Dose–Response Relationships: From Dose to Effect

From Dose to Effect: Building the Intuition

A dose–response relationship describes how the body’s observable effect changes as the amount of drug exposure increases. Early on, it helps to think in everyday terms: a small amount of a pain reliever may do nothing noticeable, a moderate amount may reduce pain, and beyond a certain point taking more may not add meaningful relief but may increase side effects.

Two practical ideas anchor this chapter:

• More exposure usually increases effect—up to a limit.
• People can have different effects at the same dose because the dose taken is not the same as the concentration at the site of action.

Qualitative pattern you will see repeatedly

• No obvious effect at very low exposure (below a threshold).
• Increasing effect over a middle range (the “working range”).
• A plateau where additional exposure produces little or no additional desired effect (but may still increase adverse effects).

Dose vs Concentration: Why the Same Dose Can Behave Differently

In clinical practice, we prescribe a dose (e.g., 10 mg by mouth). What tissues experience is a concentration over time (e.g., ng/mL in plasma, or local concentration at the effect site). Dose and concentration are related, but not identical.

Key distinction

• Dose = amount administered (mg, units, mg/kg) and route (oral, IV, inhaled).
• Concentration = amount per volume at a location (often plasma) at a given time; it reflects absorption, distribution, and clearance.

Two patients can take the same 10 mg dose and have different concentrations because of differences in:

• Absorption (food effects, gut motility, formulation).
• Distribution (body size, body composition, protein binding).
• Clearance (kidney/liver function, drug interactions, genetics).

This is why dose–response curves are often taught using concentration–response relationships: concentration is closer to what the target “sees.” Clinically, we still titrate dose, but we interpret variability through the lens of concentration.

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Graded Dose–Response Curves: The Core Tool

A graded dose–response curve shows how the magnitude of a response changes with increasing dose (or concentration) in a single subject or a typical subject. The response is continuous (e.g., mmHg drop in blood pressure, percent bronchodilation, pain score reduction).

How to read the axes

• X-axis: dose or concentration (often shown increasing left to right; sometimes plotted on a log scale in textbooks, but you can interpret the shape without math).
• Y-axis: effect size (0% to 100% of maximum, or a clinical unit like mmHg).

Key Features of the Curve (What to Look For)

1) Threshold (the “not yet” region)

The threshold is the exposure range where effects are minimal or not clinically detectable. Below this, increasing dose may still be doing something biologically, but not enough to measure or matter clinically.

Practical implication: If a patient reports “no benefit” at a very low starting dose, it may simply be below threshold—not proof the drug cannot work.

2) Slope (how quickly effect increases)

The slope describes how much the effect changes when you increase dose within the working range.

• Steep slope: small dose changes produce large effect changes (titration requires caution).
• Shallow slope: dose changes produce gradual effect changes (titration can be more forgiving).

Practical implication: With a steep slope drug, doubling the dose may overshoot the desired effect or increase adverse effects quickly.

3) Plateau / Maximum effect (Emax)

The curve eventually reaches a plateau, representing the maximum achievable effect for that drug in that system (often called Emax). Beyond this point, increasing dose adds little desired benefit.

Practical implication: If a patient is already near the plateau for the desired effect, increasing the dose may mainly increase side effects rather than benefit.

Potency vs Maximum Effect: Two Different Questions

When comparing two drugs using graded curves, separate these ideas:

• Potency: “How much drug is needed to get a given effect?” A more potent drug achieves the same effect at a lower dose (curve is left-shifted).
• Maximum effect (Emax): “How big an effect can this drug produce at best?” A drug with a higher plateau can produce a larger maximum response.

Potency matters for dosing convenience and sometimes safety margins; maximum effect matters when you need a large response (e.g., severe symptoms).

Why Individuals Respond Differently to the Same Dose

Even if two people reach the same concentration, their responses can differ. Common reasons include:

• Different baseline physiology (e.g., high sympathetic tone vs low; dehydration; salt intake).
• Different sensitivity of the response system (some patients are “more responsive” to the same concentration).
• Concurrent conditions (e.g., kidney disease affecting electrolyte balance and blood pressure response).
• Concomitant medications (one drug can blunt or amplify another’s effect).

Clinically, this is why we often start with a standard dose but adjust based on measured response (blood pressure readings, symptom scores, lab values).

Guided Interpretation: Recognizing Curve Changes

When you see two curves on the same axes, focus on two questions:

• Did the curve shift left or right? (potency/exposure needed changed)
• Did the maximum response change? (the plateau moved up or down)

Left shift vs right shift (same maximum)

If two curves reach the same plateau but one is shifted:

• Left shift: less dose needed for the same effect (apparent increased potency). Possible clinical explanations include higher concentrations achieved at the same dose (reduced clearance) or increased sensitivity.
• Right shift: more dose needed for the same effect (apparent decreased potency). Possible explanations include lower concentrations at the same dose (poor absorption, increased clearance) or reduced sensitivity.

