Analgesics: pain relief in obstetrics

Analgesics are drugs that reduce pain without treating the cause of the pain; key classes include paracetamol, non-steroidal anti-inflammatory drugs, opioids, as well as so-called 'adjuvant' drugs such as some antidepressants and anticonvulsants, and topical forms such as gels and patches. [1]

The World Health Organization's classic educational model—the "analgesic ladder"—was historically used primarily in oncology and still helps systematically select pain relief, from simpler to more potent agents as pain worsens. In current approaches, paracetamol and nonsteroidal anti-inflammatory drugs remain the basis, and escalation rules have been clarified in modern guidelines. [2]

Opioid analgesics are used primarily for moderate to severe pain when other options are ineffective. Their use is accompanied by a rigorous assessment of benefits and risks, dose and duration, and a monitoring plan. These principles are enshrined in the 2022 Clinical Practice Guidelines of the US Centers for Disease Control and Prevention. [3]

Adjuvant agents include medications for specific types of pain: duloxetine and gabapentinoids have a proven role in neuropathic pain, but regulators specifically warn against respiratory depression when used in combination with opioids and in the elderly. The choice of such agents requires individualization and consideration of comorbidities. [4]

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are important for localized muscle and joint pain: for osteoarthritis, they are comparable in effectiveness to oral medications, but potentially safer in terms of systemic effects. They are considered a first-line option for knee and wrist pain. [5]

Table 1. Key classes of analgesics and examples of indications

Class	Typical indications	Examples of situations where the first choice is appropriate
Paracetamol	Mild acute pain, fever	First line for most mild pain
Nonsteroidal anti-inflammatory drugs	Nociceptive pain with an inflammatory component	Joint pain after injury, while observing gastro- and cardio-safety measures
Opioids	Moderate to severe pain when other methods are insufficient	Short-term treatment for severe acute pain, oncological pain according to an individual plan
Adjuvants	Neuropathic, mixed pain	Duloxetine, gabapentin in the appropriate patient profile
Local forms	Local musculoskeletal pain	Osteoarthritis of the knee and wrist joints

How do different analgesics work?

Paracetamol provides central analgesia by acting on enzymatic and serotonergic pathways in the central nervous system, with virtually no anti-inflammatory effect; therefore, it is often combined with other classes depending on the clinical task. [6]

Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase and prostaglandin synthesis, which reduces pain and inflammation, but it is prostaglandins that protect the gastric mucosa and renal blood flow; hence the risks of ulcers and acute kidney injury, as well as an increase in cardiovascular events, for which regulators have strengthened warnings. [7]

Opioid analgesics activate opioid receptors, reducing pain signal transmission, but simultaneously cause sedation, constipation, and the risk of respiratory depression, and with prolonged use, dependence and overdose; current recommendations require minimally effective doses and clear time frames. [8]

Adjuvants act differently: duloxetine enhances descending antinociceptive pathways by blocking the reuptake of serotonin and norepinephrine, and gabapentinoids bind alpha-2-delta subunits of calcium channels, reducing the release of neurotransmitters; when combined with sedatives, patients with respiratory disorders remain vulnerable. [9]

Topical nonsteroidal anti-inflammatory drugs (NSAIDs) suppress pain mediators at the site of application, and capsaicin desensitizes nociceptors; the evidence base for topical NSAIDs in osteoarthritis supports analgesia comparable to oral effects with lower systemic exposure.[10]

Table 2. Mechanism of action and key clinical implications

Class	The main mechanism	Key benefits	Main risks
Paracetamol	Central pathways of pain modulation	Good tolerability	Hepatotoxicity at higher doses
Nonsteroidal anti-inflammatory drugs	Blockade of cyclooxygenases	Anti-inflammatory effect	Ulcers, bleeding, renal and cardiovascular risks
Opioids	Opioid receptor agonists	Strong analgesia	Addiction, overdose, constipation
Adjuvants	Serotonergic and noradrenergic modulation, effects on calcium channels	Targeted therapy for neuropathic pain	Sedative effects, drug interactions
Local forms	Local modulation of pain mediators	Low system load	Skin reactions, limited depth of action

Selection of an analgesic based on the type of pain and clinical situation

For mild acute pain in most adults, treatment is started with paracetamol, adhering to the maximum daily dose, or with a short course of a non-steroidal anti-inflammatory drug, with an assessment of individual gastro-cardiovascular risk; long-term use without medical supervision is not recommended. [11]

