1. GERIATRIC PRINCIPLES
Dr . Dalia Abd Al-Kader

2. Toxic exposures in the elderly may occur for several reasons.
1.Because of pharmacokinetic and pharmacodynamic changes.
2. The presentation of disease, including drug toxicity, is often atypical in the elderly. For example, falls in the elderly may be a presenting sign of xenobiotic toxicity and are commonly due to prescribed xenobiotics, with sedative–hypnotics, antipsychotics, antidepressants, and class Ia antidysrhythmics (quinidine and procainamide).

3. Xenobiotics that Pose an Increased Risk of Toxicity in the
Elderly
Anticholinergics
Anticoagulants
Antidepressants
Antipsychotics
Cardiovascular medications (β-Adrenergic antagonists ,Calcium channel blockers ,Digoxin )
Insulin and oral hypoglycemics
Magnesium-containing laxatives
Nonsteroidal antiinflammatory drugs
Opioids
Salicylates
Sedative–hypnotics
Sodium phosphate laxatives
Warfarin
a In addition, polypharmacy may lead to toxicity as a result of diverse drug–drug interactions.

4. SUICIDE AND INTENTIONAL POISONINGS
The risk of suicide by all methods increases steadily with age.
Among the elderly, the pattern of medications responsible for suicidal deaths may be changing because selective serotonin reuptake inhibitors (SSRIs) are increasingly prescribed for depression instead of TCAs. In the United States, higher suicide rates have been associated with greater use of TCAs than non-TCA antidepressants, which could be related to greater lethality of TCAs in overdose leading to nonadherence and enhanced suicide risk.

5. UNINTENTIONAL POISONING, ADVERSE DRUG EVENTS, AND THERAPEUTIC ERRORS
Although poisoning exposures are much less frequent in the elderly than in other age groups, the incidence of ADEs among adults increases steadily with age.

6. An ADE is defined as “one that occurs with normal, prescribed, labeled or recommended use of the [drug].” ADEs are more likely to be serious in the elderly than in younger adults. Serious ADEs are those resulting in death, hospitalization, life-threatening outcome, disability, or other serious outcome.

7. It may be challenging for a clinician to distinguish an intentional or unintentional overdose from an ADE in an elderly patient. The history, if available, must be explored carefully to identify and prevent recurrent problems. However, exposures in persons older than age 60 years are more likely the result of therapeutic errors and “misuse” than in younger adults. A therapeutic error is defined as “an unintentional deviation from a proper therapeutic regimen that results in the wrong dose, incorrect route of administration, administration to the wrong person, or administration of the wrong substance”.

8. These age-related differences may be because of physiologic changes that affect xenobiotic disposition or effect, patient errors caused by cognitive or visual impairment, or lack of provider proficiency in geriatric prescribing principles.

9. In contrast to serious consequences of therapeutic errors, reactions such as the serotonin syndrome and neuroleptic malignant syndrome (NMS), which are potentially life threatening, may occur with correctly prescribed therapeutic doses or drug interactions. For example, NMS must be distinguished from such geriatric syndromes as cerebrovascular events, heat stroke, or neuroleptic sensitivity syndrome seen in Lewy body dementia.

10. The elderly are at enhanced risk of severe upper gastrointestinal (GI) bleeding from nonsteroidal antiinflammatory drugs (NSAIDS). Although this could be partly explained by increased exposure to and regular use of these drugs, for chronic conditions, older adults are more vulnerable to their effects because of underlying atrophic gastritis. There is controversy as to cause of age-related gastric mucosal changes, but they may partly be caused by underlying Helicobacter pylori infection, which appears to increase with age. The elderly are also at greater risk of prolonged hypoglycemia from certain sulfonylureas, particularly glyburide.

11. SUBSTANCE ABUSE IN THE ELDERLY
For a comparable amount of alcohol ingested, the blood alcohol concentration of an elderly person will be higher than that of a younger adult because changes in body composition reduce the volume of distribution (Vd) of ethanol. Moreover, because of an age-associated diminished tolerance to alcohol, the impact on cognitive or motor function tends to be greater.

12. PHARMACOKINETICS
The most consistent pharmacokinetic change that occurs with aging is a decrease in renal function. Glomerular filtration rate (GFR) declines, on the average, by 50% between the ages of 30 and 80 years and cannot be accurately predicted by serum creatinine, which does not increase significantly with age, because muscle mass, the source of serum creatinine, declines with age.

