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Chemistry LibreTexts

18.2: Pain Relievers: From Aspirin to Oxycodone

  • Page ID
    177677
  • Learning Objectives

    • Know the difference between anti-inflammatory, analgesic and antipyretic drugs.
    • Describe how aspirin and other NSAIDs work.
    • Know the side effects of taking prescription and non-prescription medications
    • Know the risks of addiction, abuse, and overdose of prescription opioids.

    The anti-inflammatory, analgesic (pain reliever or pain killer), and antipyretic (fever reducer) drugs are a heterogeneous group of compounds, often chemically unrelated (although most of them are organic acids), which nevertheless share certain therapeutic actions and side effects. The prototype is aspirin; hence these compounds are often referred to as aspirin-like drugs. All aspirin-like drugs are antipyretic, analgesic, and anti-inflammatory, but there are important differences in their activities. For example, acetaminophen is antipyretic and analgesic but is only weakly anti-inflammatory. The reason for the differences are not clear; variations in the sensitivity of enzymes in the target tissues may be important.

    When employed as analgesics, these drugs are usually effective only against pain of low-to-moderate intensity, particularly that associated with inflammation. Aspirin drugs do not change the perception of sensory modalities other than pain. The type of pain is important; chronic postoperative pain or pain arising from inflammation is particularly well controlled by aspirin-like drugs, whereas pain arising from the hollow viscera is usually not relieved.

    Over-the-counter (OTC) medicines are good for many types of pain. There are two main types of OTC pain medicines: acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs). Aspirin, naproxen (Aleve), and ibuprofen (Advil, Motrin) are examples of OTC NSAIDs.

    If OTC medicines don't relieve ones pain, the doctor may prescribe something stronger. Many NSAIDs are also available at higher prescription doses. The most powerful pain relievers are opioids. They are very effective, but they can sometimes have serious side effects. There is also a risk of addiction. Because of the risks, you must use them only under a doctor's supervision.

    Over the Counter (OTC) Medications

    These relieve the minor aches and pains associated with conditions such as headaches, fever, colds, flu, arthritis, toothaches, and menstrual cramps.

    There are basically two types of OTC pain relievers: acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs).

    Aspirin and other NSAIDs

    colds, sinus pressure, and allergies. They act by inhibiting an enzyme that helps make a specific chemical called prostaglandins.
    Figure \(\PageIndex{1}\) Aspirin.

    Figure \(\PageIndex{2}\) Ibuprofen.

    Prostaglandins are unsaturated carboxylic acids, consisting of of a 20 carbon skeleton that also contains a five member ring and are based upon the fatty acid, arachidonic acid.

    There are a variety of physiological effects associated with prostaglandins including:

    1. Activation of the inflammatory response, production of pain, and fever. When tissues are damaged, white blood cells flood to the site to try to minimize tissue destruction. Prostaglandins are produced as a result.
    2. Blood clots form when a blood vessel is damaged. A type of prostaglandin called thromboxane stimulates constriction and clotting of platelets. Conversely, PGI2, is produced to have the opposite effect on the walls of blood vessels where clots should not be forming.
    3. Certain prostaglandins are involved with the induction of labor and other reproductive processes. PGE2 causes uterine contractions and has been used to induce labor.
    4. Prostaglandins are involved in several other organs such as the gastrointestinal tract (inhibit acid synthesis and increase secretion of protective mucus), increase blood flow in kidneys, and leukotriens promote constriction of bronchi associated with asthma

    How NSAIDs Work?

    clipboard_ecef715210c380598f3cd00e5490e71ed.png (COX-1 and COX-2). These enzymes are involved with the ring closure and addition of oxygen to arachidonic acid converting to prostaglandins. The acetyl group on aspirin is hydrolzed and then bonded to the alcohol group of serine as an ester (Figure \(\PageIndex{4}\)). This has the effect of blocking the channel in the enzyme and arachidonic acid can not enter the active site of the enzyme. By inhibiting or blocking this enzyme, the synthesis of prostaglandins is blocked, which in turn relieves some of the effects of pain and fever. Aspirin is also thought to inhibit the prostaglandin synthesis involved with unwanted blood clotting in coronary heart disease. At the same time an injury while taking aspirin may cause more extensive bleeding.
    Figure \(\PageIndex{3}\) Aspirin inhibition of COX-1 and COX-2 enzymes.

    556coxaspirin.gifFigure \(\PageIndex{4}\) The acetyl group (from aspirin) bonds to serine in COX enzyme.

