Co-analgesics (Adjuvants)
This group includes drugs that affect neuronal uptake of neurotransmitters, ion channels, and various CNS receptors. They are not opioids (with the exception of fentanyl and buprenorphine, which are true opioids and are not classified as adjuvants).
Tricyclic antidepressants This subgroup includes amitriptyline and imipramine (Imizin). The mechanism of their analgesic action involves the inhibition of the neuronal reuptake of monoamines—norepinephrine and serotonin. The accumulation of these substances in synapses leads to the activation of the descending antinociceptive system. As a result, transmission of pain impulses is inhibited directly at the spinal cord level. These drugs are strongly indicated for chronic pain, phantom limb pain, and neuralgias of various etiologies.
Antiepileptic drugs This category includes sodium channel blockers such as carbamazepine (Tegretol) and phenytoin (Diphenin). Their mechanism is based on the blockade of membrane sodium channels, which reduces pathological neuronal excitability. They have specific high efficacy in trigeminal neuralgia, which is typically accompanied by paroxysms of severe pain.
Drugs affecting the GABAergic system
- Gabapentin: an antiepileptic drug whose mechanism is related to the stimulation of GABAergic transmission in the CNS. Successfully used for migraine and severe neuropathic pain.
- Baclofen: acts as a GABA receptor agonist. Widely used to relieve painful muscle spasms and eliminate spasticity.
General anesthetics and other drugs
Some general anesthetics possess a potent ancillary analgesic effect.
- Ketamine: a phencyclidine derivative. Acts as a non-competitive NMDA receptor antagonist. The drug induces a state of so-called dissociative anesthesia and provides potent analgesia. Its primary application is general anesthesia.
- Nitrous oxide: administered by inhalation. Indicated for relieving intense pain in myocardial infarction, for analgesia during labor, and in the early postoperative period.
In addition, a certain, albeit less pronounced, analgesic effect can be exerted by drugs from other classes, for example, $H_1$-receptor antagonists (diphenhydramine), as well as somatostatin and calcitonin.
Analgesics with a mixed mechanism of action
A prominent representative of this group is tramadol (Tramal), which combines both opioid and non-opioid components of pain relief.
Pharmacodynamics of tramadol (dual mechanism):
- Opioid component: the drug acts as a central non-selective agonist of $\mu$-, $\delta$-, and $\kappa$-receptors.
- Non-opioid (monoaminergic) component: similar to antidepressants, tramadol inhibits the neuronal reuptake of norepinephrine and serotonin, thereby enhancing descending inhibitory influences on pain transmission within spinal cord structures.
Safety profile and advantages: Although tramadol is inferior in analgesic potency to classical morphine, it has a significantly better safety profile. The drug causes virtually no respiratory depression, does not decrease GI motility (minimizing the risk of chronic constipation), and does not increase urinary tract tone. Furthermore, it has a significantly lower abuse potential (the risk of drug dependence is substantially lower than that of classical opioids) and is not scheduled as a potent narcotic.
Indications for use:
- Postoperative pain.
- Pain syndromes in myocardial infarction.
- Pain in malignancies.
- Severe trauma.
The drug is versatile in delivery routes: administered parenterally, orally, and rectally.
Briefly: answers to topical questions
What side effects are characteristic of amitriptyline?
- M-cholinolytic action (M-cholinolyticum) — causes xerostomia (dry mouth), urinary retention, mydriasis, and accommodation disturbance.
- Cardiovascular effects (effectus cardiovasculares) — lowers blood pressure and has arrhythmogenic potential capable of causing arrhythmia, as well as orthostatic hypotension.
- Central and other effects (effectus centrales) — cause drowsiness, dizziness, and allergic reactions.
To remember tramadol's dual mechanism: "Tramadol works on TWO floors — it hits opioid receptors from above, and blocks serotonin and norepinephrine reuptake from below."
Class and exam questions
Why do antidepressants help with pain?
They inhibit the neuronal reuptake of norepinephrine and serotonin. The accumulation of these neurotransmitters activates the descending antinociceptive system, which inhibits pain impulse transmission in the spinal cord.
What is the main advantage of tramadol over morphine?
Tramadol has a safer profile: it causes virtually no respiratory depression, does not inhibit GI motility (lower risk of constipation), and has a low abuse potential, not being a scheduled narcotic.
In which type of pain is carbamazepine most effective?
Carbamazepine, being a sodium channel blocker, has high specific efficacy in trigeminal neuralgia, which is accompanied by severe pain attacks.
What else to study on this topic
- Detailed mechanism of activation of the descending antinociceptive system
- Comparative profile of selective and non-selective opioid receptor agonists
- The role of the GABAergic system in the regulation of muscle tone and pain sensitivity
- Features of dissociative anesthesia development during NMDA receptor blockade
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