For chronic joint pain, it is appropriate to begin with non-drug treatments and topical forms of non-steroidal anti-inflammatory drugs; if these are insufficient, short courses of oral non-steroidal drugs are considered, and, in selected patients, duloxetine is a second-line option. The decision is made taking into account comorbidity. [12]

For neuropathic pain, duloxetine or gabapentin may be the basic pharmacotherapy, with caution in the elderly and in combination with sedatives; therapy is combined with non-drug approaches and tolerability monitoring. [13]

In oncology, the approach remains stepwise, with the possibility of skipping intermediate steps in cases of severe pain and early use of rescue doses; modern reviews emphasize the role of paracetamol and non-steroidal anti-inflammatory drugs at different stages of the individual plan. [14]

In pediatrics, acetylsalicylic acid is avoided for fever and pain in children due to its association with Reye's syndrome; it is safer to use paracetamol or ibuprofen in age-appropriate doses, following the instructions and recommendations of the pediatrician. [15]

Table 3. Choice of analgesic in typical scenarios

Scenario	First line	Alternatives and additions	Security comments
Sharp mild pain	Paracetamol	A short course of nonsteroidal anti-inflammatory drug	Assessment of gastrointestinal and cardiovascular risks
Chronic osteoarthritis	Topical nonsteroidal anti-inflammatory drugs	Oral nonsteroidal drugs, duloxetine	Monitor risks and interactions
Neuropathic pain	Duloxetine or gabapentin	Combinations according to indications	Caution with sedative combinations
Oncological pain	Individual escalation	Rescue doses according to plan	Patient and family education
Pediatric pain and fever	Paracetamol or ibuprofen	-	Avoid acetylsalicylic acid

Safety and risks by class

For paracetamol in adults, the maximum daily dose is 4 g; exceeding this dose is associated with dose-dependent liver damage. In case of overdose, N-acetylcysteine serves as an antidote, which is most effective when administered early. For patients with risk factors for hepatotoxicity, the dose is reduced, and concomitant use of multicomponent medications with the same active ingredient is avoided. [16]

Nonsteroidal anti-inflammatory drugs increase the risk of ulcerative-erosive lesions and gastrointestinal bleeding, as well as the risk of heart attack and stroke, even within the first weeks of use. In patients with a moderate to high risk of bleeding, gastroprotection with proton pump inhibitors is indicated. The minimum effective dose is used for the shortest possible duration. [17]

It is particularly important to avoid the "triple whammy" on the kidneys - the combination of a renin-angiotensin system inhibitor or angiotensin receptor blocker with a diuretic and a non-steroidal anti-inflammatory drug - as this combination increases the risk of acute kidney injury, especially in the first weeks.[18]

For metamizole, EU and Spanish regulators reaffirmed the risk of agranulocytosis and recommended measures for its early recognition and limiting prescribing to short courses in selected patients; if symptoms of infection appear, treatment is stopped and blood tests are performed. The benefit-risk status will be clarified in reviews in 2023–2024. [19]

Combinations of opioids with gabapentinoids increase the risk of respiratory depression, particularly in the elderly and patients with chronic lung disease; such combinations require enhanced monitoring, minimal doses, and careful selection. Risks of addiction and overdose also remain, as reflected in current guidelines. [20]

Table 4. Key risks and how to mitigate them

Risk situation	What is known	What to do
Paracetamol, overdose	Dose-dependent liver damage	Calculate the total daily dose, avoid duplicates, and teach overdose recognition.
Nonsteroidal anti-inflammatory drugs and the gastrointestinal tract	Ulcers and bleeding	Proton pump inhibitor for high-risk patients, short courses, symptom control
Nonsteroidal anti-inflammatory drugs and the heart	Increased risk of heart attack and stroke	Minimum dose and duration, cardiac risk assessment before starting
Triple Strike to the Kidneys	Sharp increase in risk of acute kidney injury	Avoid combination, inform patient about risks of dehydration
Opioids plus gabapentinoids	Respiratory depression	Reduce doses, monitor sedation, assess the need for combination

Special groups: pregnancy, breastfeeding, elderly, cardiac and hepatorenal patients

During the second half of pregnancy, nonsteroidal anti-inflammatory drugs (NSAIDs) can cause decreased fetal urine production, oligohydramnios, and the risk of renal damage. Closer to term, NSAIDs can cause closure of the ductus arteriosus. Therefore, regulators recommend avoiding them starting around 20 weeks unless the benefit outweighs the risk. For fever and pain, paracetamol is preferred. [21]

