HillcrestLPNPharmacology

Candiduria may respond to flucytosine 50 to 150 mg/kg/day po q 6 hr for 1 to 2 wk but often is resistant. Of the newer antifungal azole derivatives, fluconazole appears best for fungal UTI because of high oral bioavailability, once-per-day dosing, and excellent penetration into urine and CSF. Flucytosine or fluconazole 200 mg/day po should be prescribed for asymptomatic candiduria.
Symptomatic cystitis in the noncatheterized patient can be treated with flucytosine or fluconazole for 1 to 4 wk. Excellent results have also been obtained with a single dose of amphotericin B 0.3 mg/kg IV. In the presence of permanent indwelling catheters, flucytosine and fluconazole may reduce but rarely eradicate the funguria; bladder irrigation may be successful.
In patients with renal candidiasis, amphotericin B and high-dose fluconazole (>= 400 mg/day) are equally effective in the primary treatment of invasive infection with C. albicans and C. tropicalis. Even when amphotericin B is used initially, oral fluconazole should be substituted early in the course of treatment. However, some less common candidal species are not susceptible to fluconazole.

Interstitial Cystitis
Interstitial cystitis (IC) is a chronic bladder disease occurring primarily in women. Etiology is unknown. The bladder wall shows inflammatory infiltration with mucosal ulceration and scarring that results in smooth muscle contraction, diminished urinary capacity, hematuria, and frequent, painful urination. Carcinoma in situ can mimic IC and must be ruled out.
Bladder distension may provide excellent, but transient, relief. Intravesical agents (eg, dimethyl sulfoxide [DMSO], methylprednisolone, heparin sulfate) and oral therapy with anticholinergics or tricyclic antidepressants offer some relief. Rarely, augmentation cystoplasty may be undertaken. Very rarely, cystectomy with urinary diversion is required.

DRUG CLASSES OF CONCERN
Some drug classes (including

1. diuretic,
2. antihypertensive,
3. antiarrhythmic,
4. antiparkinsonian,
5. anticoagulant,
6. psychoactive,
7. hypoglycemic, and
8. analgesic drugs

pose special risks for older patients.

Diuretics: Lower doses of thiazide diuretics (eg, hydrochlorothiazide or chlorthalidone 12.5 to 25 mg) can effectively control hypertension, with less risk of hypokalemia and hyperglycemia than higher doses (see also Ch. 199). Thus, potassium supplements may be required less often. Doses > 25 mg/day have been associated with increased mortality.

