she eats fast foods (cheeseburgers) 1–2x per week.
Her last cholesterol labs were done 15 months ago. At that time her total cholesterol was 255, her HDL 29, LDL 173, TG 265. Her current weight is 251 lbs, height 64 inches, BMI 43.1 kg/m, BP 237/120.

Discussion
M.G. has several risk factors for coronary heart disease: her age (64 years), hypertension, low HDL and obesity. Since she does not have any documented CHD but does have two or more risk factors, her LDL cholesterol goal should be <130 mg/dL. To calculate percent LDL reduction needed to attain goal: actual LDL-C minus desired LDL-C divided by actual LDL-C, then multiply by 100.
M.G. needs a 25% LDL-C reduction to achieve a goal of <130 mg/dL. The first step towards achieving this goal is lifestyle modification, which for this patient involves the following:
1. Modify diet

  • Step I & Step II diet — decrease intake of foods high in saturated fats and cholesterol (e.g., fried fish and fried chicken, bacon, pies and ice cream).
  • Increase intake of fruits and vegetables (e.g., carrots, beans, peas, and citrus fruits; also grains).

2. Increase physical activity

  • Patient should be encouraged to engage in regular physical activity, such as walking, gardening, etc.
  • These lifestyle changes can facilitate weight loss, decrease LDL cholesterol, increase HDL cholesterol, and decrease triglycerides. After 3–6 months of dietary intervention, if M.G.’s LDL cholesterol goal is not achieved, a trial of a lipid-lowering drug may be considered.

To prevent hypertension, African Americans should increase consumption of high-potassium foods (such as fresh fruits and vegetables), use low-fat dairy products, and avoid salt. The Dietary Approaches to Stop Hypertension (DASH) diet is particularly effective in significantly lowering high blood pressure in African Americans. This diet is low in cholesterol, high in dietary fiber, potassium, calcium, and magnesium, and moderately high in protein, and has been shown to lower blood pressure even when an individual’s weight and salt intake remained constant. One major obstacle facing many African Americans in the treatment of hypertension, is the cost of medications. Many of the newer medications are more effective and have fewer side effects than older medications, but they are costly. In addition, many African Americans do not receive proper medical care until hypertension has been present for some time. This results in otherwise avoidable damage to the kidneys and other organs. It may also account for the high rate of hypertension-related morbidity and mortality that exists among African Americans.

Counseling Patients on Lipid-Lowering Drugs
Pharmacists should discuss the following with patients receiving lipid-lowering medications:

  • Name of medication (give both the generic and brand names)
  • The expected outcomes of the medication, e.g., lowering of triglyceride or LDL cholesterol levels
  • Appropriate administration, e.g., by mouth, mixed with juice, with or without regard to food
  • When to take the medication, e.g., at bedtime

It should also be taken into consideration that African Americans tend to respond differently than other populations to treatment for high blood pressure. Because African Americans experience higher rates of diabetes, renal insufficiency and heart failure, they may benefit more from aggressive treatments to lower blood pressure.

Conclusion
Dyslipidemia is a major risk factor in the development of coronary heart disease. This risk factor, as well as other risk factors, can be altered through pharmacologic, dietary and other lifestyle modifications. Cultural norms affecting health among African Americans do exist and should not be overlooked by healthcare providers. Increased awareness by the pharmacist and the use of culturally sensitive information and materials can greatly enhance patient understanding and adherence to the prescribed regimen.
Pharmacists have a responsibility to assist in the management of lipid disorders. This can be accomplished by developing individual or collaborative practices in various healthcare settings. Pharmacists interested in strengthening their skills in this area can enroll in courses offered by several organizations.