Many factors in?uence the activity with which drugs operate. Among the factors which affect the necessary quantity are age, weight, sex, idiosyncrasy, genetic disorders, habitual use, disease, fasting, combination with other drugs, the form in which the drug is given, and the route by which it is given.
Normally, a young child requires a smaller dose than an adult. There are, however, other factors than age to be taken into consideration. Thus, children are more susceptible than adults to some drugs such as MORPHINE, whilst they are less sensitive to others such as ATROPINE. The only correct way to calculate a child’s dose is by reference to texts supplying a recommended dose in milligrams per kilogram. However, many reference texts simply quote doses for certain age-ranges.
Old people, too, often show an increased susceptibility to drugs. This is probably due to a variety of factors, such as decreased weight; diminished activity of the tissues and therefore diminished rate at which a drug is utilised; and diminished activity of the KIDNEYS resulting in decreased rate of excretion of the drug.
Weight and sex have both to be taken into consideration. Women require slightly smaller doses than men, probably because they tend to be lighter in weight. The e?ect of weight on dosage is partly dependent on the fact that much of the extra weight of a heavy individual is made up of fatty tissue which is not as active as other tissues of the body. In practice, the question of weight seldom makes much di?erence unless the individual is grossly over- or underweight.
Idiosyncrasy occasionally causes drugs administered in the ordinary dose to produce unexpected effects. Thus, some people are but little affected by some drugs, whilst in others, certain drugs – for example, psychoactive preparations such as sedatives – produce excessive symptoms in normal or even small doses. In some cases this may be due to hypersensitivity, or an allergic reaction, to the drug, which is a possibility that must always be borne in mind
(e.g. with PENICILLIN). An individual who is known to be allergic to a certain medication is strongly advised to carry a card to this e?ect, and always to inform medical and dental practitioners and/or a pharmacist before accepting a new prescription or buying an over-the-counter preparation.
Habitual use of a drug is perhaps the in?uence that causes the greatest increase in the dose necessary to produce the requisite e?ect. The classical example of this is with OPIUM and its derivatives.
Disease may modify the dose of medicines. This can occur in several ways. Thus, in serious illnesses the patient may be more susceptible to drugs, such as narcotics, that depress tissue activity, and therefore smaller doses must be given. Again, absorption of the drug from the gut may be slowed up by disease of the gut, or its e?ect may be enhanced if there is disease of the kidneys, interfering with the excretion of the drug.
Fasting aids the rapidity of absorption of drugs, and also makes the body more susceptible to their action. Partly for this reason, as well as to avoid irritation of the stomach, it is usual to prescribe drugs to be taken after meals, and diluted with water.
Combination of drugs is to be avoided if possible as it is often di?cult to assess what their combined e?ect may be. In some cases they may have a mutually antagonistic e?ect, which means that the patient will not obtain full bene?t. Sometimes a combination may have a deleterious e?ect.
Form, route and frequency of administration Drugs are now produced in many forms, though tablets are the most common and, usually, convenient. In Britain, medicines are given by mouth whenever possible, unless there is some degree of urgency, or because the drug is either destroyed in, or is not absorbed from, the gut. In these circumstances, it is given intravenously, intra-muscularly or subcutaneously. In some cases, as in cases of ASTHMA or BRONCHITIS, the drug may be given in the form of an inhalant (see INHALANTS), in order to get the maximum concentration at the point where it is wanted: that is, in the lungs. If a local e?ect is wanted, as in cases of diseases of the skin, the drug is applied topically to the skin. In some countries there is a tendency to give medicines in the form of a suppository which is inserted in the rectum.
Recent years have seen developments whereby the assimilation of drugs into the body can be more carefully controlled. These include, for example, what are known as transdermals, in which drugs are built into a plaster that is stuck on the skin, and the drug is then absorbed into the body at a controlled rate. This method is now being used for the administration of GLYCERYL TRINITRATE in the treatment of ANGINA PECTORIS, and of hyoscine hydrobromide in the treatment of MOTION (TRAVEL) SICKNESS. Another is a new class of implantable devices. These are tiny polymers infused with a drug and implanted just under the skin by injection. They can be tailored so as to deliver drugs at virtually any rate – from minutes to years. A modi?cation of these polymers now being investigated is the incorporation of magnetic particles which allow an extra burst of the incorporated drug to be released in response to an oscillating magnetic ?eld which is induced by a magnetic ‘watch’ worn by the patient. In this way the patient can switch on an extra dose of drug when this is needed: insulin, for instance, in the case of diabetics. In yet another new development, a core of drug is enclosed in a semi-permeable membrane and is released in the stomach at a given rate. (See also LIPOSOMES.)... dosage
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