Therapeutic Tag's Archives

Synopsis of Important Principles
Critical illnesses

  1. Critical illnesses are often associated with circulatory, respiratory, hepatic and/or renal dys­function that may alter the pharmacokinetics and/or pharmacodynamics of drugs.
  2. Decisions about routes of administration and doses of drugs used during medical emergen­cies must consider the physiological status of the patient, the pharmacokinetic and pharmacodynamic characteristics of the particular drug, and how the two interact.
  3. Adverse drug reactions and interactions are more likely in critically ill patients due to the effect of the disease on drug kinetics, the decreased toxic-therapeutic ratio due to severe under­lying illness, and the large number of medications that such patients receive. Adverse reactions to drugs should be considered when unexplained deterioration or failure to respond to therapy are encountered.

haemodialysisHaemodialysis, peritoneal dialysis, haemoperfusion, exchange transfusion and forced diuresis have all been used in attempts to increase the rate of removal of drugs and poisons. How­ever, the amount of active drug removed is often disappointingly small, and the indications for the use of such measures is very limited.

Never­theless, poisoned patients are often unnecessar­ily subjected to these potentially harmful meas­ures, and the literature is full of anecdotal accounts of miraculous recovery attributed to such treatment (Winchester et al. 1977). Prop­erly controlled clinical trials are difficult to carry out, and very few have been published. With the possible exception of forced alkaline di­uresis for poisoning with salicylate and long act­ing barbiturates such as phenobarbitone, none of these methods for enhancement of drug re­moval has ever been shown to reduce morbidity or mortality in poisoned patients (Todd 1984).

Indeed, some studies suggest the opposite result. This is not to say that such measures are never necessary, or indeed sometimes life saving, but a more critical appraisal of their role is required.

Medical LabThe idea that drug concentrations could be measured and used to guide therapeutic deci­sions was first applied to quinidine when it was used to convert the cardiac rhythm of patients with atrial fibrillation to sinus rhythm (Sokolow & Ball 1956).

Although quinidine is rarely used for this purpose today, because of the advent of DC cardioversion, this study is still almost unique because it defined a target concentration based upon both the probability of therapeutic success and of toxicity.

Therapeutic drugTherapeutic drug monitoring is based upon the collaboration between a health care provider (clinician, pharmacist, nurse) responsible for making quantitative and qualitative decisions about drug treatment and the clinical labora­tory providing analytical services for the measurement of drug concentrations. The in­formation provided by a drug concentration measurement is generally greater than for other substances measured by the laboratory.

This is because, unlike say sodium or glucose, the in­take of a drug is quite well known and the pro­cesses of distribution and elimination are usu­ally very simple and not under the control of a multitude of homeostatic controlling reflexes.