Another way to prevent cravings and stick to a healthy diet is to eat an assortment of smaller meals throughout the day. On top of a healthy breakfast eating small, healthy meals throughout the day will keep your energy levels up and your metabolism in good shape. This is a great tip for those that work long hours and have a hectic schedule as they don’t have the time needed to sit down and enjoy a wholesome and hearty meal, and if they did they would risk indigestion by rushing.


Fruits and vegetables are of course the foundation of a healthy diet, not only are they low in calories and nutrient dense, they are also jam packed with an assortment of much-needed vitamins, minerals, antioxidants and fibre.

Fruits and vegetables should be part of every diet and should be added to every meal. Both fruit and dried fruit is also a great first choice for a snack and everyone should aim to eat a minimum of five portions of fruit and vegetables every day. The antioxidants and other nutrients in fruits and vegetables are endless and help to combat a variety of ailments and also protect against certain types of cancer and other diseases.

When doing your weekly shop, be sure to invest in the brighter and deeper coloured fruits and vegetables as these house higher concentrations of minerals, antioxidants and vitamins and also provide a variety of benefits.

Greens, fruit and sweet vegetables are great health food options and each has endless health benefits. Try and invest in freshly grown produce or organic types, farmers markets are great places to look when trying to source any of the above.

You could also visit a health retailer and browse their selection of vitamins, minerals and herbal supplements such as vitamin D, digestive aids and antioxidants.

Circulatory failure, or the inability of the heart to provide sufficient cardiac output to sat­isfy tissue metabolic requirements, is the most important and most common cause of altered pharmacokinetics during cardiac emergencies. Circulatory failure may result from decreased myocardial contractility, arrhythmias that allow insufficient time for diastolic filling or impair atrioventricular synchrony, circulatory stresses such as increased afterload or hypovolaemia, valvular dysfunction, tamponade, or a variety of less common insults.

Regardless of the aetiology, circulatory fail­ure elicits characteristic compensatory haemodynamic adjustments, mediated in large part by activation of the sympathetic nervous system [Peniel & Benowitz 1984; Benowitz & Meister 1978]. Enhanced sympathetic tone in­creases cardiac contractility and peripheral vas­cular resistance, both of which serve to main­tain arterial blood pressure. The increase in peripheral vascular resistance, however, is not uniform among different vascular beds.

Organs with high metabolic requirements such as the heart and brain exhibit autoregulation; despite sympathetic stimulation, the vessels in these or­gans remain relatively vasodilated as a result of the local effects of hypoxia, lactic acid or other products of anaerobic metabolism that accu­mulate when organ perfusion is reduced. Blood flow to the heart and brain tends to be pre­served, while vasoconstriction decreases blood flow in other organs such as the skin, muscles, and splanchnic organs.

Pathophysiology of Cardiopulmonary Resuscitation (CPR)

Cardiac output during cardiopulmonary resuscitation (CPR) is severely compromised; in humans the mean arterial pressure is less than 50% of normal (Chandra et al. 1981; McDonald 1981), and cardiac output in dogs is less than 30% of normal (Vorhees et al. 1980). Haemodynamic measurements are difficult to obtain in patients during CPR, but animal data suggest that changes in blood flow distribution are qualitatively similar to those observed with circulatory failure and spontaneous circulation.

Blood flow during CPR in anaesthetised, electrically fibrillated dogs is reduced to all organs, but is least reduced to the brain and next least to the heart (Vorhees et al. 1980). For the purpose of pharmacokinetic considerations, CPR and circulatory failure with spontaneous circulation can be considered to be similar, in that total cardiac output is reduced and the pattern of blood redistribution during promptly initiated CPR resembles that seen in circulatory failure.

1. Specific antidotal therapy is available for very few poisons. The mainstay of treatment of severe poisoning is intensive supportive therapy and good nursing care.

2. The great majority of poisoned patients recover with intensive supportive therapy alone, and enthusiastic claims for the success of other treatment often cannot be justified.

3. With some important exceptions, the management of poisoning is not altered by knowledge of plasma drug concentrations. There are many pitfalls in the interpretation of drug concen­trations in poisoned patients, especially when nonspecific analytical methods are used.

4. Gastric lavage and induction of nemesis soon after ingestion may be effective in removing unabsorbed drug, but are unreliable. Adsorbents such as activated charcoal are usually ineffec­tive in limiting absorption when given more than 1 hour after ingestion.

