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Essentially, blood pressure is monitored by baroreceptors found in the aorta and carotid arteries and regulated by the cardiovascular centre in the medulla of the brain. Baroreceptors continually send impulses to the cardiovascular centre. If blood pressure rises, the rate of impulses being sent to the cardiovascular centre increases. In response to this, the cardiovascular centre reduces heart rate and force of contraction by decreasing sympathetic stimulation and increasing parasympathetic stimulation of the heart.
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Action potentials are generated by depolarization followed by repolarization of the cardiac muscle cell membrane. Depolarization is initiated by an influx of sodium ions into the cardiac muscle cells, followed by an influx of calcium ions.
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References Department of Health Review of Prescribing, Supply and Administration of Medicines, Department of Health London.
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Reduction in blood pressure also improves cardiac output. In addition, ACE inhibitors suppress aldosterone secretion producing a reduction in salt and water retention and improve renal blood flow, which in turn inhibits renin release.
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This is of particular significance in drugs administered orally and the oral dosage of such drugs must be reduced in older people. Older patients appear to be more at risk of developing drug-induced hepatitis particularly with the use of non-steroidal anti-inflammatory drugs. The principal organ of excretion for the majority of drugs is the kidney. The physiological functioning of this organ declines with age.
At rate is approximately half that at age via the kidney are liable to accumulate in older patients. If these are drugs with a low TR, failure to excrete them at the expected rate may result in toxicity.