Clinical final

• The elderly


  Have multiple and often chronic diseases, and are the major consumers of drugs
• Elderly people receive about one-third of National Health Service (NHS) prescriptions in the UK. In most developed countries, the elderly now account for 25–40% of drug expenditure
• Most commonly used drugs by the elderly

  • Diuretics
  • Analgesics
  • Hypnotics, sedatives and anxiolytics
  • Antirheumatic drugs
  • β-blockers
• Aging


  • Results in many physiological changes that could theoretically affect absorption, first- pass metabolism, protein binding, distribution and elimination of drugs
  • Includes reduced gastric acid secretion, gastrointestinal motility, total surface area of absorption, blood flow, liver size, glomerular filtration, and renal tubular filtration
• Absorption


  Not significantly affected for majority of drugs, although digoxin absorption was slower
• First pass metabolism


  Reduced resulting in a significant increase in the bioavailability of such drugs like nifedipine, nitrates, propranolol, and verapamil
• Distribution


  Affected by reduced lean body mass, reduced total body water, increased total body fat, lower serum albumin level. Fat soluble drugs showed increased volume of distribution while water soluble drugs showed reduced distribution. Acidic drugs bind to albumin while basic drugs bind to alpha 1 acid glycoprotein
• Renal clearance


  The dosages of drugs with predominant renal excretion should be individualized, like digoxin and aminoglycosides (narrow therapeutic index) while not necessary for penicillins (wide therapeutic index)
• Pharmacodynamics in the elderly

  • Changes due to a reduction in homeostatic reserve and those that are secondary to changes in specific receptor and target sites
• Orthostatic circulatory responses


  A normal blunting of the reflex tachycardia that occurs in young subjects on standing or in response to vasodilatation. Antihypertensive drugs, drugs with α receptor blocking effects drugs which decrease sympathetic outflow from the central nervous system and antiparkinsonian drugs are, therefore, more likely to produce hypotension in the elderly
• Postural control (static reflexes)

  With ageing, the frequency and amplitude of corrective movements increase and an age-related reduction in dopamine (D2) receptors in the striatum has been suggested as the probable cause. Drugs which increase postural sway, for example hypnotics and tranquillizers, have been shown to be associated with the occurrence of falls in the elderly
• Thermoregulation


  Increased prevalence of impaired thermoregulatory mechanisms in the elderly, although it is not universal. Accidental hypothermia can occur in the elderly with drugs that produce sedation, impaired subjective awareness of temperature, decreased mobility and muscular activity, and vasodilatation. Commonly implicated drugs include phenothiazines, benzodiazepines, tricyclic antidepressants, opioids and alcohol
• Cognitive function


  Ageing is associated with marked structural and neurochemical changes in the central nervous system. Cholinergic transmission is linked with normal cognitive function, and in the elderly the activity of choline acetyltransferase, a marker enzyme for acetylcholine, is reduced in some areas of the cortex and limbic system. Several drugs cause confusion in the elderly. Anticholinergics, hypnotics, H2 antagonists and β-blockers are common examples
• Visceral muscle function


  Constipation is a common problem in the elderly as there is a decline in gastro-intestinal motility with ageing. Anticholinergic drugs, opiates, tricyclic antidepressants and antihistamines are more likely to cause constipation or ileus in the elderly. Anticholinergic drugs may cause urinary retention in elderly men, especially those who have prostatic hypertrophy. Bladder instability is common in the elderly, and urethral dysfunction more prevalent in elderly women. (Loop diuretics may cause incontinence)
• Age-related changes in specific receptors and target sites


  Response to many drugs may be altered by the number (density) of receptors, the affinity of the receptor, post-receptor events within cells resulting in impaired enzyme activation and signal amplification, or altered response of the target tissue itself
• α-Adrenoceptors


  α2-Adrenoceptor responsiveness appears to be reduced with ageing while α1-adrenoceptor responsiveness appears to be unaffected
• β-Adrenoceptors


  Their function declines with age. The chronotropic response to isoprenaline is less marked in the elderly. Propranolol therapy in the elderly produces less β-adrenoceptor blocking effect than in young. Reduction in high-affinity binding sites with ageing, in the absence of change in total receptor numbers, impairment of post-receptor transduction mechanisms with ageing
• Cholinergic system