5. Poisoned patients are often subjected to unnecessary and potentially harmful haemodialysis, haemoperfusion and diuresis. The efficacy of these measures has been established for relatively few substances in terms of reduction in morbidity and mortality or removal of toxicologically significant amounts of active drug or poison.

6. The efficacy of methods for extracorporeal removal can be predicted from pharmacokinetic principles. It depends primarily on the volume of drug distribution, plasma protein binding, rate of transfer from peripheral to central compartments, and dialysis clearance relative to the endogenous total body clearance.

7. Haemoperfusion with activated charcoal or exchange resins is more effective than haemo­dialysis in removing drugs from the blood. Peritoneal dialysis is less effective than haemodi­alysis. Drugs with large volumes of distribution cannot be removed rapidly by any of these techniques, and indications for their use are limited.

8. Forced diuresis can only increase the renal clearance of reabsorbed compounds, and clearance may be dramatically increased by appropriate manipulation of urine pH. However, the renal excretion of most drugs is insignificant in relation to the metabolic clearance. Forced alkaline diuresis is largely restricted to salicylate and phenobarbitone poisoning.

9. Repeated oral activated charcoal effectively increases the body clearance of a number of drugs. It probably acts by irreversibly binding drug diffusing from the circulation to the gut lumen and may also interrupt the enterohepatic circulation.

10. The toxicity of a few drugs and poisons can be reversed by specific antidotal therapy. Mechanisms include pharmacological antagonism, inhibition of conversion to toxic metabolites, inactivation of highly reactive alkylating intermediates, chelation and binding with drug-specific antibodies.

Although unabsorbed drug in the stomach may be removed by gastric aspiration and lav­age its usefulness in practice has been seriously questioned (Proudfoot 1984). Most drugs and poisons seem to be absorbed rapidly and this technique is unlikely to be productive more than 4 hours after ingestion, unless gastric emptying has been delayed by opioid analgesics, anti­cholinergic agents, central nervous system de­pressants, and possibly salicylates. In such circumstances gastric lavage may be worthwhile up to 12 hours after ingestion.

It is said to be contraindicated after ingestion of corrosives and hydrocarbons such as paraffin because of the risks of perforation and lipoid pneumonia, respectively.

The patient must be correctly positioned head down in the left lateral position and a cuffed endotracheal tube inserted beforehand if the protective pharyngeal reflexes are depressed. It is essential to use a large bore tube (e.g. Jacques 30 gauge) and in adults lavage should be carried out with 300ml portions of warm tap water un­til the return is clear. Complications include pulmonary aspiration of stomach contents, and, rarely, oesophageal rupture.

Although gastric lavage is often unrewarding, large amounts of drug are occasionally re­covered. A common cause of failure is the use of too small a tube – an ordinary nasogastric tube is virtually useless. Large amounts of re­sidual drug have been found in the stomach postmortem after attempts at lavage with a nasogastric tube (Jenis et al. 1969), and in i case i large drug mass containing 25g of meproba­mate was removed by gastrotomy 40 hours after ingestion despite gastric lavage (Schwartz 1977).

Emetics

The comparative efficacy of induced emesis and gastric lavage is still debated. Neither guar­antees emptying of the stomach. Lavage is not always practicable in children because of the physical difficulty in passing a tube large enough to allow the passage of tablets, and emesis is probably preferable in young children. In 1 study in children poisoned with salicylates, emesis was claimed to be more effective than lavage (Boxer et al. 1969), but in another, only 10 to 15% of the amount of salicylate taken was recovered, even when emesis occurred within 1 hour of ingestion (Yaffe et al. 1970).

The major disadvantages are failure of eme­sis, particularly if central nervous system de­pressants have been taken, and toxicity, some­times fatal, from the retained emetic. Syrup of ipecac given with water is probably the best emetic, and is often effective within 15 to 30 minutes (Neuvonen et al. 1983).

Other agents which have been used include sodium chloride, copper sulphate, zinc sulphate, tartar emetic (antimony potassium tartrate), apomorphine and mustard. However, the over-enthusiastic use of sodium chloride and heavy metals can be ex­tremely dangerous and fatal poisoning with salt and copper sulphate has been reported (Gresham & Mashru 1982; Stein et al. 1976).

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.

