Concepts of analgesic drug action

02/06/2014 - Pain

Pain occurs as a result of mechanical trauma, thermal or chemical, or inflammation, or cancer. Then relays are triggered (prostaglandins, substance P, kinins, potassium ions, etc.) that stimulate pain receptors (nociceptors, which are in various tissues of the body, but there is no example in the brain). Of course, the stimulus must be sufficiently strong. Nerve impulse of such a receptor is sent first to the spinal cord and then to the cortex, where the sensation of pain arises. Along the way, is transferred from neuron to neuron synapses so beat – an effort in this chemicals called neurotransmitters secreted by the presynaptic membrane (before synapse) and connecting to the appropriate receptor in the postsynaptic membrane (per synapse). Analgesics act at different stages of the stimulus conduction.

Most often, we use non-narcotic analgesics. These include the popular paracetamol. It inhibits the cyclooxygenase activity of COX-3 present in the central nervous system – thus decreasing the production of prostaglandins, and this results in a reduced sensation of pain. COX-3 is a variant of COX-1 (cyclooxygenase constantly present in many cell types). There is also a COX-2 which is the inducible form of the enzyme, which induce the expression of, inter alia, proinflammatory mediators. Probably paracetamol also induces the activity of the descending road serotonin, which inhibits the transmission of pain signals in the spinal cord.

Importantly, the above potency of a given dose of paracetamol does not increase. This is called. ceiling effect. In the case of paracetamol in adults dose above which does not increase the pharmacological activity is 1000 mg. This effect also applies to other drugs. Paracetamol has very weak anti-inflammatory action. It does not inhibit prostaglandin synthesis in other tissues, so that does not cause side effects such as non-steroidal anti-inflammatory drugs (NSAIDs).

NSAIDs are also non-narcotic analgesics. Their name comes from the fact that they have a different structure of anti-inflammatory compounds – corticosteroids. Among the NSAIDs are: naproxen, meloxicam, ketoprofen, diclofenac, ibuprofen and acetylsalicylic acid (aspirin). Although they differ in chemical structure, mechanism of action is very similar – inhibit the three forms of cyclooxygenase, COX-1 (the block is responsible for the appearance of side effects, including gastric mucosa occurs to reduce mucus secretion and impaired barrier against the hydrochloric acid – this can lead to the formation of stomach ulcers), COX-2 (mainly, the inhibition of the activity of anti-inflammatory and analgesic conditions the effect of the drug, the site of inflammation is not prostaglandins, which lowers the threshold of excitability of nociceptors to other mediators of pain), and COX-3 (central action).

Non-narcotic drugs are used at relatively weaker pain ailments. When the problem is more serious – there has been extensive trauma or the patient is struggling with advanced cancer – doctors ordain stronger pharmaceuticals: medicines narcotic (opioid), for example, morphine, codeine. These combine with specific receptors present in the brain and spinal cord, binding natural substances produced by the body to relieve pain (endorphins, enkephalins, and dynorphin) – and almost immediately abolish pain. Their operation is based on the fact that they inhibit the release of neurotransmitters presynaptically pain (opening or closing the potassium channels, calcium channels) of the central terminals of primary afferents. A postsynaptic inhibition condition, since they result in membrane hyperpolarization of neurons in the posterior horn of the spinal cord (by increasing the activity of potassium channels). Differences in the operation of specific opioids occurs due to their different properties, such as differences in affinity for different types of opioid receptors.

In turn, local anesthetics (lidocaine, bupivacaine) block the movement of the pain signals in the nervous fibers. Indeed changing permeability of sodium and potassium ions determining the polarization and depolarization processes. Mechanisms of action of analgesics are therefore varied.