Leonard S. Williams

The influence of food on the absorption and metabolism of drugs

Food-drug interactions can lead to a loss of therapeutic efficacy or toxic effects of drug therapy. Generally, the effect of food on drugs results from a reduction in the drugs bioavailability; however, an alteration in drug clearance can occur due to the effect of certain foods on drug metabolism. The proportion of adverse drug reactions due to food-drug interactions is not known and unfortunately only when a serious adverse drug reaction follows a food-drug interaction does the matter usually receive any significant attention. In order to improve therapeutic efficacy and to help prevent adverse drug reactions, it is necessary that clinicians be knowledgeable of the important food-drug incompatibilities and risk factors related to the increased likelihood of developing an adverse drug reaction due to food-drug interactions.

Hypertension and cognitive function in the elderly.

Alzheimers disease is the most prevalent and common form of cognitive impairment, ie, dementia, in the elderly followed in second place by vascular dementia due to the microangiopathy associated with poorly-controlled hypertension. Besides blood pressure elevation, advancing age is the strongest risk factor for dementia. Deterioration of intellectual function and cognitive skills that leads to the elderly patient becoming more and more dependent in his, her, activities of daily living, ie, bathing, dressing, feeding self, locomotion, and personal hygiene. It has been known and demonstrated for many years that lowering of blood pressure from a previous hypertensive point can result in stroke prevention yet lowering of blood pressure does not prevent the microangiopathy that leads to white matter demyelinization which when combined with the clinical cognitive deterioration is compatible with a diagnosis of vascular dementia. It is known from many large studies, ie, SHEP, SCOPE, and HOPE, that lowering of blood pressure gradually will not and should not worsen the cognitive impairment. However, if the pressure is uncontrolled a stroke which might consequently occur would further worsen their cognitive derangement. So an attempt at slow reduction of blood pressure since cerebral autoregulation is slower as age increases is in the patients best interest. It is also important to stress that control of blood glucose can also be seen as an attempt to prevent vascular dementia from uncontrolled hyperglycemia. Vascular dementia is not considered one of the reversible causes of dementia. Reversible causes of cognitive impairment are over medication with centrally acting drugs such as sedatives, hypnotics, antidepressants, and antipsychotics, electrolyte imbalance such as hyponatremia, azotemia, chronic liver disease, and poor controlled chronic congestive heart failure. Criteria for the clinical diagnosis of vascular dementia include cognitive decline in regards to preceding functionally higher level characterized by alterations in memory and in two or more superior cortical functions that include orientation, attention, verbal linguistic capacities, visual spacial skills, calculation, executive functioning, motor control, abstraction and judgment. Patients with disturbances of consciousness, delirium (acute confusional states), psychosis, serious aphasia, or sensory-motor alterations that preclude proper execution of neuro-psychological testing are also considered to have probably vascular dementia. Furthermore, these are ten of the other essential cerebral or systematic pathologies present that would be able to produce a dementia syndrome.

The Lack of Effect of Aerobic Exercise Training on Propranolol Pharmacokinetics in Young and Elderly Adults

The effects of exercise training on the pharmacokinetics of orally administered propranolol were studied in young and elderly healthy volunteers. Twenty‐three young (30 ± 5 years of age) and 20 elderly (67 ± 5 years of age) adults were randomly assigned to endurance training (N = 12 young subjects, 10 elderly subjects) or nonexercising control (N = 11 young subjects, 10 elderly subjects) groups. Training consisted of treadmill walking, stairclimbing, or both three times per week for 40 minutes at 70–85% of maximal heart rate reserve for 16 weeks. Resting plasma propranolol concentrations after a single dose of 80 mg of oral propranolol were measured by high performance liquid chromatography with fluorescence detection, and estimated hepatic blood flow measured was measured using indocyanine green during supine rest. Aerobic training increased maximal oxygen uptake (VO2 max) by 13% and 14% in the exercising young and elderly groups, respectively. There was no change in VO2 max in either control group. Adjusted mean estimated hepatic blood flow after exercise corrected for body weight for the young subjects who did not exercise (15.6 mL/min/Kg) and those who did (18.2 mL/min/Kg) groups were of borderline significance. No statistical differences were detected in the experimental propranolol pharmacokinetic parameters (maximal concentration, time of maximal concentration, terminal half‐life, area under the curve, and protein binding) or derived pharmacokinetic parameters (intrinsic clearance, bioavailability, clearance, and volume of distribution). These results provide evidence that changes in aerobic fitness do not produce corresponding changes in propranolol pharmacokinetics in young or elderly adults.

