What is pain and analgesics? Pain is an emotional or unpleasant sensory associated with actual or potential tissue damage. It is the most common symptom of most diseases, and it’s very often the first pointer to a deviation from the normal functioning of the different parts of the body.
What is Pain and Analgesics
Understanding the physiology and classification of pain helps in the assessment and management of pain. Also, determining the type of pain helps to formulate the best treatment plan.
Pain can be classified in different ways based on:
- Duration: Acute – less than three (3) months or Chronic – greater than three (3) months
- Pathophysiological mechanism of pain i.e. nociceptive or neuropathic pain
- Anatomic location: relating to the part of the body involved such as low back pain, shoulder, ankle, etc.
- Cause of pain: including neoplastic (cancer-related) and non-neoplastic (non-cancer related)
Pharmacological intervention of pain requires the use of analgesics.
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This simply refers to those drugs which produce an insensitivity to pains without loss of consciousness. They selectively depress the Central Nervous System (CNS) at the cerebrum and medulla. They are mainly used for the relief of symptomatic pains and are grouped into:
- The centrally acting narcotics e.g. morphine
- and peripherally acting (non-narcotics) e.g. salicylates
The study of analgesics can be divided into two groups:
- Morphine and related compounds
There are other groups of drugs that do not fit into the definition of analgesic but possess analgesic properties like sedatives e.g. barbiturates, muscle relaxants e.g. methocarbamol, baclofen, and tranquilizers, etc.
Morphine and Related Compounds
Modification of morphine molecules can be considered in diverse ways
Early Morphine Modification
Morphine is obtained from opium which is a partly dried latex from incised unripe capsules of papaver somniferum. Opium contains numerous alkaloids of which morphine, codeine, noscapine, and papaverine are therapeutically the most important. The action of opium is principally due to its morphine content.
As an analgesic, opium is not as effective as morphine because of its constipation activity hence being used as an antidiarrheal preparation.
Two types of basic structures are recognized among the opium alkaloids i.e. phenanthrene (Morphine) and benzylisoquinoline (papaverine)
The pharmacological action of the two types of alkaloids is not the same.
- The morphine types act principally on the CNS as a depressant, relaxant, and a stimulant, while
- The papaverine groups have little effect on the CNS but have antispasmodic action on the smooth muscles
The depressant action of the morphine group is the most useful property resulting in increased tolerance to pain, sleepiness, lessened perception to external stimuli, and a feeling of wellbeing (euphoria).
Respiratory depression and addiction tendencies are the most serious objections. The stimulant action is illustrated by the convulsion by the same members of the group e.g., thebaine
Years back, derivatives of morphine were obtained by simple modification of the molecule e.g. esterification of the phenolic or alcoholic hydroxyl group; the resultant compounds had better activity than morphine but with greater toxicity and addiction tendencies.
Among the early compounds is codeine; the phenolic methyl ether of morphine also present in the natural sources. It is a good analgesic and cough depressant. The ethyl ether is used in ophthalmology.
The diacetyl derivative (heroine) produced by acetylation of both alcoholic and phenolic off groups have a very high degree of dependency and are not allowed for use in many countries of the world.
Morphine Modification by Small and Eddy Et. Al 1929
The aim of these researchers was:
- To separate chemically the addictive properties of morphine from the therapeutic attribute as procaine was from cocaine.
- If (a) above is not possible at least to find other synthetic molecules without the undesirable side effect such as respiratory depression, emetic properties, GIT and circulatory disturbances could be abolished.
The morphine molecules offer ease of alterations. The research did not provide an answer to the elimination of addiction potentials but suggested that any modification bringing about an increase in analgesic activity causes a concomitant increase in addiction liability.
Narcotic (Opioid) Analgesics
These are drugs that produce pain relief (analgesia), narcosis (state of stupor or sleep), and addiction (physical dependence on the drug). In most countries, the production, trade-in, and use of narcotics are limited because of their addictive properties, detrimental effect, and the incidence of narcotic drug abuse.
Opioid analgesics can be classified as follows:
Based on the origin
- Naturally occurring opioids e.g. morphine, codeine, thebaine, narcotine, papaverine, etc.
- Semi-synthetic opioids use compounds isolated from natural sources (e.g. plants) as starting material. Examples are heroin, oxycodone, oxymorphone, and hydrocodone.
- Synthetic opioids are made using total synthesis in which large molecules are synthesized from a stepwise combination of small and inexpensive building blocks. Examples are tramadol, pentazocine, methadone, alfentanil, meperidine, pethidine and fentanyl.
- Based on functions or activity at the opioid receptor;
Based on their mechanism of activity or function at the opioid receptor, opioid analgesics have traditionally been classified into three (3) pharmacologic classes:
- Full agonists – which bind tightly to the opioid receptor and undergo a significant conformational change to produce a maximal effect. Examples include codeine, morphine, heroin, hydrocodone, methacodone, and oxycodone.
- Partial agonists – which have an affinity for opioid receptors, but low intrinsic activity compared to full agonists. Note that a higher dose of a pure agonist is required in the presence of a partial agonist in order to obtain a full agonistic response. Examples are tramadol, buprenorphine, etc.
- Mixed agonist antagonists – they exert an agonistic effect at one opioid receptor and an antagonistic effect on the other. Examples are pentazocine, nalorphine.
Non–Narcotic (Non–Opioid) Analgesics
These include non-steroidal anti-inflammatory drugs (NSAIDs), selective COX-2 inhibitors, and acetaminophen (paracetamol).
- Non-steroidal anti-inflammatory drugs (NSAIDs)
Examples of drugs here include
- Ketorolac, etc.
Acute and chronic pain (particularly musculoskeletal), rheumatoid arthritis, inflammatory arthritis, headache, dysmenorrhea, fever, acute gout attack.
- Increased risk of heart attack and stroke (with exception of naproxen and aspirin)
- Gastric and duodenal ulcer with the risk of gastrointestinal bleeding and perforation. Risk increases with duration and dose of treatment and it’s 10 – 15 times higher if NSAIDs and glucocorticoids are administered simultaneously. Prevention of this side effect requires simultaneous administration of proton pump inhibitors like omeprazole, lansoprazole, rabeprazole, pantoprazole, etc.
Renal Function Impairment
- Pseudo allergic reactions
Selective COX-2 Inhibitors
Examples of drugs here include
Acute pain, rheumatoid arthritis, non-rheumatoid joint pain, etc
- Increased risk of heart attack and stroke
- Renal side effect in at-risk patients
Other Non-opioid Analgesic
Drug example: Acetaminophen
Fever and pain (good tolerability).
Hyper toxicity due to acetaminophen overdose.
Pain causes discomfort/unpleasant feelings and if ignored can become severe and as such appropriate analgesics should be used in its treatment and with appropriate doses to avoid toxicities.