Drug dose

From DrugPedia: A Wikipedia for Drug discovery

Drug dose Dose (biochemistry), the quantity of something that may be eaten by or administered to an organism, or that an organism may be exposed to. Quantities of nutrients, drugs, and toxins are referred to as doses. A dose is a quantity of something (chemical, physical, or biological) that may impact an organism biologically; the greater the quantity, the larger the dose. In nutrition, the term is usually applied to how much of a specific nutrient is in a person's diet or in a particular food, meal, or dietary supplement. In medicine, the term is usually applied to the quantity of a drug or other agent administered for therapeutic purposes. In toxicology dose may refer to the amount of a harmful agent (such as a poison, carcinogen, mutagen, or teratogen), to which an organism is exposed.

• The Drug dose is based on the Dose-response relationship.

Dose-response relationship The Dose-response relationship describes the change in effect on an organism caused by differing levels of exposure (or doses) to a stressor (usually a chemical). This may apply to individuals (eg: a small amount has no observable effect, a large amount is fatal), or to populations (eg: how many people are affected at different levels of exposure).

Studying dose response, and developing dose response models, is central to determining "safe" and "hazardous" levels and dosages for drugs, potential pollutants, and other substances that humans are exposed to. These conclusions are often the basis for public policy. When the agent is radiation instead of a drug, this is called the exposure-response relationship

Dose-response curve A dose-response curve is a simple X-Y graph relating the magnitude of a stressor (e.g. concentration of a pollutant, amount of a drug, temperature, intensity of radiation) to the response of the receptor (e.g. organism under study). The response is usually death (mortality), but other effects (or endpoints) can be studied.

The measured dose (usually in milligrams, micrograms, or grams per kilogram of body-weight) is generally plotted on the X axis and the response is plotted on the Y axis. Commonly, it is the logarithm of the dose that is plotted on the X axis, and in such cases the curve is typically sigmoidal, with the steepest portion in the middle.

In medicine and toxicology the Drug dose may be following type-

• Effective dose, the smallest amount of a substance required to produce a measurable effect on a living organism
• Absorbed dose, an amount of radiation received
• Equivalent dose, a measure of radiation dosage to tissue
• Dosing, the process of administering a measured amount of a medicine or chemical
• Reference dose, the United States Environmental Protection Agency's maximum acceptable oral dose of a toxic substance.

Effective dose An effective dose in pharmacology is the amount of drug that produces a therapeutic response in 50% of the people taking it, sometimes also called ED-50. In radiation protection it is an estimate of the stochastic effect that a non-uniform radiation dose has on a human.

Absorbed dose Absorbed dose (also known as total ionizing dose, TID) is a measure of the energy deposited in a medium by ionizing radiation. It is equal to the energy deposited per unit mass of medium, and so has the unit J/kg, which is given the special name gray (Gy).

Note that the absorbed dose is not a good indicator of the likely biological effect. 1 Gy of alpha radiation would be much more biologically damaging than 1 Gy of photon radiation for example. Appropriate weighting factors can be applied reflecting the different relative biological effects to find the equivalent dose.

The risk of stochastic effects due to radiation exposure can be quantified using the effective dose, which is a weighted average of the equivalent dose to each organ depending upon its radiosensitivity. When ionising radiation is used to treat cancer, the doctor will usually prescribe the radiotherapy treatment in Gy. When risk from ionising radiation is being discussed, a related unit, the sievert is used.

Equivalent dose The equivalent dose (HT) is a measure of the radiation dose to tissue where an attempt has been made to allow for the different relative biological effects of different types of ionizing radiation. Equivalent dose is therefore a less fundamental quantity than radiation absorbed dose, but is more biologically significant. Equivalent dose has units of sieverts. Another unit, Röntgen equivalent man (REM or rem), is still in common use in the US, although regulatory and advisory bodies are encouraging transition to sieverts (100 Röntgen equivalent man = 100 REM = 1 sievert. Equivalent dose (HT) is calculated by multiplying the absorbed dose to the organ or tissue (DT) with the radiation weighting factor, wR. This factor is selected for the type and energy of the radiation incident on the body, or in the case of sources within the body, emitted by the source. The value of wR is 1 for x-rays, gamma rays and beta particles, but higher for protons, neutrons, alpha particles etc.

H_{T,R} = w_R \times D_{T,R} \,

Where HT,R = equivalent dose to tissue T from radiation R

DT,R = absorbed dose D (in grays) to tissue T from radiation R.

Dosing Dosing generally applies to feeding chemicals or medicines in small quantities into a process fluid or to a living being at intervals or to atmosphere at intervals to give sufficient time for the chemical or medicine to react or show the results. In the case of human beings or animals the word dose is generally used but in the case of inanimate objects the word dosing is used.

Reference dose A reference dose is the United States Environmental Protection Agency's maximum acceptable oral dose of a toxic substance. Reference doses are most commonly determined for pesticides. The EPA defines an oral reference dose (abbreviated RfD) as: An estimate, with uncertainty spanning perhaps an order of magnitude, of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime.

Effects are dose dependent Dosage (the size of each dose) determines the strength and duration of the health benefits of nutrients, and also of the therapeutic effects of medical treatments. Dosage also determines the severity of adverse effects of treatments and toxins. Duration of exposure, that is, the period of time over which the dose was received (all at once or gradually) also determines its effects (the body may build tolerance to gradual exposure to a drug, while a large immediate dose could be deadly). The route by which a dose is exposed to, may affect the outcome, because some medications have different effects depending on whether they are inhaled, ingested, taken transdermally, injected, or inserted.

Biological agents Biological agents (bacteria, viruses, parasites) may have different dosage units. This is because it is the ability of the organism to cause effects that is the important unit, not a specific quantity by weight, volume or even numerical count. Often the unit used is CFU (colony forming units), which is proportionate to the number of organisms present multiplied times the number able to reproduce on a culture medium such as a Petri dish.

Toxicology In the realm of toxicology, several measures are commonly used to describe toxic dosages according to the degree of effect on an organism or a population, and some are specifically defined by various laws or organizational usage. These include:

• LD50 = Median lethal dose, a dose which will kill 50% of an exposed population;
• NOEL = No Observed Effect Level, the highest dose known to show no effect;
• NOAEL = No Observed Adverse Effect Level, the highest dose known to show no adverse effects;
• PEL = Personal Exposure Limit, the highest concentration permitted under US OSHA regulations;
• STEL = Short Term Exposure Limit, the highest concentration permitted for short periods of time, generally 15-30 minutes;
• TWA = Time Weighted Average, the average amount of an agent's concentration over a specified period of time, usually 8 hours.