Physical activity and cardiovascular health in the elderly

People over the age of 65 constitute a growing proportion of the world population both in western and in developing countries. A unique feature of this group is the high prevalence of cardiovascular diseases, which negatively affect its quality of life as well as its life expectancy. Among the interventions able to reduce the health burden of cardiovascular diseases is physical activity. The benefits of physical activity have been demonstrated both in healthy and chronically ill elderly subjects, while the risks have been found to be modest. Physicians should recommend moderate-intensity physical activity to sedentary older subjects, who are still the majority within the elderly population.

The effects of exercise training on the pharmacokinetics of digoxin.

BACKGROUND Studies have shown that digoxin binds to the working muscles during an acute bout of exercise, with a concomitant decrease in serum digoxin concentration. This study investigated the effects of 16 weeks of endurance exercise training on the pharmacokinetics of digoxin in old and young adults. METHODS Twelve subjects, aged 68.5 +/- 4.5 years, and six subjects, aged 30.3 +/- 3.8 years, completed the study. All subjects were healthy, sedentary, and taking no cardiovascular medications. After initial testing and maximum oxygen consumption (VO2max) measurements, subjects were hospitalized for 28 hours for renal function testing and digoxin clearance studies and then randomly assigned to an exercise (EG) or control (CG) group. The EG completed 16 weeks (three 1-hour bouts/week) of aerobic training at 75% to 85% of maximum capacity. The CG did not exercise. All tests were repeated at the end of the 16-week study period. RESULTS In the older EG subjects, VO2max increased by 3.4 ml/kg/min, or approximately 16% (P = 0.0002). VO2max increased in the younger EG subjects by 1.1 ml/kg/min, but the increase was not significant (P > 0.05). There were no significant changes in body composition, renal function, or time of onset, peak concentration, or elimination phase half-life of digoxin in either the old or young exercise or control groups (P > 0.05 for all variables). CONCLUSION Although 16 weeks of endurance exercise training improves cardiorespiratory fitness, the pharmacokinetics of digoxin are neither improved nor adversely affected in healthy old and young adults.

Failure to thrive related to metoclopramide therapy

To the Editor: Pneumonia is the major cause of death in demented patients. Recently, van der Steen et al. reported that short-time mortality after pneumonia was increased in patients with the most-severe dementia, 1 and that it would be important to define confounding variables. Certainly, immune system capacity to respond to infection will be an important determinant for outcome. In the blood of otherwise healthy patients with various types of dementia, increased formation of neopterin and enhanced degradation of tryptophan were reported, both indicating cellular (Thelper1-type) immune system activation. 2,3 Expression of immune activation markers correlated with the severity of dementia, 2,3 and, in patients with Huntington’s disease, higher neopterin levels and lower tryptophan levels were associated with earlier death. 3 It has been demonstrated that indoleamine (2,3)-dioxygenase (IDO) 2,3 critically influences T-cell responsiveness. 4 IDO is preferentially inducible by cytokine interferon, and IDO is rate-limiting for the conversion of tryptophan to kynurenine outside the liver. Therefore, enhanced degradation of tryptophan accompanies T-cell activation, and tryptophan deficiency may develop. Diminished availability of tryptophan prevents T-cell response to infectious agents. 4 Pneumonia is associated with immune activation, 5 which may further diminish tryptophan availability in patients with dementia and thus prevent successful immune response against the infectious agent. Thus, the data of van der Steen et al. may support the view that tryptophan availability in patients with dementia is crucial for the outcome of pneumonia. If this is true, increased blood levels of neopterin and decreased tryptophan concentrations might predict the outcome of demented patients suffering from pneumonia.

Effects of fosinopril or sustained-release verapamil on blood pressure and serum catecholamine concentrations in elderly hypertensive men.

&NA; A randomized, double-blind, placebo-controlled clinical trial showed 14 of 18 (78%) of the elderly hypertensive men in this study had an uncomplicated and beneficial response to either fosinopril or verapamil. There was a well-tolerated reduction in systolic blood pressure (SBP) and diastolic blood pressure (DRP). There were no significant adverse drug events. Only the sitting SBP and the sitting DBP were significantly lowered by fosinopril and verapamil SR. Because reduction in both SBP and DBP in elderly hypertensives has been shown to be beneficial, these findings take on further importance when considering the choice of medication for antihypertensive therapy in the elderly. The increase in norepinephrine in the fosinopril-treated patients may explain why patients treated with long-term angiotensin-converting enzyme inhibitors alone or in combination with diuretics rarely complain of orthostatic symptoms.