Pharmacology

Pharmacology

Older persons are the largest consumers of drugs – almost one third of all prescription drugs go to this group (45% of all prescriptions in NHS (UK) go to those >65yrs). Most community living older persons will have 10-12 prescription drugs per year, with 90% using as least one drug daily. The drug concentrations, duration of effect and the response of organs are different in an older person than a younger person. The combination of age, poor compliance, aging related body changes, multiple morbidities and multiple drugs  high potential for adverse effects  prescribing is complex. Effective management of the use of prescription and non-prescription drugs is one of the greatest clinical challenges in geriatric medicine.

Pharmacokinetic and Pharmacologic changes:

Pharmacokinetics is ultimately concerned with the concentration of the drug in the tissues – a number of pharmacokinetic changes occur. The net effect of these pharmacokinetic changes associated with aging is that many drugs remain active for longer periods of time  prolonged effects and greater risk for adverse effects.

Drug absorption:
Slower/delayed due to decreased small bowel surface area, decreased gastrointestinal blood flow, decreased motility, decreased emptying and acid secretory capacity and an increase in gastric pH. However, the changes may not be clinically significant and they are not considered as major factors in alterations in pharmacokinetics.

Drug distribution:
• decrease in mean body mass  normal adult dose provide more drug per kg
• total body water is less and body fat is increased  affects dose (eg some water soluble drugs will increase in concentration)
• plasma albumin may be reduced in chronic disease  more proportion of unbound or free drug
• decrease in cardiac output

Drug metabolism:
Liver mass and blood flow are decreased 
• inactivation/elimination of drugs takes longer
• drugs persist for longer in blood
First pass metabolism has been shown to be impaired in the elderly for some drugs  major increase in serum concentration and systemic availability  decreased dose needed of these drugs (eg propranolol). Clearance of drugs metabolised by the cytochrome P-450 system is often reduced (eg diazepam, amitriptyline)

Elimination/clearance:
With age, get a decrease in renal mass, renal blood flow, glomerular filtration and tubular secretion  decrease in elimination/excretion of many drugs.
eg reduced renal elimination of some antibiotics (eg ciprofloxacin, gentamicin, streptomycin); diuretics (eg amiloride, furosemide); lithium; cimetidine; methotrexate

Pharmacodynamics:
The effects of drugs and their time course of drugs may be larger or smaller in the older person than younger person. These differences will be due to changes in the interaction at drug receptor site, in post-receptor events or in other responses. Pathology in organs systems will affect the time course of drug action.

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