During breastfeeding, paracetamol and ibuprofen are preferred, while codeine and tramadol are advised against due to variable metabolism and toxicity in children; these warnings include a prohibition on use in children of certain age groups.[22]

Elderly patients have higher baseline risks of bleeding, kidney damage, and respiratory complications; gastroprotection and short courses are considered for nonsteroidal anti-inflammatory drugs, and caution and stepwise titration with monitoring of sedation and respiratory depression are recommended when prescribing gabapentinoids and opioids. [23]

In patients with cardiovascular disease, nonsteroidal anti-inflammatory drugs increase the risk of heart attack and stroke; if discontinuation is unavoidable, the lowest effective dose should be chosen for the shortest period and concomitant therapy and alternatives should be reviewed. [24]

In case of liver pathology, the daily dose of paracetamol is reduced and the total intake from all sources is strictly calculated; in case of chronic kidney disease, non-steroidal anti-inflammatory drugs and especially dangerous combinations associated with a “triple strike” are avoided. [25]

Table 5. Choice of analgesic in special groups

Group	Preference	What to avoid	Comments
Pregnancy after 20 weeks	Paracetamol	Nonsteroidal anti-inflammatory drugs	Only for strict indications
Breast-feeding	Paracetamol, ibuprofen	Codeine, tramadol	Individual risk assessment
Elderly	Local forms, low doses	Long courses of non-steroidal drugs and combinations with sedatives	Consider gastroprotection
Cardiovascular diseases	Minimum doses and durations, alternatives	High doses of nonsteroidal drugs	Review of the scheme at each visit
Liver and kidneys	Dose adjustment, avoidance of nonsteroidal drugs in chronic kidney disease	Triple Strike	Monitoring of tests and hydration

Overdose, interactions, and step-by-step safety tactics

Acute paracetamol overdose requires early administration of N-acetylcysteine; risk assessment is based on the time from ingestion and the drug's blood concentration. With early administration of the antidote, preventing severe liver damage is possible in almost all cases. Self-medication in this situation is unacceptable. [26]

Nonsteroidal anti-inflammatory drugs (NSAIDs) are more likely to cause gastrointestinal and renal complications when taken in overdose; treatment is supportive, and further use is reviewed based on individual risks. For chronic use, the rule remains the same: the lowest effective dose for the shortest duration. [27]

Dangerous combinations include the concomitant use of nonsteroidal anti-inflammatory drugs with warfarin and direct oral anticoagulants due to a multiple increase in the risk of bleeding; this combination is avoided if possible, and if unavoidable, gastroprotection and close monitoring are considered. [28]

In everyday practice, it makes sense to begin with non-drug methods, add topical forms, and then systemic drugs, with a step-by-step assessment of the effect and safety. The plan is always discussed with the patient, and treatment goals and review criteria are documented. This approach reduces the need for high doses and complex combinations. [29]

It is especially important to teach patients how to read the ingredients of over-the-counter medications to avoid “hidden duplicates” of paracetamol and to avoid taking several drugs of the same class at once; this simple rule significantly reduces the likelihood of adverse reactions and overdose. [30]

Table 6. Checklist for safe use of analgesics

Step	What to do	Why is this important?
1	Determine the type of pain and the goal of therapy	The choice of class depends on this
2	Start with non-drug and topical methods	Reducing systemic risks
3	Choose the minimum dose for the minimum period	Fewer complications
4	Consider comorbidity and interactions	Prevention of bleeding and kidney problems
5	Educate the patient and plan follow-up	Early correction and safety

Comparative benchmarks by class

Table 7. Quick Guidelines for Choosing a Class

Clinical task	Basic choice	Alternative in case of contraindications	What to look for during inspection
Mild sharp pain	Paracetamol	Local nonsteroidal anti-inflammatory drug	Overdose symptoms, total daily dose
Inflammatory pain	Nonsteroidal anti-inflammatory drug	Paracetamol plus non-drug methods	Gastrointestinal symptoms, pressure, diuresis
Neuropathic pain	Duloxetine or gabapentin	Combinations according to indications	Sedation, dizziness, shortness of breath
Severe pain	Individualized plan with possible inclusion of opioids	Regional methods, consultation with a specialist	Pain level, tolerance, risks of addiction
Oncological pain	Individual escalation	Adjuvants and rescue doses	Achieving goals, quality of life