This chapter introduces the pharmacokinetic and pharmacodynamic principles that let physiotherapists anticipate how common analgesic and cardiovascular drugs affect exercise tolerance, safety and session timing.
Why Pharmacology Matters in Rehabilitation
Most patients referred for musculoskeletal rehabilitation take at least one centrally acting, cardiovascular or anti-inflammatory drug. These drugs change heart rate, blood pressure, alertness, balance, pain perception and tissue healing. Physiotherapists do not prescribe or alter doses. They do need to recognise expected drug effects, separate them from pathology, time treatment sensibly, and communicate precisely with the prescriber or pharmacist.
Core Pharmacokinetic Concepts (ADME)
Pharmacokinetics describes what the body does to a drug:
- Absorption: movement from the site of administration into the circulation. Bioavailability (F) is the fraction reaching systemic circulation unchanged. Oral morphine has F of about 20–40% because of hepatic first-pass metabolism.
- Distribution: governed by blood flow, plasma protein binding (albumin) and lipophilicity. Older adults have more body fat, less lean mass and often lower albumin, which alters distribution.
- Metabolism: mainly hepatic (CYP450 enzymes, glucuronidation). Metoprolol is cleared by CYP2D6, and genetic variants or inhibitors can raise its levels.
- Excretion: mainly renal. Atenolol and morphine-6-glucuronide (an active morphine metabolite) accumulate when eGFR falls, which is common in people over 65.
Key parameters:
| Parameter | Meaning | Rehab relevance |
|---|---|---|
| Tmax / Cmax | Time to, and size of, peak concentration | Timing of sessions around peak effect |
| Half-life (t½) | Time for concentration to fall by 50% | Steady state is reached in about 4–5 half-lives |
| Clearance | Volume of plasma cleared per unit time | Reduced in renal or hepatic impairment |
| Formulation | Immediate vs. extended release | Alters Tmax, duration and fluctuation |
Pharmacodynamics and Vulnerable Populations
Pharmacodynamics is what the drug does to the body: receptor binding, dose–response and the therapeutic index. Older adults, those with renal or hepatic impairment, and patients taking multiple drugs (polypharmacy) show larger and less predictable responses. Post-operative patients, for example after hip replacement, often combine opioids, anticoagulants, antihypertensives and NSAIDs, so effects add together.
Clinical Presentation of Drug Effects: Three Common Scenarios
Opioids (immediate vs. extended release)
- Immediate-release oral morphine: onset 20–30 min, peak about 60 min, duration 3–4 h. A walking program is best scheduled about 45–90 minutes after a dose, when analgesia is maximal. Avoid training at peak if sedation or dizziness is present.
- Extended-release morphine (every 12 h): Tmax is typically 3–6 h, and steady state is reached in about 24 h. A patient who reports peak relief 4–6 h after a dose and "end-of-dose" pain before the next one has a pharmacokinetic pattern worth reporting to the prescriber. Do not advise the patient to change the dose or timing.
- Adverse effects: sedation, dizziness, constipation, nausea, slowed reaction time and impaired balance. In a 70-year-old with osteoporosis, opioid-related falls carry a high fracture risk.
Immediate-release oral morphine peaks at about 60 minutes. A walking program is best scheduled about 45–90 minutes after a dose, if the patient is alert.
NSAIDs and food
Taking an NSAID with food mainly delays absorption (longer Tmax, lower Cmax). The total amount absorbed is usually unchanged for ibuprofen and naproxen. The patient therefore feels slower and less intense relief, though the drug is not "less effective" overall. Food reduces gastric irritation, which is a reasonable trade-off. Relief timing, not food, should guide session planning, and any change in how the NSAID is taken should be discussed with the pharmacist. Remember the key NSAID risks: GI bleeding, renal impairment (especially with ACE inhibitors and diuretics, the "triple whammy"), fluid retention and raised blood pressure.
Beta-blockers (metoprolol, atenolol)
- Both reduce resting and exercise heart rate and blunt the response to exertion. Metoprolol is β1-selective, lipophilic, hepatically cleared, with t½ of 3–7 h. Atenolol is hydrophilic, renally cleared, with t½ of 6–7 h, so it accumulates in renal impairment and in elderly patients.
- A heart rate of 50–60 bpm in a patient on atenolol 50 mg may be an expected drug effect. Symptoms such as lightheadedness, syncope, exertional dyspnoea, chest pain or marked fatigue make it a concern.
- Lightheadedness with a BP of about 110 mmHg systolic suggests possible orthostatic hypotension, bradycardia or over-treatment, and needs further assessment.
Assessment
Medication review (every new patient): drug name, dose, formulation (IR vs. ER), timing, recent changes, adherence, over-the-counter and herbal products, alcohol, and renal or hepatic disease. Ask patients to bring a medication list.
Review every new patient's medicines: dose, formulation, timing, recent changes, adherence, and over-the-counter and herbal products. Ask them to bring a medication list.
Vital signs, pre-session:
- Resting HR, rhythm (palpate regularity) and BP seated.
- Orthostatic BP: supine 5 min, then standing at 1 and 3 min. Orthostatic hypotension is a fall of ≥20 mmHg systolic or ≥10 mmHg diastolic within 3 min (Freeman et al., 2011).
- SpO₂ and respiratory rate if opioids are being used.
Sedation and function:
- Pasero Opioid-induced Sedation Scale (POSS): 1 = awake, 2 = slightly drowsy, 3 = frequently drowsy, 4 = somnolent. Exercise is not appropriate at POSS ≥3.
- Timed Up and Go: ≥12 s indicates increased fall risk in community-dwelling older adults.