    There are other non-selective NSAIDs on the market, including diclofenac, ibuprofen, ketoprofen, meloxicam, naproxen, and oxaprozin. Ibuprofen and naproxen are available in both prescription and over-the-counter (OTC) versions. The doses in OTC ibuprofen (Advil and Motrin) or naproxen (Aleve) are about half the doses of prescription versions.

    COX-2 selective inhibitors are a newer type of medicine that block the COX-2 enzyme more than the COX-1 enzyme. The only COX-2 selective inhibitor currently on the market in the United States is the prescription drug Celebrex (celecoxib), which is marketed by Pfizer. It was believed that COX-2 inhibitors may be less likely to cause the stomach problems associated with the older NSAIDs, but all NSAIDs carry the risk of stomach problems.

    Key Points to Remember With NSAIDs

    • Too much can cause stomach bleeding. This risk increases in people who are over 60 years of age, are taking prescription blood thinners, are taking steroids, have a history of stomach bleeding or ulcers, and/or have other bleeding problems.
    • Use of NSAIDs can also cause kidney damage. This risk may increase in people who are over 60 years of age, are taking a diuretic (a drug that increases the excretion of urine), have high blood pressure, heart disease, or pre-existing kidney disease.

    Acetaminophen

    Acetaminophen, Tylenol (Figure \(\PageIndex{5}\)) is known as a non-aspirin pain reliever. It is NOT an NSAID.

    Acetaminophen relieves fever and headaches, and other common aches and pains. It does not relieve inflammation. This medicine does not cause as many stomach problems as other pain medicines do. It is also safer for children. Acetaminophen is often recommended for arthritis pain because it has fewer side effects than other pain medicines. Examples of OTC brands of acetaminophen are Tylenol, Paracetamol, and Panadol. Acetaminophen prescribed by a doctor is usually a stronger medicine. It is often combined with a narcotic ingredient.
    Figure \(\PageIndex{5}\) Acetaminophen.

    Key Points to Remember With Acetaminophen

    • Taking a higher dose than recommended will not provide more relief and can be dangerous.
    • Too much can lead to liver damage and death. Risk for liver damage may be increased in people who drink three or more alcoholic beverages a day while using acetaminophen-containing medicines.
    • Be cautious when giving acetaminophen to children. Infant drop medications can be significantly stronger than regular children's medications. Read and follow the directions on the label every time you use a medicine. Be sure that your infant is getting the infants' pain formula and your older child is getting the children's pain formula.

    Prescription Medications

    Typical prescription pain relief medicines include opioids and non-opioid medications. Types of prescription opioid medications (Figures \(\PageIndex{6}\) and \(\PageIndex{7}\)) include:

    • morphine, which is often used before and after surgical procedures to alleviate severe pain
    • oxycodone, which is also often prescribed for moderate to severe pain
    • codeine, which comes in combination with acetaminophen or other non-opioid pain relief medications and is often prescribed for mild to moderate pain
    • hydrocodone, which comes in combination with acetaminophen or other non-opioid pain relief medications and is prescribed for moderate to moderately severe pain

    Derived from opium, opioid drugs are very powerful products. They act by attaching to a specific "receptor" in the brain, spinal cord, and gastrointestinal tract. Opioids can change the way a person experiences pain. The term opium refers to the crude resinous extract obtained from the opium poppy. Crude opium contains a wide variety of ingredients, including morphine and codeine, both of which are widely used in medicine. The bulk of the ingredients of opium, however, consists of such organic substances as resins, oils, sugars, and proteins that account for more than 75 % of the weight of the opium but exert little pharmacological activity. Morphine is the major pain relieving drug found in opium, being approximately 10% of the crude exudate. Codeine is structurally close to morphine (see Figure \(\PageIndex{6}\)), although it is much less potent and amounts to only 0.5% of the opium extract. Heroin does not occur naturally but is a semisynthetic derivative produced by a chemical modification of morphine that increases the potency (see Figure \(\PageIndex{7}\)). It takes only 3 mg. of heroin to produce the same analgesic effect as 10 mg of morphine. However, at these equally effective doses, it may be difficult to distinguish between the effects of the two compounds.

    Figure \(\PageIndex{6}\) Morphine and codeine.

    Figure \(\PageIndex{7}\) Heroin.

    Oxycodone and hydrocodone are used to relieve moderate to severe pain. Oxycodone and hydrocodone extended-release tablets and extended-release capsules are used to relieve severe pain in people who are expected to need pain medication around the clock for a long time and who cannot be treated with other medications.