13. Liver mass decreases with an associated decrease in hepatic blood flow, which results in decreased efficiency of hepatic extraction. Enzymatic processes are often unpredictable, and hepatic oxidation appears to decline with age.
hepatic conjugation does not decline significantly with age, so xenobiotics such as temazepam and oxazepam that are metabolized by these processes do not have prolonged elimination half-lives.

14. In contrast, xenobiotics such as diazepam and flurazepam, which are metabolized by hepatic oxidative enzymes, are eliminated more slowly with age. Similar to many oxidized xenobiotics, metabolites of diazepam and flurazepam are active, undergo further metabolism, and remain in circulation after the parent xenobiotic has been metabolized. The active metabolites of some drugs, such as opioids, are renally eliminated, and excretion may be prolonged because of an age-related decline in renal function

15. Age-related alterations in body composition may affect xenobiotic disposition in later life. For example, lean muscle mass and total body water decline, and the fat-to-lean ratio increases with advancing age. Thus, highly lipid-soluble xenobiotics tend to have an increased volume of distribution. As a result, there may be a delay before steady state is reached, and peak effect and toxicity may occur later than expected.

16. The precise contributions of gastric and intestinal tract mechanisms to toxicity have not been adequately determined. Changes in gastric absorption with age are not substantial enough to have an important clinical impact, and if anything, there is a modest decline, partly because of delayed gastric emptying, which could cause a delay in absorption of certain xenobiotics. However, age-associated changes in the gastric mucosa may account for enzymatic changes.

17. PHARMACODYNAMICS
In general, age-related physiologic changes in target or nontarget organs lead to increased sensitivity to most xenobiotics, although sensitivity to some xenobiotics may also be decreased. For example, there is evidence that β-adrenergic receptor sensitivity declines with aging, leading to a diminished response to both β-adrenergic agonists and antagonists, although this is not necessarily demonstrated clinically.

18. ADVERSE DRUG EVENTS:
The likelihood of experiencing an ADE increases with the increasing number of xenobiotics taken. Geriatric patients take more prescription and nonprescription xenobiotics than any other patient group. ADEs may occur as a consequence of xenobiotic–xenobiotic interactions.
Concurrent disease in target or nontarget organs may also alter the patient’s sensitivity to a xenobiotic, resulting in a serious ADE even when the patient is given a standard or previously used xenobiotic dose.

19. On average, approximately 5 halflives of a xenobiotic are necessary to achieve steady-state xenobiotic concentrations. Thus, a xenobiotic with a half-life of 24 hours might not reach a steady state for 5 days, and in the presence of prolonged elimination associated with age-related factors.

20. Morbidity and mortality in elderly patients as a result of specific xenobiotics might be avoided if the responsible xenobiotics were studied under the predictably high-risk conditions typically present in the elderly. For example, xenobiotics eliminated by the kidney need to be evaluated after repeated dosing in elderly subjects.

21. Xenobiotics, such as digoxin, warfarin, and diuretics, commonly prescribed in the elderly population are frequently involved in serious drug interactions. This situation is complicated by the frequency with which elderly patients who often have multisystem disease visit multiple physicians, who prescribe medications without specific knowledge of, or attention to, the remainder of the patient’s xenobiotic regimen, thereby increasing the risk of inappropriate xenobiotic combinations.
Herbal preparations used by the elderly also may interact with prescription medications. The use of herbal preparations has increased substantially in recent years, particularly among patients with illnesses such as cancer, dementia, and depression that commonly affect the elderly.

22. use of nonprescription pharmaceuticals may also cause serious adverse effects. For example, excessive use of magnesium-containing preparations frequently causes severe toxicity in older individuals. Impaired renal clearance, decreased GI motility, and other medical comorbidities are just three risk factors that potentiate magnesium toxicity in the elderly.

23. ther age-related factors may increase the risk of unintentional poisonings in geriatric patients; impaired vision, hearing, and memory may lead to misunderstanding or an inability to follow directions concerning the use of prescription and nonprescription drugs. Dementia is another important risk factor in unintentional poisonings.

24. MANAGEMENT
GI decontamination should proceed as in younger patients. Because constipation is a more frequent problem in the elderly, when multiple-dose activated charcoal is used, particular attention must be paid to GI function and motility.
The presence of clinical or subclinical heart failure or renal failure may increase the risk of fluid overload when sodium bicarbonate is used. In the elderly, hemodialysis or hemoperfusion may be indicated earlier in cases of aspirin, lithium, or theophylline poisoning.