A concentration of 8 rag/ L was shown to have an 80% chance of converting atrial fibrillation to sinus rhythm and a 20% chance of some serious toxicity. No atten­tion was paid to pharmacokinetics, The target concentration was chosen on the basis of pharmacodynamics, i.e. the effects, both good and bad, observed at particular concentrations.

Rational therapeutics – the aim of rational ther­apeutics is to achieve the desired effect with the cor­rect dose. The foundation of decision making is based on pharmacokinetics and pharmacodynamics which provide the rational principles to link dose and effect through drug concentration.

Rational therapeutics can be defined as the administration of the correct dose to achieve the desired effect. The target concentration concept is at the centre of rational therapeutics where it links dose to effect. Pharmacokinetics is the science that links dose and concentration by defining the processes of drug distribution (volume of distribution) and elimination (clear­ance).

Pharmacodynamics, on the other hand, is the science linking concentration to effect by defining the maximum effect of the drug (Emax) and the sensitivity of the target organ (as de­termined by the EC50; M£ the concentration producing 50% of Emax).

Therapeutic drug monitoring can now be placed at the centre of this therapeutic triangle. This incorporates information about doses, concentrations, and effects in an individ­ual and integrates these data to estimate more precisely the pharmacokinetic (volume of dis­tribution, clearance) and pharmacodynamic (Emax, EC50) parameters in that individual. These new values can then be used to predict the consequences of future dosing decisions and thus enable the selection of a suitable dose to achieve the desired effect, i.e. rational therapeutics.

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.

Given an accurate dosing history and one or more drug concentrations, it is possible to de­scribe the pharmacokinetic processes of distri­bution and elimination quite precisely in an individual patient and to make accurate predic­tions of concentrations at future points in time, whatever dosing regimen is used.

The ability to interpret drug concentrations and extract infor­mation so that future concentrations can be pre­dicted and a rational dosing scheme instituted, requires a different kind of intellectual effort from that needed to interpret, say, a serum glu­cose concentration. The latter is mostly inter­preted by reference to a so-called ‘normal range’ – usually the 95% confidence interval based upon measurements from a sample of a ‘normal’ population.

Under most circumstances, if the serum glucose concentration is within the “nor­mal range”, little further attention is paid to it If it is outside of the ‘normal range’, diagnostic efforts are made to determine what pathophys­iological process is disturbed. But the precise value will be used only in a semi quantitative fashion, eg. high, very high, or extremely high, or in reference to some previously defined diag­nostic threshold value; for example, diabetes mellitus may be diagnosed if the glucose con­centration is greater than 10 mmol/L.

On the other hand, all drug concentrations exceed the “normal” range because it would be abnormal to be able to detect any therapeutic substance in the serum of a normal, healthy individual.

The quantitative information provided by a drug concentration measurement can be use­fully applied with up to 2 significant figures in the determination of, say, drug clearance. This degree of precision is implicit in use of this in­formation because individual dosage decisions will often be made with 2 significant figures in the dose size.

The quantitative approach to therapeutic decision making is relatively new to the art of medicine. Most clinicians currently practicing medicine will not have been taught very much pharmacokinetics during their undergraduate training and may therefore have only a very hazy idea of the quantitative decisions that form the basis of rational therapeutics.

Furthermore, younger clinicians may be misled into thinking that the pharmacokinetics they were taught at medical school are irrelevant to modern medi­cine because their senior colleagues pay no at­tention to pharmacokinetic detail and make therapeutic decisions in a seemingly capricious fashion. Such a conclusion may be quite false because therapeutic decisions made by an ex­perienced clinician are founded upon a wide base of knowledge gained from treating many similar patients.

This prior knowledge of the character­istics of the population being treated provides an empirical, but nevertheless frequently satis­factory, guide to making an appropriate quan­titative and qualitative therapeutic decision. Recognition of the value of such prior infor­mation when faced with an individual patient about whom little is known is the basis of the latest techniques of rational, quantitative phar­macokinetic and pharmacodynamic forecasting.

For the person who must make a therapeutic choice on behalf of an individual patient, the application of quantitative pharmacokinetic principles can substitute for the advice of a more experienced colleague. For all clinicians, young and old, these same principles can be applied to new therapeutic entities and reduce the suf­fering of patients who would otherwise be ex­posed to the vagaries of a trial and error ap­proach.