    Addiction and Overdose

    Anyone who takes prescription opioids can become addicted to them. In fact, as many as one in four patients receiving long-term opioid therapy in a primary care setting struggles with opioid addiction. Once addicted, it can be hard to stop. In 2016, more than 11.5 million Americans reported misusing prescription opioids in the past year. Taking too many prescription opioids can stop a person’s breathing—leading to death. Prescription opioid overdose deaths also often involve benzodiazepines. Benzodiazepines are central nervous system depressants used to sedate, induce sleep, prevent seizures, and relieve anxiety. Examples include alprazolam (Xanax®), diazepam (Valium®), and lorazepam (Ativan®). Avoid taking benzodiazepines while taking prescription opioids whenever possible.

    Side Effects of Prescription Opioids

    In addition to the serious risks of addiction, abuse, and overdose, the use of prescription opioids can have a number of side effects, even when taken as directed:

    • Tolerance—meaning you might need to take more of the medication for the same pain relief
    • Physical dependence—meaning you have symptoms of withdrawal when the medication is stopped
    • Increased sensitivity to pain
    • Constipation
    • Nausea, vomiting, and dry mouth
    • Sleepiness and dizziness
    • Confusion
    • Depression
    • Low levels of testosterone that can result in lower sex drive, energy, and strength
    • Itching and sweating


    Opiate Antagonists

    Naloxone, when administered to normal individuals, produces no analgesia, euphoria, or respiratory depression. However, it rapidly precipitates withdrawal in narcotic-dependent individuals. Naloxone antagonizes the actions of morphine at all its receptors.

    The uses of naloxone include the reversal of the respiratory depression that follows acute narcotic intoxication and the reversal of narcotic-induced respiratory depression in newborns of mothers who have received narcotics. The use of naloxone is limited by a short duration of action and the necessity of parenteral route of administration.

    Naltrexone became clinically available in 1985 as a new narcotic antagonist. Its actions resemble those of naloxone, but naltrexone is well is well absorbed orally and is long acting, necessitating only a dose of 50 to 100 mg. Therefore, it is useful in narcotic treatment programs where it is desired to maintain an individual on chronic therapy with a narcotic antagonist. In individuals taking naltrexone, subsequent injection of an opiate will produce little or no effect. naltrexone appears to be particularly effective for the treatment of narcotic dependence in addicts who have more to gain by being drug-free rather than drug dependant.

    Combination Pain Relievers

    Aspirin is often combined with acetaminophen in a single tablet for relief of arthritis and other painful conditions. Sometimes other drugs such as caffeine, an antihistamine, nasal drying agents, and sedatives are also added. Although some of these preparations may have special uses for certain acute conditions such as a cold or a headache, they should not be taken for a chronic (long-term) form of arthritis. If a combination is required, each drug should be prescribed separately. The dose of each should be adjusted individually to achieve the greatest benefit with the fewest side effects.

    Hydrocodone is available in combination with other ingredients, and different combination products are prescribed for different uses. Some hydrocodone combination products are used to relieve moderate-to-severe pain. Other hydrocodone combination products are used to relieve cough. Hydrocodone is in a class of medications called opiate (narcotic) analgesics and in a class of medications called antitussives. Hydrocodone relieves pain by changing the way the brain and nervous system respond to pain. Hydrocodone relieves cough by decreasing activity in the part of the brain that causes coughing.

    Web Link

    A list of different hydrocodone combination products can be found on the link below.

    https://medlineplus.gov/druginfo/meds/a601006.html

    Summary

    • Different types of medicine address different ailments. Anti-inflammatory drugs mediate inflammation, analgesics relieve pain, and antipyretic drugs help lower body temperature associated with fever.
    • Over the counter (OTC) pain relievers relieve the minor aches and pains associated with conditions such as headaches, fever, colds, flu, arthritis, toothaches, and menstrual cramps.
    • There are basically two types of OTC pain relievers: acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs).
    • Aspirin and other aspirin-like drugs work by blocking the (COX-1 and COX-2) enzymes involved in pain and inflammation.
    • Typical prescription pain relief medicines include opioids and non-opioid medications.
    • In addition to the serious risks of addiction, abuse, and overdose, the use of prescription opioids can have a number of side effects,

    Sources

    • National Institute of Health (NIH) MedlinePlus
    • US FDA
    • US CDC