Antihypertensives: Treatment of hypertension is effective in older patients; recent analysis of several studies indicates that only 18 older patients must be treated for 5 yr to prevent one cardiovascular event. Different classes of
antihypertensives
have comparable efficacy in older white patients; however,
Ca channel blockers and diuretics
are most effective in older black patients. Whether any antihypertensives are preferable because they best preserve quality of life in the elderly is unclear.
If tolerated, diuretics and -blockers are the first choice because they reduce the risk of cardiovascular complications in older patients.
Contraindications to -blockers include chronic obstructive pulmonary disease and peripheral vascular disease; to clonidine, depression; and to vasodilators and -adrenergic blockers, underlying orthostatic hypotension. Short-acting
dihydropyridines (eg, nifedipine) should not be used because of concern about increased mortality risk.
Antiarrhythmics: Antiarrhythmics (see also Ch. 205) have the same indications and efficacy in older as in younger patients. However, because of altered pharmacokinetics, the dose of some (eg, procainamide, quinidine, lidocaine) should be reduced in the elderly. In addition, the risk of significant adverse reactions to certain drugs (eg, mexiletine; class IC drugs, such as encainide and flecainide) increases with age. Digoxin clearance decreases an average of 50% in elderly patients with normal serum creatinine levels. Therefore, maintenance doses should be started low (0.125 mg/day) and adjusted according to response and serum digoxin levels.
Antiparkinsonian drugs: Levodopa clearance is reduced in older patients, who are also more susceptible to postural hypotension and confusion. Therefore, older patients should receive low starting doses of levodopa and should be carefully monitored for adverse effects (see also Ch. 179). Patients who become confused while taking levodopa may not tolerate newer dopaminergic agonists (eg, bromocriptine, pergolide, pramipexole, ropinirole) better. Because older patients with parkinsonism may be cognitively impaired, anticholinergic drugs should be avoided.
Anticoagulants: Aging does not alter the pharmacokinetics of warfarin but may increase sensitivity to its anticoagulant effect. (Studies have not confirmed that aging per se increases the overall risk of bleeding, but in some studies, patients who had atrial fibrillation and were > 75 yr had an increased risk of cerebral hemorrhage.) Older patients generally require lower loading (<> of warfarin (see also Ch. 72). If the drug has to be stopped (eg, before surgery), return to normal clotting status may be slower in older patients.
Psychoactive drugs: In nonpsychotic, agitated patients, antipsychotics control symptoms only marginally better than do placebos. Although antipsychotics can reduce paranoia, they may worsen confusion (see also Ch. 171). Older patients, especially women, are at increased risk of tardive dyskinesia, which is often irreversible. Sedation, postural hypotension, anticholinergic effects, and akathisia (subjective motor restlessness) can occur in up to 20% of older patients taking an antipsychotic, and drug-induced parkinsonism can persist for up to 6 to 9 mo after stopping the drug. When an antipsychotic is used, the starting dose should be about 1/4 the usual adult dose and increased gradually. Risk of extrapyramidal dysfunction appears to be less with the new atypical antipsychotics (eg, olanzapine, quetiapine, risperidone)--a potential advantage in the elderly. However, experience with these drugs in the elderly is limited, and dose reduction is required (eg, for risperidone, a typical dose is 1 to 2 mg/day). The elderly appear to tolerate olanzapine reasonably well.
The use of anxiolytics and hypnotics is problematic (see also Ch. 173). Different benzodiazepines appear equally effective in relieving anxiety symptoms; selection depends on the drug's pharmacokinetics and pharmacodynamics. Treatable causes of insomnia should be sought and managed before using hypnotics (see also Ch. 173). In general, short- to intermediate-acting benzodiazepines with half-lives <> (eg, alprazolam, lorazepam, oxazepam, temazepam) are preferable to induce sedation or sleep. Longer-acting benzodiazepines should be avoided because risk of accumulation and of toxicity is increased, leading to drowsiness, memory impairment, and impaired balance with falls and fractures. Treatment of anxiety or insomnia should be limited in duration if possible because tolerance and dependence may develop; withdrawal may lead to rebound insomnia and anxiety. Buspirone, a partial serotonin agonist, is as effective as benzodiazepines in the treatment of general anxiety disorder; elderly patients tolerate doses up to 30 mg/day well. Its slow onset of anxiolytic action (up to 2 to 3 wk) can be a disadvantage in urgent cases. Zolpidem is a nonbenzodiazepine hypnotic that binds mainly to a benzodiazepine receptor subtype; older patients with insomnia appear to tolerate doses of 5 to 10 mg well. Zolpidem's advantages over benzodiazepines are less disturbance of the sleep profile, fewer rebound effects, and less dependence potential. Histamine blockers (eg, diphenhydramine, hydroxyzine) are not recommended because of their anticholinergic effects.