Clinical translation: A right shift means your usual dose may underperform; a left shift means your usual dose may be too strong.

Change in maximum response (plateau changes)

If the plateau differs:

• Lower maximum response: even high doses cannot achieve the previous peak effect. Clinically, this suggests the drug cannot deliver the needed magnitude of response in that patient/system, or another factor is limiting the response (e.g., disease severity, competing physiology).
• Higher maximum response: the drug (or condition) allows a larger achievable effect.

Clinical translation: If the maximum is lower, simply increasing the dose may not solve the problem; you may need a different drug or combination strategy.

Step-by-Step: Using Dose–Response Thinking to Titrate a Blood Pressure Medicine

Imagine a medication that lowers systolic blood pressure (SBP). Your goal is a safe, controlled reduction without excessive hypotension.

Step 1: Define the measurable response and target

• Response: change in SBP (mmHg) from baseline.
• Target: for example, SBP reduction of ~10–20 mmHg while avoiding dizziness or SBP < 100 mmHg (targets vary by patient).

Step 2: Start in the lower working range

Begin near the expected threshold/early working range to avoid overshooting, especially if the drug has a steep slope or the patient is older, volume-depleted, or on interacting medications.

Step 3: Reassess after an appropriate interval

Measure BP at consistent times and conditions. If there is no meaningful change, you may still be below threshold or the curve may be right-shifted for this patient (low exposure or low sensitivity).

Step 4: Increase dose in planned increments

Move along the curve gradually:

• If the curve is steep, use smaller increments and monitor closely.
• If the curve is shallow, increments may be larger, but still systematic.

Step 5: Recognize the plateau

If BP improves with early increases but then stops improving despite further increases, you may be approaching the plateau for that drug in this patient. At that point, consider switching or adding a complementary medication rather than continuing to escalate.

Simplified Curves for Practice (ASCII Graphs)

Use these simplified graphs to practice identifying shifts and maximum changes. The y-axis is effect (e.g., BP reduction), and the x-axis is dose.

Graph A: Left shift (same maximum)

Effect ^                 _________  Drug A (less potent; rightward)  |               _/         |            _/           Drug B (more potent; leftward)  |         _/             |      _/                |___ _/__________________> Dose

Interpretation prompt: Which drug needs a lower dose to achieve the same effect? Do they reach the same maximum?

Graph B: Lower maximum response

Effect ^                 _________  Drug A (higher max)  |               _/         |            _/           Drug B (lower max)  |         _/______        |      _/                |___ _/__________________> Dose

Interpretation prompt: If a patient needs a large effect, which drug is more capable of achieving it?

Graph C: Right shift (same maximum)

Effect ^                 _________  Baseline curve  |               _/         |            _/            Shifted right (needs more dose)  |         _/                 _/  |      _/                 _/     |___ _/__________________> Dose

Interpretation prompt: What are two clinical reasons a curve might shift right when you prescribe the same dose?

Practice Questions (Curves + Clinical Vignettes)

1) Identifying a left shift

A patient starts a new medication that inhibits the clearance of your blood pressure drug. After a week, the same dose produces a larger BP drop than before.

• On a dose–response curve, would you expect a left shift or right shift?
• Would the maximum effect necessarily change?

2) Recognizing the plateau

A patient’s SBP falls by 12 mmHg when you increase the dose from 5 mg to 10 mg, but it falls only 1 mmHg when you increase from 10 mg to 20 mg. Side effects increase at 20 mg.

• Where on the curve is the patient likely moving (early working range vs near plateau)?
• What is a reasonable next step in strategy (dose escalation vs alternative/add-on)?

3) Right shift vs nonadherence (dose vs concentration)

Two patients are prescribed 10 mg daily. Patient A shows the expected BP reduction; Patient B shows almost none. Patient B also reports taking the medication “most days.”

• Name two reasons Patient B could appear right-shifted compared with Patient A.
• Which reason relates to dose taken and which relates to concentration achieved?

4) Lower maximum response

A patient with severe hypertension shows only modest BP reduction even at higher doses, and further increases do not help.

• Does this pattern fit a right shift, a lower maximum response, or both?
• What does a lower maximum response suggest about simply “pushing the dose”?

5) Curve reading drill

Look back at Graphs A and B.

• In Graph A, which curve represents higher potency?
• In Graph B, which curve represents higher maximum effect?
• Give one clinical situation where potency matters more than maximum effect, and one where maximum effect matters more than potency.