Drugs And Dosage For Hypertension.....
In practice, the dosage of many drugs and this applies particularly to I lie older ones is determined solely by experience, provided they have been accurately standardized either chemically or biologically, with little or no regard to the age or size of the patient. With newer drugs it is often necessary to determine the dose with great care to meet the needs of a particular patient and sometimes the presence of unwanted effects will determine the safe upper limit of dosage. Thus, the dose of a powerful anti- hypertensive drug needs to be carefully adjusted in order that postural hypo tension is not produced in a given patient.
The formulation or presentation of a drug can have a profound effect upon its dosage. For example, it is no longer possible to assume that equal doses of a pure chemically standardized drug will always produce the same response in the same patient. With many of the new synthetic drugs which have low solubility in water, the particle size of the drug within a tablet can have a marked bearing on the patient's response to it. When the makers of conspiratorial tablets ('Aldactone') first marketed their product, it was in tablets containing 100 mg of active drug.
An average dose was 400 mg daily in divided doses. It was discovered that if the drug was powdered much more finely before it was incorporated into tablets it was possible to reduce the dosage by 75 per cent, and the tablets marketed today contain only 25 mg of the finely powdered drug.
Another factor which affects the dosage of a drug is the possibility that a second drug which a patient is taking concurrently may potentate its action. For example, aspirin, potentates the anticoagulant action of phenylalanine,. and sodium bicarbonate by delaying its excretion by the kidneys produces an enhanced effect when a standard dose of amphetamine is administered. Chloroquine enhances the response to some analgesics and sedatives and use is made of this to achieve a given response to morphine without increasing the dose.
Sometimes the size of a patient is used as a guide to correct dosage of a drug. Size has been interpreted as weight in the past, and the dose of a drug such as nitrofurantoin, for example, has been stated as 5 to 8 mg per kg body-weight daily in divided doses. More recently it has been suggested that surface area of the patient is a better criterion than body- weight in assessing the size of a patient.
Infants and children pose a special problem and a number of formula have been devised as aids to the calculation of doses for children. Young's formula has served as a rough guide for many years:
Dose 4)-I.Child X adult dose age of child-1—Q
An alternative to Young's formula is given in the British National For mu-lary which is no doubt more reliable though less easy to memorize. Provided the child is of average weight for his age the dose for most drugs can be expressed as a percentage of the adult dose as follows:
Age 12 years 75 per cent
Age 7 years ,,50 per cent
Age 3 years ..33 per cent
Age I year =25 per cent
For infants below one year the dose is based on body-weight and is 2.5 per cent of the adult dose per kg body-weight of the infant.
Idiosyncrasy. This term implies an inherent grossly abnormal reaction to a normal dose of a drug and is probably due to a genetic abnormality. This is different from hypersensitivity which is due to an antibody- antigen reaction, and a patient who is hypersensitive to penicillin, for example, must have been exposed to the antibiotic on a previous occasion without ill-effect.
Cumulation. Drugs should only be administered at the rate at which they will be metabolized or excreted. This explains why some drugs may need to be given four times a day whereas others which are slowly eliminated are only given once a day. If a drug which is slowly excreted is given too frequently, a toxic level is built up and a cumulative effect is produced. This applies to drugs such as the digitalis triglycerides.
Tolerance is said to have developed when a patient requires increased doses of a drug to obtain an effect which was previously obtained with smaller doses. This is very liable to happen with the opium alkaloids such as morphine. Tolerance may lead to dependence which can be either physical, which means that the patient is physically ill if the drug is with¬held, or psychological.
This state is very liable to occur in the case of central nervous system stimulants or depressant drugs and powerful analgesics which produce euphoria.
It will be seen from this examination of the subject that there are many criteria which govern the choice of the correct dosage of any drug for a given patient.
In practice, the dosage of many drugs and this applies particularly to I lie older ones is determined solely by experience, provided they have been accurately standardized either chemically or biologically, with little or no regard to the age or size of the patient. With newer drugs it is often necessary to determine the dose with great care to meet the needs of a particular patient and sometimes the presence of unwanted effects will determine the safe upper limit of dosage. Thus, the dose of a powerful anti- hypertensive drug needs to be carefully adjusted in order that postural hypo tension is not produced in a given patient.
The formulation or presentation of a drug can have a profound effect upon its dosage. For example, it is no longer possible to assume that equal doses of a pure chemically standardized drug will always produce the same response in the same patient. With many of the new synthetic drugs which have low solubility in water, the particle size of the drug within a tablet can have a marked bearing on the patient's response to it. When the makers of conspiratorial tablets ('Aldactone') first marketed their product, it was in tablets containing 100 mg of active drug.
An average dose was 400 mg daily in divided doses. It was discovered that if the drug was powdered much more finely before it was incorporated into tablets it was possible to reduce the dosage by 75 per cent, and the tablets marketed today contain only 25 mg of the finely powdered drug.
Another factor which affects the dosage of a drug is the possibility that a second drug which a patient is taking concurrently may potentate its action. For example, aspirin, potentates the anticoagulant action of phenylalanine,. and sodium bicarbonate by delaying its excretion by the kidneys produces an enhanced effect when a standard dose of amphetamine is administered. Chloroquine enhances the response to some analgesics and sedatives and use is made of this to achieve a given response to morphine without increasing the dose.
Sometimes the size of a patient is used as a guide to correct dosage of a drug. Size has been interpreted as weight in the past, and the dose of a drug such as nitrofurantoin, for example, has been stated as 5 to 8 mg per kg body-weight daily in divided doses. More recently it has been suggested that surface area of the patient is a better criterion than body- weight in assessing the size of a patient.
Infants and children pose a special problem and a number of formula have been devised as aids to the calculation of doses for children. Young's formula has served as a rough guide for many years:
Dose 4)-I.Child X adult dose age of child-1—Q
An alternative to Young's formula is given in the British National For mu-lary which is no doubt more reliable though less easy to memorize. Provided the child is of average weight for his age the dose for most drugs can be expressed as a percentage of the adult dose as follows:
Age 12 years 75 per cent
Age 7 years ,,50 per cent
Age 3 years ..33 per cent
Age I year =25 per cent
For infants below one year the dose is based on body-weight and is 2.5 per cent of the adult dose per kg body-weight of the infant.
Idiosyncrasy. This term implies an inherent grossly abnormal reaction to a normal dose of a drug and is probably due to a genetic abnormality. This is different from hypersensitivity which is due to an antibody- antigen reaction, and a patient who is hypersensitive to penicillin, for example, must have been exposed to the antibiotic on a previous occasion without ill-effect.
Cumulation. Drugs should only be administered at the rate at which they will be metabolized or excreted. This explains why some drugs may need to be given four times a day whereas others which are slowly eliminated are only given once a day. If a drug which is slowly excreted is given too frequently, a toxic level is built up and a cumulative effect is produced. This applies to drugs such as the digitalis triglycerides.
Tolerance is said to have developed when a patient requires increased doses of a drug to obtain an effect which was previously obtained with smaller doses. This is very liable to happen with the opium alkaloids such as morphine. Tolerance may lead to dependence which can be either physical, which means that the patient is physically ill if the drug is with¬held, or psychological.
This state is very liable to occur in the case of central nervous system stimulants or depressant drugs and powerful analgesics which produce euphoria.
It will be seen from this examination of the subject that there are many criteria which govern the choice of the correct dosage of any drug for a given patient.
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