- 30-second Chair Stand and the 4-Stage Balance Test (inability to hold tandem stance for 10 s signals risk).
Exertion monitoring in beta-blocked patients: use Borg RPE (6–20), target 11–14, or CR10 of 3–4, together with the talk test. Age-predicted HRmax (220 – age) is invalid.
Outcome measures: NPRS (MCID about 2 points or 30%), Roland-Morris Disability Questionnaire (MCID about 5 points), Oswestry Disability Index (MCID about 10 points), and a daily medication and pain diary to link relief to dose timing.
Physiotherapy Management: Staged Approach
Stage 1 – Screen and plan (session 1): Complete the medication review and orthostatic BP. Do not start exercise if resting SBP >200 or DBP >110 mmHg, or if the patient has unstable angina, acute symptoms or POSS ≥3. Agree session times relative to dosing.
Stage 2 – Low-intensity graded exposure (weeks 1–2):
- Walking for 5–10 min bouts, RPE 9–11 ("light"), progressing by 10–20% per week.
- Slow position changes, with seated rest before standing and a gradual cool-down (5–10 min) to avoid post-exercise hypotension, which is more pronounced with beta-blockers and vasodilators.
- Encourage hydration, particularly with NSAIDs and diuretics (reduced renal perfusion raises AKI risk).
Stage 3 – Progressive loading (weeks 3–8):
- Aerobic work at RPE 11–14, 3–5 days a week, building to 20–30 min.
- Resistance training at 2–3 sets of 8–12 repetitions at moderate load (about 60–70% 1RM) for osteoporosis and OA. Avoid the Valsalva manoeuvre in patients with hypertension or angina.
- Re-measure NPRS, TUG and function every 2–4 weeks and review medication changes.
Stage 4 – Maintenance and self-management: Promote independent exercise, medication-timing awareness, falls prevention and a plan for symptom escalation.
Timing summary:
- IR morphine: exercise about 45–90 min post-dose, if alert.
- ER morphine: exercise at 2–4 h post-dose if relief is adequate and POSS is 1–2. Reassess balance if sedation peaks.
- NSAID: if rapid relief is needed before a session, allow 60–90 min after a dose taken with food.
- Cardiac drugs: avoid assuming a normal HR response. Schedule sessions away from the peak effect only in consultation with the prescriber, and never withhold medication.
Red Flags and Contraindications
Stop the session and seek medical review for:
- Resting HR <40 bpm, or <50 bpm with symptoms, an irregular pulse, or syncope or near-syncope.
- SBP <90 mmHg or a symptomatic drop of ≥20 mmHg on standing.
- Chest pain not relieved by rest or the patient's GTN (angina).
- Respiratory rate <10/min, SpO₂ <92%, pinpoint pupils or reduced responsiveness (opioid toxicity; call emergency services).
- Black stools, haematemesis or epigastric pain (NSAID GI bleed).
- New oedema, reduced urine output or weight gain (NSAID renal or fluid effects).
- Heat applied over transdermal fentanyl patches. This increases absorption and the risk of overdose, so heat is contraindicated over the patch.
Evidence and Clinical Pearls
- Guidelines recommend non-pharmacological therapy, including exercise, as first-line management for chronic low back pain, with NSAIDs second-line and opioids only when benefits outweigh risks (Qaseem et al., 2017). The CDC advises caution at ≥50 morphine milligram equivalents (MME) per day (Dowell et al., 2022).
- Food delays the absorption of ibuprofen without substantially reducing total exposure (Davies, 1998).
- Pearl: Treat the patient's symptoms and RPE, not the heart rate. Beta-blockade can mask tachycardia from pain, bleeding or infection.
- Pearl: Document the time of the last dose in every note. Session timing is part of the treatment plan.
- Pearl: Report concerns to the prescriber with objective data (BP readings, POSS, TUG, pain diary), not just impressions.
- Pearl: Exercise raises skin and muscle blood flow, so absorption of transdermal and injected drugs can change. Heat, vigorous exercise and saunas increase transdermal uptake.
- Practise within scope: advise and communicate, but never advise stopping, skipping or doubling a drug.
Summary
Pharmacokinetics (absorption, distribution, metabolism and excretion) determines when a drug acts and for how long, and this should shape session timing and monitoring. IR opioids peak at about 1 h, ER opioids at about 3–6 h, and food delays NSAID absorption without lowering total exposure. Beta-blockers blunt heart rate, so RPE replaces HR targets. A structured medication review, orthostatic BP, sedation scoring and falls-risk testing support safe, graded exercise progression, and clear red-flag recognition and communication complete the picture.
References
- Brunton LL, Knollmann BC, eds. Goodman & Gilman's The Pharmacological Basis of Therapeutics. 14th ed. New York: McGraw-Hill; 2023.
- Shargel L, Yu ABC. Applied Biopharmaceutics & Pharmacokinetics. 7th ed. New York: McGraw-Hill; 2016.
- Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain — United States, 2022. MMWR Recomm Rep. 2022;71(3):1–95.
- Qaseem A, Wilt TJ, McLean RM, Forciea MA. Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2017;166(7):514–530.
- Davies NM. Clinical pharmacokinetics of ibuprofen: the first 30 years. Clin Pharmacokinet. 1998;34(2):101–154.
- Freeman R, Wieling W, Axelrod FB, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011;21(2):69–72.
- Liguori G, Feito Y, Fountaine C, Roy B, eds. ACSM's Guidelines for Exercise Testing and Prescription. 11th ed. Philadelphia: Wolters Kluwer; 2021.
- Pasero C, McCaffery M. Pain Assessment and Pharmacologic Management. St. Louis: Mosby; 2011.