  The effect of ageing on cholinergic mechanisms is less well known. Atropine produces less tachycardia in elderly humans than in the young
• Benzodiazepines


  The elderly are more sensitive to benzodiazepines than the young, and the mechanism of this increased sensitivity is not known. Habituation to benzodiazepines occurs to the same extent in the elderly as in the young
• Digoxin


  The elderly appear to be more sensitive to the adverse effects of digoxin, but not to the cardiac effects
• Warfarin


  The elderly are more sensitive to warfarin. This phenomenon may be due to age-related changes in pharmacodynamic factors. The exact mechanism is unknown
• Accidental hypothermia can occur in elderly patients taking sedatives
• Ageing is associated with marked structural changes in the central nervous system
• Constipation is a common problem with decline in gastric motility
• Anticholinergics may cause urinary retention
• Dementia


  Characterized by a gradual deterioration of intellectual capacity. Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies and frontotemporal dementia are the most important diseases of cognitive dysfunction in the elderly
• Alzheimer's disease (AD)


  Has a gradual onset, and it progresses slowly. Forgetfulness is the major initial symptom. The patient has difficulty in dressing and other activities of daily living. He or she tends to get lost in his or her own environment. Eventually, the social graces are lost
• Vascular dementia (VaD)


  Usually occurs in patients in their 60s and 70s, and is more common in those with a previous history of hypertension or stroke. It is commonly associated with mood changes and emotional lability
• Cholinergic neurons in AD

  Damage to the cholinergic neurons connecting subcortical nuclei to the cerebral cortex has been observed
• Anticholinesterases


  Block the breakdown of acetylcholine and enhance cholinergic transmission
• Donepezil, galantamine and rivastigmine

  Recommended for treatment of patients with AD of moderate severity only. The treatment effect should be reviewed critically every 6 months, before a decision to continue drug therapy is made
• Memantine


  An N-methyl-d-aspartate (NMDA) antagonist, has also been used for the treatment of moderate to severe AD. It acts mainly on subtypes of glutamate receptors related to memory (i.e. NMDA), resulting in improvements in cognition. It has also been shown to have some beneficial effects on behavior
• Aspirin therapy


  Has also been reported to slow the progression of VaD. The incidence of VaD is likely to decrease with other stroke prevention strategies such as smoking cessation, anticoagulation for atrial fibrillation, control of hypertension and hyperlipidemia
• Parkinsonism


  A relatively common disease of the elderly with a prevalence between 50 and 150 per 100,000. It is characterized by resting tremors, muscular rigidity and bradykinesia (slowness of initiating and carrying out voluntary movements). The patient has a mask-like face, monotonous voice and walks with a stoop and a slow shuffling gait
• Levodopa therapy


  Can cause serious ventricular dysrhythmias in elderly patients. Psychiatric adverse effects such as confusion, depression, hallucinations and paranoia occur with dopamine agonists and levodopa preparations
• Bromocriptine and other ergot derivatives


  Should be avoided in elderly patients with severe peripheral arterial disease as they may cause peripheral ischemia
• 'Drug holidays'


  Which involve discontinuation of drugs, for example, for 2 days per week, may reduce the incidence of adverse effects of antiparkinsonian drugs
• Stroke


  The third most common cause of death and the most common cause of adult disability. The incidence of stroke increases by 100-fold from the fourth to the ninth decade. About 85% of strokes are ischaemic and 15% are due to hemorrhages
• Thrombolytic agents


  Thrombolysis with tissue plasminogen activator (rt-PA) within 3 h of onset of ischaemic stroke improved clinical outcome at 3 months despite increased incidence (6%) of symptomatic intracranial bleeding. Most of the clinical trials with rt-PA have excluded patients over 80 years of age. However, analysis of data from studies which have included patients over the age of 80 years, indicates that thrombolysis is effective in this age group
• Aspirin


  In doses of 150–300 mg commenced within 48 h of onset of ischaemic stroke has been shown to reduce the relative risk of death or dependency by 2.7% up to 6 months after the event