Pain relievers

Generality

Painkillers (or analgesics) - as their name suggests - are drugs used to treat pain of different nature and extent.

Although effective in "turning off" the pain, these drugs generally do not solve the cause that led to the onset of the painful stimulus.
The following classes of drugs belong to the group of painkillers:

NSAIDs (non-steroidal anti-inflammatory drugs);
The analgesics-antipyretics;
Opioid analgesics.

The characteristics of these drug classes will be briefly illustrated below.

NSAIDs

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) constitute a rather broad category of drugs.
The active ingredients belonging to this class are endowed - to a greater or lesser extent - with anti-inflammatory, pain-relieving and antipyretic properties.
Only some of the main characteristics of NSAIDs will be briefly outlined below. For more detailed information, please refer to the dedicated articles already present on this site ("NSAIDs: History, Mechanism of action, Indications", "NSAIDs: Classification based on chemical structure", "NSAIDs: Side effects and Contraindications").
NSAIDs can be classified according to their chemical structure and according to their mechanism of action.
Among the most known and used NSAIDs we find:

Salicylates, among which acetylsalicylic acid stands out;
Propionic acid derivatives, such as ibuprofen, naproxen, ketoprofen, dexketoprofen and flurbiprofen;
Acetic acid derivatives, among which ketorolac, diclofenac and indomethacin stand out;
Sulfonylides, among which we find nimesulide;
Derivatives of enolic acid, among which we find piroxicam, meloxicam, tenoxicam and lornoxicam;
Derivatives of phenamic acid, among which we find mefenamic acid and flufenamic acid;
Selective COX-2 inhibitors, including celecoxib and etoricoxib.

Mechanism of action of NSAIDs

NSAIDs exert their anti-inflammatory, antipyretic and above all analgesic action through the inhibition of cyclooxygenase.
Cyclooxygenase is an enzyme of which three different isoforms are known: COX-1, COX-2 and COX-3.
These enzymes convert the arachidonic acid present in our body into prostaglandins, prostacyclines and thromboxanes.
Prostaglandins - and in particular prostaglandins G2 and H2 - are involved in inflammatory processes and mediate painful responses. While prostaglandins type E (PGE) induce fever.
COX-1 is a "constitutive isoform, normally present in cells and involved in the mechanisms of cellular homeostasis. COX-2, on the other hand, is an" inducible isoform that is produced by activated inflammatory cells (inflammatory cytokines).
Through the inhibition of COX-2, therefore, the formation of prostaglandins responsible for the onset of fever, inflammation and pain is hindered.
However, many NSAIDs (except selective COX-2 inhibitors) are also capable of inhibiting the constitutive isoform COX-1. This inhibition is at the origin of some of the typical side effects of non-selective NSAIDs.

Side effects

Of course, the side effects vary according to the active ingredient used, but some side effects are common to the entire class of drugs.
Among the adverse effects common to all NSAIDs we find those of the gastrointestinal type, such as:

Nausea;
He retched;
Diarrhea or constipation
Gastrointestinal ulceration, perforation and / or bleeding.

Furthermore, the use of NSAIDs in high doses and for long periods of time can cause an increased risk of developing myocardial infarction or stroke.

Analgesics-antipyretics

This class includes drugs that induce antipyretic and pain-relieving effects, but which do not possess anti-inflammatory activity.
In fact, the only active ingredient still on the market belonging to this class of drugs is paracetamol.
The mechanism of action by which this drug carries out its activity, however, has not yet been fully understood.
The most accredited hypothesis is that according to which paracetamol exerts its antipyretic and pain-relieving action by inhibiting one of the isoforms of the cyclooxygenase enzyme: COX-3.

Opioid analgesics

All those drugs that produce analgesia following the stimulation of endogenous opioid receptors belong to this class of painkillers.
Also in this case, only some of the characteristics of this class of drugs will be briefly illustrated below; for more detailed information, see the dedicated article already present on this site ("Opioid drugs").
Among the best known opioid painkillers are morphine, codeine (also used for its antitussive properties), fentanyl (or fentanyl, or fentanyl), methadone, oxycodone and buprenorphine.

Mechanism of action of opioid analgesics

As mentioned, painkillers belonging to this class of drugs exert their action by stimulating endogenous opioid receptors.
There are several types of opioid receptors:

Μ receptor (also known as MOP);
Δ receptor (also known as DOP);
Κ receptor (also known as LAD);
Orphan receptor (otherwise known as NOP).

These receptors are located along the pain pathways of our body and are involved, in fact, in the neurotransmission of painful stimuli. More specifically, their stimulation causes the activation of a cascade of chemical signals which culminates in the induction of an analgesic effect.
Most opioid analgesics used in therapy are agonists (partial or total, selective or not) of μ-receptors. Therefore, the mechanism of action of these drugs consists in stimulating the aforementioned receptors, thus inducing analgesia.