Antidepressants are the mainstay of treatment of depression in the elderly (see also Ch. 189), and selective serotonin reuptake inhibitors (SSRIs--eg, fluoxetine, paroxetine, sertraline) are generally considered the antidepressant of choice. These drugs appear to be as effective as tricyclic antidepressants and produce less toxicity, especially in overdose. One possible disadvantage of fluoxetine is its long elimination half-life, especially of its active metabolite. Paroxetine is more sedating, has anticholinergic action, and can inhibit hepatic cytochrome P-450 2D6 enzyme activity, with risk of impairing the metabolism of several drugs, including some antipsychotics, antiarrhythmics, and tricyclic antidepressants. Sertraline is more activating; diarrhea is a common adverse effect. Doses of these drugs should be reduced by up to 50%.
Tricyclic antidepressants are effective. Those with the least adverse effects are best for the elderly, and those with significant anticholinergic (eg, amitriptyline, imipramine), antihistaminic (eg, doxepin), and antidopaminergic (eg, amoxapine) effects are best avoided. The norepinephrine reuptake inhibitors nortriptyline and desipramine, starting at 10 to 25 mg/day, are most suitable. Both have low anticholinergic potency, and nortriptyline has the least -adrenergic blocking (hypotensive) action. Overdose produces cardiac and neurologic toxicity, precluding the use of these drugs in patients at risk of suicide. Trazodone is useful in agitated patients, has low anticholinergic potency, and is less cardiotoxic than tricyclics, but it can produce priapism. Bupropion is noncardiotoxic but can increase risk of seizures. Newer drugs (eg, mirtazapine, nefazodone, venlafaxine) should be reserved for patients not responding to or intolerant of SSRIs. Methylphenidate can be useful in treating selected elderly patients with depression who have had a stroke or who have a medical illness. The drug's onset of action is rapid.
Hypoglycemics: Doses of hypoglycemics, including insulin and sulfonylureas, should be titrated to prevent symptomatic hyperglycemia without causing hypoglycemia (see also Ch. 13). Aging can reduce insulin clearance, but dose requirements depend on the level of insulin resistance, which varies widely among patients with type II diabetes. The incidence of hypoglycemia due to sulfonylurea use may increase with age. Chlorpropamide is not recommended because older patients are at increased risk of hyponatremia and because the drug's prolonged duration of action is dangerous if toxicity or hypoglycemia occurs.
Metformin, a biguanide excreted by the kidney, increases peripheral tissue sensitivity to insulin and can be effective in older patients alone or in combination with sulfonylureas. However, long-term efficacy and safety in older patients is not well established. Risk of lactic acidosis, a rare but serious complication, increases with the degree of renal impairment and the patient's age.
Troglitazone, which can be used with insulin or oral hypoglycemics, sensitizes peripheral tissue to insulin's effects. Older patients appear to tolerate it well. However, concern about hepatotoxicity makes it a reserve drug. Troglitazone should be withdrawn if efficacy (eg, reduction of Hb A1c by > 1%) is not shown.
Acarbose, administered with food, reduces postprandial glucose elevations and, in combination with other hypoglycemics, can help improve blood sugar control in some patients. GI intolerance may be a problem.
Analgesics: NSAIDs are among the most widely used drugs, and several are available without prescription (see Ch. 167 and Rheumatoid Arthritis in Ch. 50). Some data indicate that the clearance of salicylate, oxaprozin, and naproxen is decreased in older patients. Peptic ulceration and upper GI bleeding are serious consequences of NSAIDs; risk is greater when an NSAID is begun and when dose is increased. Certain NSAIDs (eg, ibuprofen, diclofenac, salsalate) may be slightly less likely to cause upper GI bleeding. Aging does not seem to increase risk of NSAID-induced adverse GI effects, but if such complications occur, morbidity and mortality are considerably greater in elderly patients. The risk of upper GI hemorrhage increases more than tenfold when NSAIDs are combined with warfarin. For patients with a high risk of NSAID-induced gastropathy complications, misoprostol or a more potent gastric acid inhibitor (eg, omeprazole, lansoprazole) can be added. Such drugs can reduce the risk of peptic ulcer formation. The risk of NSAID-induced renal impairment may be increased in older patients. Monitoring serum creatinine is a reasonable approach, especially for patients with other risk factors (eg, heart failure, renal impairment, cirrhosis with ascites, volume depletion, diuretic use). Cyclooxygenase-2 (COX-2) inhibitors, or coxibs, may decrease risk of GI complications, however, one member of the class, rofecoxib (withdrawn from market), appears to increase the risk of cardiovascular events after long-term use. The risk for cardiovascular events with other coxibs is undergoing evaluation. Because one study has shown a 2.5-fold increase in cardiovascular events with celecoxib, FDA recommendations, pending further evidence, are to limit use of any coxib to patients who are at a high risk of GI bleeding, have a history of intolerance to nonselective NSAIDs, or are not doing well on nonselective NSAIDs. Use of coxibs for long periods or in patients with cardiovascular risk factors should be approached cautiously.