Doses of medicinal substances

Therapeutic doses: from minimum to maximum

In clinical practice, therapeutic effects are achieved using therapeutic doses. Depending on the strength of the developing effect, they are divided into several grades:

• Minimum effective (threshold) doses. This is the smallest amount of a substance capable of producing a detectable therapeutic effect. Usually, they are 2–3 times lower than standardly used values.
• Average therapeutic doses. These are the very doses that provide the necessary therapeutic effect in the overwhelming majority of patients. Due to individual biological sensitivity and varying disease severity, the average dose is often indicated not as a fixed number, but as a working range (for example, for diclofenac, this is 0.025–0.05 g). Regarding the time of administration, a single dose (pro dosi — per single dose) and a daily dose (pro die — the amount of substance taken over 24 hours) are distinguished.
• Maximum therapeutic doses. These are limit values. Physicians prescribe them only if average doses do not yield the desired result. Exceeding this threshold is extremely dangerous, as it threatens the development of severe toxic effects. There are maximum single and maximum daily doses. When prescribing poisonous and potent substances, strict legal rules apply: if the prescription exceeds the maximum dose without special formalization by the physician, the pharmacist has no right to dispense the drug to the patient.

Dose-response graphical relationship

To analyze drug kinetics and dynamics, pharmacologists use special graphs (coordinates: abscissa axis $X$ — dose $D$ or logarithm of the dose $\log D$; ordinate axis $Y$ — severity of the effect $E$).

The shape of the curve depends on the chosen coordinate system:

1. In arithmetic (linear) coordinates, the graph takes the form of a hyperbola.
2. In semi-logarithmic coordinates, the curve has a characteristic S-shaped (sigmoid) form.

The graph is used to determine key pharmacological parameters:

• $E_{max}$ — the maximum effect that a given substance can theoretically produce. This indicator is a measure of the intrinsic activity of the drug.
• $ED_{50}$ (Median Effective Dose) — the dosage that produces an effect equal to exactly half of the maximum possible ($1/2 E_{max}$). This parameter allows assessment of the affinity (activity) of the drug.

Specialized dosing regimens

Depending on the chosen treatment tactics, various drug administration regimens are used:

• Loading dose. It always exceeds the average therapeutic dose. Its main goal is the very rapid creation of a high concentration of the substance in the blood (so-called saturation). This approach is often used in antimicrobial therapy (for example, when prescribing antibiotics or sulfonamides).
• Maintenance dose. Prescribed immediately after the loading dose or after the desired clinical response has already been achieved with regular doses. Its task is to maintain the required concentration of the medicinal substance in the body to sustain the effect.
• Course dose. Represents the total amount of the medicinal substance prescribed to the patient for the entire course of treatment.

Toxicity, lethality, and safety parameters

Globally, based on the biological effect produced, all doses are divided into three categories: therapeutic, toxic, and lethal. If the amount of administered drug exceeds the maximum therapeutic values, dangerous consequences ensue.

• Toxic doses — the amount of a substance that causes toxic effects, leads to poisoning and organ damage.
• Lethal doses (from Lat. Letum — death) — the amount of a drug that leads to a fatal outcome. These values are always established exclusively at the preclinical research stage.

The main indicator of a drug's safety is the therapeutic index. This is the range between the minimum effective dose and the maximum therapeutic dose. The clinical significance of this parameter is enormous: the wider the therapeutic index, the safer the drug is to use and the lower the risk of accidental overdose.

Class and exam questions

What else to study on this topic

• Mathematical justification of hyperbolic and sigmoid dose-response curves
• Intrinsic drug activity ($E_{max}$) vs. affinity ($ED_{50}$)
• Rules for issuing prescriptions for doses exceeding maximum therapeutic levels
• Methodology for determining lethal doses in preclinical studies

Other topics in "General Pharmacology"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.